Archives of Dermatology

Vol. 143 No. 12, pp. 1480-1612, December 2007

This Month in Archives of Dermatology This Month in Archives of Dermatology Arch Dermatol. 2007;143(12):1480.

Studies The Risk of Mortality in Patients With Psoriasis: Results From a Population- Based Study Joel M. Gelfand; Andrea B. Troxel; James D. Lewis; Shanu Kohli Kurd; Daniel B. Shin; Xingmei Wang; David J. Margolis; Brian L. Strom Arch Dermatol. 2007;143(12):1493-1499.

A 3-Year Causative Study of Pompholyx in 120 Patients Marie Hélène Guillet; Ewa Wierzbicka; Stephanie Guillet; Guy Dagregorio; Gerard Guillet Arch Dermatol. 2007;143(12):1504-1508.

Teledermatological Monitoring of Leg Ulcers in Cooperation With Home Care Nurses Barbara Binder; Rainer Hofmann-Wellenhof; Wolfgang Salmhofer; Aslihan Okcu; Helmut Kerl; H. Peter Soyer Arch Dermatol. 2007;143(12):1511-1514.

Reliability of the Roenigk Classification of Liver Damage After Methotrexate Treatment for Psoriasis: A Clinicopathologic Study of 160 Liver Biopsy Specimens Maartje A. M. Berends; Martijn G. H. van Oijen; Josje Snoek; Peter C. M. van de Kerkhof; Joost P. H. Drenth; J. Han van Krieken; Elke M. G. J. de Jong Arch Dermatol. 2007;143(12):1515-1519.

Results of Radiotherapy in 153 Primary Cutaneous B-Cell Lymphomas Classified According to the WHO-EORTC Classification Nancy J. Senff; Juliette J. Hoefnagel; Karen J. Neelis; Maarten H. Vermeer; Ed M. Noordijk; Rein Willemze; for the Dutch Cutaneous Lymphoma Group Arch Dermatol. 2007;143(12):1520-1526.

Angiogenesis in Cutaneous Lesions of Leprosy: Implications for Treatment Sulochana S. Bhandarkar; Cynthia Cohen; Maria Kuruvila; Thomas H. Rea; Jamie B. MacKelfresh; Delphine J. Lee; Robert L. Modlin; Jack L. Arbiser Arch Dermatol. 2007;143(12):1527-1529.

Patterns of Indoor Tanning Use: Implications for Clinical Interventions Joel Hillhouse; Rob Turrisi; Alan L. Shields Arch Dermatol. 2007;143(12):1530-1535.

A Comparison of Oral Methylprednisolone Plus Azathioprine or Mycophenolate Mofetil for the Treatment of Bullous Pemphigoid Stefan Beissert; Thomas Werfel; Uta Frieling; Markus Böhm; Michael Sticherling; Rudolf Stadler; Detlef Zillikens; Berthold Rzany; Nicolas Hunzelmann; Michael Meurer; Harald Gollnick; Thomas Ruzicka; Hans Pillekamp; Volker Junghans; Gisela Bonsmann; Thomas A. Luger Arch Dermatol. 2007;143(12):1536-1542.

Observations Smoking and Skin Aging in Identical Twins Daven N. Doshi; Kaija K. Hanneman; Kevin D. Cooper Arch Dermatol. 2007;143(12):1543-1546.

Ex Vivo Dermoscopy of Melanocytic Tumors: Time for Dermatopathologists to Learn Dermoscopy Alon Scope; Klaus J. Busam; Josep Malvehy; Susana Puig; Steve A. McClain; Ralph P. Braun; Ashfaq A. Marghoob Arch Dermatol. 2007;143(12):1548-1552.

Long-term Follow-up of a Patient With Eruptive Melanocytic Nevi After Stevens-Johnson Syndrome Allison Gelfer; Jason K. Rivers Arch Dermatol. 2007;143(12):1555-1557.

Evidence-Based Dermatology: Studies Incidence and Risk Factors for Psoriasis in the General Population Consuelo Huerta; Elena Rivero; Luis A. García Rodríguez Arch Dermatol. 2007;143(12):1559-1565.

Evidence-Based Dermatology: Research Commentaries Level of Agreement With the British Guidelines for the Use of Biological Therapies for Psoriasis Tamar Nijsten Arch Dermatol. 2007;143(12):1567-1569.

Evidence-Based Dermatology: Reviews The Role of Furry Pets in Eczema: A Systematic Review Sinéad M. Langan; Carsten Flohr; Hywel C. Williams Arch Dermatol. 2007;143(12):1570-1577.

Editorials Acute and Recurrent Vesicular Hand Dermatitis Not Pompholyx or Dyshidrosis Frances J. Storrs Arch Dermatol. 2007;143(12):1578-1580.

Teledermatology: Extending Specialty Care Beyond Borders Anne E. Burdick Arch Dermatol. 2007;143(12):1581-1582.

skINsight A Dermoscopy Subpattern of Plaque-Type Psoriasis: Red Globular Rings Francisco Vázquez-López; Pedro Zaballos; Alejandro Fueyo-Casado; Jesus Sánchez- Martín Arch Dermatol. 2007;143(12):1612.

Off-Center Fold Solitary Cutaneous Nodule in an Immunocompromised Patient—Quiz Case Minal N. Singh; Susan Andrew; David Fitzgerald Arch Dermatol. 2007;143(12):1583-1588.

Solitary Cutaneous Nodule in an Immunocompromised Patient—Diagnosis Arch Dermatol. 2007;143(12):1583-1588.

Generalized Papules in a Patient With Acute Myeloid Leukemia—Quiz Case Kyoko Nakahigashi; Miki Tanioka; Yoshiki Miyachi Arch Dermatol. 2007;143(12):1583-1588.

Generalized Papules in a Patient With Acute Myeloid Leukemia—Diagnosis Arch Dermatol. 2007;143(12):1583-1588.

The Cutting Edge Fractional Resurfacing: A New Therapeutic Modality for Becker's Nevus Adrienne S. Glaich; Leonard H. Goldberg; Tianhong Dai; Joy H. Kunishige; Paul M. Friedman Arch Dermatol. 2007;143(12):1488-1490.

Archives a Century Ago The Opsonic Method in Skin Diseases. Arch Dermatol. 2007;143(12):1484.

Research Letters

Discoid and Subacute Lupus Erythematosus Treated With 0.5% R-Salbutamol Cream Hans Christian Wulf; Susanne Ullman Arch Dermatol. 2007;143(12):1589-1590. High Procalcitonin Levels in Patients With Severe Drug Reactions Mehdi Sfia; Peggy Boeckler; Dan Lipsker Arch Dermatol. 2007;143(12):1591.

Quality of Dermatologic Care Delivered by Physician Assistants: An Analysis of Prescribing Behavior for the Combination Antifungal Agent Clotrimazole- Betamethasone Anita Satyaprakash; Rajesh Balkrishnan; Fabian T. Camacho; Sujata S. Jayawant; Alan B. Fleischer Jr; Steven R. Feldman Arch Dermatol. 2007;143(12):1591-1592.

Quality of Care From a Patient’s Perspective Christie G. Regula; Jeffrey J. Miller; David T. Mauger; James G. Marks Arch Dermatol. 2007;143(12):1592-1593.

Correspondence Psoriasiform Eruptions During Anti–TNF- Treatment: Psoriasis or Not? Julien Seneschal; Sébastien Lepreux; Brigitte Milpied; Thierry Schaeverbeke; Alain Taïeb Arch Dermatol. 2007;143(12):1593-1595.

Psoriasiform Eruptions During Anti–TNF- Treatment: Psoriasis or Not?— Reply Gillian C. de Gannes; Mehran Ghoreishi; Janet Pope; Anthony Russell; David Bell; Stewart Adams; Kamran Shojania; Magdalena Martinka; Jan P. Dutz Arch Dermatol. 2007;143(12):1595.

British Guidelines on the Use of Biological Therapies for Psoriasis: A Note of Clarification on the Role of Etanercept Catherine H. Smith; Anthony D. Ormerod Arch Dermatol. 2007;143(12):1595-1596.

Multiple Subcutaneous Lipomas Induced by HAART in the Absence of Protease Inhibitors Elena Balestreire; Justin M. Haught; Joseph C. English III Arch Dermatol. 2007;143(12):1596-1597.

Clinical Improvement of Pityriasis Rubra Pilaris With Combination Etanercept and Acitretin Therapy Kristy F. Davis; Jashin J. Wu; Jenny E. Murase; Fredric R. Rosenberg; Erik P. Sorenson; Azin Meshkinpour Arch Dermatol. 2007;143(12):1597-1599.

A Case of Zosteriform Pigmented Purpuric Dermatosis Takahiro Hamada; Yoshihiko Inoue; Takekuni Nakama; Takashi Hashimoto Arch Dermatol. 2007;143(12):1599-1600. Subungual Melanoma In Situ in a Hispanic Girl Treated With Functional Resection and Reconstruction With Onychocutaneous Toe Free Flap Adriana Motta; Carlos López; Alvaro Acosta; Camilo Peñaranda Arch Dermatol. 2007;143(12):1600-1602.

Docetaxel Monotherapy for Angiosarcoma in an Elderly Patient Tohru Nagano; Yukimasa Tai; Yuka Higashida; Norihiro Fujiwara; Masahiro Oka; Chikako Nishigori Arch Dermatol. 2007;143(12):1602-1603.

Annual Reviewers List Our Thanks to the ARCHIVES Peer Reviewers June K. Robinson; Jeffrey P. Callen Arch Dermatol. 2007;143(12):E1-E3.

Corrections Error in Text in: Nephrogenic Systemic Fibrosis: Relationship to Gadolinium and Response to Photopheresis Arch Dermatol. 2007;143(12):1565.

Archives Web Quiz Winner September 2007 Web Quiz Winner Arch Dermatol. 2007;143(12):1577.

Announcement

Manuscript Submission Arch Dermatol. 2007;143(12):1526.

Archives Feature Arch Dermatol. 2007;143(12):1569.

Index for This Volume

Index to Volume 143 Arch Dermatol. 2007;143(12):E1-E36.

Archives of Dermatology Masthead Lists editorial and production staff, editorial board, and other information.

ARCHIVES OF DERMATOLOGY Mission Statement: The Archives of Dermatology publishes information concerning the skin, its diseases, and their treatment. Its mission is to explicate the structure and function of the skin and its diseases and the art of using this information to deliver optimal medical and surgical care to the patient. We attempt to enhance the understanding of cutaneous pathophysiology and improve the clinician’s ability to diagnose and treat skin disorders. This journal has a particular interest in publishing clinical and laboratory studies that reveal new information pertinent to the interests and needs of the medical dermatologist, dermatologic surgeon, and all those concerned with state-of-the-art care of cutaneous disease. We believe that knowledge derived from well-designed clinical trials and studies of cost-effectiveness are especially important for improving the practice of dermatology. Studies that increase the understanding of the outcome of treatment or the means by which the burden of dermatologic disease can be measured and reduced to promote the health of patients with skin disease will receive special priority. The Archives regularly publishes reports on clinical investigations, editorials, and reviews. It also features reports and discussions on clinicopathologic correlations; clinical disorders of unique didactic value; pharmacologic, medical and surgical therapeutics; and ethical, moral, socioeconomic, and political issues.

Editor: June K. Robinson, MD Chicago, Illinois Web Editor: Ashish C. Bhatia, MD Naperville, Illinois International Advisory Committee Associate Editor: Jeffrey P. Callen, MD Louisville, Kentucky CME Editor: Andrew D. Samel, MD Attleboro, Massachusetts Editorial Assistant: Mark D. Matthews Chicago, Illinois skINsight: James M. Grichnik, MD, PhD Durham, North Carolina Alvaro E. Acosta, MD Bogota, Colombia Editorial Office: Archives of Dermatology Assistant Section Editors: Ashfaq A. Marghoob, MD Jan Nico Bouwes Bavinck, MD Leiden, the Netherlands 132 E Delaware Pl, #5806, Chicago, IL 60611 New York, New York Reuven Bergman, MD Haifa, Israel Fax: (312) 943-7752 Alon Scope, MD New York, New York Francisco G. Bravo, MD Lima, Peru Telephone: e-mail for appointment This Month: Robin L. Travers, MD Boston, Massachusetts Lorenzo Cerroni, MD Graz, Austria e-mail: [email protected] Yahya Dowlati, MD, PhD Tehran, Iran Section Editors Editorial Board Reinhard Dummer, MD Zurich, Switzerland Archives a Century Ago: Mark Bernhardt, MD Ft Lauderdale, Florida Murad Alam, MD Chicago, Illinois James Ferguson, MD Dundee, Scotland The Cutting Edge: George J. Hruza, MD St Louis, Missouri Ashish C. Bhatia, MD Naperville, Illinois Miguel Ruben Guarda, MD Santiago, Chile Assistant Section Editors: Michael P. Heffernan, MD Dayton, Ohio Michael Bigby, MD Boston, Massachusetts John L. M. Hawk, MD London, England Christie Ammirati, MD Hershey, Pennsylvania Mary-Margaret Chren, MD San Francisco, California Jana Hercogova, MD Prague, Czech Republic Evidence-Based Dermatology: Michael Bigby, MD Robert P. Dellavalle, MD, PhD, MSPH Denver, Colorado Chung-Hong Hu, MD, FACP Taipei, Taiwan Boston, Massachusetts Alan B. Fleischer Jr, MD Winston-Salem, North Carolina Abdul-Ghani M. Kibbi, FACP, MD Beirut, Lebanon Assistant Section Editors: Damiano Abeni, MD, MPH Rome, Italy James M. Grichnik, MD, PhD Durham, North Carolina Andreas D. Katsambas, MD Athens, Greece Rosamaria Corona, DSc, MD Rome, Italy Thomas D. Horn, MD Little Rock, Arkansas Steven Kossard, MD Sydney, Australia Urbà González, MD, PhD Barcelona, Spain George J. Hruza, MD St Louis, Missouri Margarita M. Larralde, MD Buenos Aires, Argentina Abrar A. Qureshi, MD, MPH Boston, Massachusetts Sungnack Lee, MD Suwon, Korea Hywel Williams, MSc, PhD, FRCP Nottingham, England Moise L. Levy, MD Houston, Texas Feature Editor: Michael J. Sladden, MAE, MRCP(UK) Michael E. Ming, MD, MSCE Philadelphia, Pennsylvania Thomas A. Luger, MD Munster, Germany Launceston, Tasmania Ronald L. Moy, MD Los Angeles, California Gillian Murphy, MD Dublin, Ireland Off-Center Fold: Michael E. Ming, MD, MSCE Philadelphia, Pennsylvania Anthony E. Oro, MD, PhD Stanford, California Oumeish Y. 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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1480 ©2007 American Medical Association. All rights reserved. STUDY The Risk of Mortality in Patients With Psoriasis Results From a Population-Based Study

Joel M. Gelfand, MD, MSCE; Andrea B. Troxel, ScD; James D. Lewis, MD, MSCE; Shanu Kohli Kurd, MHS; Daniel B. Shin, BA; Xingmei Wang, MS; David J. Margolis, MD, PhD; Brian L. Strom, MD, MPH

Objective: To determine the risk of mortality in pa- Main Outcome Measure: Hazard ratio (HR) of time tients with psoriasis. to death using Cox proportional hazards models adjusted for age and sex. Design : Cohort study. Results: There was no overall effect of mild psoriasis on mortality (HR, 1.0; 95% confidence interval [CI], 0.97-1.02), Setting: General practitioners participating in the Gen- whereas patients with severe psoriasis demonstrated an in- eral Practice Research Database in the United Kingdom, creased overall mortality risk (HR, 1.5; 95% CI, 1.3-1.7). The 1987-2002. association of severe psoriasis with mortality persisted after adjustment for risk factors for mortality (HR, 1.4; 95% Patients: Mild psoriasis, defined as any patient with a CI, 1.3-1.6) and after exclusion of patients with inflamma- diagnostic code of psoriasis but no history of systemic tory arthropathy (HR, 1.5; 95% CI, 1.3-1.8). Male and fe- therapy; severe psoriasis, any patient with a diagnostic male patients with severe psoriasis died 3.5 (95% CI, 1.2- code of psoriasis and a history of systemic therapy con- 5.8) and 4.4 (95% CI, 2.2-6.6) years younger, respectively, sistent with severe psoriasis. The unexposed (control) than patients without psoriasis (PϽ.001). population was composed of patients with no history of Conclusion: Severe but not mild psoriasis is associated a psoriasis diagnostic code. Control patients were with an increased risk of death. selected in a 5:1 ratio from the same practice and date in practice as the patients with psoriasis. Arch Dermatol. 2007;143(12):1493-1499

SORIASIS IS A COMMON, ized for treatment.10-13 Previous studies chronic inflammatory dis- from Sweden and Finland10-12 have dem- ease of the skin and joints onstrated an increased risk in all-cause that is heterogeneous in pre- and/or cause-specific mortality among sentation. Approximately patients hospitalized for psoriasis com- 80%P to 85% of patients have limited skin pared with the general population. How- involvement, whereas 15% to 20% have ever, in 1 Swedish study, hospitalized more extensive skin involvement that may patients with psoriasis had an increased require systemic therapy.1,2 Psoriasis has risk of cardiovascular mortality, whereas been associated with multiple comorbidities, including obesity, cardiovascular dis- See also page 1567 Author Affiliations: Center for ease, and certain internal malignant neo- Clinical Epidemiology and plasms such as lymphoma, and with patients with mild psoriasis who were Biostatistics (Drs Gelfand, smoking and alcohol use, all of which treated exclusively as outpatients did Troxel, Lewis, Margolis, and could increase the risk of mortality in pa- not.11 In contrast to studies of patients Strom and Ms Wang), tients with psoriasis.3-5 In addition, cer- hospitalized for severe psoriasis, a study Department of Biostatistics and tain systemic therapies for psoriasis may of US patients with severe psoriasis Epidemiology (Drs Troxel, rarely be associated with mortality due to derived from a clinical trial of psoralen– Lewis, Margolis, and Strom), chronic cumulative drug toxicity or idio- UV-A (PUVA) therapy did not identify and Department of syncratic reactions, and the disease itself an increased risk of mortality.13 The Dermatology (Drs Gelfand 6-9 and Margolis, Ms Kurd, and may lead to death in rare instances. studies that focused on patients hospital- Mr Shin), University of Few studies have assessed the risk of ized for psoriasis may not be generaliz- Pennsylvania School of mortality in patients with psoriasis, and able to the broader population of Medicine, Philadelphia. most have focused on patients hospital- patients with psoriasis because only a

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1493

©2007 American Medical Association. All rights reserved. few patients with the most severe disease require hospi- SAMPLING OF EXPOSED talization. Furthermore, patients hospitalized for any AND UNEXPOSED COHORTS condition generally have higher rates of comorbidities, smoking, and alcohol use, which can increase the risk We included all patients defined as having mild or severe pso- of death compared with individuals who are not hospi- riasis (according to our definitions) who were 18 years or older talized.14 Presently, there are mixed data regarding the at the study start date and who had at least 1 day of observa- risk of mortality among patients with severe psoriasis, tion time. Up to 5 control subjects who were 18 years or older at the start date were selected for each patient with psoriasis, and the available data suggest a hypothesis that the risk matched on practice and start date in the practice (defined as of mortality may be related to disease severity. the later of either the date when the patient registered with the To further investigate the relationship of psoriasis and practice or the date the practice was deemed UTS). mortality, we performed a population-based cohort study in the United Kingdom to determine the risk of mortal- PERSON-TIME CALCULATION ity in patients with psoriasis. For patients with mild psoriasis, follow-up started at the latest METHODS date of when the patient first received a psoriasis code, when the patient registered with the practice, or when the practice was deemed UTS. For patients with severe psoriasis, fol- STUDY POPULATION AND DATA SOURCE low-up started at the latest date of when the patient could first be defined as having severe psoriasis (eg, received a treatment We conducted a retrospective cohort study using the General code consistent with severe disease), when the patient regis- Practice Research Database (GPRD), which is a medical rec- tered with the practice, or when the practice was deemed UTS. ords database in the United Kingdom that was established for For unexposed subjects (controls), follow-up started at the lat- epidemiologic research in 1987.15 Data through 2002 were in- est date of when the patient registered with the practice or when cluded in this study. The GPRD is representative of the UK popu- the practice was deemed UTS. For all groups, follow-up ended lation in terms of age, sex, and geographic distribution. Ap- at the earliest date of one of the following: death, transfer out proximately 5% of the UK population is represented in the of the practice, or the end of UTS for the practice. GPRD, and cumulative data are available for more than 9 million patients with more than 40 million person-years of follow- OUTCOME OF INTEREST up. In the United Kingdom, greater than 99% of patients are registered with a general practitioner (GP) through the Na- The outcome of interest was death. Deaths were identified via tional Health Service; the GP coordinates all of the patient’s medi- registration codes indicating that a patient was removed from cal care. Data on diagnoses and prescriptions are recorded by a practice because of that person’s death. Patients who had a the GPs as part of the patient’s electronic medical record. Pa- medical diagnosis or prescription recorded 100 or more days tients with complex medical conditions are seen by specialists after having received a death registration status code were re- (at the request of the GP), who may initiate a new treatment; classified as living and were censored at the date they received however, patients are then referred back to the GP for long- the change in registration status. This reclassification oc- term monitoring as necessary. Certain treatments, such as PUVA curred in approximately 1% of all death records. and oral retinoids, are restricted to dermatologists in the United Kingdom; however, GPs capture these treatments through their COVARIABLES OF INTEREST electronic medical record. The GPRD has been shown to capture information on diagnoses and treatments from specialists 16,17 Risk factors for death were identified by adapting a comorbid- through the GP’s electronic medical record. General prac- ity index for use in a medical record database.19 The following titioners receive specific training and are subject to induce- covariables were assessed: smoking (classified as current smoker, ments and penalties to ensure high-quality data. The data are former smoker, or nonsmoker), body mass index, myocardial also audited for completeness, and a practice receives an up- infarction, congestive heart failure, peripheral vascular dis- to-standard (UTS) designation when at least 95% of relevant ease, cerebrovascular disease, dementia, chronic pulmonary prescriptions and diagnoses are captured electronically. More disease, rheumatologic disease, peptic ulcer disease, mild liver than 250 peer-reviewed scientific articles have been published 15 disease, moderate or severe liver disease, diabetes mellitus, dia- using GPRD data. The GPRD has also been assessed in nu- betes with chronic complications, hemiplegia or paraplegia, merous validation studies, including those on psoriasis and mor- renal disease, malignant neoplasm, metastatic solid tumor, and tality, to demonstrate whether it captures these diseases and 2,5,15,18 AIDS. These covariates were classified as present if they oc- outcomes accurately. We used data from 1987-2002 for curred at any time during the study. patients who were 18 years or older when their person-time recording began. ANALYSIS

DEFINITION OF EXPOSURE The sample size was determined by including the maximum number of eligible patients with severe psoriasis based on age We defined mild psoriasis as a diagnostic code of psoriasis in criteria. We randomly selected 5 control subjects per patient patients with no history of systemic therapy. Severe psoriasis with psoriasis because additional matching yields minimal in- was defined as a diagnostic code of psoriasis in patients with a creases in statistical power. Data were summarized descrip- history of systemic therapy consistent with severe psoriasis. Sys- tively. Dichotomous variables were tested with the Fisher ex- temic therapy included phototherapy, PUVA, methotrexate so- act test and continuous variables were tested with an unpaired, dium, azathioprine, cyclosporine, oral retinoids (etretinate and 2-tailed t test. We fit age- and sex-adjusted Cox proportional acitretin), hydroxyurea, and mycophenolate mofetil. The un- hazards regression models to determine the overall hazard ra- exposed (control) population comprised patients with no his- tio (HR) of death in patients with psoriasis.20 When indicated tory of a psoriasis diagnostic code. by an association of psoriasis with mortality based on the Cox

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1494 Table 1. Characteristics of Study Groups

Study Group

Mild Psoriasis Severe Psoriasis

Controls Patients Controls Patients Characteristic (n=560 358) (n=133 568) (n=15 075) (n=3951) Sex, No. (%) Male 261 710 (46.7) 64 004 (47.9) 7023 (46.6) 1921 (48.6) Female 298 648 (53.3) 69 564 (52.1)a 8052 (53.4) 2030 (51.4)b Age, mean (median; IQR), y 45.3 (42.0; 29.2-59.5) 46.9 (44.8; 31.4-61.3)a 45.9 (42.8; 29.8-60.3) 52.4 (52.3; 38.7-65.8)c Systemic therapies, No. (%) NA NA NA Methotrexate 2302 (58.3) Psoralen or phototherapy 662 (16.8) Azathioprine 651 (16.5) Cyclosporine 408 (10.3) Etretinate or acitretin 350 (8.9) Hydroxyurea 224 (5.7) Mycophenolate mofetil 11 (0.3) Follow-up, mean (median; IQR), y 5.6 (5.2; 2.2-9.2) 4.5 (3.8; 1.6-7.1) 5.9 (5.6; 2.4-9.5) 3.6 (2.8; 1.3-5.3) Cumulative person-years 3 147 693 600 902 88 391 14 203 Deaths, No. 38 258 7198 1064 303 Incidence rate of mortality 12.2 (12.0-12.3) 12.0 (11.7-12.3) 12.0 (11.3-12.8) 21.3 (19.0-23.9) per 1000 person-years (95% CI)

Abbreviations: CI, confidence interval; IQR, interquartile range; NA, not applicable. a PϽ.001 (mild psoriasis group vs mild control group). b P=.02 (severe psoriasis group vs severe control group). c PϽ.001 (severe psoriasis group vs severe control group). models, we fit models with covariates for death included (as strictions on the prescription of these modalities to the already described) and models with age and sex interaction terms specialist. to determine whether the relative risk of mortality in patients The absolute incidence of death in controls and pa- with psoriasis differed by sex or age characteristics. Each di- tients with psoriasis is shown in Table 1. The overall in- chotomous variable in the model was checked for proportion- cidence was similar in the 2 control groups and similar ality while adjusting for the other covariates in the model by examining diagnostic log-log plots. Multiple sensitivity analy- to rates of death reported using national statistics from 22 ses were performed to test the underlying assumptions of our England and Wales. The unadjusted overall risk of death primary analysis. All analyses were performed using Stata sta- per 1000 person-years was similar in patients with mild tistical software, version 9.2 (StataCorp, College Station, Texas). psoriasis (12.0; 95% CI, 11.7-12.3) and their controls (12.2; 95% CI, 12.0-12.3). The unadjusted overall risk PROTECTION OF HUMAN SUBJECTS of death per 1000 person-years was higher in the patients with severe psoriasis (21.3; 95% CI, 19.0-23.9) than This study was approved by the University of Pennsylvania in- in their controls (12.0; 95% CI, 11.3-12.8). stitutional review board and by the Independent Scientific Advi- As expected, age and male sex were associated with a sory Committee of the Medicines and Healthcare Products Regu- higher risk of death (data not shown). Based on Cox pro- latory Agency of the UK Department of Health. The study was portional hazards regression models, there was no over- conducted in accordance with the Declaration of Helsinki. all effect on mortality of psoriasis of any severity (1.00; 95% CI, 0.99-1.04) or mild psoriasis (HR, 1.00; 95% CI, RESULTS 0.97-1.02) (Table 2). In contrast, Cox models in patients with severe psoriasis demonstrated an increased We identified 133 568 patients with mild psoriasis, 3951 overall mortality risk (HR, 1.50; 95% CI, 1.32-1.71). Ad- patients with severe psoriasis, and 560 358 and 15 075 justment of the overall mortality risk in patients with se- matched controls, respectively (Table 1). Patients with vere psoriasis for major risk factors of death (described psoriasis were older and more likely to be male com- in the “Methods” section) did not result in a clinically pared with controls, and the psoriasis groups had less ob- significant reduction in the association between severe servation time than the control groups. Most patients iden- psoriasis and mortality (fully adjusted HR, 1.42; 95% CI, tified as having severe psoriasis were treated with 1.25-1.62). The increased relative risk of mortality in pa- methotrexate (Table 1). The overall use of oral systemic tients with severe psoriasis was similar in men and women therapy for psoriasis in the GPRD is similar to other popu- (sex interaction term, P=.86); the relative risk, how- lation-based estimates in the United Kingdom21; however, did vary with age (Table 2). For example, the rela- ever, phototherapy and PUVA are likely to be under- tive risk of mortality for a 45-year-old patient with se- reported in the GPRD owing to difficulties in capturing vere psoriasis compared with controls was 2.2 (95% CI, these therapies in the electronic medical record and re- 1.6-2.9), whereas the relative risk of mortality for a 75-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1495 Table 2. Hazard Ratio of Mortality in Patients With Psoriasis Table 4. Sensitivity Analyses

Hazard Ratio (95% Confidence Interval)a Mortality in Severe All Patients Patients Patients Psoriasis, With With Mild With Severe Analysis HR (95% CI)a Age, y Psoriasis Psoriasis Psoriasis Patients with psoriatic arthritis excluded from severe 1.5 (1.3-1.8) All ages (Ն18) 1.0 (0.99-1.04) 1.0 (0.97-1.02) 1.5 (1.3-1.7) psoriasis group 35 2.5 (1.7-3.7) Patients with rheumatologic diseases excluded from 1.5 (1.3-1.8) 45 2.2 (1.6-2.9) psoriasis group 55 1.9 (1.5-2.3) Person-time starts with first diagnosis of psoriasis 1.1 (1.0-1.3) 65 1.6 (1.4-1.9) during UTS time 75 1.4 (1.3-1.6) Start date for severe psoriasis control group matched 1.7 (1.5-2.0) 85 1.3 (1.0-1.5) to start date for severe psoriasis group 95 1.1 (0.8-1.5) Severe psoriasis group restricted to patients who 1.3 (1.1-1.5) received methotrexate sodium a Data are adjusted for age and sex. Severe psoriasis group excluding patients treated with 1.9 (1.6-2.2) methotrexate Severe psoriasis group restricted to patients who had 1.8 (1.3-2.3) been prescribed an oral retinoid Table 3. Attributable Risk (AR) and Excess Risk of Death in Patients With Severe Psoriasis Abbreviations: CI, confidence interval; HR, hazard ratio; UTS, up-to-standard designation. a Mortality Rate Adjusted for age and sex. per 1000 Patient-Years AR, No. in Severe of Deaths Excess Risk, of mortality was attenuated but remained elevated when Psoriasis per 1000 No. of Excess a b we varied the start of follow-up time in the severe pso- Age Group, y Control Group Patient-Years Deaths riasis group to the earliest date at which psoriasis could All ages (Ն18) 12.0 6.0 1/166 Patients per year be identified. The risk of mortality in patients with se- 30-39 0.8 1.8 1/856 Patients per year vere psoriasis remained elevated when we adjusted the 40-49 2.0 2.3 1/440 Patients per year 50-59 6.4 5.6 1/179 Patients per year start of follow-up time in the severe psoriasis control group 60-69 20.1 12.9 1/78 Patients per year to coincide with the start of follow-up time in the severe 70-79 48.5 20.9 1/48 Patients per year psoriasis group, indicating that the increased risk of mor- 80-89 106.7 26.7 1/38 Patients per year tality in patients with severe psoriasis was not due to the shorter follow-up time in that group as was noted in our a AR=risk of mortality for patients in the severe psoriasis group−risk of primary analysis. Finally, the risk of mortality in pa- mortality for persons in the severe psoriasis control group. b Excess risk=1/AR. tients with severe psoriasis remained elevated in patients who did or did not receive methotrexate; however, the risk appeared most elevated for those who did year-old patient with severe psoriasis was 1.4 (95% CI,1.3- not receive methotrexate therapy. 1.6). Although the relative risk of mortality in patients with severe psoriasis decreased with age, the attribut- COMMENT able risk of mortality associated with severe psoriasis (calculated by subtracting the risk of mortality for persons The results of this study demonstrate that patients with in the control group from the risk of mortality in pa- severe psoriasis have a 50% increased risk of mortality, tients with severe psoriasis) increased with age (as did whereas patients with milder psoriasis have no overall the excess risk) because the baseline risk of mortality in- increased risk. Male and female patients with severe pso- creases significantly with age (Table 3). Among pa- riasis died 3.5 and 4.4 years younger, respectively, than tients who died, those with severe psoriasis died at a patients without psoriasis, which provides further in- younger age than controls. For example, men with se- sight into the effect of excess mortality risk associated vere psoriasis died 3.5 years (95% CI, 1.2-5.8 years; with having severe psoriasis. The increased risk of death PϽ.001) younger than men without psoriasis, and women in patients with severe psoriasis persisted when we ex- with severe psoriasis died 4.4 years (95% CI, 2.2-6.6 years; cluded patients with diagnoses of psoriatic arthritis and PϽ.001) younger than women without psoriasis. rheumatoid diseases. Likewise, the increased risk of death Several additional analyses were performed to fur- persisted when we restricted the severe psoriasis group ther investigate the association of severe psoriasis with to patients treated with oral retinoids, which are highly mortality (Table 4). Sensitivity analyses demonstrated specific for severe psoriasis, suggesting that our obser- that the increased relative risk of mortality in patients vations do not result from misclassification of disease sta- with severe psoriasis persisted when we excluded pa- tus.23 The increased risk of death in patients with severe tients with concomitant psoriatic arthritis or rheumato- psoriasis was not significantly diminished when we con- logic disease and when we restricted the severe psoria- trolled for major risk factors for mortality. This finding sis group to those who received oral retinoids, therapies suggests that severe psoriasis is an important predictor that are highly specific for psoriasis. The increased risk of mortality risk. It is also possible that comorbid ill-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1496 nesses that predict death are incompletely detected in sentative population-based methods to examine the risk medical practice. of mortality in patients with mild and severe psoriasis, The relative risk of mortality was greatest in younger which minimizes selection bias and improves the gen- patients with severe psoriasis; however, the excess risk eralizability of the results. Furthermore, mortality rates of death attributable to having severe psoriasis in- were determined by the same method in the exposed and creases with age, since the baseline risk of death in- unexposed populations (ie, the controls), which further creases sharply with age. The lower relative risk of death substantiates the validity of our findings. in older patients with severe psoriasis may be due to deple- As with all studies, there are important limitations to tion in the number of patients with severe psoriasis who consider. In database studies, there remains the possi- are susceptible to mortality (ie, through death) in the older bility for misclassification of death due to coding errors, groups available for this study because we did not study although this is believed to be uncommon. Although some incident psoriasis exclusively (see the discussion of study may be present, there is little reason to believe that coding- limitations in a subsequent paragraph). Alternatively, as related misclassification differed between the patients with patients age, the competing risks of death in patients with psoriasis and the controls. If present, such nondifferen- severe psoriasis and those without psoriasis may be- tial misclassification would be expected to bias our re- come more similar. Our findings are consistent with those sults toward the null. of our previous study,24 which indicated that the rela- Another potential limitation is that we did not exam- tive risk of myocardial infarction is highest in younger ine patients with exclusively incident (new-onset) pso- patients with psoriasis, and with those of another study,11 riasis because such cases are difficult to identify in a which indicated that the relative risk of cardiovascular database setting. If patients with psoriasis died before mortality is highest in younger patients (those aged Ͻ40 entering the cohort, we may have underestimated the years) with severe psoriasis. relative risk of death associated with psoriasis. Examin- Our mortality findings in patients with severe psoria- ing patients with severe psoriasis from the first time sis are in agreement with previous studies of patients hos- psoriasis was documented in the electronic medical rec- pitalized for severe psoriasis.10-12 For example, a study10 ord rather than from the first time they could be classi- of patients hospitalized for psoriasis in Gothenburg, Swe- fied as having severe psoriasis based on treatment, as den, found an increased risk of death in men (standard- was done in our primary analysis, resulted in attenua- ized mortality ratio [SMR], 2.03) and women (SMR, 3.32) tion of the estimated relative risk of mortality. However, for those born between 1911 and 1940 compared with this analysis introduces a form of immortal time bias the general population. Excesses in cause-specific mor- that would underestimate the association of psoriasis tality were seen only in women for ischemic heart dis- and mortality because the patients we classified as hav- ease and lung cancer. A study12 of Finnish patients with ing severe psoriasis could not have developed the out- psoriasis who were hospitalized for their disease also ob- come (ie, death) prior to receiving a therapy that identi- served excess mortality in men (SMR, 1.62; 95% CI, 1.52- fies them as having severe psoriasis.26 Furthermore, we 1.71) and women (SMR, 1.54; 95% CI, 1.43-1.64), with did not directly determine the severity of psoriasis alcohol-related deaths being the major cause for excess based on the extent of skin disease, which may intro- mortality. Finally, a Swedish study11 demonstrated that duce misclassification of mild and severe psoriasis when patients hospitalized for psoriasis have an increase in car- using therapy as a marker of psoriasis phenotype. Our diovascular mortality (SMR, 1.52; 95% CI, 1.44-1.60), mild psoriasis group likely contains a small subset of whereas patients with milder psoriasis who are treated patients with severe disease because systemic therapies as outpatients have no increased alteration of cardiovas- are used infrequently for psoriasis in the general popu- cular mortality risk (SMR, 0.94; 95% CI, 0.89-0.99); this lation. Our severe group likely contains a small subset finding is consistent with the results of the present all- of patients with mild skin disease despite the use of sys- cause mortality study. temic therapy. This misclassification would result in an In contrast to the excess mortality observed in pa- overestimation and underestimation of the risk of mor- tients hospitalized for severe psoriasis, there was no al- tality in the patients with mild and severe psoriasis, teration in the risk of mortality in US patients with se- respectively. Therefore, such misclassification is vere psoriasis exposed to PUVA on an outpatient basis unlikely to have explained our results. at dermatology referral centers (SMR, 0.9; 95% CI, 0.8- Finally, we did not determine why patients with se- 1.1) compared with the general population.13 The death vere psoriasis died at higher rates than patients without rates of patients with psoriasis in the PUVA cohort were psoriasis. We have previously demonstrated that pa- compared with US national statistics, which may have tients with severe psoriasis in the GPRD have higher preva- introduced bias because it is unclear whether PUVA co- lences of smoking, diabetes mellitus, obesity, hyperten- hort patients who were initially part of an experimental sion, and hyperlipidemia and a higher incidence of clinical trial at selected tertiary care medical centers are myocardial infarction and lymphoma.5,24,27-29 In addi- representative of the general US population. Further- tion, psoriasis has been associated with excess alcohol more, use of external national data for calculating stan- intake, psychiatric disorders, and various types of inter- dardized mortality ratios (as opposed to use of an internal malignant neoplasms such as lung, liver, pancreatic, nal comparison group, as was done in the present study) breast, bladder, and kidney cancers, which could fur- may introduce additional bias toward underestimating ther explain the excess mortality observed in the severe the mortality risk.25 Our study advances the literature of psoriasis group.4,30 Severe psoriasis itself can lead to death psoriasis and mortality because we used broadly repre- in very rare instances, as could cumulative drug toxicity

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1497 nesses that predict death are incompletely detected in sentative population-based methods to examine the risk medical practice. of mortality in patients with mild and severe psoriasis, The relative risk of mortality was greatest in younger which minimizes selection bias and improves the gen- patients with severe psoriasis; however, the excess risk eralizability of the results. Furthermore, mortality rates of death attributable to having severe psoriasis in- were determined by the same method in the exposed and creases with age, since the baseline risk of death in- unexposed populations (ie, the controls), which further creases sharply with age. The lower relative risk of death substantiates the validity of our findings. in older patients with severe psoriasis may be due to deple- As with all studies, there are important limitations to tion in the number of patients with severe psoriasis who consider. In database studies, there remains the possi- are susceptible to mortality (ie, through death) in the older bility for misclassification of death due to coding errors, groups available for this study because we did not study although this is believed to be uncommon. Although some incident psoriasis exclusively (see the discussion of study may be present, there is little reason to believe that coding- limitations in a subsequent paragraph). Alternatively, as related misclassification differed between the patients with patients age, the competing risks of death in patients with psoriasis and the controls. If present, such nondifferen- severe psoriasis and those without psoriasis may be- tial misclassification would be expected to bias our re- come more similar. Our findings are consistent with those sults toward the null. of our previous study,24 which indicated that the rela- Another potential limitation is that we did not exam- tive risk of myocardial infarction is highest in younger ine patients with exclusively incident (new-onset) pso- patients with psoriasis, and with those of another study,11 riasis because such cases are difficult to identify in a which indicated that the relative risk of cardiovascular database setting. If patients with psoriasis died before mortality is highest in younger patients (those aged Ͻ40 entering the cohort, we may have underestimated the years) with severe psoriasis. relative risk of death associated with psoriasis. Examin- Our mortality findings in patients with severe psoria- ing patients with severe psoriasis from the first time sis are in agreement with previous studies of patients hos- psoriasis was documented in the electronic medical rec- pitalized for severe psoriasis.10-12 For example, a study10 ord rather than from the first time they could be classi- of patients hospitalized for psoriasis in Gothenburg, Swe- fied as having severe psoriasis based on treatment, as den, found an increased risk of death in men (standard- was done in our primary analysis, resulted in attenua- ized mortality ratio [SMR], 2.03) and women (SMR, 3.32) tion of the estimated relative risk of mortality. However, for those born between 1911 and 1940 compared with this analysis introduces a form of immortal time bias the general population. Excesses in cause-specific mor- that would underestimate the association of psoriasis tality were seen only in women for ischemic heart dis- and mortality because the patients we classified as hav- ease and lung cancer. A study12 of Finnish patients with ing severe psoriasis could not have developed the out- psoriasis who were hospitalized for their disease also ob- come (ie, death) prior to receiving a therapy that identi- served excess mortality in men (SMR, 1.62; 95% CI, 1.52- fies them as having severe psoriasis.26 Furthermore, we 1.71) and women (SMR, 1.54; 95% CI, 1.43-1.64), with did not directly determine the severity of psoriasis alcohol-related deaths being the major cause for excess based on the extent of skin disease, which may intro- mortality. Finally, a Swedish study11 demonstrated that duce misclassification of mild and severe psoriasis when patients hospitalized for psoriasis have an increase in car- using therapy as a marker of psoriasis phenotype. Our diovascular mortality (SMR, 1.52; 95% CI, 1.44-1.60), mild psoriasis group likely contains a small subset of whereas patients with milder psoriasis who are treated patients with severe disease because systemic therapies as outpatients have no increased alteration of cardiovas- are used infrequently for psoriasis in the general popu- cular mortality risk (SMR, 0.94; 95% CI, 0.89-0.99); this lation. Our severe group likely contains a small subset finding is consistent with the results of the present all- of patients with mild skin disease despite the use of sys- cause mortality study. temic therapy. This misclassification would result in an In contrast to the excess mortality observed in pa- overestimation and underestimation of the risk of mor- tients hospitalized for severe psoriasis, there was no al- tality in the patients with mild and severe psoriasis, teration in the risk of mortality in US patients with se- respectively. Therefore, such misclassification is vere psoriasis exposed to PUVA on an outpatient basis unlikely to have explained our results. at dermatology referral centers (SMR, 0.9; 95% CI, 0.8- Finally, we did not determine why patients with se- 1.1) compared with the general population.13 The death vere psoriasis died at higher rates than patients without rates of patients with psoriasis in the PUVA cohort were psoriasis. We have previously demonstrated that pa- compared with US national statistics, which may have tients with severe psoriasis in the GPRD have higher preva- introduced bias because it is unclear whether PUVA co- lences of smoking, diabetes mellitus, obesity, hyperten- hort patients who were initially part of an experimental sion, and hyperlipidemia and a higher incidence of clinical trial at selected tertiary care medical centers are myocardial infarction and lymphoma.5,24,27-29 In addi- representative of the general US population. Further- tion, psoriasis has been associated with excess alcohol more, use of external national data for calculating stan- intake, psychiatric disorders, and various types of inter- dardized mortality ratios (as opposed to use of an internal malignant neoplasms such as lung, liver, pancreatic, nal comparison group, as was done in the present study) breast, bladder, and kidney cancers, which could fur- may introduce additional bias toward underestimating ther explain the excess mortality observed in the severe the mortality risk.25 Our study advances the literature of psoriasis group.4,30 Severe psoriasis itself can lead to death psoriasis and mortality because we used broadly repre- in very rare instances, as could cumulative drug toxicity

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1497 Table 2. Hazard Ratio of Mortality in Patients With Psoriasis Table 4. Sensitivity Analyses

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1496 STUDY A 3-Year Causative Study of Pompholyx in 120 Patients

Marie He´lène Guillet, MD; Ewa Wierzbicka, MD; Stephanie Guillet, MD; Guy Dagregorio, MD; Gerard Guillet, MD

Objective: To assess the relative frequency of the dif- giene products as the main factor (31.7%), followed by ferent causes of pompholyx evoked in the literature. metals (16.7%); and internal reactivation from drug, food, or haptenic (nickel) origin (6.7%). The remaining 15.0% Design: Prospective survey. of patients were classified as idiopathic patients, but all were atopic. (Percentages do not total 100 because of Setting: Clinical outpatient setting. rounding.)

Patients: A total of 120 consecutive patients with pom- Conclusions: Our data confirm the existence of reac- pholyx referred to our department from 2000 through tional pompholyx to interdigital-plantar intertrigos and 2003. endogenous reactions to metals or other allergens, but they mainly point at the unexpected importance of a so- Main Outcome Measures: Systematic investigation called contact pompholyx in which cosmetic and hy- of different causes of pompholyx: fungal intertrigo, hygiene products play a preponderant role compared with perhidrosis, atopy, contact eczema, and internal reac- metals. The great frequency of atopic conditions, even if tions with systematic provocation tests to metals, bal- idiopathic pompholyx is not inferred as an equivalent of sam of Peru, and food allergen when suspected. atopy, should lead to further causative investigations before undertaking more expensive or extensive treat- Results: The present study found the following causes ments of refractory pompholyx. of pompholyx in the 120 patients: mycosis (10.0%); allergic contact pompholyx (67.5%), with cosmetic and hy- Arch Dermatol. 2007;143(12):1504-1508

OMPHOLYX OR PALMOPLAN- mittee. Lesions were palmar (70.0%), plantar tar dyshidrosis is a common (10.0%), or palmoplantar (20.0%). The mean disorder characterized by re- age of patients was 35 years (range, 7-72 years). current crops of vesicles or Of the patients, 80.0% were between the ages bullae on the lateral aspects of of 30 and 40 years. There were more females (n=65) than males (n=55); the female-male ra- the fingers and the palms and soles with tio was 1.18. Selection criteria excluded pa- P 1 nonerythematous skin. Various caus- tients who had erythema associated with ative factors have been proposed, includ- vesicles, thus eliminating contact eczemas. A ing mycoses, hyperhidrosis, nickel allergy, and internal reactivation of contact allergy. To better understand the caus- For editorial comment ative profile of this multifactorial disease, see page 1578

CME available online at second important selection criterion was the www.archdermatol.com cyclic pattern of recurrent short-term attacks. A detailed history was obtained from each pa- we prospectively studied 120 patients in tient and from a series of 100 controls matched search of atopy, hyperhidrosis, mycosis, by age and sex to determine if some of them contact eczema, and reaction to tobacco, were aware of an atopic condition, contact sensitization, possible food or drug allergy, or in- food, and drugs. terdigital dermatitis. All of them were ques- tioned about smoking habits and perspiration, METHODS and patients with pompholyx were specifically interviewed and asked about the likeli- A total of 120 consecutive patients were re- hood of potential trigger factors, such as per- Author Affiliations: ferred for pompholyx over 3 years, from 2000 spiration, smoking, drugs, foods, and emotional Department of Dermatology, to 2003. All 120 patients and control subjects stress. Centre Hospitalo–Universitaire gave oral consent to participate in this study, Patients and controls were examined for de Poitiers, Poitiers, France. which was approved by the local ethics com- clinical signs of interdigital-plantar fungal in-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1504 tertrigo. Patients with pompholyx underwent systematic skin scraping of the fourth interdigital space of the right foot (Sab- Table 1. Causative Study of Pompholyx ouraud culture) and of the interdigital dermatitis site, if any. To According to Number of Patientsa look for possible internal reactivation, all patients were orally chal- lenged in a double-blinded intake with a single dose of 2.5 mg of Patients With Relevance nickel given as nickel sulfate and 1 mg of cobalt given as cobalt Cause of Pompholyx Suspected Causation Analysis sulfate in accordance with the model initially proposed by Veien Intertrigo 19 (15.8) 13 (10.8) 2 et al. All patients were tested for contact allergy to their per- Patch test positive result 89 (74.2) 80 (66.7)b sonal hygiene products diluted to 0.1% (soap, shower gel, sham- Tobacco patch positive result 5 (4.2) 2 (1.7) poo, and shaving cream), to a battery of ingredients that we com- Idiopathic and atopic 0 18 (15.0) monly use for investigating cosmetic allergy (lanolin alcohol, Endogenous cause 13 (10.8) 8 (6.7) cocamidopropyl betaine, lauryl sulfate, thimerosal, propylene gly- Nickel 6 (5.0)c 2 (1.7) col, and octyl gallate), and to the allergen standard European panel Drugs 3 (2.5)c 3 (2.5) (Experimental Contact Dermatitis Research Group panel). All al- Food 4 (3.3)c 3 (2.5) lergens were placed in aluminum patch test chambers (Finn chambers) taped to the skin of the back, removed after 48 hours, and a Data are given as number (percentage) of the 120 patients. b This included cosmetics (31.7%) and metals (16.7%). read at 72 and 96 hours in the event of a positive reaction to dif- c ferentiate allergic and irritant reactions. If erythema decreased at There was suspicion in these patients. 96 hours, a positive test result was considered to be due to irritation phenomena. The skin reactions were scored on a scale from 0 to 3 (0 indicates no reaction; ϩ, erythema; ϩϩ, erythema and in 20.0% of cases. After a 3-week treatment with topical papule; and ϩϩϩ, erythema and vesicle or bullae). imidazole salicylate, clinical remission without later re- The presence of atopy was assessed in accordance with the currence of pompholyx symptoms was obtained in only criteria of Hannifin and Rajka, and total IgE levels were mea- 13 of the 19 patients. Therefore, the fungal cause was at- sured. Skin tests with immediate reading and determination of tributed only to these 13 patients, which represents a little specific IgE were performed whenever the responsibility of food more than 10% of all surveyed patients. In 3 of these pa- was suspected. Smokers were systematically tested with patch tients, a simultaneous recurrence of pompholyx and in- tests for smoked tobacco, and fresh tobacco was placed on aluminum chambers covered with petroleum jelly and taped to tertrigo was observed during the next 6 months. the skin of the back, with removal after 48 hours and reading A contact allergy was found in 74.2% of patients pre- at 72 hours. Moreover, all smoking patients were asked to stop senting 1 or several positive epicutaneous test results, with smoking for 15 days, and then to resume smoking to evaluate an average of 2.2 tests, for 193 positive test results. Listed the occurrence of disease during a period of smoking and a pe- by decreasing order, test results were positive to nickel, riod of nonsmoking, to assess if pompholyx was triggered or shower gel, chromium, fragrance, shampoo, balsam of exacerbated by tobacco. Peru, lanolin, cobalt, thiuram, lauryl sulfate, p- In case of confirmed mycosis, patients were prescribed bi- phenylenediamine (PPD), fresh tobacco (5 times), for- fonazole for 3 weeks; they were examined 1, 2, and 6 months maldehyde, parabens, and octyl gallate. In 97 cases of the later to assess the effect of this antifungal treatment on pom- 193 positive test results, there was a concordance be- pholyx. In case of a positive patch reaction, the clinical relevance of the test was confirmed by an elimination program tween external application and disease recurrence. For and open external provocation, patients being thus evaluated cosmetic products, the relevance of positive test results on the results of both outcome of the elimination program and for shower gel was confirmed 28 of 30 times; for sham- challenge with later checkups at 1 and 2 months. The external poo, 14 of 17 times. The relevance analysis confirmed challenge involved commercial products or devices contain- the diagnosis of what might be considered allergic con- ing substances giving a positive skin reaction. If some foods or tact pompholyx in 67.5% (81 of 120) of patients. The spe- drugs were suspected in triggering or exacerbating pathologi- cific involvement of contact allergens was confirmed by cal symptoms, 2 open elimination blinded challenge tests were the eviction test regarding any positive patch test re- performed to assess the possibility of internal reactivation. sults, including personal cosmetics. Regarding shower gel and/or shampoo, the main allergens were fragrances (14 RESULTS times) and preservatives (2 times), in consideration of other associated positive patch test results (Table 2). During history taking, 40.0% of the 120 patients ex- More in detail, 16.7% of surveyed patients had pompho- plained that they had a tendency to palmar-plantar hy- lyx related to metals, 18.3% linked to other allergens of perhidrosis compared with 7.0% of the controls, and the standard panel, and 31.7% to a cosmetic allergy. As 12.5% thought it could be a facilitating factor of pom- a whole, contact pompholyx cases were broken down into pholyx. Of the 120 patients, 48.3% smoked, compared hygiene product intolerance (46.7%), metal allergy with 28.0% of the controls; 24.1% suspected the role of (25.0%), and reaction to various other allergens, such as stress. The responsibility of a specific contact was evoked rubber, formaldehyde, lanolin, PPD, and balsam of Peru by 20.0% of patients; 8.0% of controls without pompho- (28.3%). Hygiene product allergy was related 10 times lyx considered themselves as having contact allergy. Of to a fragrance allergy and 4 times to a balsam of Peru al- the patients, 5.0% believed they had detected an inter- lergy (Table 2). nal cause linked to food or drug; 46.7% of patients had Internal cause regarding possible metal, food, drug, an atopic condition vs 20.0% of controls (Table 1). In- or tobacco allergy was identified from data on the ques- terdigital dermatitis was observed in 5.0% of controls with- tionnaires and clinical history. None of the 75.0% of pa- out pompholyx and in 15.8% (19 of 120) of patients, be- tients with a negative patch test result to metals demon- cause of a dermatophyte in 80.0% of cases and Candida strated flare-up of pompholyx after metal oral intake.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1505 pathic cases of pompholyx concerning exclusively atopic Table 2. Data for Contact Pompholyx patients (Table 1). (Percentages do not total 100 because of rounding.) In comparison, the control popula- Patch Test tion of patients without pompholyx presented with in- Positive Result Clinical Relevance Allergen (n = 193)a (n = 97)b terdigital dermatitis in 5.0%, contact allergy in 8.0%, hyperhidrosis in 7.0%, smoking in 28.0%, and atopy in Nickel 32 12 20.0%. Chromium 25 6 Fragrance 18 12 The mean age of the patients included in the present Balsam of Peru 15 8 study confirms that the peak of frequency of pompho- Lanolin 12 4 lyx is between the ages of 30 and 40 years.3,4 In addition, Cobalt 10 2 the predominance of isolated hand pompholyx (70.0%) Thiuram 8 3 vs the mixed palmar-plantar lesions (20.0%) and the iso- Lauryl sulfate 7 0 lated plantar manifestations (10.0%) is consistent with PPD 6 3 Isothiazolinone 4 1 the literature, which gives figures of 80%, 12%, and 3%, 5 Octyl gallate 3 2 respectively. Parabens 3 0 Formaldehyde 3 2 Shower gel 30 28 COMMENT Shampoo 17 14 The present study allows the classification of the classic Abbreviation: PPD, p-phenylenediamine. a A positive result was found in 89 of the 120 patients (74.2%). causative hypotheses formulated in the literature by or- b Clinical relevance was found in 50.2% of the 193 tests and in 81 of the der of frequency. The initial hypothesis of pompholyx 120 patients (67.5%). triggered by sudation had led Fox1 to choose the word dyshidrosis from the Greek idros in 1873, but later the histological features of spongiosis definitively discarded Of the 30 patients presenting with a positive patch test this theory and linked pompholyx to the eczema fam- result to metals, challenge testing elicited a vesicle palmar- ily.6 However, the great frequency of hyperhidrosis (40.0% plantar eczema flare-up in only 2, although 6 had been of patients) must be underlined. The responsibility of fun- suspected of having possible internal reactivation through gal interdigital-plantar intertrigo is known as a classic metallic denture material. The fact that the dorsal as- cause of pompholyx, but is perhaps overrated.7-9 In the pect of the hands was spared in these 2 patients during present series, this cause has been proved in 10.0% of those provoked palmar-plantar pompholyx flare-ups was cases, whereas 15.8% of all patients experienced inter- suggestive of a sudoral elimination of the nickel concen- digital-plantar intertrigo. Recently, an epidemiologic trated in perspiration. study10 of 198 patients with a history of hand eczema con- Of 58 smoking patients, tobacco gave a positive confirmed statistically the relationship between palmar ve- tact reaction in only 5. The effect of smoking avoidance sicular flare-up and the presence of tinea by establish- or the smoking test confirmed the exclusive responsi- ing 3.58 as the relative risk of vesicle eruption in case of bility of tobacco smoking as a triggering factor in only 2 intertrigo. With regard to internally reactivated pom- patients. Drug allergy was suspected on clinical history pholyx, nickel allergy described in the literature11-13 has and confirmed by oral intake or chronology in 3 pa- been formally accepted in only 2 patients presenting ag- tients (amoxicillin in 2 and intravenous immunoglobu- gravation or elicitation of intense vesicle flare-ups. Nev- lin in 1). In the 2 patients suspected of having an amoxi- ertheless, the number of reactions of internal origin re- cillin allergy, the blinded challenge test result to mains minor compared with contact pompholyx; still, it amoxicillin was positive. In the patient whose pompho- concerns 8 of 120 patients, including these 2 cases of lyx had appeared on 4 occasions the day after an intra- nickel allergy, 3 cases of pompholyx triggered by foods, venous immunoglobulin injection for dermatomyositis, and 3 cases elicited by drugs. A drug origin has been re- chronology allowed the conclusion of a causation rela- ported in the literature,14 with reactivation of contact tionship without challenge testing. dermatitis after intake of neomycin sulfate. Other drugs Concerning the hypothesis of food-related pompho- have been presented as responsible for pompholyx: io- lyx, food involvement was suspected in 4 cases (paprika dine products, salicylic acid, paracetamol, oral contra- in 2, orange juice in 1, and crustaceans in 1), leading to ceptives,15 mycophenolate mofetil,16 and intravenous im- an open oral challenge. A double oral test performed with munoglobulins.17-20 an in-between period of 3 weeks demonstrated that pom- Concerning tobacco and its responsibility, it has been pholyx was reactivated in 3 of the 4 cases. The concor- reported in the present study that 58 patients (48.3%) dant presence of specific IgE was found in all these 3 cases smoked regularly, which is consistent with the epide- (2 for paprika and 1 for orange juice). Therefore, the total miologic observations of Edman15; only 5 of them evoked number of internal cause pompholyx amounted to 8 (6.7% a chronology suggestive of causation. Nevertheless, the of all surveyed patients). fact that 58 of 120 patients were smokers leads to ques- To sum up, the causative study found 67.5% of con- tioning about the role of tobacco. The few patients with tact pompholyx, including cosmetic products (31.7%) and a positive test result to tobacco do not exclude the pos- metals (16.7%); interdigital-plantar intertrigo (10.0%); sibility that smoking might intervene through a nonal- and internal cause (6.7%), which left 15.0% of idio- lergic adjuvant mechanism. This hypothesis is sug-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1506 gested by the absence of contact eczema on the smokers’ pompholyx.28 The possibility of a concentrated flux of fingers and the conclusions of the epidemiologic study inflammatory cytokines in sweat has been advocated.29 of Linneberg et al.21 They observed that contact allergy For this reason, the use of antiperspirants may repre- to nickel had more severe manifestations in patients smok- sent an interesting adjunct treatment in refractory idio- ing 15 pack-years, and they established a significant dose- pathic pompholyx. response relation that was independent of exposure to In conclusion, this epidemiologic study confirms the nickel. Given that the elimination challenge test results existence of pompholyx triggered by interdigital-plantar confirmed only 2 cases of tobacco-induced pompholyx fungal intertrigo and by endogenous nickel, but in smaller of 120 (1.7%) in the present series, it seems that the di- proportions than contact pompholyx (67.5%), in which rect role of tobacco is accessory compared with its real cosmetic and personal hygiene products play a predomi- indirect aggravating potential. The few cases of pompho- nant role. The high rate of contact pompholyx is note- lyx exclusively related to tobacco do not exclude the pos- worthy because patients with pompholyx are generally con- sibility that smoking may act as an aggravating cofactor sidered to have a lower incidence of contact dermatitis than in many more cases. those with common hand eczema. This study points to a Although pompholyx is generally considered to be an major decrease of so-called idiopathic and internally re- endogenous dermatosis, this series points to the impor- activated pompholyx, with a high level of cases induced tance of contact allergy representing the exclusive cause by personal hygiene products. In light of these statistics, in up to 81 of 120 patients. It may be speculated that the it seems that the role of metals might have been overrated small percentage of cases of internal reactivation is not during the past years30 because there is no argument to representative of the real proportion of endogenous pom- think that this series is not representative of the overall pholyx, but the main point of these results is to confirm condition of pompholyx. Of the cases, 6.7% are related to the existence of so-called contact pompholyx that has alan internal reactivation from food, drug, or haptenic ori- ready been mentioned in the literature. Indeed, several gin. Although it is impossible to state that idiopathic pom- articles report that hand eczema may present a pompho- pholyx represents an equivalent of atopy, its association lyx form in percentages varying from 7%22 to 30%.9 Di- with atopy leads logically to planning additional caus- rect contact is one of the most important causes of pom- ative investigations31 before undertaking more expensive pholyx in the present series, with 67.5% of contact or extensive treatments of refractory pompholyx.32 pompholyx. In 1979, Meneghini and Angelini9 evaluated contact pompholyx at 30%, listing by order of fre- Accepted for Publication: February 20, 2007. quency various chemical molecules (PPD, chromium, co- Correspondence: Marie He´lène Guillet, MD, Depart- balt, mercaptobenzothiazole, nickel, and formaldehyde). ment of Dermatology, Centre Hospitalo–Universitaire de Among metallurgists, for whom pompholyx represents Poitiers, 2 Rue de la Mile´trie, BP 577, 86021 Poitiers half of the observed dermatoses, cutting oil is massively CEDEX, France ([email protected]). at the origin of the lesions,23 but the literature considers Author Contributions: Dr M. H. Guillet had full access nickel the dominant allergen of pompholyx,3 before co- to all of the data in the study and takes responsibility for balt and chromates (28% and 16%, respectively).24 Other the integrity of the data and the accuracy of the data analy- studies have confirmed the disappearance of cases of pom- sis. Study concept and design: M. H. Guillet and G. Guil- pholyx during nonworking periods, with a percentage let. Acquisition of data: M. H. Guillet and G. Guillet. Analy- evaluated at 7%.25 Generally speaking, the allergens in- sis and interpretation of data: M. H. Guillet, Wierzbicka, volved in pompholyx are PPD (9.3%), chromium (7.4%), and S. Guillet. Drafting of the manuscript: M. H. Guillet, cobalt (3.0%), mercaptobenzothiazole (2.7%), nickel Dagregorio, and G. Guillet. Critical revision of the manu- (1.7%), and formaldehyde (1.8%).9 In the present se- script for important intellectual content: M. H. Guillet, ries, the responsibility of pompholyx has been attrib- Wierzbicka, S. Guillet, and G. Guillet. Study supervi- uted to metals in 16.7% of all patients, representing 24.7% sion: M. H. Guillet, S. Guillet, and G. Guillet. of cases of contact pompholyx. But the most significant Financial Disclosure: None reported. conclusion of the present study is the importance of pompholyx related to personal hygiene products, which represent 47.2% of contact pompholyx and 31.7% of all cases REFERENCES of pompholyx. The cause of pompholyx remained unknown in 15.0% of cases at the end of the present study, 1. Fox T. Clinical lecture on dyshidrosis (an undescribed eruption). BrJMed. 1873: 365-366. but all these patients were atopic or had hyperhidrosis. 2. Veien NK, Hattel T, Justesen O, Norholm A. Oral challenge with metal salts, II: Of the patients in the present study, 46.7% had an atopic various types of eczema. Contact Dermatitis. 1983;9(5):407-410. condition. These figures are close to those reported in 3. Lodi A, Betti R, Chiarelli G, Urbani CE, Crosti C. Epidemiological, clinical and aller- the literature, which vary from 41% to 50%3,26 and sug- gological observations on pompholyx. Contact Dermatitis. 1992;26(1):17-21. gest that pompholyx could represent an equivalent of 4. Meding B, Swanbeck G. Epidemiology of different types of hand eczema in an 27 industrial city. Acta Derm Venereol. 1989;69(3):227-233. atopic palmar plantar dermatitis. 5. Rook A, Wilkinson DS, Ebling FJ. Pompholyx. In: Textbook of Dermatology.3rd The existence of observed hyperhidrosis in 33.3% of ed. Oxford, England: Blackwell Scientific Publications; 1979:324-327. the 120 patients led us to consider hyperhidrosis as an 6. Kutzner H, Wurzel RM, Wolff HH. Are acrosyringia involved in the pathogenesis important cofactor. Other researchers have reported the of “dyshidrosis”? Am J Dermatopathol. 1986;8(2):109-116. 7. Menne T, Hjorth N. Pompholyx-dyshidrotic eczema. Semin Dermatol. 1983;2:75- coexistence of hyperhidrosis in smaller proportions, vary- 80. 3,13 ing between 7.5% and 19%, but iontophoreses have 8. Tagami H, Watanabe S, Ofuji S, Minami K. Trichophytin contact sensitivity in pa- already been proposed with success in the treatment of tients with dermatophytosis. Arch Dermatol. 1977;113(10):1409-1414.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1507 9. Meneghini CL, Angelini G. Contact and microbial allergy in pompholyx. Contact 22. Agrup G. Hand eczema and other dermatoses in southern Sweden. Acta Derm Dermatitis. 1979;5(1):46-50. Venereol. 1969;49(suppl):61. 10. Bryld LE, Agner T, Menne´ T. Relation between vesicular eruptions on the hands 23. de Boer EM, Bruynzeel DP, van Ketel WG. Dyshidrotic eczema as an occupa- and tinea pedis, atopic dermatitis and nickel allergy. Acta Derm Venereol. 2003; tional dermatitis in metal workers. Contact Dermatitis. 1988;19(3):184-188. 83(3):186-188. 24. Yokozeki H, Katayama I, Nishioka K, Kinoshita M, Nishiyama S. The role of metal 11. Burrows D, Creswell S, Merrett JD. Nickel, hands and hip prostheses. Br J Dermatol. allergy and local hyperhidrosis in the pathogenesis of pompholyx. J Dermatol. 1981;105(4):437-443. 1992;19(12):964-967. 12. Jordan WP Jr, King SE. Nickel feeding in nickel-sensitive patients with hand eczema. 25. Thelin I, Agrup G. Pompholyx: a one year series. Acta Derm Venereol. 1985;65(3): J Am Acad Dermatol. 1979;1(6):506-508. 214-217. 13. Christensen OB, Mo¨ller H. External and internal exposure to the antigen in the 26. Oddoze L, Temime P. Dyshidrosis and atopy: 2nd note: atopic component in dys- hand eczema of nickel allergy. Contact Dermatitis. 1975;1(3):136-141. hidrosis [in French]. Bull Soc Fr Dermatol Syphiligr. 1968;75(3):378-380. 14. Ekelund AG, Mo¨ller H. Oral provocation in eczematous contact allergy to neo- 27. van Ketel WG, Aalberse RC, Reerink-Brongers E, Woerdeman-Evenhuis JT. mycin and hydroxy quinolines. Acta Derm Venereol. 1969;49(4):422-426. Comparative examination of the results of the RAST and intracutaneous tests in 15. Edman B. Palmar eczema: a pathogenetic role for acetylsalicylic acid, contra- eczema dyshidroticum [proceedings]. Dermatologica. 1978;156(5):304-306. ceptives and smoking? Acta Derm Venereol. 1988;68(5):402-407. 28. Odia S, Vocks E, Rakoski J, Ring J. Successful treatment of dyshidrotic hand 16. Semhoun-Ducloux S, Ducloux D, Miguet JP. Mycophenolate mofetil–induced dys- eczema using tap water iontophoresis with pulsed direct current. Acta Derm hidrotic eczema. Ann Intern Med. 2000;132(5):417. Venereol. 1996;76(6):472-474. 17. Ikeda K, Iwasaki Y, Ichikawa Y, Kinoshita M. Pompholyx after IV immunoglob- 29. Reitamo S, Anttila HS, Didierjean L, Saurat JH. Immunohistochemical identifi- ulin therapy for neurologic disease. Neurology. 2000;54(9):1879. cation of interleukin I alpha and beta in human eccrine sweat-gland apparatus. 18. Whittam LR, Hay RJ, Hughes RA. Eczematous reactions to human immune globulin. Br J Dermatol. 1990;122(3):315-323. Br J Dermatol. 1997;137(3):481-482. 30. Fowler JF Jr, Storrs FJ. Nickel allergy and dyshidrotic eczema: are they related? 19. Barucha C, McMillan JC. Eczema after intravenous infusion of immunoglobulin. Am J Contact Dermat. 2001;12(2):119-121. Br Med J (Clin Res Ed). 1987;295(6606):1141. 31. Lischka G. Testing for food allergy in dyshidrotic eczema [in German]. Hautarzt. 20. Chevrant-Breton J, Moutarda I, Penfornis C, Ollivier H, Allain H, Huault-Dupuy 1996;47(1):65. L. Toxidermies eczematiformes après traitement par immunoglobulines intra- 32. Schnopp C, Remling R, Mo¨hrenschlager M, Weigl L, Ring J, Abeck D. Topical veineuses (5 cas). Ann Dermatol Venereol. 1998;125(suppl):3515. tacrolimus (FK506) and mometasone furoate in treatment of dyshidrotic palmar 21. Linneberg A, Nielsen NH, Menne T, Madsen F, Jorgensen T. Smoking might be eczema: a randomized, observer-blinded trial. J Am Acad Dermatol. 2002;46 a risk factor for contact allergy. J Allergy Clin Immunol. 2003;111(5):980-984. (1):73-77.

Annual Reviewers List

We thank all of the reviewers who have generously and thoughtfully assisted the Editorial Board, our authors, and our readers during the past year. A full list of our reviewers from 2007 is available at http://www .archdermatol.com. June K. Robinson, MD Editor Jeffrey P. Callen, MD Associate Editor

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1508 STUDY Teledermatological Monitoring of Leg Ulcers in Cooperation With Home Care Nurses

Barbara Binder, MD; Rainer Hofmann-Wellenhof, MD; Wolfgang Salmhofer, MD; Aslihan Okcu, MD; Helmut Kerl, MD; H. Peter Soyer, MD

Objectives: To examine the feasibility and acceptance cellent or sufficient and the experts were confident in giv- of teledermatology for wound management for patients ing therapeutic recommendations. Of the 45 ulcers, 32 with leg ulcers by home care nurses and evaluate the re- (71%) decreased in size and 14 (31%) healed com- duction of costs and the acceptance of teledermatology pletely, whereas 10 of the 45 ulcers (22%) increased by patients and home care nurses. slightly in size despite the teledermatological monitoring. In 3 ulcers (7%), no measurement was possible ow- Design: Case series of telemonitored patients with leg ing to the overly large size of the ulcers. The acceptance ulcers including cost-effectiveness analysis. of telemedicine was very good by most patients. Of 15 home care nurses working in the district, 7 were very sat- Setting: Home monitoring by home care nurses. isfied with teledermatological monitoring of wound care. There was a reduction of 46% in transportation costs for Patients: Sixteen patients with 45 leg ulcers of differ- the insurance companies as well as for the patients ow- ent origin were included. ing to a significant decrease in the number of visits to general physicians or the wound care center. Main Outcome Measures: After an initial outpatient visit when the leg ulcers were assessed and classified, tele- Conclusions: The acceptance of teledermatological moni- dermatological follow-up was done by home care nurses. toring of wound care was very high by patients, home Relevant clinical information and 1 to 4 digital images care nurses, and wound experts. Decreased health care of the wound and surrounding skin were transmitted costs by reducing the number of visits to wound care cen- weekly via a secure Web site to an expert at the wound ters or specialist physicians and improvement in quality care center, who assessed the wound and made thera- of life for patients with leg ulcers using telemedicine seems peutic recommendations. possible. Teledermatology offers great potential for long- term wound care. Results: Of the 707 images transmitted for teleconsultation, in 644 (89%) the quality of the images was ex- Arch Dermatol. 2007;143(12):1511-1514

HRONIC LEG ULCERS ARE A inconveniences related to regular clinical significant problem for visits cause a major discomfort to the pa- both patients and health tient and reduce the patient’s quality of life. service resources.1 Leg ulcers are dynamic, requir- For editorial comment ingC frequent assessment of wound status and surrounding skin, coupled with ad- see page 1581 justments to therapy. Repeated visits to specialized wound care centers are often Teledermatology is a new rapidly necessary. These visits can be time con- evolving area in dermatology.2 Reason- suming because of long travel distances ably priced photographic equipment and and prolonged waiting time, thus being a quick electronic transfer of high-quality significant burden for the patients who are digital images make it possible to get an almost exclusively elderly. In Styria, a prov- expert’s opinion for diagnosis or recom- ince of Austria with a total population of mendation for management without de- 1.2 million inhabitants, about 12 000 pa- lay. By using teledermatological support Author Affiliations: tients are being treated for leg ulcers of dif- in managing leg ulcers, the patients re- Department of Dermatology, ferent causes at any given time. Only a few ceive expert medical consultation while Medical University of Graz, specialized centers have been established avoiding the costs and inconvenience of Graz, Austria. for the treatment of chronic wounds. The long-distance travel to specialized cen-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1511 ters. Preliminary results of the studies by Wilbright et Table. Clinical Data of the Ulcers al3 and Debray et al4 suggest that clinical images together with additional data from the patient’s history Changes Size, cm2 are usually sufficient for a correct diagnosis and appro- Ulcer No. Duration, of Therapy a priate therapy of diabetes-related foot ulcers and by Patient Cause mo Modalities, No. Before After wounds in elderly patients. Patient 1 We build on our previous report of feasibility and 1 Venous 48 5 10.3 5.6 acceptance of telemedicine for wound care in patients 2 Venous 6 147.8 79.7 5,6 3 Venous 5 0.5 0 with chronic leg ulcers. In the present study, we 4 Venous 5 125.0 63.2 report on the efficacy of telemedicine for managing leg Patient 2 ulcers in a setting with home care nurses in 16 5 Mixed 1 3 0.5 8.0 patients with 45 leg ulcers of different origin. In addi- 6 Mixed 3 1.0 7.7 tion, the reduction of costs and the acceptance of tele- 7 Mixed 5 14.9 52.1 dermatology by patients and home care nurses are Patient 3 evaluated. 8 Venous 120 2 0.5 1.8 9 Venous 2 0.5 1.0 10 Venous 1 1.9 2.3 METHODS 11 Venous 1 5.2 6.3 Patient 4 12 Venous 240 4 NM NM Sixteen patients aged between 47 and 86 years (median, 73 years) 13 Venous 3 NM NM with 45 leg ulcers of different causes were included in this study Patient 5 (male to female ratio, 4:12) (Table). Informed consent was ob- 14 Venous 7 4 24.2 1.1 tained from all patients. Initially, the patients came to the wound 15 Venous 2 10.2 9.2 care center at the Department of Dermatology, Medical Uni- 16 Venous 3 4.3 3.7 versity of Graz, Graz, Austria, where their leg ulcers were as- 17 Venous 2 22.4 3.1 sessed by the same wound care experts over the duration of Patient 6 the study. The following visits within the next 3 months or un- 18 Mixed 24 3 1.5 2.7 til the leg ulcer was healed were conducted by home care nurses, 19 Mixed 3 2.0 2.2 who were trained in taking and transmitting the images and 20 Mixed 4 1.1 0 trained in wound care. Once a week, 1 to 4 digital images of Patient 7 each ulcer and surrounding skin including relevant clinical in- 21 Mixed 36 2 0.3 0 formation were transmitted to the wound care center. At the 22 Mixed 2 1.6 1 end of the study, the patient was examined once again in- Patient 8 person at the wound care center. 23 Venous 24 2 17.5 7.3 Digital images were taken with a 3.3-megapixel camera (Cool- 24 Venous 1 0.4 0 pix 995; Nikon Corporation, Tokyo, Japan) and stored on a 25 Venous 2 1.4 0 built-in flash card. The image size was 2048ϫ1536 pixels, and Patient 9 the images were compressed to approximately 1.5 megabytes 26 Venous 2 2 2.3 1.7 in Joint Photographics Experts Groups (JPEG) format. All im- 27 Venous 3 1.0 0.2 ages had a standardized color graduation included and were Patient 10 28 Venous 0.5 1 1.9 0 taken without flash, with uniform room illumination and a high- 29 Venous 1 1.1 0 sensitivity setting on the camera. Patient 11 After logging in to a secure Web site (http://www.teleulcus 30 Venous 12 2 1.5 0 .at), specifically designed for this study, the images were down- Patient 12 loaded from the camera to a server via universal serial bus (USB) 31 Venous 3 3 7.8 0 connection without any modification or processing. Selected 32 Venous 1 8.3 0 clinical data were also transmitted via this Web application to 33 Venous 1 1.3 0 an expert in wound care for independent teledermatological Patient 13 assessment. The procedure took about 5 minutes per ulcer. The 34 Venous 0.5 2 0.6 0.5 experts provided an assessment of wound status and therapeu- 35 Venous 0 0.8 0 tic recommendations within 24 hours. 36 Venous 0 0.6 0 The acceptance of teledermatology was assessed by ques- Patient 14 tionnaires (patients and home care nurses); the patients com- 37 Venous 300 2 NM NM pleted one unvalidated questionnaire before and one at the end 38 Venous 0 4.7 5.1 of the study. The transport costs for each patient from his or 39 Venous 0 17.2 15.6 her home to the wound care center in Graz or to their general Patient 15 practitioners 3 months before the beginning of the study were 40 Venous 5 3 9.5 5.3 compared with those 3 months during the study. 41 Venous 3 2.1 0.5 Patient 16 42 Venous 12 5 3.5 2.9 RESULTS 43 Venous 2 1.7 0.9 44 Venous 2 1.0 0 GENERAL FINDINGS 45 Venous 1 6.6 4.5

Abbreviation: NM, no measurement. The 45 chronic leg ulcers in the 16 patients were moni- aDuration refers to the duration of all ulcers of a given patient. tored by teledermatology during the 3-month period. In

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1512 total, 470 teleconsultations were performed. Alto- consultations has been reported in all of them.7-9 Up to gether, 707 digital images were sent to the experts. Of now, only a few reports have discussed the use of tele- 724 images, 644 (89%) were of excellent or sufficient qual- dermatology in the diagnosis and care of patients with ity. The grading was performed for each image sepa- leg ulcers.3-6,10,11 rately and included the categories excellent, sufficient, The diagnosis of leg ulcers is usually straightfor- and insufficient. For the remaining 63 cases, the images ward, whether it is made by clinical examination or based were slightly blurred, underexposed, or the framing of on a digital image. A correct classification of the leg ul- the image was not optimum. cer can usually be made, based on clinical presentation Certain questions about pain, inflammation, and itch- and additional data from the patient’s history, concerning of the surrounding skin, among other questions, were ing both the ulcer and concomitant diseases. Treatment brought to the experts’ attention in 79 cases. Experts made suggestions are commonly based on the clinical presen- changes in treatment plan in 108 of the 470 teleconsultation of the leg ulcer and the surrounding skin, the clas- tations (23%). sification of the leg ulcer, information on previous thera- As outlined in the Table, the sizes of the ulcers be- peutic modalities and therapeutic response, known allergic fore and after treatment changed as follows: of the 45 ul- reactions of the patient, and the clinician’s personal ex- cers, 32 (71%) decreased in size and 14 (31%) healed com- perience with wound healing. pletely, whereas 10 of the 45 ulcers (22%) increased In general, the quality of digital images in our study slightly in size despite the teledermatological monitor- was excellent and the experts were able to give thera- ing. In 3 ulcers (7%), no measurement was possible ow- peutic recommendations, which subsequently were caring to the overly large size of the ulcers. Remarkably, in ried out by the home care nurses. Based on this com- these 3 ulcers, no notable change in size was observed. bined approach of teledermatological expert monitoring and treatment performance by home care nurses, a good ACCEPTANCE BY PATIENTS healing rate was achieved. More than 70% of the ulcers showed a decrease in size, and approximately one-third Before starting the study, the patients were asked about healed completely. In addition, the home care nurses suc- their expectations concerning telemedicine. Seven pa- cessfully requested help in the treatment of different ul- tients thought that telemedicine could be useful, but the cers in 79 instances. The acceptance of the new method other 9 patients were not optimistic about this new form was very good in most patients and was remarkably bet- of wound care. At the end of the study, 9 patients were ter in patients with good wound healing. Unsurpris- very satisfied, 3 partly satisfied, and 4 were not satisfied ingly, all 4 patients who were not satisfied with this com- with telemedicine in wound care. All 4 patients who were bined approach showed a poor healing rate. not satisfied showed a poor healing rate. Twelve pa- The acceptance of teledermatology was also high by tients thought that teledermatology was able to replace home care nurses. Following a short settling-down phase, a personal consultation with a general physician or with they learned to take images, upload them, and use the an expert of the wound care center. Web application for the store-and-forward communication with the experts. In their opinion, this method im- NURSES AND COSTS proves the quality of the treatment. In general, our patients with leg ulcers consult the gen- All 7 home care nurses participating in the study were eral physician or our wound care center every 3 weeks satisfied with the teledermatological monitoring by ex- for therapy adjustment. In our study, we found a marked perts, and they believed that the quality of their treat- reduction in these outpatient visits. Therefore, a distinct reduction in transport costs for the patients was ment was improved. The possibility of consulting the ex- 12 perts every week was a great advantage for them. achieved, an advantage of teledermatology over the usual In the 3 months before the inclusion into the study, the treatment modalities. patients together required 64 consultations with the gen- Teledermatology holds great potential for the future of eral physician or the dermatology department. Over the long-term wound care. It could increase the quality of medical care13 for patients by enabling general practitioners and course of the study, only 9 consultations of a general phy- 14 sician were required. The reasons for these consultations home care nurses in any location to receive diagnostic and were fever, mechanical debridement of the ulcer, and an- treatment support from experts in wound care. By reduc- tibiotic prescriptions. This trend led to a significant de- ing the need for travel, wound care teleconsultations might crease in transportation costs (46%) on the basis of the lower the health care costs. Improvement in the patient’s original data from the insurance companies, although not quality of life will be possible by reducing inconveniences all patients had been treated in the wound care center regu- such as long waiting times for appointments at specialty larly during the 3 months before participating in the study. clinics, often located some distance away, and repeated visits to those clinics. Training of home care nurses in taking and transmitting images as well as special training in wound COMMENT care are prerequisites to successfully implement telemoni- toring for patients with chronic leg ulcers. Several studies showing the feasibility and the usefulness of teleconsultations in dermatology have already been Accepted for Publication: April 6, 2007. described in the literature, and high accordance for di- Correspondence: H. Peter Soyer, MD, Department of Der- agnosis and treatment between face-to-face visits and tele- matology, Research Unit of Teledermatology, Medical Uni-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1513 versity of Graz, Auenbruggerplatz 8, A-8036 Graz, Aus- REFERENCES tria ([email protected]). Author Contributions: Dr Soyer takes responsibility for 1. Simon DA, Dix FP, McCollum CN. Management of venous leg ulcers. BMJ. 2004; the integrity of the article. Study concept and design: Binder, 328(7452):1358-1362. Hofmann-Wellenhof, Salmhofer, and Soyer. Acquisition of 2. Eedy DJ, Wooton R. Teledermatology; a review: wound teleconsultation in patients with chronic leg ulcers. Br J Dermatol. 2001;144(4):696-707. data: Binder, Hofmann-Wellenhof, Salmhofer, and Okcu. 3. Wilbright WA, Birke JA, Patout CA, et al. The use of telemedicine in the manage- Analysis and interpretation of data: Binder, Hofmann- ment of diabetes-related foot ulcers: a pilot study. Adv Skin Wound Care. 2004; Wellenhof, Salmhofer, and Soyer. Drafting of the manu- 17(5, pt 1):232-238. 4. Debray M, Couturier P, Greuillet F, et al. A preliminary study of the feasibility of script: Binder. Critical revision of the manuscript for impor- wound telecare for the elderly. J Telemed Telecare. 2001;7(6):353-358. tant intellectual content: Binder, Hofmann-Wellenhof, 5. Salmhofer W, Hofmann-Wellenhof R, Gabler G, et al. Wound teleconsultation in Salmhofer, Okcu, Kerl, and Soyer. Administrative, techni- patients with chronic leg ulcers. Dermatology. 2005;210(3):211-217. cal, and material support: Binder, Salmhofer, and Okcu. Study 6. Hofmann-Wellenhof R, Salmhofer W, Binder B, et al. Feasibility and acceptance of telemedicine for wound care in patients with chronic leg ulcers. J Telemed supervision: Hofmann-Wellenhof, Kerl, and Soyer. Telecare. 2006;12(suppl 1):15-17. Financial Disclosure: Dr Soyer is cofounder and man- 7. Collins K, Walters S, Brown I. Patient satisfaction with teledermatology: quan- aging director of e-derm-consult GmbH, a spin-off of the titative and qualitative results from a randomized controlled trial. J Telemed Telecare. 2004;10(1):29-33. Medical University of Graz. The Web application on which 8. Braun RP, Vecchietti JL, Thomas L, et al. Telemedical wound care using a new the Web site http://www.teleulcus.at runs has been degeneration of mobile phones. Arch Dermatol. 2005;141(2):254-258. veloped and provided by e-derm-consult GmbH. 9. Massone C, Lozzi GP, Worm E, et al. Cellular phones in clinical teledermatology. Funding/Support: This study was supported in part by Arch Dermatol. 2005;141(10):1319-1320. 10. Samad A, Hayes S, Dodds S. Telemedicine: an innovative way of managing pa- a grant from the Austrian Ministry of Education, Sci- tients with leg ulcers. Br J Nurs. 2002;11(6)(suppl):S38-S52. ence, and Culture. 11. Tsai HH, Pong YP, Liang CC, Lin PY, Hsieh CH. Teleconsultation by using the Role of the Sponsor: The sponsor had no role in the de- mobile camera phone for remote management of extremity wound. Ann Plast Surg. 2004;53(6):584-587. sign and conduct of the study; in the collection, analy- 12. Knol A, van den Aker TW, Dastar RJ, de Han J. Teledermatology reduces the number sis, and interpretation of data; or in the preparation re- of patient referrals to a dermatologist. J Telemed Telecare. 2006;12(2):75-78. view, or approval of the manuscript. 13. Baer CA, Williams CM, Vickers L, Kvedar JC. A pilot study of specialized nursing Additional Contributions: Walter Burgdorf, MD, pro- care for home health patients. J Telemed Telecare. 2004;10(6):342-345. 14. Chae YM, Heon Lee J, Hee Ho S, Ja Kim H, Hong Jun K, Uk Won J. Patient sat- vided critical review of the manuscript and editorial isfaction with telemedicine in home health services for elderly. Int J Med Inform. help. 2001;61(2-3):167-173.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1514 STUDY Reliability of the Roenigk Classification of Liver Damage After Methotrexate Treatment for Psoriasis A Clinicopathologic Study of 160 Liver Biopsy Specimens

Maartje A. M. Berends, MD; Martijn G. H. van Oijen, MSc; Josje Snoek, MSc; Peter C. M. van de Kerkhof, MD, PhD; Joost P. H. Drenth, MD, PhD; J. Han van Krieken, MD, PhD; Elke M. G. J. de Jong, MD, PhD

Objective: To determine the interobserver reliability Main Outcome Measure: Interobserver variation was of the Roenigk score as a classification system of liver evaluated using ␬ statistics. damage and its possible consequences for clinical practice. Results: A high concordance was present in the evaluation of the Roenigk grade of fibrosis (weighted ␬=0.73; Design: Retrospective study. 95% confidence interval, 0.63-0.83). Agreement was good regarding the number of biopsy specimens for patients Setting: Academic research. whose clinical management should be changed (␬=0.71; 95% confidence interval, 0.56-0.87). Patients: One hundred sixty liver biopsy specimens from patients with psoriasis receiving methotrexate treat- Conclusion: The Roenigk classification in the assessment were rereviewed and analyzed blindly by an expe- ment of liver fibrosis is a reliable scoring system. rienced pathologist with an interest in liver pathologic conditions. Arch Dermatol. 2007;143(12):1515-1519

EPATIC FIBROSIS AND CIR- pleomorphism) of unclear significance, rhosis represent a conse- and is insensitive to small changes, par- quence of methotrexate ticularly when assessing fibrosis.1,15,16 Al- treatment in patients with though scoring seems to consider changes psoriasis.1-6 Therefore, the such as steatosis and inflammation, their assessmentH of liver damage is essential in presence or absence has no weight in the the clinical management of these pa- allocation to more advanced grades. The tients. Sequential liver biopsies followed system categorizes all biopsy specimens by Roenigk grading by a pathologist are with more than minimal fibrosis as ad- the mainstay in the assessment of the stage vanced fibrosis (Roenigk grade 3b) and and degree of liver damage.7-9 Unfortu- overestimates the degree of histologic nately, liver biopsies may be associated change. Accurate assessment is essential with sampling error, potential complica- because misclassification of pathologic tions, and interobserver variability.1,7,9-13 changes affects clinical management. For Methotrexate-associated liver damage example, if the degree of fibrosis is up- in patients with psoriasis is graded accord- graded from none (Roenigk grade 2) to ing to the Roenigk classification.1 The re- mild (Roenigk grade 3a), guidelines call sults of the Roenigk scoring system should for a second liver biopsy within 6 months be reproducible, with little interobserver instead of a 1.5-g cumulative dose of error. methotrexate.9 In the case of Roenigk grade Author Affiliations: The Roenigk classification was devel- 3b or 4, the guidelines recommend dis- Departments of Dermatology oped by the Psoriasis Task Force (led by continuation of therapy. (Drs Berends, van de Kerkhof, dermatologists), is based on clinical ob- In some European countries, the num- and de Jong), Gastroenterology servations, and has been recommended in ber of liver biopsies has declined for sev- and Hepatology (Mr van Oijen, the American Academy of Dermatology eral reasons. The use of the aminotermi- Ms Snoek, and Dr Drenth), and Pathology (Dr van Krieken), guidelines for monitoring methotrexate- nal propeptide of type III procollagen 1,9,14 Radboud University Nijmegen induced liver injury. However, the (PIIINP) has reduced the number of liver Medical Centre, Nijmegen, Roenigk grading system is subjective, in- biopsies in Scandinavia and in Great Brit- the Netherlands. cluding some features (such as nuclear ain. Until recently, no noninvasive method

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1515 Table 1. Roenigk Classification System

Fatty Change Nuclear Pleomorphism Fibrosis Necroinflammation Roenigk Gradea Mild or none Mild or none None With or without mild portal inflammation 1 Moderate or severe Moderate or severe None Moderate or severe portal inflammation 2 With or without With or without Mild (fibrosis extending into acini) With or without 3a With or without With or without Moderate or severe With or without 3b With or without With or without Cirrhosis With or without 4

a See the “Pathologic Examination” subsection of the “Methods” section for an explanation of Roenigk grades.

has been available that could completely replace the liver fatty changes, nuclear pleomorphism, and portal inflamma- biopsy. In the case of a persistently elevated PIIINP, liver tion. Grade 3a indicates mild fibrosis, portal fibrotic septa, ex- biopsy is still advised.11,13,17 Given the critical nature of tension into the lobuli, and portal tract enlargement. Grade 3b this tool, we evaluated interobserver variation using a indicates moderate or severe fibrosis. Grade 4 indicates cirrho- sample of 160 liver biopsy specimens from methotrexate- sis, regenerating noduli, and bridging of the portal tracts. treated patients with psoriasis. STATISTICAL ANALYSIS METHODS To judge the degree of interobserver agreement, we calculated ␬ PATIENTS weighted statistics for the 5-point Roenigk scale. For analysis of clinical consequences, we dichotomized the Roenigk score We evaluated interobserver variation between several differ- into “no changes of treatment necessary” (Roenigk grades 1 and ent pathologists with an interest in liver pathologic routine clini- 2) and “change of treatment necessary” (Roenigk grades 3a, 3b, and 4) for all observations. For agreement of the dichoto- cal practice and 1 of us (J.H.v.K.) in the assessment of the his- ␬ ␬ topathologic degree of liver damage according to the Roenigk mized data, we again used statistics. Interpretation of the scale in patients with psoriasis receiving methotrexate treat- statistics was performed using the scale described by Landis and Koch,18 in which ␬ statistics less than 0.4 indicate poor agreement. All pathologists were trained at the same department of ␬ pathology at the same hospital. ment, statistics between 0.4 and 0.6 indicate moderate agreement, between 0.6 and 0.8 good agreement, and greater than One hundred twenty-five patients with psoriasis had un- 19 dergone 278 liver biopsies while receiving methotrexate treat- 0.8 indicate excellent agreement. ment from November 1, 1976, to December 31, 2005. We ex- To visualize agreement, we plotted a Bland-Altman curve cluded biopsies performed before December 31, 1995, because for the 5-point Roenigk score. Using a 2-sided t test, we tested these specimens were unavailable for review. In addition, 9 bi- whether the overall mean differences differed statistically sig- opsy specimens were excluded from analysis (6 because they nificantly from 0. All analyses were undertaken using statisti- were unavailable from the department’s archives, 1 was too small cal software (SAS version 8.2; SAS Institute Inc, Cary, North to evaluate the degree of fibrosis, and 2 because the van Gieson– Carolina). stained slide was unavailable). One hundred sixty liver biopsy specimens from 95 patients were reexamined independently RESULTS by 1 of us (J.H.v.K.) who was blinded to the clinical details of the patients. Liver biopsy specimens were graded according to the Roenigk classification (Table 1).1 DEMOGRAPHICS Ninety-five patients with psoriasis (44 female and 51 male) HISTOLOGIC EXAMINATION underwent a liver biopsy between December 31, 1995, Percutaneous liver biopsy was performed via a right intercos- and December 31, 2005. The maximum prescribed weekly tal approach using local lidocaine hydrochloride anesthesia. The dosage of methotrexate was 12.5 mg (range, 7.5-25 mg). biopsy specimen was immersed in 2% formaldehyde and was Patients received a median cumulative methotrexate dose subsequently fixed with paraffin. Hematoxylin-eosin–stained of 2051 mg (range, 119-20 235 mg) during a median fol- sections of liver tissue were examined for steatosis, nuclear vari- low-up period of 202 weeks (range, 20-1763 weeks). ability, hepatocyte necrosis, and lobular and portal tract inflammation. A van Gieson stain for collagen was used to as- LIVER BIOPSY SPECIMENS sess for the expansion of the portal tracts and for the presence of pericellular and perivenular fibrosis. The concordance between the Roenigk grades as scored during routine assessment and at subsequent scoring by PATHOLOGIC EXAMINATION the second pathologist was high (weighted ␬=0.73; 95% confidence interval, 0.63-0.83). The agreement All liver biopsy specimens, sampled as part of the monitoring was higher for biopsy specimens that were graded as process of methotrexate-induced hepatic injury, were graded according to the Roenigk classification. A description of the Roenigk grade 1, which was the most common Roenigk Roenigk classification is given in Table 1. Roenigk grade 1 in- score (Figure). The mean difference was 0.03 and did dicates normal tissue with no fibrosis, no or mild portal in- not significantly differ from 0 (PϾ.05). Among liver bi- flammation, and no or mild fatty changes and nuclear pleo- opsy specimens that resulted in a change of clinical morphism. Grade 2 indicates no fibrosis and moderate or severe management (Roenigk grades 3a, 3b, and 4), we like-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1516 Table 2. Numbers of Slides Assigned to the Roenigk Grades by the Pathologistsa 2 Roenigk Grade First Pathologist Second Pathologist 1 113 118 1 22118 3a 22 18 3b 3 4 41 2 0 a See the “Pathologic Examination” subsection of the “Methods” section Difference Score for an explanation of Roenigk grades. –1 biopsies after 9 and 14 months that demonstrated histologic findings corresponding to grade 3a. One of these –2 patients is still being treated with methotrexate. In the other patient, methotrexate treatment was continued, and 2 more biopsies were performed. Both biopsy speci- 1 2 3a 3b 4 mens demonstrated histologic findings corresponding to Mean Score grade 3a. Methotrexate treatment was discontinued for an unknown reason. Figure. Bland-Altman curve. The graph shows the absolute difference between the initial and subsequent scores (on the y-axis) against the mean of both scores (on the x-axis) for each observation. In the graph, the size of COMMENT the crosses indicates how often a pair of observations is found. The red line indicates the 0.03 overall mean difference between the initial and subsequent scores. Our objectives were to determine the interobserver reliability of the Roenigk score as a classification system wise observed a good correlation (␬=0.71; 95% confi- of methotrexate-induced liver damage and to assess the dence interval, 0.56-0.87). consequences for clinical practice. The results of this study The initial routine examination had graded 113 liver show that the Roenigk classification is a reliable scoring biopsy specimens as Roenigk grade 1, 21 as grade 2, 22 system for the assessment of liver fibrosis. as grade 3a, 3 as grade 3b, and 1 as grade 4 (Table 2). The study revealed high concordance between the first After reexamination of all liver biopsy specimens by the and second observations. Also, there was good agree- second pathologist, 118 were graded as grade 1, 18 as ment on biopsy specimens that resulted in a Roenigk grade grade 2, 18 as grade 3a, 4 as grade 3b, and 2 as grade 4. that necessitated change of clinical management (bi- Six liver biopsy specimens originally scored as Roenigk opsy specimens with grades 3a, 3b, and 4). Although only grade 1 were scored differently by the second patholo- a small percentage of the biopsy specimens was scored gist (3 as grade 2 and 3 as grade 3a). Ten liver biopsy differently by the second pathologist, it would have re- specimens originally scored as grade 2 were subse- sulted in a clear change in the clinical decisions made. quently scored differently (2 were upgraded to grade 3a, Grade 3a requires more frequently performed liver bi- while 8 were downgraded to grade 1). Nine liver biopsy opsies (within 6 months instead of a 1.5-g cumulative specimens originally scored as grade 3a were scored dif- dose of methotrexate), and grades 3b and 4 necessitate ferently by the second pathologist (2 as grade 3b, 4 as interruption and cessation of methotrexate treatment.9 grade 2, and 3 as grade 1). Finally, 1 liver biopsy speci- Periodic liver biopsies are recommended by interna- men originally scored as grade 3b was subsequently up- tional guidelines4,9,14 on methotrexate treatment in pa- staged to grade 4. tients with psoriasis, and the Roenigk score has been recommended in the American Academy of Dermatology CLINICAL CONSEQUENCES guidelines4,9,14 to classify methotrexate-induced liver dam- OF DIFFERENCES IN SCORING age. However, the Roenigk scale has not been validated or used (to our knowledge) in the evaluation of any other Fourteen biopsy specimens were downgraded or up- liver disease.1 Furthermore, the Roenigk scale is subjec- graded to such an extent that it would have affected clini- tive and is insensitive to small changes, particularly when cal management (Table 3). Seven biopsy specimens assessing fibrosis.1,16 Scoring systems for liver damage such graded as Roenigk grade 3a were downgraded by the sec- as the Metavir, Scheuer, and Ishak classifications are well ond pathologist to grade 2 or 1. Because of the original established for hepatitis C and for some forms of nonvi- grade, follow-up biopsies in 3 patients were performed ral hepatitis; these scoring systems are more sensitive to after 5 to 10 months, and methotrexate treatment in small changes, and studies1,20-24 demonstrated good agree- 1 patient was discontinued after 5 months. Three bi- ment for fibrosis assessment. As far as we know, there opsy specimens were upgraded by the second patholo- are no studies evaluating the validity and interobserver gist from grade 1 to 3a, 2 biopsy specimens from grade 2 reliability of the Roenigk score. However, 2 studies com- to 3a, and 2 biopsy specimens from grade 3a to 3b. In pare the Roenigk classification with other scoring sys- the latter 2 cases, this assessment resulted in follow-up tems. One study15 compares the Roenigk score with a

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1517 Table 3. Slides Scored Differently by the Pathologists

Roenigk Gradea No. of Slides Upgrade Clinical First Pathologist Second Pathologist Scored Differently or Downgrade Consequences 1 2 3 Upgrade No 1 3a 3 Upgrade Yes 2 1 8 Downgrade No 2 3a 2 Upgrade Yes 3a 1 3 Downgrade Yes 3a 2 4 Downgrade Yes 3a 3b 2 Upgrade Yes 3b 4 1 Upgrade No

a See the “Pathologic Examination” subsection of the “Methods” section for an explanation of Roenigk grades. semiquantitative histologic scoring system for the evalu- dividually (by the first pathologist) could have resulted ation of hepatic fibrosis in patients with rheumatoid ar- in some of the differences. thritis treated with methotrexate. A statistically signifi- One biopsy specimen was excluded from the study be- cant correlation was found between the 2 classification cause it was too small to evaluate the degree of fibrosis. A systems, but the semiquantitative histologic scoring sys- hepatologist experienced in performing liver biopsies and tem was much more sensitive than the Roenigk score for in repeating liver biopsy procedures is essential for obtain- the assessment of hepatic fibrosis. Another study1 coming adequate specimens and for the safety of the patient. pared 3 scoring systems for the evaluation of hepatic fi- Based on this study, we conclude that the interob- brosis in patients with psoriasis treated with methotrex- server reliability of the Roenigk classification is good and ate. The Roenigk classification was compared with the that it can be used as a scoring system for methotrexate- Scheuer and Ishak scoring systems and seemed to cor- induced liver damage. However, the clinical conse- relate poorly with both systems. quences of rereview were substantial. Experienced patholo- The already described simplification of the Roenigk gists with an interest in liver pathologic conditions are classification may have improved the interobserver reli- recommended, as well as particular attention to biopsy speci- ability in our study. This raises the question of whether mens with Roenigk grades 3a and 3b. The search for non- the Roenigk classification is the best-designed scoring sys- invasive alternatives to liver biopsy should be continued. tem to classify methotrexate-induced liver injury. How- ever, that was not the objective of our study. The Roenigk Accepted for Publication: April 6, 2007. classification is used by many pathologists to classify Correspondence: Maartje A. M. Berends, MD, Depart- methotrexate-induced liver fibrosis. In this study, it is ment of Dermatology, Radboud University Nijmegen shown that the interobserver reliability is good. Medical Centre, PO Box 9101, 6525 GL Nijmegen, the In 8% of the liver biopsy specimens, a different clini- Netherlands ([email protected]). cal decision would have been made based on disagree- Author Contributions: Dr Berends had full access to all ment between the first and second observers. When this of the data in the study and takes responsibility for the leads to more frequently performed liver biopsies, seri- integrity of the data and the accuracy of the data analy- ous consequences arise for the patient. Patients will be sis. Study concept and design: Berends, van Oijen, van de at greater risk for morbidity and mortality associated with Kerkhof, Drenth, van Krieken, and de Jong. Acquisition liver biopsies such as postprocedural pain, bleeding, and of data: Berends, Snoek, Drenth, van Krieken, and de Jong. (less often) pneumothorax. Also, an increase in liver bi- Analysis and interpretation of data: Berends, van Oijen, opsies has socioeconomic consequences such as ab- van de Kerkhof, Drenth, van Krieken, and de Jong. Draft- sence from work. Unnecessary liver biopsies should be ing of the manuscript: Berends, Snoek, Drenth, van Krieken, avoided, and there is a need for alternative noninvasive and de Jong. Critical revision of the manuscript for impor- and reliable methods to monitor methotrexate-induced tant intellectual content: Berends, van Oijen, van de Kerk- liver injury in patients with psoriasis. Several noninva- hof, Drenth, van Krieken, and de Jong. Statistical analy- sive methods have been tested as a screening for liver fi- sis: van Oijen and de Jong. Obtained funding: van de brosis and liver cirrhosis (eg, the Fibrotest, Fibroscan, 11,13,17,25 Kerkhof. Administrative, technical, or material support: and PIIINP). Another serious consequence would Berends, Drenth, and de Jong. Study supervision: van de be the risk of missed pathologic findings that would ne- Kerkhof, Drenth, van Krieken, and de Jong. cessitate discontinuing methotrexate treatment or un- Financial Disclosure: None reported. dergoing another liver biopsy in 6 months. This study was composed of a rereview of 160 liver biopsy specimens by 1 of us (J.H.v.K.). 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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1519 STUDY Results of Radiotherapy in 153 Primary Cutaneous B-Cell Lymphomas Classified According to the WHO-EORTC Classification

Nancy J. Senff, MD; Juliette J. Hoefnagel, MD, PhD; Karen J. Neelis, MD, PhD; Maarten H. Vermeer, MD, PhD; Ed M. Noordijk, MD, PhD; Rein Willemze, MD, PhD; for the Dutch Cutaneous Lymphoma Group

Objective: To evaluate the results of radiotherapy in pa- Main Outcome Measures: Complete remission rate, tients with primary cutaneous B-cell lymphoma (CBCL) relapse rate, 5-year relapse-free survival, 5-year overall classified according to the criteria of the World Health survival, and 5-year disease-specific survival. Organization–European Organization for Research and Treatment of Cancer (WHO-EORTC) classification. Results: Complete remission was reached in 151 of 153 patients (99%). Relapse rates for PCMZL, PCFCL, Design: Multicenter, 20-year, retrospective, cohort analysis. and PCLBCL, LT were 60%, 29%, and 64%, and the 5-year disease-specific survival was 95%, 97%, and 59%, Setting: Eight dermatology departments collaborating respectively. The PCFCLs presenting on the legs had a in the Dutch Cutaneous Lymphoma Group. higher relapse rate (63%) and a much lower 5-year disease-specific survival (44%) than PCFCLs at other Patients: From 1985 until 2005, a total of 153 patients sites (relapse rate, 25%; 5-year disease-specific survival, with CBCL were initially treated with radiotherapy with 99%). curative intent. These cases were classified according to the WHO-EORTC classification and consisted of 25 pri- Conclusions: Radiotherapy is a suitable treatment for a mary cutaneous marginal zone lymphomas (PCMZLs), 101 primary cutaneous follicle center lymphomas (PCFCLs), large group of patients with CBCL. However, patients with and 27 primary cutaneous large B-cell lymphomas, leg type PCFCL presenting with lesions on the leg and patients (PCLBCLs, LT). with PCLBCL, LT display a more unfavorable clinical course and should therefore be treated with more ag- Interventions: Local radiotherapy with a median dose gressive treatment modalities. of 40 Gy (range, 20-46 Gy) applied to all visible skin lesions. Arch Dermatol. 2007;143(12):1520-1526

HE TERM PRIMARY CUTANE- (PCFCL), both indolent types of CBCL with ous B-cell lymphoma (CBCL) a 5-year disease-specific survival (DSS) refers to a heterogeneous greater than 95%; and primary cutaneous group of B-cell non-Hodg- diffuse large B-cell lymphoma, leg type kin lymphomas that pre- (PCLBCL, LT), which represents a more ag- sentT in the skin without evidence of extra- gressive type of CBCL with a 5-year DSS of cutaneous disease at the time of diagnosis. approximately 50%.1 There has been much debate regarding the Previous studies have shown that radio- terminology and classification of these lym- therapy (RT) is a suitable treatment in both Author Affiliations: phomas. Recently, representatives of the Eu- types of indolent CBCL, and perhaps also Departments of Dermatology (Drs Senff, Hoefnagel, Vermeer, ropean Organization for Research and Treat- in PCLBCL, LT presenting with solitary or 2-6 and Willemze) and Clinical ment of Cancer (EORTC) classification and localized skin lesions. However, data from Oncology (Drs Neelis and the World Health Organization (WHO) the literature regarding efficacy and re- Noordijk), Leiden University classification have reached consensus relapse rate show a wide variation.2,4,6-10 More- Medical Centre, Leiden, the garding a new classification for primary cu- over, these studies are all based on cases clas- Netherlands. taneous lymphomas. In this WHO- sified according to the EORTC11 or WHO12 Group Information: A complete 13 list of the participants in the EORTC classification, 3 main types of CBCL classifications. In a recent study, we Dutch Cutaneous Lymphoma are recognized: primary cutaneous mar- showed that approximately 5% and 36% of Group is available from the ginal zone lymphoma (PCMZL) and pri- cases formerly classified according to the authors. mary cutaneous follicle center lymphoma EORTC and WHO classifications, respec-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1520 tively, were assigned to another prognostic category when STATISTICAL ANALYSIS the WHO-EORTC classification was used. These observations prompted us to evaluate the results of RT as initial Overall survival was calculated from the date of diagnosis un- treatment in CBCL reclassified according to the criteria of til the patient’s death or last follow-up without event. Disease- the new WHO-EORTC classification. specific survival was calculated from the date of diagnosis un- The purpose of this retrospective study was to define til death from lymphoma or last follow-up without event. complete remission (CR) rates, relapse rates, relapse- Relapse-free survival was calculated from the date CR was reached until first relapse or last follow-up without event. Sur- free survival (RFS), 5-year overall survival (OS), and 5-year vival curves were estimated by the method of Kaplan and Meier, DSS after RT for these newly defined groups of CBCL, and curves were statistically compared by log-rank testing. The and to establish for which patients RT is a safe and ef- ␹2 test was used to analyze differences between subgroups. All fective mode of treatment. statistical analyses were done with SPSS software, version 12.0.1 (SPSS Inc, Chicago, Illinois). METHODS RESULTS SELECTION OF PATIENTS The total group consisted of 87 men and 66 women, with Between October 1, 1985, and July 31, 2005, a total of 320 pa- a median age of 62 years (range, 23-92 years). Median tients with CBCL were included in the registry of the Dutch follow-up for the whole group was 62 months (range, Cutaneous Lymphoma Working Group. Follow-up data had 3-336 months). The clinical characteristics, results of RT, been collected each year from patients’ medical charts or re- and follow-up data for the total group of patients with 13 ferring physicians. In a recent study, clinical data and histo- CBCL are presented in the Table. Clinical characteris- logic sections of 300 CBCLs were reviewed and reclassified ac- tics, treatment results, and follow-up data for the 3 sub- cording to the criteria of the new WHO-EORTC classification. groups of CBCL are also summarized in the Table and This group included 174 patients who had received RT as initial treatment. Patients in whom RT was administered in pal- will be described in more detail in the subsequent para- liative dosages with no intention to be curative were excluded graphs. (n=7), as were patients with a follow-up of less than 12 months (n=14). However, patients who died of their lymphoma within PRIMARY CUTANEOUS MARGINAL 12 months after diagnosis were not excluded from the study. ZONE B-CELL LYMPHOMA The final study group consisted of 153 patients with CBCL. Ac- cording to the WHO-EORTC classification, this group in- The group of patients with PCMZL consisted of 18 men cluded 25 PCMZLs, 101 PCFCLs, and 27 cases of PCLBCL, LT and 7 women, with a median age of 49 years (range, 23-79 (Figure 1). The following data were recorded for all patients: age at di- years). Nine patients had a solitary lesion, 5 patients had agnosis, sex, involved skin site, extent of involved skin, result localized skin lesions, and 11 patients presented with mul- of initial therapy, occurrence and site of relapse, relapse treat- tifocal disease. Most patients presented with lesions on ment, result of relapse treatment, duration of follow-up, and the trunk or arms (Table). status at last follow-up. Extent of involved skin was defined as Treatment with RT resulted in CR in all 25 patients. solitary when it concerned a single tumor, localized when the Fifteen patients (60%) experienced a relapse after a me- lesion consisted of multiple plaques and/or tumors that could dian relapse-free interval of 16 months (range, 3-144 be irradiated within 1 radiation field, and multifocal if mul- months). Twelve of these patients showed relapses con- tiple nonadjacent body sites were involved or when the le- fined to the skin, 1 had a cutaneous and an extracuta- sions could not be irradiated within 1 radiation field. neous relapse, and 2 experienced an extracutaneous relapse without concurrent skin lesions. Cutaneous relapses TREATMENT always occurred at nonirradiated sites. Patients with a PCMZL had an excellent prognosis, with a 5-year OS and Most patients had been treated with electron beam irradiation DSS of 90% and 95%, respectively (Figure 2). (4-10 MeV), while 9 patients had received 6 to 10 MV of pho- ton beams. The radiation dose varied between 20 and 46 Gy, PRIMARY CUTANEOUS FOLLICLE with a median dose of 40 Gy (to convert the radiation dose to rad, multiply by 100). In all patients, a margin of at least 2 cm CENTER LYMPHOMA of healthy skin was included in the radiation field. In PCFCL localized on the trunk, which often presents with tumors sur- The PCFCL group consisted of 61 men and 40 women, rounded by annular erythemas, the erythematous areas were with a median age of 58 years (range, 27-85 years). Most included in the radiation field because they represent early mani- patients (92% [93 of 101]) presented with solitary le- festations of the neoplastic process.14-16 Treatment response was sions (48 patients) or localized skin lesions (45). Only 8 evaluated 4 to 6 weeks after the end of RT by clinical exami- of 101 patients had multifocal disease at the time of pre- nation and classified as CR, partial remission, no response, and sentation. Most presented with the typical lesions on the progressive disease. Complete remission was defined as the dis- head (41 patients) or trunk (55). Eight patients had le- appearance of all visible skin lesions; partial remission, 50% or more remission of clinical lesions; no response, less than 50% sions on 1 (7 patients) or both (1) legs. Six of these 8 remission; and progressive disease, development of new skin patients were previously classified as having primary cu- lesions during treatment. Outcome measures for results of RT taneous large B-cell lymphoma of the leg (PCLBCL, leg), were CR rate, relapse rate, 5-year RFS, 5-year OS, and 5-year following the EORTC classification. Treatment with RT DSS. resulted in CR in all 101 patients. A relapse was noted

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Figure 1. Clinical examples of the studied disease entities. A, Primary cutaneous marginal zone lymphoma. B, Primary cutaneous follicle center lymphoma. C, Primary cutaneous large B-cell lymphoma, leg type. in 29 patients 2 to 62 months (median, 12 months) after 8 patients with PCFCL presenting with lesions on the legs initial treatment. In 21 patients the relapse was con- had a higher relapse rate (63% [5 of 8] vs 26% [24 of 93]; fined to the skin, 3 had a relapse in the skin and an ex- P=.03), more often developed extracutaneous disease tracutaneous localization, and 5 had a relapse at an ex- (38% [3 of 8] vs 8% [7 of 93]; P=.006), and had a con- tracutaneous site without concurrent skin lesions. All siderably lower 5-year DSS (44% vs 99%; PϽ.001) than cutaneous relapses occurred outside the irradiated area. did the patients without lesions on the legs. Skin relapses were generally treated with an additional Our study group contained only 5 patients with PCFCL course of RT, which resulted in another CR in all cases. presenting with multifocal skin lesions without involve- Ultimately, 10 of 101 patients developed extracutane- ment of the leg. Three of these 5 patients had a relapse ous disease and 4 of 101 patients died of lymphoma. The in the skin; 1 of the 3 patients eventually developed in- 5-year OS and DSS were 90% and 97%, respectively tracerebral lesions and died of the lymphoma 26 months (Figure 2). after the initial diagnosis. Comparison between PCFCL with solitary or local- Comparison between PCFCL with a follicular or fol- ized lesions confined to the head (n=38) or trunk (n=48) licular and diffuse growth pattern (32 cases; classified as showed no difference in relapse rate (26% [10 of 38] vs cutaneous follicle center lymphoma in the WHO classifi- 21% [10 of 48]) or 5-year DSS (95% vs 98%). However, cation) and PCFCL with a diffuse growth pattern (69 cases;

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1522 Table. Patient Characteristics, Therapy Results, and Follow-up Data

No. (%)

Total Group PCMZL PCFCL PCLBCL, LT (N=153) (n=25) (n=101) (n=27) Age, median (range), y 62 (23-92) 49 (23-79) 58 (27-85) 78 (50-92) Sex Male 87 (57) 18 (72) 61 (60) 8 (30) Female 66 (43) 7 (28) 40 (40) 19 (70) Ratio, M/F 1.3 2.6 1.5 0.4 Skin sitea Head 46 (30) 4 (16) 41 (41) 1 (4) Trunk 68 (44) 13 (52) 55 (54) 0 Upper extremities 12 (8) 9 (36) 2 (2) 1 (4) Lower extremities 38 (25) 5 (20) 8 (8) 25 (93) Other 1 (1) 0 1 (1) 0 Extent Solitary 69 (45) 9 (36) 48 (48) 12 (44) Localized 65 (43) 5 (20) 45 (45) 15 (56) Multifocal 19 (12) 11 (44) 8 (8) 0 Status after RT CR 151 (99) 25 (100) 101 (100) 25 (93) PR 0 0 0 0 (0) NR 0 0 0 0 (0) PD 2 (1) 0 0 2 (7) First relapseb None 91 (59) 10 (40) 72 (71) 9 (36) Skin 40 (26) 12 (48) 21 (21) 7 (28) Skin and extracutaneous 8 (5) 1 (4) 3 (3) 4 (16) Extracutaneous 12 (8) 2 (8) 5 (5) 5 (20) Time to first relapse, median (range), mo 16 (1-144) 16 (3-144) 12 (2-62) 17 (1-61) Extracutaneous dissemination 23 (15) 3 (12) 10 (10) 10 (37) Status at last follow-up Alive and well 117 (76) 23 (92) 84 (83) 10 (37) Alive with disease 3 (2) 0 2 (2) 1 (4) Died of lymphoma 16 (10) 1 (4) 4 (4) 11 (41) Died of other cause 17 (11) 1 (4) 11 (11) 5 (19) 5-y RFS, % 60 45 70 36 5-y DSS, % 90 95 97 59

Abbreviations: CR, complete remission; DSS, disease-specific survival; NR, no response; PCFCL, primary cutaneous follicle center lymphoma; PCLBCL, LT, primary cutaneous large B-cell lymphoma, leg type; PCMZL, primary cutaneous marginal zone lymphoma; PD, progressive disease; PR, partial remission; RFS, relapse-free survival; RT, radiotherapy. a Some patients had more than 1 affected site. b Relapses were considered only in patients who achieved a complete remission (n=151). classified as diffuse large B-cell lymphoma [DLBCL] in the merly classified as primary cutaneous follicle center cell WHO classification) showed no significant difference in lymphoma (PCFCCL) in the EORTC classification. Ac- relapse rate (41% [13 of 32] vs 23% [16 of 69], respec- cording to the WHO classification, all 27 patients would tively; P=.07) and no difference in DSS (100% vs 95%, re- have been classified as having DLBCL. Twelve patients spectively; P=.71) between the 2 groups. This illustrates had a solitary lesion at initial diagnosis and 15 patients that the growth pattern of the malignant infiltrate has no presented with localized disease. This group did not con- prognostic significance and does not justify more aggres- tain patients presenting with multifocal skin lesions. sive treatment. Treatment with RT resulted in CR in 25 of 27 patients (93%). In 2 patients, including the patient pre- PRIMARY CUTANEOUS LARGE B-CELL senting with a solitary tumor on the scalp, new skin le- LYMPHOMA, LEG TYPE sions developed outside the irradiated areas during initial RT, and both patients died of lymphoma 3 and 9 months The PCLBCL, LT group contained 8 men and 19 women. after diagnosis. The patient previously classified as hav- The age at diagnosis in this group (median, 78 years; range, ing PCFCCL (EORTC classification) and presenting with 50-92 years) was considerably higher than that of the other skin lesions on the left forearm reached CR that had been 2 groups. Twenty-five of 27 patients presented with skin sustained for more than 5 years at last follow-up. lesions on the legs, while 1 patient presented with a soli- Of the 25 patients who did reach CR, 7 patients had tary tumor on the scalp and another patient had lesions relapses only in the skin, 4 in the skin as well as in an localized to the left forearm. These 2 cases were for- extracutaneous site, and 5 only extracutaneously. Two

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0.8 0.8

0.6 0.6

0.4 0.4 Cumulative Survival Cumulative Survival

0.2 0.2

PCMZL (n = 25) PCFCL (n = 101) PCFCL (n = 101) PCMZL (n = 25) PCLBCL, LT (n = 27) PCLBCL, LT (n = 27) 0 0.0

02412364860 72 84 96 108 120 02412364860 72 84 96 108 120 Follow-up, mo Disease-Free Interval, mo

Figure 2. Kaplan-Meier curve of disease-specific survival after radiotherapy Figure 3. Kaplan-Meier curve of relapse-free survival after radiotherapy according to diagnostic category. PCFCL indicates primary cutaneous follicle according to diagnostic category. PCFCL indicates primary cutaneous follicle center lymphoma; PCLBCL, LT, primary cutaneous large B-cell lymphoma, center lymphoma; PCLBCL, LT, primary cutaneous large B-cell lymphoma, leg type; and PCMZL, primary cutaneous marginal zone lymphoma. leg type; and PCMZL, primary cutaneous marginal zone lymphoma. of the 11 skin relapses were located within the irradi- group were 97% and 90%, respectively. These observa- ated area, although the cumulative dose in these pa- tions are consistent with the results of most previous stud- tients (36 and 40 Gy) was comparable to that of the other ies in patients with PCFCCL as defined by the criteria of patients. the EORTC classification2,4,7,10 but differ considerably from Ultimately, 10 patients showed extracutaneous dis- the results reported by Piccinno and coworkers.8,9 These semination and 11 patients died of lymphoma. For the authors performed a retrospective study of 102 PCFCCLs total group of patients with PCLBCL, LT, the 5-year OS and found a relapse rate of 75% and a 5-year RFS of only was 40% and the 5-year DSS was 59% (Figure 2). Com- 23%. Moreover, in-field relapses were noted in 18 of 102 parison between patients presenting with a solitary le- cases. These differences might be explained by the use sion and patients presenting with multiple localized skin of orthovoltage techniques and the narrow margins (0.5- lesions did not show significant differences in 5-year RFS 1.0 cm) of clinically uninvolved skin included in the ir- (40% vs 32%; P=.51) or 5-year DSS (61% vs 58%; P=.73). radiation field, as previously postulated.7 The reported survival data and the low proportion of patients devel- COMMENT oping extracutaneous disease, however, are comparable in all of these studies, which illustrates the favorable bio- In this study we evaluated the results of RT in 153 pa- logical behavior of this lymphoma. tients with CBCL, reclassified according to the criteria Subgroup analysis showed that patients presenting with of the WHO-EORTC classification. The PCFCL cat- skin lesions on the leg more often had relapses, more of- egory formed the largest group (101 of 153 patients ten developed extracutaneous disease, and had a much [66%]). In the WHO-EORTC classification, PCFCL is de- more unfavorable prognosis than did patients present- fined as a tumor of neoplastic follicle center cells, with a ing with skin lesions on the head or trunk. These obser- predominance of large centrocytes and variable num- vations confirm the results of recent studies and suggest bers of centroblasts, which may have a follicular, follicu- that presentation on the leg is an unfavorable risk factor lar and diffuse, or diffuse growth pattern, and which gen- in PCFCL.13,17 It also suggests that such cases should not erally present on the head or trunk or, uncommonly, on be treated routinely with RT. the legs.1 In the EORTC classification, these rare cases Patients presenting with multifocal skin lesions rep- presenting on the legs were included in the category resent another subgroup subjected to much de- PCLBCL, leg.11 The results of our study showed CR fol- bate.2,6,9,18 A previous study by our group6 found that lowing initial RT in all 101 cases. The 5-year RFS was PCFCLs presenting with multifocal skin lesions have the 70% (Figure 3). Twenty-one patients showed 1 or mul- same clinical behavior and prognosis as PCFCLs pre- tiple relapses confined to the skin, while 8 patients had senting with solitary or localized skin lesions. Radio- relapses at extracutaneous sites with or without concur- therapy of all visible skin lesions proved as effective as rent skin lesions. No in-field recurrences were ob- multiagent chemotherapy. In fact, skin relapses were observed. In most patients, skin relapses were successfully served in 3 of 9 patients treated with multiagent chemo- treated again with RT. The 5-year DSS and OS of the total therapy and in none of the 5 patients treated with RT.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1524 The present study group contained only 5 cases of PCFCL As described recently,20 RT is also a highly effective presenting with multifocal skin lesions, but not located treatment in PCMZL presenting with a solitary or few scat- on the leg. Three of these 5 patients had relapses in the tered lesions. However, the relapse rate in PCMZL proved skin, and 1 of them died of central nervous system in- much higher than in PCFCL (5-year RFS, 45% vs 70%, volvement. Recent analysis of 13 PCFCLs with multifo- respectively; Figure 3). In patients presenting with many cal skin lesions (excluding localization on the leg) treated scattered skin lesions, RT is no longer the first choice of with multiagent chemotherapy showed relapses (in the treatment. In such patients, beneficial effects have been skin) in 4 of 13 patients, while 1 of them developed ex- reported with chlorambucil20 or intralesional treatment tracutaneous disease during follow-up (N.J.S. and R.W., with interferon alfa 2A or rituximab.21-23 In patients de- unpublished data, November 2006). Taken together, these veloping chronically relapsing disease, treatment is aimed small series do not allow firm conclusions to be drawn. at palliation and no longer at cure, and therefore the ben- Prospective collaborative studies on larger numbers of efits of treatment should be weighed carefully against their patients are required to evaluate whether PCFCL pre- potential side effects. In such patients, an expectant policy senting with multiple skin lesions can indeed be treated should be considered.20 The results of a recent pilot study safely and effectively with RT. suggest that low-dose RT with 2ϫ2 Gy is a useful alter- The lesions in the PCLBCL, LT category are defined native for such patients experiencing multiple skin re- as tumors with a predominance or confluent sheets of lapses (K.J.N., E.C. Schimmel, MD, M.H.V., N.J.S., R.W., centroblasts and immunoblasts, characteristically pre- and E.M.N., unpublished data, 2006). senting with skin lesions on the lower legs. Cases with In conclusion, the results of our study indicate that similar morphologic features and phenotype (strong Bcl-2 RT is a safe and effective treatment in many patients [B-cell CLL/lymphoma 2] and MUM-1 [multiple my- with CBCL. In PCFCL and PCMZL, RT is the first line eloma oncogene 1] expression) arising at sites other than of treatment, not only in patients presenting with soli- the leg are included in this group. In the EORTC classi- tary or localized skin lesions, but probably also in fication, such cases were included in the group of patients presenting with a few scattered skin lesions. PCFCCLs. Recent studies13,17 found that cases present- However, prospective, collaborative studies are required ing on the leg and cases presenting at other sites have a to confirm this latter conclusion. Patients with similar clinical behavior and prognosis, indicating that PCLBCL, LT and the rare patients with a PCFCL pre- reclassification of such cases as PCLBCL, LT is an im- senting with skin lesions on the leg appear to have a provement. In the present study, 25 of 27 patients pre- more aggressive clinical course, and RT should not be sented with skin lesion on the legs, while 2 patients pre- considered as the first choice of treatment in these sented with skin lesions at other sites. In general, PCLBCL, patients. LT should be treated in the same way as other systemic DLBCLs, for instance, with a regimen of cyclophospha- Accepted for Publication: April 6, 2007. mide, doxorubicin, vincristine, and prednisone in com- Correspondence: Nancy J. Senff, MD, Department of Der- bination with rituximab (anti-CD20 antibody). How- matology, B1-Q, Leiden University Medical Center, PO 19 ever, in a previous European multicenter study including Box 9600, 2300 RC Leiden, the Netherlands (N.J.Senff 48 patients with PCLBCL, leg, patients presenting with @LUMC.nl). a solitary tumor on 1 leg had a significantly better prog- Author Contributions: Dr Senff had full access to all data nosis than did patients presenting with multiple tumors in the study and takes responsibility for the integrity of on 1 or both legs. It was therefore suggested that pa- the data and the accuracy of the data analysis. Study con- tients with a solitary tumor could be treated with RT, while cept and design: Senff and Willemze. Acquisition of data: all other patients in this group should be treated with sys- Senff, Hoefnagel, Neelis, Vermeer, Noordijk, and temic chemotherapy. The results of the present study do Willemze. Analysis and interpretation of data: Senff, not support this suggestion. No difference in relapse rate, Vermeer, and Willemze. Drafting of the manuscript: Senff OS, and DSS was observed between patients with a soli- and Willemze. Critical revision of the manuscript for im- tary lesion and patients presenting with multiple local- portant intellectual content: Senff, Hoefnagel, Neelis, ized lesions. Vermeer, Noordijk, and Willemze. Statistical analysis: Moreover, 2 patients developed new skin lesions out- Senff. Administrative, technical, and material support: side the irradiated areas during initial treatment, and 16 Hoefnagel, Vermeer, and Willemze. Study supervision: of the other 25 patients showed relapses after initial Vermeer and Willemze. therapy. In addition, this was the only group in which Financial Disclosure: None reported. skin relapses developed within a previously irradiated area (2 patients). Only 9 of 27 patients showed a sustained REFERENCES CR after initial RT. 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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1526 STUDY Angiogenesis in Cutaneous Lesions of Leprosy Implications for Treatment

Sulochana S. Bhandarkar, MD; Cynthia Cohen, MD; Maria Kuruvila, MD; Thomas H. Rea, MD; Jamie B. MacKelfresh, MD; Delphine J. Lee, MD, PhD; Robert L. Modlin, MD; Jack L. Arbiser, MD, PhD

Objective: To examine the potential role of angiogen- Main Outcome Measure: CD31 microvessel counts. esis in leprosy. Results: The mean CD31 microvessel count in border- Design: Immunohistochemical analysis of leprosy lesions. line tuberculoid, midborderline, and lepromatous leprosy lesions was significantly higher than in indetermi- Setting: Department of Dermatology, Venereology, and nate leprosy lesions. Leprology, Kasturba Medical College; Division of Derma- tology, University of California at Los Angeles; and Depart- Conclusions: Increased bacterial load is associated with ments of Dermatology and Pathology, Emory University. increased angiogenesis. Angiogenesis inhibitors may be of benefit in the treatment of leprosy. Patients: Thirty-two cutaneous lesions that represented the spectrum of leprosy were obtained from 32 patients. Arch Dermatol. 2007;143(12):1527-1529

EPROSY IS A CHRONIC INFEC- ability of the host to mount an IL-12 re- tion caused by Mycobacte- sponse to the pathogen.7 IL-12 was shown rium leprae and is endemic to to be a potent angiogenesis inhibitor, as tropical areas of the world, in- were some of the cytokines induced by IL- cluding the Indian subconti- 12, including interferon-inducible pro- nent,L1 Indochina, and South America.2 Lep- tein 10 and interferon gamma.8-13 Thalido- rosy causes much morbidity through mide, a drug used to treat leprosy, also has formation of trophic ulcers, eye disabili- antiangiogenic properties.14 Minocy- ties, neuropathy, and social isolation. Al- cline, a drug that is a part of the rifampin, though leprosy is currently treatable, treat- ofloxacin, and minocycline regimen given ment of leprosy requires long courses of for single skin lesions such as paucibac- multiple antibiotics, which can decrease illary leprosy, has antiangiogenic proper- compliance.3 During treatment, patients can ties through inhibition of matrix metallo- experience debilitating erythema nodo- proteinases.15 Given the potential role of Author Affiliations: sum leprosum and reversal reactions.4 Fi- angiogenesis in leprosy and also since Departments of Dermatology nally, the irreversible neural damage and its M leprae, the causative organism of lep- (Drs Bhandarkar, MacKelfresh, associated sensory defects lead to the de- rosy, cannot be cultured, we wanted to and Arbiser) and Pathology formities and disabilities that form a part of study the vascularity of the entire spec- (Dr Cohen), Emory University 5 School of Medicine, Atlanta, the social stigma associated with leprosy. trum of leprosy through histologic assess- Georgia; Department of Leprosy exists in a clinical spectrum of ment. Our findings demonstrate an Microbiology, Immunology, and disease, ranging from solitary inflamma- increase in angiogenesis toward the lep- Molecular Genetics, University tory lesions called tuberculoid to dissemi- romatous spectrum lesions and raise the of California at Los Angeles nated disease characterized by formation possibility that angiogenesis inhibitors may (Drs Lee and Modlin); of highly bacilliferous granulomas, which be useful in the treatment of leprosy. Department of Dermatology, is termed lepromatous.6,7 Leprosy, like other Venereology, and Leprology, mycobacterial infections (tuberculosis), METHODS Kasturba Medical College, leishmaniasis, and syphilis, requires in- Mangalore, India 7 (Drs Bhandarkar and Kuruvila); tact cellular immunity for clearance. In- We studied 32 cutaneous lesions that repre- and Department of terleukin 12 (IL-12) has been demon- sented the spectrum of leprosy from 32 pa- Dermatology, University of strated to play a pivotal role in the tients for expression of CD31. Twenty-eight par- Southern California, clearance of these pathogens, and the clini- affin blocks were received from the Department Los Angeles (Dr Rea). cal spectrum of leprosy likely reflects the of Dermatology, Venereology, and Leprology,

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1527 Kasturba Medical College, and 4 sections were received from the for 15 minutes. The mean CD31 microvessel density was quan- Division of Dermatology, University of California at Los Ange- titated microscopically by 2 independent observers (C.C. and les. The diagnosis of leprosy in the patients was supported by he- J.B.M.). The number of CD31-positive blood vessels in the whole matoxylin-eosin–stained histologic analyses of the biopsied le- biopsy specimen and in 2 hot spots at a power of ϫ20 was de- sions and the clinical history of the patients. We studied 4 sections termined according to the method of Weidner et al.18 Hot spots of indeterminate leprosy, 5 of tuberculoid leprosy, 12 of border- were areas determined by the observers to represent the fields of line tuberculoid leprosy, 3 of midborderline leprosy, 3 of bor- greatest vascular density within a given section.19 The mean num- derline lepromatous leprosy, and 5 of lepromatous leprosy. ber of microvessels in 2 hot spots from each section was determined, and the total mean of each spectrum was compared with IMMUNOHISTOCHEMICAL ANALYSIS indeterminate leprosy.

A total of 32 sections (5 mm) of formalin-fixed, paraffin- STATISTICAL ANALYSIS embedded tissue (5 µm) were immunostained with monoclonal Ͻ antibodies against CD31 (1:80) (clone JC170A, 1/80; Dako Corp, P .05 was considered statistically significant. A t test was used Carpinteria, California) using a horseradish peroxidase–labeled for statistical analysis, which was performed with Excel (Mi- polymer, a heat-induced antigen retrieval, and an autostainer crosoft Inc, Redmond, Washington). (Dako).16,17 The Dako Envision system is a 2-step horseradish peroxidase–labeled polymer that is conjugated with secondary an- RESULTS tibodies and is used in combination with the automated Dako Au- tostainer. Hematoxylin was used as the counterstain, and the The results of lesion vascularity evaluated with CD31 negative control was a primary antibody replaced by buffer. Sec- ranged from a low of 7 vessels per high-powered field in tions of myometrium (blood vessels) were used as the positive the indeterminate leprosy lesions to a high of 68.5 in control for CD31. Diaminobenzidine was the chromogen used, lepromatous leprosy lesions. The mean±SEM CD31 and Dako automation hematoxylin was used as a counterstain microvessel density was 25.34±3.70 vessels per high- powered field in the borderline tuberculoid lesions, 36.25±5.20 in the midborderline lesions, and 60 ∗ 44.0±9.80 in the lepromatous lesions. These numbers 50 were significantly higher (P=.02, .004, and .03, respec- ∗ tively) when compared with a mean of 13.37±3.68 ves- 40 sels per high-powered field in indeterminate leprosy ∗ 30 lesions. The mean CD31 microvessel densities in the different leprosy types are shown in Figure 1.Aϫ20 20

Mean CD31 Count high-power view of indeterminate leprosy with a mean Figure 2 10 CD31 value of 7 is shown in A. For this patient, a total of 3 hot spots with 8, 6, and 7 vessels 0 Indeterminate Tuberculoid Borderline Borderline Borderline Lepromatous were counted, and the mean number of microvessels in Tuberculoid Lepromatous 2 hot spots was 7.5. Figure 2B shows a borderline lep- Leprosy Type romatous lesion, with a mean CD31 value of 39. For this slide, a total of 5 hot spots with values of 38, 31, Figure 1. Mean CD31 microvessel density for each leprosy type. Error bars 26, 40, and 23 were calculated, and the mean number indicate SEM. *PϽ.05 compared with indeterminate leprosy. of microvessels in 2 hot spots was 39.

A B

Figure 2. Immunohistochemical staining for CD31 in different stages of leprosy. A, High-power view (original magnification ϫ20) of an indeterminate leprosy lesion stained with CD31 polyclonal antibody and diaminobenzidine as the chromogen. A low microvessel count (7.5, which indicates a mean number of microvessels in 2 hot spots) is observed in the dermis. B, High-power view (original magnification ϫ20) of a borderline lepromatous lesion stained with monoclonal anti-CD31 antibody and diaminobenzidine as the chromogen. A high microvessel count (39, which indicates a mean number of microvessels in 2 hot spots) is observed in the dermis.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1528 COMMENT of the manuscript: Bhandarkar, Kuruvila, MacKelfresh, Modlin, and Arbiser. Critical revision of the manuscript for important intellectual content: Cohen, Rea, Lee, Modlin, Leprosy or Hansen disease is a chronic infectious disease and Arbiser. Statisical analysis: Bhandarkar. Obtained fund- that primarily affects the peripheral nerves and the skin. ing: Arbiser. Administrative, technical, or material sup- Mycobacterium leprae has a unique predilection for Schwann port: Bhandarkar, Cohen, Kuruvila, Rea, Lee, Modlin, and cells20 and replicates inside the Schwann cells slowly Arbiser. throughout the years.21 The clinical response of the sus- Financial Disclosure: None reported. ceptible patient forms a spectrum according to the type of Funding/Support: Dr Arbiser was supported by National host immune response to M leprae and forms the basis of Institutes of Health grants RO1 AR47901 and RO1 AR02030 various classifications of leprosy. Ridley and Jopling7 clas- and Emory Skin Disease Research Core Center Grant P30 sified the clinical response into tuberculoid, borderline tu- AR42687, a Veterans Administration Hospital Merit Award, berculoid, borderline, borderline lepromatous, and lepro- also from the National Institutes of Health. matous leprosy. Patients with tuberculoid leprosy with strong cell-mediated immunity are at one end of the spectrum, and patients with lepromatous leprosy and poor cell- REFERENCES mediated immunity are at the other end of the spectrum. Indeterminate leprosy was first described as a new clinical 1. Padma TV. With scores still infected, India declares leprosy “eliminated.” Nat 22 Med. 2006;12(4):372. variant by Findlay and was included in the World Health 2. Deps PD, Guedes BV, Bucker Filho J, Andreatta MK, Marcari RS, Rodrigues LC. Organization 1952 classification. Indeterminate leprosy is Characteristics of known leprosy contact in a high endemic area in Brazil. Lepr often the clinical beginning of the disease, and approxi- Rev. 2006;77(1):34-40. 3. Williams MC. How can adherence with multi-drug therapy in leprosy be improved? mately 80% of susceptible patients will show spontaneous Lepr Rev. 2005;76(2):160-161. regression of lesions, and 20% will progress to a more de- 4. Ustianowski AP, Lawn SD, Lockwood DN. Interactions between HIV infection and finitive form of leprosy.23,24 The role of immunologic re- leprosy: a paradox. Lancet Infect Dis. 2006;6(6):350-360. sponses in all the different forms of leprosy has been long 5. Cross H. Interventions to address the stigma associated with leprosy: a perspective on the issues. Psychol Health Med. 2006;11(3):367-373. established, but data are lacking on the role of angiogen- 6. Ridley DS, Jopling WH. A classification of leprosy for research purposes. Lepr esis in the spectrum of leprosy. We wanted to determine Rev. 1962;33:119-128. the role of angiogenesis, if any, in the entire spectrum of 7. Ridley DS, Jopling WH. Classification of leprosy according to immunity—a five- leprosy, including indeterminate leprosy. group system. Int J Lepr Other Mycobact Dis. 1966;34(3):255-273. 8. Voest EE, Kenyon BM, O’Reilly MS, Truitt G, D’Amato RJ, Folkman J. Inhibition of Mycobacterium leprae has been found in endothelial cells angiogenesis in vivo by interleukin 12. J Natl Cancer Inst. 1995;87(8):581-586. of blood vessels, and anti–factor VIII–related antigen an- 9. Kim J, Uyemura K, Van Dyke MK, et al. A role for IL-12 receptor expression and tibody has been used to demonstrate a difference in the mi- signal transduction in host defense in leprosy. J Immunol. 2001;167(2):779-786. 10. Libraty DH, Airan LE, Uyemura K, et al. Interferon-gamma differentially regu- crovascular pattern between the 2 ends of the spectrum, lates interleukin-12 and interleukin-10 production in leprosy. J Clin Invest. 1997; with lepromatous leprosy demonstrating a tortuous mesh 99(2):336-341. of microvessels among the M leprae–laden macrophages; 11. Ueno T, Toi M, Saji H, et al. Significance of macrophage chemoattractant pro- however, the microvessels in the tuberculoid lesions were tein-1 in macrophage recruitment, angiogenesis, and survival in human breast 25 cancer. Clin Cancer Res. 2000;6(8):3282-3289. restricted to the periphery of the granulomas. We stud- 12. Drexler HG, Uphoff CC, Gaidano G, Carbone A. Lymphoma cell lines: in vitro mod- ied the microvessel counts in the entire Ridley-Jopling spec- els for the study of HHV-8 primary effusion lymphomas (body cavity-based trum and found an apparent overall increase in microves- lymphomas). Leukemia. 1998;12(10):1507-1517. 13. Hatanaka H, Abe Y, Naruke M, et al. Significant correlation between interleukin sel count toward lepromatous lesions compared with 10 expression and vascularization through angiopoietin/TIE2 networks in non- indeterminate leprosy lesions. The microvessel count was small cell lung cancer. Clin Cancer Res. 2001;7(5):1287-1292. significantly higher in borderline tuberculoid lesions, mid- 14. Arbiser JL, Johnson D, Cohen C, Brown LF. High-level expression of vascular borderline lesions, and lepromatous lesions when com- endothelial growth factor and its receptors in an aphthous ulcer. J Cutan Med Surg. 2003;7(3):225-228. pared with indeterminate lesions. We observed that the in- 15. Tamargo RJ, Bok RA, Brem H. Angiogenesis inhibition by minocycline. Cancer crease in microvessel count follows the same pattern of Res. 1991;51(2):672-675. increase as M leprae loads toward the lepromatous end of 16. Arbiser JL, Flynn E, Barnhill RL. Analysis of vascularity of human neurofibromas. the spectrum. We propose that new treatments, such as an- J Am Acad Dermatol. 1998;38(6, pt 1):950-954. 17. Arbiser JL, Brat D, Hunter S, et al. Tuberous sclerosis-associated lesions of the giogenesis inhibitors directed toward leprosy, could po- kidney, brain and skin are angiogenic neoplasms. J Am Acad Dermatol. 2002; tentiate the current multidrug treatment for leprosy. 46(3):376-380. 18. Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Accepted for Publication: April 19, 2007. Inst. 1992;84(24):1875-1887. Correspondence: Jack L. Arbiser, MD, PhD, Depart- 19. Macaron NC, Cohen C, Chen SC, Arbiser JL. Cutaneous lesions of secondary syphilis are highly angiogenic. J Am Acad Dermatol. 2003;48(6):878-881. ment of Dermatology, Emory University School of Medi- 20. Rambukkana A, Yamada H, Zanazzi G, et al. Role of alpha-dystroglycan as a Schwann cine, WMB 5309, 1639 Pierce Dr, Atlanta, GA 30322 cell receptor for Mycobacterium leprae. Science. 1998;282(5396):2076-2079. ([email protected]). 21. Britton WJ, Lockwood DN. Leprosy [review]. Lancet. 2004;363(9416):1209-1219. Author Contributions: Dr Arbiser had full access to all 22. Findlay GH. Indeterminate leprosy: a new clinical variety. Br J Dermatol. 1951;63 (3):100-104. of the data in the study and takes responsibility for the 23. Yawalkar SJ. Leprosy: For Medical Practitioners and Paramedical Workers.7th integrity of the data and the accuracy of the data analy- ed. Basel, Switzerland: Novartis Foundation for Sustainable Development; 2002. sis. Study concept and design: Bhandarkar and Arbiser. Ac- 24. Mira MT. Genetic host resistance and susceptibility to leprosy. Microbes Infect. quisition of data: Bhandarkar, Cohen, Kuruvila, Rea, Lee, 2006;8(4):1124-1131. 25. Antunes SL, Motta E, de Almeida SM, Gallo ME, Nery JA, Lenzi HL. Distinct pat- and Modlin. Analysis and interpretation of data: terns of microvasculature in the cutaneous lesions of leprosy. Int J Lepr Other Bhandarkar, Cohen, MacKelfresh, and Arbiser. Drafting Mycobact Dis. 2000;68(2):143-151.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1529 STUDY Patterns of Indoor Tanning Use Implications for Clinical Interventions

Joel Hillhouse, PhD; Rob Turrisi, PhD; Alan L. Shields, PhD

Objective: To identify indoor tanning patterns with rel- Results: Event tanners tanned the least, started tanning evance for health screening and prevention efforts. the latest, and scored lowest on measures of attitudes, social norms, and tanning dependence measures. Regular Design: We collected data on indoor tanning patterns year-round tanners started the earliest, tanned at the high- from January 17, 2006, through April 14, 2006. By clus- est levels, and scored the highest on the attitude, social ter analysis, 4 patterns of indoor tanning were identi- norms, and tanning dependence measures. Spontaneous fied: special event, spontaneous or mood, mixed, and regu- or mood tanners were similar to event tanners but with a lar year-round tanning. These 4 types of indoor tanning mood component to their tanning. Mixed tanners, as the were compared by demographic, behavioral, and psy- name implies, exhibited behavior that appeared to be a mix- chosocial variables for clinically significant differences. ture of the regular and event tanning types.

Setting: Midsized (ie, approximately 12 000 students) Conclusions: The results of this study emphasize the fact southeastern university. that “one size fits all” does not apply when it comes to indoor tanning. Tanning behavioral types, which can be Participants: A total of 168 women who tanned clinically assessed, can serve as a guide to physicians so indoors. that they can tailor their skin cancer prevention messages to be more effective. Main Outcome Measures: Self-reported attitudes, intentions and tanning behaviors, and tanning dependence. Arch Dermatol. 2007;143(12):1530-1535

VIDENCE THAT INDOOR TAN- In focus group studies and interviews ning (IT) poses a serious conducted in our laboratory, indoor tan- public health risk is increas- ners have reported 2 general patterns and ing. Numerous case-con- 2 subpatterns of IT behavior. One gen- trolled studies1-7 report posi- eral pattern involves IT on a regular weekly tive relationships between IT and melanoma or biweekly basis (eg, 3 times per week). E 8 morbidity. A recent meta-analysis indi- In the other, indoor tanners tan numer- cated a significantly increased melanoma ous times during a short period associ- risk associated with sunlamp or sun bed ex- ated with a special event, followed by exposure. Cohort studies9-11 have confirmed tended periods of no tanning. However, this relationship for both melanoma and some of these nonregular tanners also de- nonmelanoma skin cancers. A recent re- scribe a more spontaneous pattern. Other port12 from the International Agency for Re- tanners report both regular tanning peri- search on Cancer concluded that expo- ods and shorter periods of tanning asso- sure to sun beds before the age of 35 years ciated with particular special events. Fi- significantly increases the risk of mela- nally, we noted a group of tanners who noma and squamous cell carcinoma. report being strongly influenced by mood The IT industry is experiencing explo- factors in their tanning, and these indi- sive growth and attracting unprec- viduals seem to be spread across the 2 main edented numbers of young people to its groups described herein.15 tanning bed salons. Nearly 2 million The purpose of the present study was to Author Affiliations: Americans tan indoors each day, with the explore IT patterns empirically using clus- Departments of Public Health number of individual users in the United ter analysis and then explore each identi- (Dr Hillhouse) and Psychology States having doubled to nearly 30 mil- fied cluster in terms of potential health risk (Dr Shields), East Tennessee 13 State University, Johnson City; lion in the past decade. Our investiga- and motivations. We developed simple and Department of tions of IT have suggested that there may items designed to assess IT behavioral pat- Biobehavioral Health, be subtypes of tanning behavior that have terns that were used for the cluster analy- Pennsylvania State University, clinical significance in terms of health risk sis. Behavioral profiles were then com- University Park (Dr Turrisi). and clinical prevention messages.14 pared by relevant demographic, behavioral,

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1530 Indoor Tanning Behavioral Pattern Questionnaire Please indicate your level of agreement as to whether or not the following patterns describe your pattern of indoor tanning I indoor tan…

Strongly Moderately Neither Agree Moderately Strongly Disagree Disagree nor Disagree Agree Agree –2 –1 0 1 2 1. Occasionally, for example, when some of my friends go I might go along 2. Only before certain events such as formals or important dates, before spring break, before the start of summer, etc 3. Regularly, 1-7 times each week during particular seasons 4. Regularly, 1-7 times each week all year long (more or less)

5. Do you tend to indoor tan in response to a negative mood state or because you are feeling down or bad? Yes No

Categorization Event Tanners: Spontaneous/Mood Tanners: Mixed Tanners: Regular Tanners: 1. Score 1 or 2 on item No. 2 1. Score 1 or 2 on items No. 1 and 1. Score 1 or 2 on items No. 1, No. 2, 1. Score –1 or –2 on items No. 1 and 2. Score –1 or –2 on items No. 3 and No. 2 and No. 3 No. 2 No. 4 2. Score 0, –1 or –2 on item No. 3 2. Score –1 or –2 on item No. 4 2. Score 1 or 2 on items No. 3 and 3. Answer No to item No. 5 3. Score –1 or –2 on item No. 4 3. Answer No to item No. 5 No. 4 4. Answer Yes to item No. 5 3. Answer Yes to item No. 5

Figure. Categorization of indoor tanners into behavioral patterns. and psychosocial variables. We believe that the identifi- Indoor tanning was assessed by asking respondents to es- cation of these behavioral subtypes of tanning behavior is timate their IT frequencies during 12, 6, and 3 months using important for moving prevention efforts beyond the “one open-ended responses.18-20 These items were then weighted to size fits all” approach commonly used currently. account for different time frames, summed, and averaged as an estimate of IT behavior during the past year (Cronbach ␣=0.91).1

METHODS IT Intentions

STUDY PARTICIPANTS Study participants were asked to indicate how strongly they in- tended to engage in IT-related behaviors in the next year. Indi- We collected data on indoor tanning patterns from January 17, viduals responded to each item on 7-point scales anchored by 2006, through April 14, 2006. After receiving approval for the an intend or do-not-intend response format (Cronbach ␣=0.93). study from the East Tennessee State University institutional review board, a total of 168 women who tanned indoors (mean Attitudes and Perceptions About IT age, 20.2 years; range, 18-50 years) signed informed consent documents and then completed the assessments. Female stu- Individuals were asked to indicate whether they agreed or dis- dents were selected from a larger universitywide study that as- agreed with a set of statements that described the potential ad- sessed IT behavior. The larger study involved a random selec- vantages and disadvantages of IT behavior on 5-point Likert- tion of female participants from a pool of all female students at type scales (Cronbach ␣=0.89). a midsized (ie, approximately 12 000 students) southeastern university. The larger sample reported a mean age of 21.8 years Descriptive IT Norms (range, 18-54 years) and a past-year tanning bed prevalence rate of 60%. This mean age closely approximates the institutional The Indoor Tanning Norms Rating Form21 is a measure that mean age (22.2 years), and this prevalence rate is congruent evaluates descriptive norms of IT use for “all college stu- with previous studies we have performed in this population dents,” “popular college students,” “attractive college stu- (54%-67% past-year IT prevalence among female partici- dents,” “close friends,” and “media stars” (Cronbach ␣=0.88). pants16,17), so we are confident that the larger study is a relatively representative sample of this population. We used a ran- Perceived Subjective Norms domization scheme to sample 180 female students from all students in this larger study who indicated that they tanned We used the methods suggested by Ajzen and Madden22 to as- indoors. Participation rates were more than 90% for this study sess perceived subjective or injunctive norms, including per- (168 of 180 selected students agreed to participate). ceived approval of friends, typical college students, popular college students, family members, and partners (if they had one). OUTCOME MEASURES This scale evidenced good internal consistency (Cronbach ␣=0.89). In addition, we asked individuals with current ro- IT Behavioral Pattern Items mantic partners how dark a tan their partner preferred (Part- ner Tan Preference Rating). The IT pattern was assessed by giving respondents descriptions of various hypothesized IT patterns and asking them to IT Attitude Predictors rate these on 5-point Likert-type scales. They were also given dichotomous items that described IT behavioral patterns and Respondents indicated the degree to which they believe tan- asked to agree or disagree with whether these fit them (Figure). ning improves attractiveness with 5 items (Cronbach ␣=0.93).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1531 Table 1. Indoor Tanning Patterns by Cluster

Event Spontaneous or Mood Mixed Regular Total Tanning Pattern (n=90 [53.6%]) (n=10 [6.0%]) (n=48 [28.6%]) (n=20 [11.9%]) (N=168) Event, mean (SD)a 1.26 (0.96) 1.20 (0.42) 1.52 (0.77) −0.15 (1.57) 1.16 (1.10) Spontaneous, mean (SD)a 0.17 (1.30) 1.10 (0.60) 0.98 (1.08) −0.25 (1.52) 0.40 (1.33) Regular seasonal, mean (SD)a −1.66 (0.60) 0.00 (0.00) 1.08 (0.40) 1.35 (1.27) −0.42 (1.51) Regular year round, mean (SD)a −1.70 (0.76) −0.60 (0.84) −0.54 (1.13) 0.45 (1.61) −1.05 (1.26) Regular (dichotomous), No./total No. (%)b 4/78 (5.1) 1/8 (12.5) 10/45 (22.2) 11/18 (61.1) 26/149 (17.4) Mood (dichotomous), No./total No. (%)b 14/77 (18.2) 4/8 (50.0) 16/45 (35.6) 10/17 (58.8) 44/147 (29.9)

a Measured on 5-point Likert scales (−2, strongly disagree, to ϩ2, strongly agree). See the Figure for the actual items. b Measured on dichotomous yes or no scales. See the Figure for the actual items.

Expectancies related to IT were assessed with 8 items (Cron- scales. This cluster seemed to be a subcategory of event tan- bach ␣=0.99). The perception that IT is a good way to relax ners who also reported tanning spontaneously and for mood and relieve stress was assessed with 6 items (Cronbach ␣=0.97). reasons. This cluster composed 6.0% of the total sample.

Tanning Dependence CLUSTER 3: MIXED TANNERS (TYPE 3) We have been exploring the idea that some tanners exhibit de- This cluster showed spikes for the event, spontaneous, pendence-like behaviors, such as tanning obsessions, physical and regular seasonal tanning scales. It had low scores on and psychological tolerance, loss of control, tanning consequences that parallel the effects of endogenous opioids, and cog- the regular year-round scale and moderate scores on the nitions that reflect dissatisfaction with their skin color.23 Eu- mood scale. It appears to include tanners who not only phoria and other opioid-like tanning effects were measured with tan regularly in certain seasons but also will event tan a 5-item scale (eg, “I feel euphoric after an indoor tanning ses- during their off-season. The mixed tanner cluster con- sion”; Cronbach ␣=0.88). Belief that tanning is out of control sisted of 28.6% of the sample. was measured with a 5-item scale (Cronbach ␣=0.77). Toler- ance to tanning effects was measured with 3 items (eg, “I think CLUSTER 4: REGULAR TANNERS (TYPE 4) the amount I indoor tan leaves me less rather than more attractive”; Cronbach ␣=0.69). Obsession with tanning was mea- This cluster had a spike on the regular seasonal and mood sured with 4 items (Cronbach ␣=0.73). Dissatisfaction with tanning scales and a spike on the regular year-round scale. ␣ skin color was measured with 4 items (Cronbach =0.78). It demonstrated low scores on the event and spontaneous tanning scales. This cluster made up 11.9% of the RESULTS total sample. Next we used analysis of variance to test for differences DATA ANALYSIS in demographic, psychosocial, and behavioral domains. Initially, we performed cluster analysis for the purpose of DEMOGRAPHIC AND BEHAVIORAL VARIABLES establishingITbehavioraltypes.Oncecategorizedintotypes, we examined the behavioral and psychological patterns Statistically significant differences were found among clus- among the types to explore potential clinical implications. ters for age, age at first IT session, IT frequency in the past Cluster analysis was performed using the squared euclid- year, and IT intentions for the coming year (Table 2). ean distance metric and the Ward minimum variance clus- Mixed and regular tanners were statistically significantly tering algorithm24 according to procedures described by younger than the spontaneous or mood tanners (F3,163=2.88; Milligan and Hirtle.25 A 4-cluster solution generated 4 dis- P=.04). Regular tanners reported their first IT session at a tinct pattern profiles. Table 1 presents the means and stan- statistically significantly younger age than event tanners dard deviations for the Likert-type assessments and the (F3,164=2.83; P=.04). Event tanners reported tanning less percentages that agree with the dichotomous assessments. than either mixed or regular tanners (eg, event tanners reported tanning 60 times less per year than regular tan- CLUSTER 1: EVENT TANNERS (TYPE 1) ners), and regular tanners tanned indoors at statistically significantly higher levels than spontaneous or mood or mixed Ͻ This cluster demonstrated a spike on the event tanning tanners in the past year (F3,164=36.69; P .001). scale and had relatively low scores on the spontaneous, mood, regular seasonal, and regular year-round scales. PSYCHOSOCIAL VARIABLES This cluster made up 53.6% of the total sample. Statistically significant differences were found for IT at- CLUSTER 2: SPONTANEOUS titudes, IT descriptive and subjective norms, tanning at- OR MOOD TANNERS (TYPE 2) titudes, belief that IT is stress relieving, partner preference, and 4 of the tanning dependence scales (ie, euphoria, This cluster had spikes on the event, spontaneous, and mood obsession, out of control, and skin color dissatisfaction tanning scales. It had low scores for both regular tanning but not tolerance) (Table 3).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1532 Table 2. Demographic and Behavioral Variables by Cluster

Event Spontaneous or Mood Mixed Regular Variable (n=90 [53.6%]) (n=10 [6.0%]) (n=48 [28.6%]) (n=20 [11.9%]) P Value Age, mean (SD), y 20.6 (5.4) 23.7 (10.2) 19.5 (2.8) 18.6 (0.9) .04 Age at first indoor tanning session, 16.2 (2.4) 16.4 (3.6) 15.3 (3.2) 14.6 (1.3) .04 mean (SD), y IT intentions, mean (SD)a 4.5 (1.7) 5.2 (1.8) 6.3 (0.9) 7.0 (0.1) Ͻ.001 IT use, mean (SD)b 11.8 (16.5) 17.8 (16.1) 27.3 (20.1) 72.3 (48.8) Ͻ.001

Abbreviation: IT, indoor tanning. a Measured on 7-point Likert scales (1=definitely do not intend; 7=definitely intend). b Represented self-reported number of times used IT in the past 12 months.

Table 3. Mean (SD) Psychosocial and Pathologic Scores by Cluster

Event Spontaneous or Mood Mixed Regular Variable (n=90 [53.6%]) (n=10 [6.0%]) (n=48 [28.6%]) (n=20 [11.9%]) P Value IT attitudesa 14.6 (5.0) 17.1 (4.2) 19.0 (4.0) 21.4 (2.6) Ͻ.001 IT descriptive normsa 17.5 (3.6) 19.3 (3.7) 20.0 (3.5) 18.7 (3.7) Ͻ.001 IT injunctive normsb 0.8 (5.0) 5.1 (5.5) 3.7 (4.4) 4.9 (4.0) Ͻ.001 Partner preferencec 3.0 (1.1) 3.3 (1.5) 3.7 (1.3) 4.1 (1.4) .008 Tanning attitudesa 30.5 (5.6) 32.8 (4.5) 32.2 (4.3) 33.8 (4.0) .03 Tanning expectationsd 27.6 (6.3) 30.3 (5.0) 30.5 (4.9) 32.5 (4.2) .002 Belief IT relieves stresse 18.0 (6.1) 22.7 (5.8) 21.9 (4.9) 23.9 (3.5) Ͻ.001 IT euphoriaa 10.3 (5.2) 14.8 (4.4) 13.9 (5.0) 15.6 (5.3) Ͻ.001 IT obsessionf 5.3 (2.2) 5.8 (2.4) 7.2 (3.6) 7.5 (3.1) .001 IT out of controla 6.9 (2.8) 9.6 (2.6) 8.6 (4.0) 9.5 (3.6) .002 IT toleranceg 4.8 (2.1) 3.9 (2.1) 5.4 (2.4) 4.8 (2.6) .29 Dissatisfaction with skin colorf 11.1 (4.3) 13.1 (3.3) 12.7 (3.9) 14.1 (3.1) .01

Abbreviation: IT, indoor tanning. a Scores range from 5 to 25; 15 would represent a neutral attitude. b Scores range from −21 to ϩ21; 0 represents neutral norms. c Scores range from 1 (partner prefers no tan) to 7 (partner prefers very dark tan). d Scores range from 8 to 40; 24 would represent a neutral attitude. e Scores range from 6 to 30; 18 would represent a neutral attitude. f Scores range from 4 to 20; 12 would represent a neutral attitude. g Scores range from 3 to 15; 9 would represent a neutral attitude.

Regular tanners reported significantly more positive at- withITthanwereeventtanners(F3,150=5.91;P=.001).Event titudes toward IT than other clusters, and event tanners had tanners were the least likely of the clusters to report that significantly less positive attitudes than either mixed or regu- they believed their tanning was out of control (F3,151=5.36; Ͻ lar tanners (F3,160=17.45; P .001). Event tanners were less P=.002). Finally, mixed and regular tanners were more likely to believe that their peers and media stars were in- likely to express dissatisfaction with the color of their skin door tanners than either mixed or regular tanners than were event tanners (F3,151=3.67; P=.01). Ͻ (F3,158=8.92; P .001). Similarly, event tanners reported significantly lower subjective norms than any other cluster Ͻ COMMENT of tanners (F3,157=7.28; P .001). Event tanners also reported that their partners preferred the lightest tans when compared with either mixed or regular tanners (F3,109=4.17; This study identified 4 tanning subtypes that appear to P=.008). Regular tanners reported more positive atti- differ in demographic, psychosocial, and behavioral di- tudes toward tans than event tanners (F3,158=3.03; P=.03). mensions. Table 4 represents a hypothesized frame- Event tanners reported less positive expectancies associ- work for matching IT type to clinical intervention meth- ated with tanning than either mixed or regular tanners ods based on the psychosocial and behavioral differences (F3,157=5.21; P=.002). Event tanners were also the least likely found in this study. Of course, controlled studies would to believe that IT was stress relieving compared with the be needed to confirm the efficacy of each behavioral in- Ͻ other clusters (F3,155=9.28; P .001). tervention for the various types of IT. However, we Next we examined differences in IT clusters using the thought it would be useful to propose this initial frame- tanning dependence scales. Event tanners were least likely work as a starting place. to report euphoria or other endogenous opioid-like effects The event tanning (type 1) cluster composed more than Ͻ fromITthantheotherclusters(F3,152=9.11;P .001).Mixed 50% of this sample. These individuals tend to tan at mod- and regular tanners were more likely to report obsessions erate to low levels (ie, an average of 12 times per year)

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1533 However, they tan significantly less than the regular tan- Table 4. Hypothetical Indoor Tanning Subtype ners, although still at high rates (mean of Ͼ25 times per by Intervention Framework year), and have weaker attitudes toward IT. Perhaps most important, they seem much less influenced by mood is- Type Hypothetical Intervention sues than do regular tanners. Tanning is likely an im- Event tanner Appearance-related discussion or brochure portant part of lifestyle and social group interaction in based on behavioral change models with these tanners. We hypothesize that this group would prob- emphasis on alternatives. Spontaneous or Screening and referrals of patients with ably benefit from a harm reduction approach, since it may mood tanner seasonal affective disorder. be difficult to get them to eliminate tanning from their Appearance-related discussion or brochure lives altogether because of the likely importance of tan- based on behavioral change models. ning to their current social image. For example, a clini- Mixed tanner Harm reduction approach focusing on cal discussion that provided information on alternative reducing to Ͻ10 times per year or sunless tanning products. Motivational safe tanning choices, such as sunless tanning, might prove interviewing–type information regarding reasonably effective. However, we also hypothesize that peers’ tanning preference or behavior. this group may need additional booster interventions to Regular year-round Seasonal affective disorder screening and see sustained behavioral change. tanner referral. In-depth discussion using motivational interviewing techniques. The regular tanners (type 4) make up approximately 12% of the sample and are the most at-risk group. They tan at high levels (mean of Ͼ70 times per year). They start tanning at the youngest age, have high intentions and have relatively low intentions to tan indoors in the of continuing tanning, have positive attitudes toward tans future relative to other tanners. They report the least posi- and IT, and have a strong mood component to their tan- tive attitudes toward IT, the lowest normative ratings re- ning. This group of tanners is similar to the mixed tan- lated to IT, and the weakest tanning expectancies and are ners in terms of their tanning being an integral part of the least likely to report that IT is relaxing or stress re- their lifestyle and social group. However, we believe that lieving. They also scored lowest on all of the tanning the mood component seen in regular tanners may help pathologic measures. These individuals appear to be ca- to account for the much greater tanning levels seen. We sual tanners who may view tanning as a fashion acces- hypothesize that this group could benefit from depres- sory for special events. These are the individuals we hy- sion and SAD screening and referral for those demon- pothesize that dermatologists or other health care strating significant depression and SAD symptoms. Of professionals are most likely to affect with appearance- course, the fact that many of these individuals tan in- related messages during the brief discussions that may doors throughout the year suggests multiple tanning mo- occur in clinical settings. In our previous research, we tives and the likely need to incorporate interventions that demonstrated that even relatively short brochures based address more than depression and SAD issues, such as on behavioral principles can have significant effects on the body dysmorphic disorder or substance-related dis- skin cancer risk behavior in these casual tanners.19,26 order issues hinted at in the tanning pathologic assess- The spontaneous or mood (type 2) tanners, who made ment results. However, we believe that initial treatment up approximately 6% of the sample, appear to be a spe- of SAD symptoms may be needed before addressing other cial subcategory of the event tanners. They are the oldest motives. We hypothesize that this group has the least tanners (mean age,23.7 years) and tan at levels interme- chance for change in response to the brief clinical dis- diate between the event tanners and the mixed and regu- cussions that occur in physicians’ offices and may in fact lar tanners. They demonstrate weak intentions to con- experience reactance2 to some messages presented.28 We tinue their tanning and intermediate attitudes and beliefs believe that this hard-core group of tanners may benefit related to tanning. It has been our experience that many the most from intensive interventions that address the of our event tanners tend to reduce their tanning as they social, appearance, health, and mood aspects of tanning get older and particularly as they leave college and enter in an integrated package. Such promising intervention a world with different social and financial contexts. Spon- techniques as motivational interviewing may be appro- taneous or mood tanners appear to be event tanners who priate for this group of tanners at high risk. do not follow this common progression but instead sus- This study is limited by its restricted college sample. tain their tanning behaviors. It is possible that this persis- However, the university from which this sample was tence may be partly due to mood influences on their tan- drawn has a primarily nonresidential, nontraditional ning. For this reason, we hypothesize that it may be useful population of students (eg, older, many married and with to include a brief screening for seasonal affective disorder children, and most employed full time). Thus, this sample (SAD) symptoms and depression for patients who tan in- is probably more reflective of typical indoor tanners than doors. Patients who show evidence of depression and SAD many traditional college populations. The study did not symptoms could be referred to mental health care profes- assess SAD, although an earlier study16 has already dem- sionals for diagnosis and treatment.27,28 onstrated a strong relationship between tanning and SAD The mixed tanners (type 3) constitute close to 30% symptoms (ie, depression, sleep problems, lethargy, anxi- of the sample and, as the name implies, represent a group ety, and social problems that usually recur regularly each that reports mixed patterns of tanning behavior. They re- winter). This study did not address other potential co- semble the regular tanners most in their intentions, at- morbidities hinted at in the tanning pathologic assess- titudes, beliefs, and scores on tanning dependence scales. ment results. For example, several of the scales on that

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1534 measure may reflect forms of body dysmorphic disorder and the risk of cutaneous melanoma. BMJ. 1988;297(6649):647-650. or substance-related disorders. Currently, we have only 4. Swerdlow AJ, Weinstock MA. Do tanning lamps cause melanoma? an epidemiologic assessment. J Am Acad Dermatol. 1998;38(1):89-98. empirical data on the relationship of SAD to tanning, al- 5. Walter SD, Marrett LD, From L, Hertzman C, Shannon HS, Roy P. The associa- though promising work is attempting to link these other tion of cutaneous malignant melanoma with the use of sunbeds and sunlamps. conditions to UV-risk behaviors.29-31 Future work should Am J Epidemiol. 1990;131(2):232-243. explore the association of other pathologic conditions with 6. Westerdahl J, Ingvar C, Masback A, Jonsson N, Olsson H. Risk of cutaneous ma- tanning so that physicians can consider the need to ex- lignant melanoma in relation to use of sunbeds: further evidence for UV-A carcinogenicity. Br J Cancer. 2000;82(9):1593-1599. tend screening beyond SAD. This is a cross-sectional study, 7. Westerdahl J, Olsson H, Masback A, et al. Use of sunbeds or sunlamps and ma- which makes it difficult to establish cause and effect (eg, lignant melanoma in southern Sweden. Am J Epidemiol. 1994;140(8):691-699. we do not know if attitudes precede IT or vice versa). 8. Gallagher RP, Spinelli JJ, Lee TK. Tanning beds, sunlamps, and risk of cutane- Finally, the relatively small number of regular users in- ous malignant melanoma. Cancer Epidemiol Biomarkers Prev. 2005;14(3): cluded in this study means that the results must be rep- 562-566. licated in a larger sample before we can be certain that 9. Karagas MR, Stannard VA, Mott LA, Slattery MJ, Spencer SK, Weinstock MA. Use of tanning devices and risk of basal cell and squamous cell skin cancers. the clear behavioral differences between event and regu- J Natl Cancer Inst. 2002;94(3):224-226. lar tanners are generalizable. 10. Lazovich D, Sweeney C, Weinstock MA, Berwick M. Re: A prospective study of In conclusion, we hypothesize that physicians who tai- pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. lor their approach to the various tanning subtypes will J Natl Cancer Inst. 2004;96(4):335. experience better results in terms of reductions in IT in- 11. Veierød MB, Weiderpass E, Thorn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. J Natl Can- tentions and behavior. This study represents prelimi- cer Inst. 2003;95(20):1530-1538. nary results in a restricted sample; therefore, these re- 12. International Agency for Research on Cancer Working Group on artificial ultra- sults need to be replicated in larger, more representative violet (UV) light and skin cancer. The association of use of sunbeds with cuta- samples using more sophisticated analytic techniques such neous malignant melanoma and other skin cancers: a systematic review. Int J as latent class analysis. It would also be interesting to ex- Cancer. 2007;120(5):1116-1122. 13. International Tanning Association. Positive effects of UV light. http://www.theita plore the potential fluidity of these tanning types and .com/. Accessed January 10, 2007. whether individuals transition from one type to another 14. Hillhouse J, Turrisi R, Stapleton J, Shields A. Indoor tanning behavioral patterns. (eg, from event tanners to regular tanners) in a predict- In: Developing Consensus Measures of Skin Cancer Prevention Behaviors. At- able way. By labeling tanners by behavioral type and ad- lanta, GA: An Investigators Workshop; December 1-2, 2005. justing our interactions based on those types, we will have 15. Hillhouse J, Stapleton J, Turrisi R. Association of frequent indoor UV tanning with seasonal affective disorder. Arch Dermatol. 2005;141(11):1465. a more accurate picture of our patients and be more ef- 16. Hillhouse J, Turrisi RH, Holwiski F, McVeigh S. An examination of psychological fective in our health care messages. variables relevant to artificial tanning tendencies. J Health Psychol. 1999;4 (4):507-516. Accepted for Publication: August 13, 2007. 17. Hillhouse JJ, Stair AW, Adler CM. Predictors of sunbathing and sunscreen use Correspondence: Joel Hillhouse, PhD, Department of in college undergraduates. J Behav Med. 1996;19(6):543-561. 18. Hillhouse J, Adler JJ, Drinnon CM, Turrisi R. Application of Ajzen’s Theory of Public Health, PO Box 70674, East Tennessee State Uni- Planned Behavior to predict sunbathing, tanning salon use, and sunscreen in- versity, Johnson City, TN 37614 ([email protected]). tentions and behaviors. J Behav Med. 1997;20:363-376. Author Contributions: Study concept and design: Hill- 19. Hillhouse JJ, Turrisi R. Examination of the efficacy of an appearance focused in- house, Turrisi, and Shields. Acquisition of data: Hill- tervention to reduce UV exposure. J Behav Med. 2002;25(4):395-409. house, Turrisi, and Shields. Analysis and interpretation of 20. Hillhouse JJ, Turrisi R, Kastner M. Modeling tanning salon behavioral tenden- data: Hillhouse. Drafting of the manuscript: Hillhouse. Criti- cies using appearance motivation, self-monitoring and the theory of planned behavior. Health Educ Res. 2000;15(4):405-414. cal revision of the manuscript for important intellectual con- 21. Hale C, Hillhouse JJ, Stair A, Lane F. Predicting sunscreen use: a comparison of tent: Hillhouse, Turrisi, and Shields. Statistical analysis: two models. Paper presented at: American Psychological Society Annual Meet- Hillhouse, Turrisi, and Shields. Obtained funding: Hill- ing; May 26, 2000; Miami, FL. house and Turrisi. Administrative, technical, and mate- 22. Ajzen I, Madden TJ. Prediction of goal-directed behavior: attitudes, intentions, rial support: Hillhouse, Turrisi, and Shields. and perceived behavioral control. J Exp Soc Psychol. 1986;22(5):453-474. 23. Hillhouse J, Abbott K, Hamilton J, Turrisi R. This (tanning) bed’s for you: addic- Financial Disclosure: None reported. tive tendencies in intentional tanning. Paper presented at: Western Psychologi- Funding/Support: This research was supported in part by cal Association Annual Meeting; May 2, 2003; Vancouver, British Columbia, Canada. grant RSGPB-05-011-01-CPPB from the American Can- 24. Ward JH Jr. Hierarchical grouping to optimize an objective function. J Am Stat cer Society and grant R21 CA116384-01 from the Na- Assoc. 1963;58(301):236-244. tional Cancer Institute to East Tennessee State University. 25. Milligan G, Hirtle SC. Clustering and classification methods. In: Schinka J, Velicer W, eds. Comprehensive Handbook of Psychology. Vol 2. New York, NY: Wiley & Additional Contributions: Jerod Stapleton, BS, and Sons; 2003:165-186. Preston Visser, BS, assisted in conducting this study 26. Turrisi R, Hillhouse J, Heavin S, Adams M, Berry J. Examination of the short- and preparing the manuscript. term efficacy of a parent-based intervention to prevent skin cancer. J Behav Med. 2004;27(4):393-412. 27. Rosenthal N. Winter Blues. 3rd ed. New York, NY: Guilford Press; 2005. REFERENCES 28. Rosenthal NE. Diagnosis and treatment of seasonal affective disorder. JAMA. 1993;270(22):2717-2720. 1. Autier P, Joarlette M, Lejeune F, Lienard D, Andre J, Achten G. Cutaneous ma- 29. Lazovich D, Forster J, Sorensen G, et al. Characteristics associated with use or lignant melanoma and exposure to sunlamps and sunbeds: a descriptive study intention to use indoor tanning among adolescents. Arch Pediatr Adolesc Med. in Belgium. Melanoma Res. 1991;1(1):69-74. 2004;158(9):918-924. 2. Chen YT, Dubrow R, Zheng T, Barnhill RL, Fine J, Berwick M. Sunlamp use and 30. Phillips KA, Conroy M, Dufresne RG, et al. Tanning in body dysmorphic disorder. the risk of cutaneous malignant melanoma: a population-based case-control study Psychiatr Q. 2006;77(2):129-138. in Connecticut, USA. Int J Epidemiol. 1998;27(5):758-765. 31. Warthan MM, Uchida T, Wagner RF Jr. UV light tanning as a type of substance- 3. Swerdlow AJ, English JSC, MacKie RM, et al. Fluorescent lights, ultraviolet lamps, related disorder. Arch Dermatol. 2005;141(8):963-966.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1535 STUDY A Comparison of Oral Methylprednisolone Plus Azathioprine or Mycophenolate Mofetil for the Treatment of Bullous Pemphigoid

Stefan Beissert, MD; Thomas Werfel, MD; Uta Frieling, MD; Markus Bo¨hm, MD; Michael Sticherling, MD; Rudolf Stadler, MD; Detlef Zillikens, MD; Berthold Rzany, MD; Nicolas Hunzelmann, MD; Michael Meurer, MD; Harald Gollnick, MD; Thomas Ruzicka, MD; Hans Pillekamp, MD; Volker Junghans, MD; Gisela Bonsmann, MD; Thomas A. Luger, MD

Objective: To investigate the safety and efficacy of oral Results: In 38 of 38 patients in the azathioprine group methylprednisolone combined with azathioprine so- (100%), complete remission was achieved after a dium or mycophenolate mofetil for the treatment of bul- mean±SD of 23.8±18.9 days vs 42.0±55.3 days for 35 lous pemphigoid. of 35 patients in the mycophenolate mofetil group (100%). In the azathioprine group, the median±SD total cumu- Design: A prospective, multicenter, randomized, non- lative methylprednisolone dose used was 4967.0±12 190.7 blinded clinical trial to compare 2 parallel groups of mg vs 5754.0±9692.8 mg in the mycophenolate mofetil patients with bullous pemphigoid undergoing different group. Nine of 38 patients in the azathioprine group (24%) treatments. experienced grade 3 or 4 adverse effects vs 6 of 35 patients in the mycophenolate mofetil group (17%). Aza- Setting: Thirteen departments of dermatology in thioprine therapy induced significantly elevated liver func- Germany. tion test results compared with mycophenolate mofetil (PϽ.001). Importantly, patients in the azathioprine group Patients: Patients with bullous pemphigoid (n=73) as evi- showed significantly higher toxicity grades for aspartate denced by clinical lesions suggestive of bullous pemphi- aminotransferase (P=.03), alanine aminotransferase goid, signs of subepidermal blistering on histologic analy- (P=.03), and ␥-glutamyltransferase (P=.01) than did those sis of skin biopsy specimens, linear deposition of IgG and in the mycophenolate mofetil group. C3 along the dermoepidermal junction, and deposition of autoantibodies at the blister roof in split-skin analysis. Conclusions: Mycophenolate mofetil or azathioprine demonstrate similar efficacy during treatment of bullous pem- Interventions: Treatment with oral methylpredniso- phigoid, and similar cumulative corticosteroid doses were lone plus azathioprine (azathioprine group) or oral meth- given in both treatment arms to control disease. However, ylprednisolone plus mycophenolate mofetil (mycophe- mycophenolate mofetil showed a significantly lower liver nolate mofetil group). toxicity profile than azathioprine therapy.

Main Outcome Measures: The cumulative total meth- Trial Registration: clinicaltrials.gov Identifier: ylprednisolone doses and rates of remission. Secondary NCT00431119 outcome measures were safety profiles and duration of remission. Arch Dermatol. 2007;143(12):1536-1542

LTHOUGH IN GENERAL RARE, ingly, autoantibodies directed against the bullous pemphigoid (BP) 2 proteins can be detected by both direct represents the most com- and indirect immunofluorescence. Bul- mon cutaneous subepider- lous pemphigoid treatment is based more mal bullous autoimmune on clinical experience than on controlled disorder.A1-3 The disease typically pre- studies. Systemic corticosteroids represents in elderly patients with a general- sent the best-validated and therefore stan- ized bullous eruption and, more rarely, dard therapeutic regimen. Oral predni- mucous membrane involvement.4,5 Bul- sone doses range from 0.3 to 1.25 mg/kg lous pemphigoid is potentially associ- of body weight per day, which usually con- ated with substantial morbidity. The cu- trols disease within 1 to 2 weeks.9-11 The taneous autoantigens are BP antigens 1 and dose is then progressively tapered. How- 2 (BP 180 and BP 230), which are ex- ever, the use of systemic corticosteroids Author Affiliations are listed at pressed in hemidesmosomal plaques as in elderly patients is associated with con- the end of this article. well as anchoring filaments.6-8 Accord- siderable adverse effects.12-14 Occasion-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1536 ally, corticosteroid pulse therapy is used for the rapid con- gardless of disease severity, to receive either 0.5 mg/kg of meth- trol of BP. ylprednisolone (Urbason; Aventis Pharma, Frankfurt, Ger- Several uncontrolled and 1 controlled investigation many) with 2 mg/kg of azathioprine sodium (Imurek; suggested the use of concomitant immunosuppressant GlaxoSmithKline, Munich, Germany) once daily or 0.5 mg/kg drugs to achieve a corticosteroid-sparing effect.15-17 Com- of methylprednisolone once daily with 1000 mg of mycophenolate mofetil (CellCept; Hoffmann-La Roche AG, Grenzach- bination therapy may be also useful to successfully treat Wyhlen, Germany) twice daily (2 g/d). The initial dose was main- widespread and/or chronic and/or severe forms of BP via tained until blister formation ceased, crusts and erosions induction of more potent immunosuppression. The most disappeared, and reepithelialization of lesions started. The cor- frequently used agent is azathioprine at doses ranging from ticosteroid dose was then sequentially reduced by 10 mg every 0.5 to 2.5 mg/kg of body weight. Other case series have 2 weeks until a dose of 20 mg/d was reached followed by a re- reported the successful use of cyclophosphamide, metho- duction in 5-mg steps every 2 weeks until 10 mg/d. After- trexate, cyclosporine A, and combination tetracycline/ wards, corticosteroid reduction was performed in 2.5-mg steps minocycline along with nicotinamide and, more re- every 2 weeks until a dose of 0 was reached. cently, mycophenolate mofetil for the treatment of After discontinuation of corticosteroid treatment, azathio- disease.18-24 Among the immunosuppressants, mycophe- prine or mycophenolate mofetil administration was maintained at the initial dose as monotherapy for an additional nolate mofetil has shown great promise for the treat- 4 weeks. Then the azathioprine sodium dose was reduced by ment of cutaneous bullous autoimmune disorders. Since 0.5 mg/kg every 4 weeks to a dose of 100 mg/d. Thereafter, complications related to the use of oral corticosteroids azathioprine therapy was tapered in 25-mg steps every may contribute substantially to the prognosis of pa- 4 weeks until discontinuation of treatment. Mycophenolate tients with BP, we conducted a randomized trial com- mofetil treatment was reduced in 500-mg steps every 4 weeks paring oral corticosteroids in combination with either aza- to 1000 mg/d. From then on, the mycophenolate mofetil dose thioprine sodium or mycophenolate mofetil. The aim of was decreased in 250-mg steps every 4 weeks until discon- this investigation was to assess the efficacy and adverse tinuation of treatment. event profiles of both immunosuppressant agents in a If new blisters developed 7 days or more after the initiation combination therapy regime with corticosteroids for the of therapy, this was considered disease progression, and the methylprednisolone dose was increased weekly by 0.5 mg/kg every treatment of BP. We also assessed the cumulative doses 7 days until blister development ceased. of corticosteroids used in each combination. Relapse was defined as the formation of new blister formation during dose reduction of either methylprednisolone or im- METHODS munosuppressant. If a relapse was noticed at a dose of methylprednisolone higher than 40 mg/d, the previous corticosteroid dose that achieved disease control was given. If a relapse was PATIENTS noticed at a dose lower than 40 mg/d of methylprednisolone, including during the phase of immunosuppressant mono- Thirteen dermatologic centers in Germany participated in this therapy or its reduction, the corticosteroid dose was increased prospective, randomized investigation. The study protocol was to 40 mg/d, and the initial immunosuppressant dose was given. approved by the ethics committee of the University of Mu¨n- ster, Mu¨ nster, Germany, and written informed consent was obtained from each patient. Consecutive patients with BP were BASELINE AND FOLLOW-UP EVALUATION eligible for entry if the following criteria were met: clinical lesions suggestive of BP, subepidermal blistering on histologic At baseline, each patient underwent a physical examination fol- analysis of skin biopsy specimens, linear deposition of IgG and lowed by a complete blood cell count, liver function tests, blood C3 along the dermoepidermal junction, and deposition of au- pressure evaluation, hemoccult test, and urinanalysis. Addi- toantibodies at the blister roof on split-skin analysis. Exclu- tionally, they underwent abdominal ultrasonography, chest ra- sion criteria were treatment with oral or topical corticoste- diography, electrocardiography, quantitative computed tomog- roids and other immunosuppressive drugs during the previous raphy for determination of bone density, and ophthalmologic 4 weeks. evaluation to measure inner eye pressure and to determine cata- ract status. The extent and location of blisters and erosions were documented by a physician not otherwise involved in the study. STUDY DESIGN At each follow-up visit (on days 7, 14, 30, 60, 90, 120, 150, 180, 270, 360, 540, and 720), the patient underwent physical This multicenter, randomized, nonblinded clinical trial com- examination, blood cell count, liver function tests, blood pres- pared 2 parallel groups of patients with BP treated with oral sure evaluation, and stool and urine analysis. The extent and methylprednisolone in combination with either azathioprine locations of their blisters and erosions were noted, as was the (azathioprine group) or mycophenolate mofetil (mycopheno- cumulative amount of methylprednisolone they had taken. The late mofetil group). Since complete healing (also called com- date of any relapse was noted. Any adverse effects of treatment plete remission), defined as a complete reepithelization of all were assessed, and their severity was graded 1 for mild effects, lesions, was a primary outcome measure, blinding was not con- 2 for moderate effects, 3 for severe effects, or 4 for life- sidered necessary. The second primary outcome measure was threatening effects, according to the standard criteria of the the cumulative oral corticosteroid dose used until complete heal- World Health Organization. ing was achieved; this outcome allowed us to compare the corticosteroid-sparing effects of the 2 alternative immunosuppressants. Secondary outcome measures were duration of remission STATISTICAL ANALYSIS and safety profiles of the 2 treatments. Randomization was stratified according to the clinical cen- Cumulative corticosteroid doses as the primary end point of ter and performed centrally with the use of random numbers the study were compared using the Wilcoxon rank sum test of three for each stratum. Patients were randomly assigned, re- for independent observations. All other analyses presented are

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1537 a Table 1. Baseline Characteristics of the Study Patients 100 Mycophenolate mofetil Treatment Group Azathioprine sodium 80 Azathioprine Mycophenolate All Characteristic Sodium Mofetil Patients 60 Age, mean±SD, y 75.5±12.8 74.8±13.4 75.3±12.6 Men 12 15 27 40 Women 26 20 46 Time from diagnosis 117.6±540 79.5±283 99.0±432

to randomization, Rate Without Remission, % 20 mean±SD, d BP diagnosis 38 35 73 Prior BP treatment 3 (8) 1 (3) 4 (5) 0 No prior BP treatment 35 (92) 34 (97) 69 (95) 0 100 200 300 400 500 600 700 BSA involvement, % Time, d 0000 Ͻ5 2 (6) 5 (15) 7 (10) Figure 2. Rate and duration until clinical remission. Patients with bullous Ͻ10 9 (25) 7 (21) 16 (24) pemphigoid were randomized to receive treatment with either azathioprine Ͻ20 6 (17) 12 (36) 18 (26) sodium (n=38) or mycophenolate mofetil (n=35) as adjuvants in Ն20 19 (53) 9 (27) 28 (41) combination with oral methylprednisolone. The Kaplan-Meier graph shows OM involvement 21 (64) 15 (50) 36 (58) the rate without remission over time (P=.09). No OM involvement 12 (36) 15 (50) 27 (43) reasons for exclusion were use of other medication ef- Abbreviations: BP, bullous pemphigoid; BSA, body surface area; OM, oral fective against BP (1 patient), diagnosis of another skin mucosa. a Unless otherwise indicated, data are reported as number or number disorder (1 patient), and severe cardiac insufficiency (2 (percentage) of patients. patients). The remaining 73 patients were randomly assigned to either the azathioprine group (n=38) or the mycophenolate mofetil group (n=35) (Figure 1). After randomization all 73 patients were analyzed. Sixty-nine 80 Assessed for eligibility patients (95%) represented newly diagnosed BP cases, and 4 patients (5%) had been previously treated for their dis- 7 Excluded ease. The mean duration of follow-up among the pa- 4 Did not meet inclusion criteria tients with BP was 303 days for the azathioprine group 3 Refused to participate and 303 days for the mycophenolate mofetil group.

73 Randomized DISEASE CONTROL AND RELAPSE

In all 38 patients with BP who were assigned to the aza- 38 Allocated to steroid/azathioprine 35 Allocated to steroid/ sodium mycophenolate mofetil thioprine group and in all 35 patients with BP who were 38 Received allocated treatment 35 Received allocated treatment assigned to the mycophenolate mofetil group, disease progression was inhibited by around day 6. In 35 (92%) of 38 Analyzed 35 Analyzed the 38 azathioprine patients, complete healing of the lesions and remission was achieved (Figure 2). For the Figure 1. Trial enrollment and analysis flowchart. 3 patients with incomplete healing (8%), 2 died from conditions unrelated to the study medication, and so the treatments were prematurely discontinued; the third patient of a descriptive or hypothesis-generating nature. Dichoto- was lost to follow-up. Complete healing of the lesions mous and ordered categorical data were analyzed with the Fisher and disease remission was noted in all 35 of the myco- exact and a corresponding exact permutation version of the Man- phenolate mofetil patients (100%). Complete healing was tel-Haenszel test, respectively. Event-related data such as time achieved after a median±SD duration of 23.8±18.9 days to achieve complete healing or time to recurrence were esti- of treatment in the azathioprine group. In the myco- mated according to the Kaplan-Meier method and eventually phenolate mofetil group, complete healing was noted af- compared using the log-rank test. All event or censoring times ter 42.0±55.3 days (P=.09). The disease-free interval from were calculated from the point of randomization. All reported the time when complete remission was achieved until re- P values are 2-sided. currence of lesions was 164.5±135.8 days for the azathioprine group and 126.0ϩ89.6 days for the mycophe- RESULTS nolate mofetil group. The Kaplan-Meier graph in Figure 3 shows the rate without relapse in patients with BP over PATIENTS time, indicating that both adjuvant therapies in the 2 treatment arms control disease equally well. Between October 1997 and October 2000, 80 patients with The data in Figure 4 depict the duration until re- BP were assessed for eligibility (Table 1). Three pa- lapse of disease was documented from the time of ran- tients declined written consent and were excluded. Other domization. The 2 curves show a very similar course and

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1538 100 100 Mycophenolate mofetil Mycophenolate mofetil Azathioprine sodium Azathioprine sodium 80 80

60 60

40 40

Rate Without Recurrence, % 20 Rate Without Recurrence, % 20 ≤ 7 d (n = 50)

> 7 d (n = 23) 0 0 0 100 200 300 400 500 600 700 0 100 200 300 400 500 600 700 Time, d Time, d

Figure 3. Disease-free interval. The Kaplan-Meier graph shows the rate Figure 5. Effects of length of time between diagnosis and initiation of without recurrence of disease since once remission was achieved in patients treatment on the recurrence of disease. The Kaplan-Meier graph shows the with bullous pemphigoid patients treated with either azathioprine sodium rate without recurrence of bullous pemphigoid over time in patients treated (n=38) or mycophenolate mofetil (n=35) as adjuvants (P=.72). for more than 7 days or for 7 days or less after the diagnosis of bullous pemphigoid (P=.07).

100 Mycophenolate mofetil Table 2. Total Cumulative Corticosteroid Doses Azathioprine sodium Used to Control Bullous Pemphigoid 80 Corticosteroid Dose, mg Adjuvant Patients, 60 Treatment No. (%) Median (SD) Range Azathioprine sodium 38 (52) 4967.0 (12 190.7) 1283-73 231 40 Mycophenolate mofetil 35 (48) 5754.0 (9692.8) 980-40 715 Combined groups 73 (100) 5131.0 (11 064.3) 980-73 231

Rate Without Remission, % 20

0 0 100 200 300 400 500 600 700 Table 3. Groups of Cumulative Corticosteroid Doses Time, d Patients, No. (%) Figure 4. Duration until relapse. The Kaplan-Meier graph shows the time since randomization until patients with bullous pemphigoid developed a Azathioprine Mycophenolate recurrence of disease during the reduction phase of treatment medication Corticosteroid Sodium Mofetil Total (P=.74). Dose, mg (n=38) (n=35) (n=73) 1-10 000 28 (74) 28 (80) 56 (77) 10 001-20 000 7 (18) 3 (9) 10 (14) are, therefore, not significantly different. In addition, the 20 001-30 000 2 (5) 1 (3) 3 (4) duration until relapse was differentiated in relation to the 30 001-40 000 0 2 (6) 2 (3) time between diagnosis of BP and beginning of treat- 40 001-50 000 0 1 (3) 1 (1) ment. The results represented in Figure 5 show that the 50 001-60 001 0 0 0 Ͼ duration between diagnosis and initiation of therapy (Յ7 75 000 1 (3) 0 1 (1) or Ͼ7 days) did not significantly influence the time until a relapse of disease was noted. These findings indicate that BP can be successfully controlled with both treat- 4967.0±12 190.7 mg of methylprednisolone. In the pa- ment regimens. tient group that was randomized to receive mycophenolate mofetil, 5754.0±9692.8 mg of methylprednisolone CUMULATIVE CORTICOSTEROID was given. In general, these numbers are very similar and DOSES USED possibly reflect a comparable immunosuppressive potential of the 2 drugs. One of the aims of this investigation was to determine if The results in Table 3 furthermore demonstrate that the corticosteroid-sparing effect of either of the 2 immu- each of the 56 patients with BP (77%) received less than nosuppressants would be superior. Therefore, the cu- 10 000 mg of methylprednisolone as a cumulative dose mulative corticosteroid dose was calculated for each pa- during the course of treatment. Ten of the patients tient with BP from the beginning of treatment to the end received between 10 001 and 20 000 mg (14%). The dis- of the documentation period (Ͼ720 days). The data in tribution of the patients with BP to the different corti- Table 2 indicate that patients with BP who were ran- costeroid dose groups (Table 3) was similar for azathio- domized to the azathioprine group received a median±SD prine or mycophenolate mofetil as adjuvant treatment.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1539 Table 4. Incidence of Grades 3 and 4 Adverse Events Table 5. Liver Function Test Findings During Treatment After the Initiation of Treatment Patients With BP, No. (%) Adverse Event Grade, No. % Toxicity Azathioprine Sodium Mycophenolate Mofetil Total Grade (n = 36) (n = 34) Symptom 34Patients, No. Aspartate Aminotransferase Azathioprine Sodium Group 0 25 (69) 31 (91) Hypokalemia 0 0 37 1 4 (11) 2 (6) Hyperglycemia 1 (3) 0 37 2 5 (14) 0 Infection 0 1 (3) 38 3 1 (3) 1 (3) Abnormal liver function 4 (11) 2 (5) 37 4 1 (3) 0 Myalgia and/or arthralgia 1 (3) 0 37 Alanine Aminotransferase Dizziness 2 (5) 0 37 0 18 (50) 25 (74) Mycophenolate Mofetil Group 1 11 (31) 8 (24) Hypokalemia 1 (3) 0 35 2 3 (8) 0 Hyperglycemia 5 (15) 0 34 3 4 (11) 1 (3) Infection 4 (11) 0 35 40 0 Abnormal liver function 0 1 (3) 35 ␥-Glutamyltransferase Myalgia and/or arthralgia 1 (3) 1 (3) 35 0 14 (390) 20 (59) Dizziness 0 0 35 1 5 (14) 8 (24) 2 6 (17) 3 (9) 3 6 (17) 2 (6) In summary, similar cumulative corticosteroid doses were 4 5 (14) 1 (3) taken during therapy in the 2 treatment arms. Abbreviation: BP, bullous pemphigoid. COMPLIANCE WITH TREATMENT AND ADVERSE EVENTS COMMENT The treatments were prematurely discontinued in 2 patients from the azathioprine group who died due to con- In this randomized study, each treatment arm had simi- ditions unrelated to the study medications. Another pa- lar therapeutic benefit. Because no corticosteroid mono- tient from the azathioprine group was lost to follow-up. therapy arm was included in the study, the level of cor- Overall, 24 severe (grade 3) or life-threatening (grade ticosteroid-sparing effects of each adjuvant agent cannot 4) adverse effects were reported in 15 patients (Table 4). be determined. Azathioprine induced more liver toxic- Grade 3 or 4 adverse effects were documented in 9 of the ity than mycophenolate mofetil, suggesting a therapeu- 38 patients randomized to the azathioprine group (24%) tic benefit for patients receiving mycophenolate mofetil. compared with 6 of the 35 patients from the mycopheno- Since only 1 dose regimen of immunosuppressants was late mofetil group (17%). Adverse effects typically asso- used, we cannot determine if different drug doses would ciated with the immunosuppressants used in this inves- have had another clinical outcome. Another difference tigation, including nausea (azathioprine vs mycophenolate between the 2 arms is the daily cost of treatments. For a mofetil, P=.60), vomiting (P=.64), and infections (P=.67), 75-kg patient, the cost was €2.58 for azathioprine (2 mg/kg did not differ significantly between treatment arms. per day) and €14.32 for mycophenolate mofetil (1 g twice However, patients with BP randomized to the aza- daily), azathioprine being 5.5 times less expensive than thioprine group showed significant elevated liver func- mycophenolate mofetil. tion test results compared with patients in the mycophe- For several decades, systemic corticosteroids were con- nolate mofetil group (PϽ.001). To investigate the liver sidered the standard treatment for BP.9-11,19 They may be function, serum concentrations of aspartate aminotrans- responsible for the increased mortality rate, especially in ferase (AST), alanine aminotransferase (ALT), and ␥-glu- elderly patients. Indeed, in a large study using 1 mg/kg of tamyltransferase (GGT) were determined and classified prednisone, a 1-year mortality rate of 41% was observed, according to toxicity grades. Patients with BP in the aza- regardless of the extent of disease. This finding suggests thioprine group showed significantly higher serum con- that the treatment rather than the extent of the disease de- centrations of ALT than patients in the mycophenolate termined the poor prognosis.10 Therefore, the develop- mofetil group (P=.03). This was not true of AST and GGT ment of corticosteroid-sparing treatment regimens is of par- (P=.06 and P=.15, respectively). Importantly, patients ticular practical relevance. In a randomized investigation with BP in the azathioprine group showed significantly topical application of clobetasol propionate, a very po- higher toxicity grades for AST (P=.03), ALT (P=.03), and tent corticosteroid agent, resulted in successful control of GGT (P=.01) than patients in the mycophenolate mofetil even extensive BP without inducing increased mortal- group (Table 5). Together, these results suggest that the ity.10 Based on these findings, some proposed that topical efficacy between both treatment arms was similar. How- corticosteroid treatment should be considered standard ever, the mycophenolate mofetil treatment involved a sig- treatment for patients with even extensive BP. However, nificantly lower liver toxicity profile than did azathio- topical application of 40 g/d of clobetasol propionate over prine. large body surface areas for long time periods leads to sig-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1540 nificant skin atrophy, especially in elderly patients. Since mend the use of an adjuvant immunosuppressive agent the epidermal barrier in BP and in the skin of elderly pa- at the beginning of the treatment. Adjuvant azathio- tients is impaired, topical clobetasol propionate may pen- prine and mycophenolate mofetil are equally effective etrate the skin at significant concentrations and induce sys- to induce clinical remission in BP. However, mycophe- temic corticosteroid effects.25-28 In our experience, the nolate mofetil showed less liver toxicity. In contrast to disease in a number of patients with BP is difficult to con- azathioprine, mycophenolate mofetil is nonmutagenic trol with topical treatment (S.B., G.B., and T.A.L., unpub- and has significant antitumoral effect in solid organ lished data 2007). transplant recipients receiving long-term mycopheno- Some physicians prefer to use immunosuppressive drugs late mofetil therapy.31-34 The antitumor effect may be as second-line therapy when corticosteroids alone fail to relevant for patients with BP requiring longer-term im- control disease or when the use of corticosteroids is con- munosuppressive treatment. traindicated. Thus, the use of an immunosuppressant drug follows a period of corticosteroid monotherapy. Since some immunosuppressant agents need several weeks to induce Accepted for Publication: April 20, 2007. therapeutically relevant immunosuppression, we prefer to Author Affiliations: Departments of Dermatology, Uni- treat BP initially with an oral combination of corticoste- versity of Mu¨ nster, Mu¨ nster (Drs Beissert, Frieling, Bo¨hm, roids plus immunosuppressant drug. The most frequent Bonsmann, and Luger), Medical School Hannover, Han- adjuvant agent is azathioprine,15-17,19 which has been used nover, (Dr Werfel), University of Kiel, Kiel (Dr Sticher- successfully for nearly 4 decades, in a range between 1.5 ling), University of Erlangen, Erlangen (Dr Sticherling), and 3.0 mg/kg. Our findings concur with the reported ef- Municipal Hospital Minden, Minden (Dr Stadler), Uni- ficacy of combination azathioprine/corticosteroid treat- versity of Wu¨ rzburg, Wu¨ rzburg (Dr Zillikens), Univer- ment in patients with BP. sity of Lu¨ beck, Lu¨ beck (Dr Zillikens), Faculty of Clini- In the present study, 1 patient had a severe herpes zos- cal Medicine Mannheim, University of Heidelberg, ter infection, which required antiviral therapy; 2 pa- Mannheim (Dr Rzany), Division of Evidence-Based Medi- tients developed dizziness; and 1 had muscle pain. cine, Charite´- Universita¨tsmedizin, Berlin (Dr Rzany), Uni- Recently, mycophenolate mofetil was shown to be ef- versity of Cologne, Cologne (Dr Hunzelmann), Univer- fective and well tolerated.18,21 Our study supports the ef- sity of Dresden, Dresden (Dr Meurer), University of fectiveness in that all of our patients with BP treated with Magdeburg, Magdeburg (Dr Gollnick), University of Du¨s- mycophenolate mofetil–methylprednisolone combina- seldorf, Du¨ sseldorf (Dr Ruzicka), Ludwig-Maximilians tion experienced remission. The time needed to achieve University of Munich, Munich (Dr Ruzicka), University complete remission in 100% of the patients was about of Ulm, Ulm (Dr Pillekamp), and University of Go¨ttin- 90 days in the azathioprine group compared with about gen, Go¨ttingen (Dr Junghans), Germany. 280 days in the mycophenolate mofetil group (Figure 2). Correspondence: Stefan Beissert, MD, Department of Der- Perhaps interference with 3 enzymatic pathways by aza- matology, Von-Esmarch-Strasse 58, D-48149 Mu¨ nster, thioprine compared with the suppression of a single path- Germany ([email protected]). way by mycophenolate mofetil might reflect the earlier Author Contributions: Drs Beissert and Luger initiated and remission after onset of azathioprine treatment. designed the trial, had full access to all data for interpre- The adverse effect profile of mycophenolate mofetil tation, and had final responsibility for the decision to sub- was similar to that of azathioprine except for liver tox- mit for publication. Study concept and design: Beissert, Fri- icity. If elevation of liver function test results occurred, eling, Zillikens, Bonsmann, and Luger. Acquisition of data: immunosuppressant medication dose was reduced or dis- Beissert, Werfel, Bo¨hm, Sticherling, Stadler, Zillikens, continued. Since in our investigation azathioprine dose Rzany, Hunzelmann, Meurer, Gollnick, Ruzicka, Pille- was not adjusted to thiopurine methyltransferase (TPMT) kamp, Junghans, and Bonsmann. Analysis and interpreta- activity, we cannot completely rule out that patients ex- tion of data: Beissert, Rzany, Hunzelmann, Meurer, Goll- periencing adverse events had lower TPMT activity. How- nick, Bonsmann, and Luger. Drafting of the manuscript: ever, lower TPMT levels usually result in increased my- Beissert. Critical revision of the manuscript for important in- elotoxicity affecting blood cell counts rather than impaired tellectual content: Beissert, Werfel, Frieling, Sticherling, liver function findings.29,30 On the other hand, patients Stadler, Zillikens, Rzany, Hunzelmann, Meurer, Goll- with high TPMT activity might have been undertreated. nick, Ruzicka, Pillekamp, Junghans, Bonsmann, and Luger. One patient from the mycophenolate mofetil treatment Statistical analysis: Beissert and Luger. Obtained funding: group had muscle pain requiring no treatment; 3 pa- Beissert and Luger. Administrative, technical, and material tients had upper respiratory tract infections treated with support: Beissert, Werfel, Frieling, Stadler, Zillikens, Hun- antibiotics; and 1 developed a recurrent herpes simplex zelmann, Meurer, Bonsmann, and Luger. Study supervi- infection, which required oral prophylactic antiviral treat- sion: Beissert, Bo¨hm, Bonsmann, and Luger. ment. Because patients with BP are usually elderly, they Financial Disclosure: Drs Beissert and Luger have served usually present with significant comorbidity. as consultants for Hoffmann-La Roche AG; Dr Beissert In our investigation, we used methylprednisolone at has served as a paid speaker for Hoffmann-La Roche AG. a lower dose than was used in other reported trials.9 Funding/Support: This trial was supported by an unre- Methylprednisolone is therapeutically superior to pred- stricted grant from Hoffmann-La Roche AG, which also nisolone in reducing pruritic pemphigoid lesions, and provided the CellCept used in the study. there was no increased mortality observed in either Additional Contributions: Jochen Dress and Axel Hinke, treatment arm (data not shown). Therefore, we recom- PhD, helped with the statistical analysis of the data.

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Systemic effects of local treatment with high doses of potent 250. corticosteroids in psoriatics. Acta Derm Venereol. 1979;59(3):245-248. 8. Stanley JR, Tanaka T, Mueller S, Klaus-Kovtun V, Roop D. Isolation of comple- 27. Siklar Z, Bostanci I, Atli O, Dallar Y. An infantile Cushing syndrome due to mis- mentary DNA for bullous pemphigoid antigen by use of patients’ autoantibodies. use of topical steroid. Pediatr Dermatol. 2004;21(5):561-563. J Clin Invest. 1988;82(6):1864-1870. 28. Young CA, Williams IR, MacFarlane IA. Unrecognised Cushing’s syndrome and 9. Dreno B, Sassolas B, Lacour P, et al. Methylprednisolone versus prednisolone adrenal suppression due to topical clobetasol propionate. Br J Clin Pract. 1991; methylsulfobenzoate in pemphigoid: a comparative multicenter study. Ann Der- matol Venereol. 1993;120(8):518-521. 45(1):61-62. 10. Joly P, Roujeau JC, Benichou J, et al. A comparison of oral and topical cortico- 29. Snow JL, Gibson LE. The role of genetic variation in thiopurine methyltransfer- steroids in patients with bullous pemphigoid. N Engl J Med. 2002;346(5):321- ase activity and the efficacy and/or side effects of azathioprine therapy in der- 327. matologic patients. Arch Dermatol. 1995;131(2):193-197. 11. Morel P, Guillaume JC. Treatment of bullous pemphigoid with prednisolone only: 30. Snow JL, Gibson LE. A pharmacogenetic basis for the safe and effective use of 0.75 mg/kg/day versus 1.25 mg/kg/day. Ann Dermatol Venereol. 1984;111 azathioprine and other thiopurine drugs in dermatologic patients. J Am Acad (10):925-928. Dermatol. 1995;32(1):114-116. 12. Roujeau JC, Lok C, Bastuji-Garin S, Mhalla S, Enginger V, Bernard P. High risk 31. Carter SB, Franklin TJ, Jones DF, et al. Mycophenolic acid: an anti-cancer com- of death in elderly patients with extensive bullous pemphigoid. Arch Dermatol. pound with unusual properties. Nature. 1969;223(5208):848-850. 1998;134(4):465-469. 32. Robson R, Cecka JM, Opelz G, Budde M, Sacks S. Prospective registry-based 13. Rzany B, Partscht K, Jung M, et al. Risk factors for lethal outcome in patients observational cohort study of the long-term risk of malignancies in renal trans- with bullous pemphigoid: low serum albumin level, high dosage of glucocorti- plant patients treated with mycophenolate mofetil. Am J Transplant. 2005; costeroids, and old age. Arch Dermatol. 2002;138(7):903-908. 5(12):2954-2960. 14. Savin JA. The events leading to the death of patients with pemphigus and 33. Birkeland SA, Hamilton-Dutoit S. Is posttransplant lymphoproliferative disorder pemphigoid. Br J Dermatol. 1979;101(5):521-534. (PTLD) caused by any specific immunosuppressive drug or by the transplanta- 15. Burton JL, Harman RR, Peachey RD, Warin RP. Azathioprine plus prednisone in tion per se? Transplantation. 2003;76(6):984-988. treatment of pemphigoid. Br Med J. 1978;2(6146):1190-1191. 34. Cherikh WS, Kauffman HM, McBride MA, Maghirang J, Swinnen LJ, Hanto DW. 16. Greaves MW, Burton JL, Marks J, Dawber RP. Azathioprine in treatment of bul- Association of the type of induction immunosuppression with posttransplant lym- lous pemphigoid. Br Med J. 1971;1(5741):144-145. phoproliferative disorder, graft survival, and patient survival after primary kid- 17. Guillaume JC, Vaillant L, Bernard P, et al. Controlled trial of azathioprine and plasma ney transplantation. Transplantation. 2003;76(9):1289-1293.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1542 OBSERVATION Smoking and Skin Aging in Identical Twins

Daven N. Doshi, MD; Kaija K. Hanneman, DO; Kevin D. Cooper, MD

Background: A twin pair can provide a rare opportu- sun exposure. However, the twins differed markedly in nity to control for genetic susceptibility and exposure vari- regard to smoking history; the twin with an approxi- ables, which often serve as major confounders in popu- mately 52.5–pack-year smoking history showed more se- lation-based studies on the relationship between smoking vere skin aging than did the nonsmoking twin. and skin aging. Conclusion: The difference in skin aging illustrated Observations: We describe a unique twin pair who spent by this twin pair may serve as a motivator for smoking not only their first 2 decades of life together but also in cessation. their later decades had the same type of job at the same latitude, resulting in well-matched levels of significant Arch Dermatol. 2007;143(12):1543-1546

HE UNDERLYING MECHA- cades of life, they lived in multiple re- nism of skin aging regions of the country because their father mains to be elucidated, but was an active-duty military officer with ro- the magnitude of the prob- tating assignments. Both twins’ third lem is of increasing con- through fifth decades of life were spent in Tcern. More than $160 billion was spent in the same town in Tennessee; in the year 2005 on products and procedures aimed before the examination, twin 1 relocated at reversing the signs of skin aging. to a town 60 miles south of twin 2. Twin 1 reported a medical history significant for REPORT OF CASES tonsillectomy, hysterectomy, vertebral disk herniation, and recently diagnosed hyper- We describe a pair of identical female twins tension; twin 2 also reported a hysterec- (twin 1 and twin 2) with a marked dis- tomy, as well as a cholecystectomy and de- parity in the degree of facial aging. Twin generative joint disease. Neither twin had 1’s facial skin exhibited extensive deep a documented history of any skin dis- wrinkling, widespread lentigines, scat- ease, including skin cancer. Both twins re- tered hypopigmentation, and moderate counted having “frequent sunburns that skin laxity (Figure 1). Although twin 2’s were red and tender but not blistered” dur- facial skin exhibited signs of mild to mod- ing their childhood. Both twins reported erate photoaging (mild fine wrinkling, scat- “somewhat regular” sun exposure dur- tered lentigines, mild-density hypopig- ing adulthood (on a scale of 0 [never] to mentation, and mild skin laxity), her 4 [very regularly]) because they both had degree of facial aging was significantly less worked as drivers for a delivery service for than that of her sister (Figure 2). We approximately 10 years. In addition, they scored each twin’s skin aging according to never spent time in the sun trying to get a the 6-point photographic scale for pho- tan (on a scale of 0 [never] to 4 [very regu- todamage created by Larnier et al.1 Ac- larly]) and never used a tanning bed dur- cording to that scale, grade 1 indicates ing adulthood (on a scale of 0 [never] to mild; grade 2, mild to moderate; grade 3, 4 [very regularly]). When they were in the moderate; grade 4, moderate to severe; sun without sunscreen, twin 1 reported grade 5, severe; and grade 6, very severe that her skin burns moderately and tans 1 Author Affiliations: photodamage. Twin 1 was assigned a gradually and twin 2 reported that her skin Department of Dermatology, grade of 5, whereas twin 2 was given a always burns easily and tans a little (on a University Hospitals, Case grade of 2. scale of 0 [always burns easily, never tans] Western Reserve University, At the time of the examination, the to 5 [never burns]). Within the preced- Cleveland, Ohio. twins were 52 years old. In their early de- ing year, twin 2 had started using a daily

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1543 A B

Figure 1. Twin 1, right (A) and left (B) profiles.

A B

Figure 2. Twin 2, right (A) and left (B) profiles. moisturizer with a sun protection factor of 15, whereas was absent in twin 2 (Table). This variable likely served twin 1 used no skin care products. Neither reported use as the major contributor to advanced skin aging in twin 1. of a topical retinoid. Both twins reported minimal to no alcohol consumption, no routine exercise (on a scale of 1 [yes] to 2 [no]), and described themselves as very over- COMMENT weight (on a scale of 1 [very underweight] to 5 [very overweight]). Twin 1 was a cigarette smoker with an approxi- The first proposed correlation between smoking and pre- mately 52.5–pack-year history, whereas twin 2 was a mature skin aging was made by Solly2 in 1856, when he nonsmoker and had never smoked. reported a sallow complexion, wrinkled skin, and gaunt In this pair of twins with an identical genetic back- facial appearance in smokers. In 1971, Daniell3 empha- ground, minor medical histories, and similar significant sun sized a link between prominent periorbital wrinkling and exposure histories, the clear difference between twin 1 and smoking habits. In 1985, Model4 associated the term smok- 2 was the extensive history of tobacco use in twin 1 that er’s face with a list of telltale signs physicians can watch

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1544 Table. Demographic and Clinical Characteristics of Identical Female Twins

Characteristic Twin 1 Twin 2 Age, y 52 52 Geographic location Southeastern US Southeastern US Education BS, elementary education BS, elementary education Ethnicity White White Fitzpatrick skin type II II Medical history Tonsillectomy, hysterectomy, vertebral disk herniation, Cholecystectomy, hysterectomy, degenerative recently diagnosed hypertension joint disease BMI 30.1 33.0 Alcohol use, drinks/mo Ͻ50 Smoking history, pack-yearsa Approximately 52.5 0 Skin care regimen None Recent use of moisturizer with SPF 15 Use of retinoids None None Sun exposure history, hb Ͼ50 000 Ͼ50 000

Abbreviations: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); BS, bachelor of science; SPF, sun protection factor; US, United States. a Number of packs of cigarettes smoked per day multiplied by the total number of years smoked. b Cumulative lifetime sun exposure.

for to determine which of their patients had been smok- Each study subject was clinically examined and scored ing for at least 10 years. for facial wrinkling. Standardized photographs of the study Despite these clinical impressions, O’Hare et al5 as- subjects were also taken, and results of a blinded evalu- serted that cigarette smoking played a minor role in causation of the photographs were generally consistent with ing wrinkling, noting that previous studies2,3 linking the clinical examination findings. A self-administered smoking and increased wrinkling failed to consider con- questionnaire combined with an interview assessed age, founding variables such as sun exposure history and were sex, smoking history, sun exposure history, body mass unblinded and therefore subject to bias. O’Hare et al evalu- index, and alcohol consumption. With age, average sun ated 82 smokers and 118 nonsmokers who were 35 to exposure, and body mass index controlled for, the esti- 75 years of age and white. After controlling for confound- mated relative risk of moderate to severe wrinkling for ing variables, the overall wrinkle score was greater for current smokers compared with never smokers was 2.3 the smokers than for the nonsmokers, but the differ- (95% CI, 1.2-4.2) among men and 3.1 (95% CI, 1.6-5.9) ence was not statistically significant (PϽ.17). O’Hare et among women. However, age was still the strongest in- al found that a positive smoking history accounted for dependent predictor of facial wrinkling. Average daily sun only 6% of the explained variance in wrinkle scores be- exposure was positively associated with facial wrin- tween smokers and nonsmokers. Age was found to be kling in women but was not consistent in men, whereas the strongest independent predictor of facial wrinkling. body mass index was inversely associated with facial wrin- On the other hand, several studies6-9 support a rela- kling in both sexes. tionship between cigarette smoking and wrinkling. Ka- Chung et al8 investigated the independent effect of ciga- dunce et al6 were the first to evaluate a possible relation- rette smoking on wrinkling in an Asian population. Four ship between cigarette smoking and wrinkling while hundred seven volunteers participated in the study, of controlling for age, sex, sun exposure, and skin pigmen- which 194 participants had a smoking history of 0 to 0.9 tation. Their study used a convenience sample of 109 pack-year and 213 participants had a smoking history of smokers and 23 nonsmokers who were 35 to 59 years of 1 to 120 pack-years. After controlling for age, sex, and sun age and of white western European ancestry. A self- exposure, an association was established between ciga- administered questionnaire assessed age, sex, skin pig- rette smoking and wrinkling that showed a significant trend mentation, sun exposure history, and smoking history. Two with increasing pack-years. Compared with participants clinicians who were blinded to the information provided with a smoking history of 0 to 0.9 pack-year, participants in the questionnaire evaluated the degree of wrinkling by with a smoking history of more than 30 pack-years showed examining photographs of each subject. A smoking his- a 2.8 (95% CI, 1.2-6.4) increase and those with a smok- tory of more than 0.9 pack-year was associated with a 3-fold ing history of more than 50 pack-years showed a 5.5 (95% (95% confidence interval [CI], 0.4-158.0) increase in wrin- CI, 2.0-15.6) increase in the prevalence odds ratio for wrinkling (when controlled for age, sex, sun exposure, and skin kling. Sun exposure longer than 5 h/d and female sex were pigmentation). A sun exposure history of more than 50 000 also found to be strong independent factors in wrinkling. hours was associated with an 8-fold (95% CI, 0.3-500.0) While developing a photonumeric scale to assess pho- increase in wrinkling (when controlled for age, sex, smok- toprotected skin aging, Helfrich et al9 were able to link ing history, and skin pigmentation). the degree of aging in nonfacial, photoprotected skin to In 1995, Ernster et al7 conducted a cross-sectional study a history of smoking. Eighty-two patients participated in of 227 never smokers, 456 former smokers, and 228 cur- the study, of which 41 reported a history of cigarette smok- rent smokers who were 40 to 69 years of age and white. ing at some point in their lives (50%). Helfrich and col-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1545 leagues found a correlation between the degree of aging Accepted for Publication: April 18, 2007. in photoprotected skin and the number of years of smok- Correspondence: Daven N. Doshi, MD, Department of ing (r=0.39; PϽ.001), packs smoked per day (r=0.41; Dermatology, Case Western Reserve University, Bol- PϽ.001), and pack-years of smoking (r=0.41; PϽ.001). well Health Center, 11100 Euclid Ave, Ste 3100, Cleve- After controlling for the participant’s age and other vari- land, OH 44106 ([email protected]). ables in a multiple regression model, they found that only Author Contributions: Study concept and design: Cooper. the number of packs of cigarettes smoked per day was a Acquisition of data: Doshi and Hanneman. Analysis and major predictor of the degree of aging in photopro- interpretation of data: Doshi and Cooper. Drafting of the tected skin.9 manuscript: Doshi. Critical revision of the manuscript for Although these studies appear to implicate smoking important intellectual content: Hanneman and Cooper. Study as an independent risk factor for wrinkling, the patho- supervision: Cooper. physiologic process of wrinkling in smokers is not ex- Financial Disclosure: None reported. act; it is likely multifactorial10 and may be convergent with other mechanisms of skin aging. For example, cigarette REFERENCES smoke appears to induce matrix metalloproteinases in the skin11 and modulate type I transforming growth fac- 1. Larnier C, Ortonne JP, Venot A, et al. Evaluation of cutaneous photodamage using ␤ 12 tor (TGF) in cultured fibroblasts. Similarly, UV ir- a photographic scale. Br J Dermatol. 1994;130(2):167-173. radiation has been shown to induce matrix metallopro- 2. Solly S. Clinical lectures on paralysis. Lancet. 1856;2:641-643. teinases13,14 in the skin and inhibit type I and type III 3. Daniell HW. Smoker’s wrinkles: a study in the epidemiology of “crow’s feet.” Ann procollagen synthesis through alteration of the nuclear Intern Med. 1971;75(6):873-880. ␤ ␤ 4. Model D. Smoker’s face: an underrated clinical sign? Br Med J (Clin Res Ed). transcription factor AP-1, type I TGF- , and type II TGF- 1985;291(6511):1760-1762. 15 receptor ; these changes have been linked to the degra- 5. O’Hare PM, Fleischer AB Jr, D’Agostino RB Jr, et al. Tobacco smoking contributes dation of dermal collagen,15 a finding also central to little to facial wrinkling. J Eur Acad Dermatol Venereol. 1999;12(2):133-139. chronologic aging. Collagen abnormalities may also im- 6. Kadunce DP, Burr R, Gress R, Kanner R, Lyon JL, Zone JJ. Cigarette smoking: risk part elasticity to the skin, with studies reporting mor- factor for premature facial wrinkling. Ann Intern Med. 1991;114(10):840-844. 7. Ernster VL, Grady D, Miike R, Black D, Selby J, Kerlikowske K. Facial wrinkling in phologic changes of elastic fibers found in the reticular men and women, by smoking status. Am J Public Health. 1995;85(1):78-82. 16 17 dermis of smokers. Just et al established a correla- 8. Chung JH, Lee SH, Youn CS, et al. Cutaneous photodamage in Koreans: influ- tion between deteriorating lung function and abnormal ence of sex, sun exposure, smoking, and skin color. Arch Dermatol. 2001; elastic fibers in the reticular dermis. In a histologic study 137(8):1043-1051. 18 9. Helfrich YR, Yu L, Ofori A, et al. Effect of smoking on aging of photoprotected by Boyd et al comparing the facial skin of 17 smokers skin: evidence gathered using a new photonumeric scale [published correction with that of 14 nonsmokers, a significantly higher amount appears in Arch Dermatol. 2007;143(5):633]. Arch Dermatol. 2007;143(3): of elastosis was noted in the smokers. However, be- 397-402. cause these studies did not control for sun exposure and 10. Freiman A, Bird G, Metelitsa AI, Barankin B, Lauzon GJ. Cutaneous effects of age, the results must be interpreted with caution. smoking. J Cutan Med Surg. 2004;8(6):415-423. 11. Lahmann C, Bergemann J, Harrison G, Young AR. Matrix metalloproteinase-1 Smoking’s effect on cutaneous microvasculature serves and skin aging in smokers. Lancet. 2001;357(9260):935-936. as yet another contributing factor. The nicotine found in 12. Yin L, Morita A, Tsuji T. Tobacco smoke extract induces age-related changes due cigarettes increases the level of vasopressin in the blood,19,20 to modulation of TGF-␤. Exp Dermatol. 2003;12(suppl 2):51-56. which in turn causes peripheral vasoconstriction and a pro- 13. Fisher GJ, Datta SC, Talwar HS, et al. Molecular basis of sun-induced premature 19-21 skin aging and retinoid antagonism. Nature. 1996;379(6563):335-339. posed local dermal ischemia. Postischemic reperfu- 14. Fisher GJ, Wang ZQ, Datta SC, Varani J, Kang S, Voorhees JJ. Pathophysiology sion is a well-known source of reactive oxygen species of premature skin aging induced by ultraviolet light. N Engl J Med. 1997;337 (ROS); in addition, cigarette smoke compounds generate (20):1419-1428. ROS.22,23 Reactive oxygen species are thought to be a ma- 15. Fisher GJ, Kang S, Varani J, et al. Mechanisms of photoaging and chronological jor component of UV injury and photoaging.14 Reactive skin aging. Arch Dermatol. 2002;138(11):1462-1470. 16. Smith JB, Fenske NA. Cutaneous manifestations and consequences of smoking. oxygen species are generated through photochemical in- J Am Acad Dermatol. 1996;34(5, pt 1):717-732. teractions with biomolecules during irradiation itself and 17. Just M, Monso´ E, Ribera M, Lorenzo JC, Morera J, Ferrandiz C. Relationships also in the post-UV period, when both keratinocytes and between lung function, smoking and morphology of dermal elastic fibres. Exp infiltrating leukocytes are thought to contribute ROS.15 Dermatol. 2005;14(10):744-751. 18. Boyd AS, Stasko T, King LE Jr, Cameron GS, Pearse AD, Gaskell SA. Cigarette Many theories of chronologic aging implicate ROS, pro- smoking–associated elastotic changes in the skin. J Am Acad Dermatol. 1999; viding another area of convergent mechanisms between 41(1):23-26. smoking, time, and photodamage. 19. Reus WF, Robson MC, Zachary L, Heggers JP. Acute effects of tobacco smok- Our observation of the striking effect of smoking on ing on blood flow in the cutaneous micro-circulation. Br J Plast Surg. 1984; skin aging in this twin pair is compelling because it pro- 37(2):213-215. 20. Richardson D. Effects of tobacco smoke inhalation on capillary blood flow in hu- vides the closest possible control of several key con- man skin. Arch Environ Health. 1987;42(1):19-25. founding variables in skin aging. Such obvious visual dem- 21. Tur E, Yosipovitch G, Oren-Vulfs S. Chronic and acute effects of cigarette smok- onstrations of the relationship between cigarette smoking ing on skin blood flow. Angiology. 1992;43(4):328-335. and premature skin aging are valuable in public educa- 22. Zang LY, Stone K, Pryor WA. Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free Radic Biol Med. 1995;19(2):161- tion. Wrinkles, rather than the deadly consequences of 167. smoking, may prove to be the most powerful motivator 23. Pryor WA. Cigarette smoke radicals and the role of free radicals in chemical for smokers to stop smoking. carcinogenicity. Environ Health Perspect. 1997;105(suppl 4):875-882.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1546 OBSERVATION Ex Vivo Dermoscopy of Melanocytic Tumors Time for Dermatopathologists to Learn Dermoscopy

Alon Scope, MD; Klaus J. Busam, MD; Josep Malvehy, MD; Susana Puig, MD, PhD; Steve A. McClain, MD; Ralph P. Braun, MD; Ashfaq A. Marghoob, MD

Background: We have identified cases of skin cancer readily correlated between the in vivo and ex vivo im- with discordances between clinical, dermoscopic, and his- ages for 2 melanomas and 4 dysplastic nevi. Blood ves- topathologic findings that were likely due to sampling sels were not observed in the ex vivo dermoscopic im- errors in the pathology laboratory. This has prompted ages, which limited their correlation with the in vivo us to explore the use of ex vivo dermoscopy as an ancil- dermoscopic images for basal cell carcinoma. lary method of gross pathology, which may serve to guide tissue sectioning. Noncontact polarized dermoscopy was Conclusions: Dermoscopy can be applied to fixed tis- applied to pigmented lesions before excision and at least sues, with findings comparable to those of in vivo ex- 6 hours after specimen fixation in formalin. amination. This observation may serve as the first step toward using dermoscopy to guide tissue sectioning in Observations: The orientation of the lesion, overall der- gross pathology. moscopic pattern, and dermoscopic pigmented structures (network, globules, and peripheral streaks) were Arch Dermatol. 2007;143(12):1548-1552

HE SYNERGISM BETWEEN Currently, few clinical dermatologists clinical dermatology and (or clinicians) evaluate the histologic slides dermatopathology in classi- created by the pathology laboratory from fying primary morphologic their patients’ biopsy specimens, and der- features of skin disease was matopathologists (or pathologists) rarely Trealized by Paul Gerson Unna in the text- if ever see the clinical lesions. Moreover, book section entitled “Histopathology of the gross specimen evaluation and sec- Skin Disease,” published in 1894.1 Unna un- tioning is often performed by pathology derstood that “the dermatologist is fortu- laboratory technicians; thus, patholo- nate in being able to study the clinical pic- gists evaluate only the final processed ture with his histologically trained eye and slides, which represent less than 2% of the the microscopic picture with his dermato- entire lesion.3 Clinicopathologic disen- logically trained eye” (translated by Al- gagement can lead to diagnostic discor- fred W. Hollander, who studied under dance and, in cases of skin cancer, this may Author Affiliations: Unna).2(pp729-730) In this view, meticulous have serious medicolegal implications.4 To Dermatology Service, clinicopathologic correlation leads to more safeguard against such discordance, many Department of Medicine precise diagnosis, and for many years clini- clinicians and pathologists communicate (Drs Scope and Marghoob), and cal dermatologists were performing the der- with each other before rendering a final Department of Pathology matopathologic analysis of biopsy speci- diagnosis,5 and many academic institu- (Dr Busam), Memorial Sloan-Kettering Cancer Center, mens taken from their patients. However, tions have regular clinicopathologic cor- New York, New York; and during the 20th century, subspecializa- relation conferences. Departments of Dermatology, tion emerged, in part because of the grow- We have identified cases of skin cancer Hospital Clinic, Institut ing complexity of medicine, and clinical with discordances between clinical, dermo- d’Investigacions Biomèdiques dermatology and dermatopathology be- scopic, and histopathologic findings that August Pi i Sunyer (IDIBAPS), gan to separate into independent but in- were likely due to sampling errors in the pa- and U726, CIBERER, ISCIII, terdependent branches of medicine. thology laboratory. If the lesional area of Barcelona, Spain (Drs Malvehy Whereas dermatology was established as the clinical concern is carefully sampled and and Puig), Stony Brook fourth US board-certified specialty in 1932, properly oriented, the pathologists will more University Medical Center, Stony Brook, New York it was only in 1974 that certification in der- likely see the most relevant findings and ren- (Dr McClain), and University matopathology was possible (American der a correct diagnosis. Adding clinical and Hospital Zurich, Zurich, Board of Dermatology, oral communica- dermoscopic images to the pathology de- Switzerland (Dr Braun). tion, November 2006). partment requisition form and highlight-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1548 ing areas of concern in the specimen with ink marks, ori- A B entation sutures, or punch incisions have been suggested as methods for reducing sampling errors.6-8 Given the added value of dermoscopy for the clinician,9 we reasoned that dermoscopy can benefit the pathologist examining excised specimens in identifying areas that were of concern to the clinician and in the decision regarding how to section the lesion and where to focus the histopathologic analysis. This idea has prompted us to explore the use of ex vivo dermoscopy as an ancillary method of gross pathology that may serve to guide tissue sectioning. As a first step in this direction, we demonstrate that dermoscopy can be applied to fixed tis- C D sues, with findings comparable to those of in vivo examination.

METHODS

As part of routine patient care at Memorial Sloan-Kettering Can- cer Center, all biopsied lesions are photographed clinically and dermoscopically before surgery. We obtained polarized dermoscopic images of a series of pigmented lesions before biopsy (in vivo dermoscopy) and after at least 6 hours of fixation in formalin (ex vivo dermoscopy). The clinical images were E F obtained using a digital camera (Nikon CoolPix 4500; Nikon Inc, Melville, New York). All in vivo dermoscopic images were captured using the same camera attached to a polarized noncontact dermoscopy lens (DermLite FOTO; 3GEN, LLC, Dana Point, California). Lesions were excised according to routine protocol and fixed in formalin. After the specimen was in formalin for at least 6 hours, it was removed and placed on gauze; ex vivo dermoscopic images of the lesion were obtained with the same polarized noncontact dermoscopy lens. The in vivo and ex vivo polarized dermoscopic imaging was performed using a noncontact technique, ie, there was no physical contact between the camera and the tissue.10 In addition, one of us (A.A.M.) Figure 1. Ulcerated melanoma (A) that shows on in vivo dermoscopy (B) a evaluated the lesions in vivo and ex vivo using a commercially dark blotch with a blue-white veil and an irregular scalloped border. The area available, handheld, polarized noncontact dermoscope (Der- depicted by the left yellow rectangle in B is shown at higher magnification in mLite Pro-HR; 3GEN, LLC). vivo (C) and ex vivo after 6 hours in formalin (D). The same irregular peripheral streaks can be seen readily in both images (arrows). Similarly, the area depicted by the right yellow rectangle in B, shown at higher RESULTS magnification in vivo (E) and ex vivo after 6 hours in formalin (F), demonstrates the same peripheral network in both images (arrows). The lesions consisted of 2 melanomas, 4 dysplastic nevi, and 1 basal cell carcinoma. All lesions were located on the torso; 6 of the lesions were less than 1.5 cm in diameter COMMENT and 1 melanoma was 3 cm in diameter (Figure 1). The orientation of the lesion, overall dermoscopic pattern, and Dermoscopy has been shown to increase the sensitivity dermoscopic pigmented structures (network, globules, and and specificity of clinical diagnosis of melanoma,9 which peripheral streaks) were readily correlated between the in has led to the detection of earlier, more subtle melano- vivo and ex vivo images for the melanomas and nevi mas.11 Most structures seen on dermoscopy have been (Figures 1, 2, and 3). Blood vessels and vascular blush correlated with distinct microscopic alterations in tis- were not observed in the ex vivo dermoscopic images, which sue morphologic features.6,8,12 Thus, dermoscopy can be limited the correlation with the in vivo images for the non- viewed not only as a diagnostic aid at the bedside but also pigmented basal cell carcinoma. as a useful tool in evaluating gross pathology and in pre- A technical limitation noted during ex vivo imaging dicting histopathologic findings.13 Herein, we present pre- with the polarized noncontact dermoscopy lens was that liminary findings suggesting that dermoscopic evalua- specimens tended to develop subtle undulations, mak- tion can also be performed ex vivo in the pathology ing it difficult to obtain images in which the entire le- laboratory. Pigmented structures in melanocytic lesions sion was in sharp focus. However, this problem was over- visualized with in vivo dermoscopy were also observed come during handheld noncontact dermoscopic by means of polarized dermoscopy of the excised speci- evaluation by making simple, slight adjustments to the men after at least 6 hours of fixation in formalin. focal distance from the specimen (ie, moving slightly Thus, we propose the following scheme for improving closer to or further from the specimen). communication between clinicians and pathologists con-

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C D

Figure 2. Comparison of in vivo (A and C) and ex vivo (B and D) dermoscopy in 2 dysplastic nevi. A and B, The peripheral globules (arrows) and areas with clustered globules (asterisks) can be identified in both images. The in vivo dermoscopic image shows telangiectatic vessels and a pinkish veil (A) that cannot be seen in the ex vivo image (B), whereas the latter shows ecchymotic areas. C and D, Corresponding irregular network areas (arrows) can be seen in both images. Both ex vivo dermoscopic images (B and D) show suboptimal focus, which may relate to specimen surface undulation after fixation. cerning pigmented lesions: (1) The clinician will attach clini- to be rewarding for pathologists as a way of adding mean- cal and dermoscopic images (or, less preferably, a hand- ingful gross analysis to their practices. drawn figure if photographic equipment is not available) Melanoma can be overlooked because of improper tis- to the pathology department requisition form, indicating sue sectioning, particularly in cases of early melanoma as- on the images areas and structures of concern. Surface mark- sociated with a preexisting nevus14-16 and, in our experi- ings on the specimen, as previously described,7 will facili- ence, in wide-excision specimens when remaining tate the correct orientation of the specimen in the pathol- melanoma may be subtle on gross inspection. An advan- ogy laboratory. (2) The pathologist will then extract the tage of dermoscopy is the en face plane of view, ensuring specimen from the bottle and observe the gross pathology gross examination of the entire surface of the lesion. Fur- with the use of a handheld, polarized noncontact dermo- thermore, if dermoscopic evaluation becomes part of the scope (Figure 3C), comparing personal observations with gross examination protocol, it is more likely that the pro- the clinician’s notes on the in vivo images. As we have pre- sector will be trained in and become familiar with subtle liminarily demonstrated, the pathologist should be able to dermoscopic and clinical features requiring more atten- identify the dermoscopic structures ex vivo. (3) The pa- tion than occurs in the current setting of most pathology thologist will then guide the tissue sectioning so as to in- laboratories. Adding a dermoscopic image of equivocal me- clude the areas of concern. lanocytic lesions has been shown to improve histopatho- One could envision that dermoscopic terms and per- logic interobserver agreement (␬ values increased from 0.81 haps even the dermoscopic image may find their way into to 0.88),17 probably reflecting a more accurate diagnosis. the gross description of the pathologic analysis report read This has been supported by other studies in which dermo- by the clinician. Thus, the clinician and pathologist who scopic findings were added when assigning the histopatho- use dermoscopy as a common lesion map are likely to logic diagnosis.18,19 In some lesions, the correct diagnosis have a better correlation. To realize our suggested method, was made after a more extensive search for subtle clues in the pathologist need not be an expert in dermoscopy. the specimen, driven by the appreciation of suggestive der- However, proficiency in dermoscopy may eventually prove moscopic findings by the pathologist.17

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C D

E F

Figure 3. Images of a 4-mm pigmented lesion that had recently become larger and was on the knee of a 53-year-old woman. A, Clinical photograph of the lesion. B, In vivo dermoscopy shows a lightly pigmented lesion with a central blue-white area that is particularly worrisome (asterisk), dotted vessels (circle), and an atypical broken network (arrow). The lesion was excised and sent for analysis with a dermoscopic image on which the blue-white area was highlighted. C, The pathologist uses dermoscopy to perform gross examination of the lesion. D, The blue-white area (asterisk) and atypical network (arrow) are readily identified in this ex vivo dermoscopic image; however, the dotted vessels are now not apparent. The pathology report specified which sections contain the blue area (the direction of sectioning is shown by the diagonal lines). E, The histopathologic specimen of a portion of a melanocytic nevus corresponding to the blue area illustrates nests and fascicles of pigmented spindle and epithelioid melanocytes at the dermoepidermal junction and superficial dermis. The blue-white area noted on dermoscopy likely correlates with melanophages (arrows) and coarse fibrosis (asterisks) in the superficial dermis, along with the overlying acanthotic epidermis with hyperkeratosis and hypergranulosis (hematoxylin-eosin, original magnification ϫ200). F, In contrast, histopathologic findings from the brown reticulated periphery of the lesion show junctional melanocytic nests and pigmented basal keratinocytes, without melanophages or fibrosis in the dermis and without the epidermal changes seen in the blue-white area (hematoxylin-eosin, original magnification ϫ100). The final diagnosis was a moderately dysplastic nevus with Spitzoid features.

One limitation is the inability to obtain sharp focus for a glass contact plate. Pressing the scope against the speci- the entire surface of the ex vivo dermoscopic image. This men will flatten it and provide sharp focus for the entire limitation can be remedied by using a dermoscopy lens with image. However, we avoided contact dermoscopy for the

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1551 ex vivo specimens because we foresaw this to be a barrier Author Contributions: All authors have contributed to to practice in the pathology laboratory. We anticipate that the study in a manner that meets authorship criteria, have handheld polarized noncontact dermoscopy, rather than seen the final draft of the manuscript, and approve the contact dermoscopy, will be used by pathologists. An- validity of the data presented. Study concept and design: other limitation is the loss of vascular structures and vas- Scope, Malvehy, Puig, Braun, and Marghoob. Acquisi- cular blush (pink veil) that occurs in fixed tissue. This limi- tion of data: Scope, Busam, and Marghoob. Analysis and tation affected the correlation of in vivo and ex vivo images interpretation of data: Scope, Malvehy, Puig, McClain, and of nonpigmented basal cell carcinoma, in which arboriz- Marghoob. Drafting of the manuscript: Scope, Busam, ing vessels are pertinent to diagnosis. This may limit the Malvehy, Puig, and Marghoob. Critical revision of the usefulness of ex vivo dermoscopy to pigmented lesions and manuscript for important intellectual content: Malvehy, Puig, obviate its use for amelanotic melanoma, nonmelanoma skin McClain, and Braun. Study supervision: Marghoob. cancer, and inflammatory dermatoses. Financial Disclosure: None reported. In times when the economics of tissue processing can- Funding/Support: The polarized noncontact dermos- not be ignored, a concern is that dermoscopy at the pa- copy lens was provided by 3GEN, LLC. thology laboratory would slow the gross examination pro- Additional Contributions: Alexandros D. Polydorides, cess, require additional time from the pathologists, and MD, PhD, fellow at the Department of Pathology, Me- thereby be impractical and too costly. We are cognizant of morial Sloan-Kettering Cancer Center, tested the appli- these issues and do not suggest applying dermoscopy for cability of dermoscopy in gross pathology. pathologic examination of excisions of clinically benign nevi removed for cosmetic reasons. However, we believe that REFERENCES the disadvantages of extra time and cost are outweighed by the benefit of a more accurate diagnosis for excisions 1. Unna P. Die Histopathologie der Hautkrankheiten. In: Orth J, ed. Lehrbuch der of lesions clinically suggestive of melanoma. The statisti- speziellen pathologischen Anatomie. Vol 8. Berlin, Germany: A Hirschwald; 1894. cal probability of making the correct diagnosis in mela- 2. Hollander AW. Development of dermatopathology and Paul Gerson Unna. JAm Acad Dermatol. 1986;15(4, pt 1):727-734. noma currently relies on random sampling of less than 2% 3. Dyson SW, Bass J, Pomeranz J, Jaworsky C, Sigel J, Somach S. Impact of thor- 3 of the lesion. A more exhaustive sectioning of the block ough block sampling in the histologic evaluation of melanomas. Arch Dermatol. has been shown to increase the assessment of melanoma 2005;141(6):734-736. thickness in 40% of lesions, resulting in a change in clini- 4. Troxel DB. Pitfalls in the diagnosis of malignant melanoma: findings of a risk 3 management panel study. Am J Surg Pathol. 2003;27(9):1278-1283. cal management in 10% of patients. Such exhaustive sec- 5. Charles CA, Yee VS, Dusza SW, et al. Variation in the diagnosis, treatment, and tioning is also cumbersome and expensive. Thus, guided management of melanoma in situ: a survey of US dermatologists. Arch Dermatol. sectioning can be viewed as a way to improve the statisti- 2005;141(6):723-729. cal probability of reaching the correct diagnosis. Proper se- 6. Yadav S, Vossaert KA, Kopf AW, Silverman M, Grin-Jorgensen C. Histopatho- logic correlates of structures seen on dermoscopy (epiluminescence microscopy). lection of the tissue section may be particularly important Am J Dermatopathol. 1993;15(4):297-305. for large complex excisions, such as medium to large con- 7. Braun RP, Kaya G, Masouye´ I, Krischer J, Saurat JH. Histopathologic correlation genital nevi with focal features that are suggestive of mela- in dermoscopy: a micropunch technique. Arch Dermatol. 2003;139(3):349-351. noma or wide-excision specimens with a focal remnant of 8. Soyer HP, Kenet RO, Wolf IH, Kenet BJ, Cerroni L. Clinicopathological correlation of pigmented skin lesions using dermoscopy. Eur J Dermatol. 2000;10 pigmentation. Whether ex vivo dermoscopy will be ap- (1):22-28. plied only to a subset of excised melanocytic lesions with 9. Kittler H, Pehamberger H, Wolff K, Binder M. Diagnostic accuracy of dermoscopy. a higher clinical index of suspicion for malignancy or greater Lancet Oncol. 2002;3(3):159-165. morphologic heterogeneity remains to be seen. A formal 10. Benvenuto-Andrade C, Dusza SW, Agero ALC, et al. Differences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of study is needed to assess the possible influence of ex vivo skin lesions. Arch Dermatol. 2007;143(3):329-338. dermoscopy on pathologic diagnosis, clinicopathologic cor- 11. Kittler H, Guitera P, Riedl E, et al. Identification of clinically featureless incipient relation, and proper selection of lesions for this technique melanoma using sequential dermoscopy imaging. Arch Dermatol. 2006;142 (eg, based on size, anatomic site, and the distribution of (9):1113-1119. 12. Soyer HP, Smolle J, Ho¨dl S, Pachernegg H, Kerl H. Surface microscopy: a new dermoscopic structures). approach to the diagnosis of cutaneous pigmented tumors. Am J Dermatopathol. In summary, dermoscopy can be applied to fixed tis- 1989;11(1):1-10. sues, with findings comparable to those of in vivo ex- 13. Kaya G, Braun RP. Histopathological correlation in dermoscopy. In: Marghoob amination. This observation may serve as the first step AA, Braun RP, Kopf AW, eds. Atlas of Dermoscopy. New York, NY: Taylor & Fran- cis; 2005:23-41. toward using dermoscopy to guide tissue sectioning in 14. Bauer J, Metzler G, Rassner G, Garbe C, Blum A. Dermatoscopy turns histopa- gross pathology. Precise correlations between in vivo and thologist’s attention to the suspicious area in melanocytic lesions. Arch Dermatol. ex vivo images can reduce errors, help determine the ap- 2001;137(10):1338-1340. propriate areas to step section, and ultimately improve 15. Soyer HP, Massone C, Ferrara G, Argenziano G. Limitations of histopathologic analysis in the recognition of melanoma: a plea for a combined diagnostic ap- patient care. Such a system would translate to better com- proach of histopathologic and dermoscopic evaluation. Arch Dermatol. 2005; munication between the pathologist and the clinician— 141(2):209-211. the next best thing to the time when dermatologists were 16. Ferrara G, Argenziano G, Cerroni L, et al. A pilot study of a combined dermoscopic- pathological approach to the telediagnosis of melanocytic skin neoplasms. both clinicians and pathologists. J Telemed Telecare. 2004;10(1):34-38. 17. Bauer J, Leinweber B, Metzler G, et al. Correlation with digital dermoscopic im- Accepted for Publication: May 15, 2007. ages can help dermatopathologists to diagnose equivocal skin tumours. Br J Correspondence: Ashfaq A. Marghoob, MD, Dermatol- Dermatol. 2006;155(3):546-551. 18. Massi D, De Giorgi V, Soyer HP. Histopathologic correlates of dermoscopic criteria. ogy Service, Department of Medicine, Memorial Sloan- Dermatol Clin. 2001;19(2):259-268, vii. Kettering Cancer Center, 160 E 53rd St, New York, NY 19. Crotty KA, Menzies SW. Dermoscopy and its role in diagnosing melanocytic le- 10022 ([email protected]). sions: a guide for pathologists. Pathology. 2004;36(5):470-477.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1552 OBSERVATION Long-term Follow-up of a Patient With Eruptive Melanocytic Nevi After Stevens-Johnson Syndrome

Allison Gelfer, MD; Jason K. Rivers, MD, FRCPC

Background: Eruptive melanocytic nevi (MN) are a rare with bullous disorders and those with systemic immu- phenomenon characterized by the simultaneous, abrupt nosuppression. onset of hundreds of MN, often in a grouped distribution. There are few studies on this topic in the litera- Conclusions: We postulate that the etiology and natural ture. We followed up a patient who developed eruptive course of eruptive MN may differ between the 2 main popu- MN 38 years ago after Stevens-Johnson syndrome. Herein lations of patients at risk for eruptive MN, with MN arising we document this patient’s progress and review the lit- after bullous disorders being more likely to remain benign erature on this unusual phenomenon. compared with those in patients with ongoing immunosuppression. However, this hypothesis has yet to be proved, and Observations: For 38 years, the patient’s lesions have it will require long-term surveillance of individuals who have remained stable, without signs of malignant degenera- developed eruptive MN to determine its merit. tion. We discuss the possible etiology and natural history of this condition in 2 major patient populations: those Arch Dermatol. 2007;143(12):1555-1557

OMMON ACQUIRED MELA- nosuppression from human immunode- nocytic nevi (MN) ap- ficiency virus infection,11,12 neoplastic pear during the first 3 de- disease,13,14 organ transplantation,15,16 cades of life, reaching a Crohn disease,17-19 or chemotherapy.20 peak of approximately 30 Eruptive MN have been described less to 40 nevi per individual.1 They have a ten- frequently in association with Addison C 21 dency to develop individually and to be disease and psoralen–UV-A photo- distributed on sun-exposed sites of the therapy.22 More recently,19 eruptive MN skin. However, crops of MN may appear have been described in patients undergo- abruptly during adolescence and preg- ing immunosuppressive therapy with aza- nancy. It has been suggested that com- thioprine, biological agents (infliximab, mon acquired MN tend to gradually dis- etanercept, and alefacept), or combina- appear or decrease in number with tions of these drugs. Occasionally, erup- increasing age,1 but this may be a cohort tive MN may arise without any apparent effect. precipitating factors.6,17,23,24 In contrast to this is the rare phenom- We had the unique opportunity to fol- enon of eruptive MN. Eruptive MN are char- low up a patient who developed eruptive acterized by the simultaneous, abrupt on- MN 38 years ago. This patient was first de- set of hundreds of nevi, often in a grouped scribed by Kopf et al5 in 1977. Herein, we distribution. This condition was first de- document the patient’s progress and re- scribed in 1868,2 and since that time there view the literature on this unusual phe- have been only a few subsequent reports. nomenon. Eruptive MN are most likely to arise in association with bullous dermatoses or sys- REPORT OF A CASE temic immunosuppression. With the Author Affiliations: former, eruptive MN have been reported Department of Dermatology in patients with erythema multiforme,3 In 1969, an 8-year-old boy developed ru- and Skin Science, University of Stevens-Johnson syndrome,4-6 toxic epi- beola complicated by a widespread bul- British Columbia (Drs Gelfer 3-5,7 and Rivers), and Pacific dermal necrolysis, epidermolysis bullous eruption diagnosed as Stevens- 8,9 DermAesthetics (Dr Rivers), losa, and bullae induced by mustard Johnson syndrome. He was extremely ill, Vancouver, British Columbia, gas.10 There have also been reports of erup- and his disease resulted in temporary uni- Canada. tive nevi arising in patients with immu- versal alopecia and exfoliation of the nail

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1555 Figure 2. Current photograph demonstrating eruptive nevi on the right side of the back, middle thoracic region.

dispose the patient to an increased risk of melanoma. Al- though we cannot answer this question conclusively, we can comment on this patient who developed eruptive MN after Stevens-Johnson syndrome more than 38 years ago. Figure 1. Photograph of the original eruption on the back taken in 1974. During this time, his lesions have remained stable, with no evidence of malignant degeneration. Eruptive MN occur in 2 major patient populations: plates. Six to 8 weeks after the bullous lesions resolved, those with bullous cutaneous disorders and those who he abruptly developed hundreds of MN on his back, con- develop this event in association with systemic immu- fined to areas that had previously blistered. The lesions nosuppression. The pathogenesis of eruptive MN in the appeared over several months, after which they did not setting of bullous disorders remains unknown. Several change appreciably in appearance. The patient was ex- researchers6,10,13 have postulated that during epidermal amined 5 years later by Dr Kopf. At that time, 2 biopsies regeneration, specific cytokines and growth factors are were performed, and photographs were taken (Figure 1). elaborated and secreted, leading to epithelial regenera- The biopsy findings were compatible with benign com- 5 tion and melanocyte proliferation. This hypothesis is con- pound MN. sistent with the work of Lanschuetzer et al,9 who dem- Before being cared for by us, this patient had numer- onstrated several growth factors along with individual ous biopsy specimens obtained from the areas of the erup- melanocytes in blister fluid overlying an “epidermolysis tive MN. Most often these specimens showed benign com- bullosa nevus,” an eruptive MN that occurred at the site pound MN, but occasionally these were described as MN of a previous bulla. Because most of the bullous disor- with mild architectural or cytologic atypia consistent with ders associated with eruptive MN are transient, the atypical nevi. In 1990, one of us (J.K.R.) assumed the changes in local growth factors may also be transient. care of this patient, and as of October 2006, the patient Therefore, we believe that without further stimuli, these has remained healthy, with no other intervening health MN would remain stable without a propensity to malig- issues. There was no personal or family history of mul- nant degeneration. To our knowledge, no reports of ma- tiple MN, atypical MN, or melanoma. lignant degeneration of eruptive nevi in a patient with a On recent examination, the patient was fair skinned bullous disorder have been described. with limited sun damage. He had typical MN distrib- In contrast, in patients with eruptive MN associated uted symmetrically across the cutaneous surface. How- with immunosuppression, the pathogenesis and natural ever, on the middle thoracic region of his back were hun- history may be quite different. Acquired MN are af- dreds of 2- to 5-mm light to dark brown, round or oval fected by a variety of factors, including genetics, pheno- MN. In addition, there were 2 zosteriform collections of typic traits, and sun exposure.25 In addition, there is ac- MN on the right side of the middle thoracic region of his cumulating evidence of the role of the immune system back and on the right flank (Figure 2). There was a single in melanogenesis.19,25 In 1989, Ross26 first suggested that clinically atypical MN on the abdomen compared with immune surveillance is integral in preventing mela- photographs taken in 1974 and again in 1990. The erup- noma growth in and around MN. This theory has been tive MN have not changed appreciably during the past supported by some of the literature on eruptive MN. Sev- 38 years. At no time have there been any clinical or his- eral researchers believe that an intact immune system nor- tologic findings suggestive of melanoma. mally limits the proliferation of melanocytes, whereas a disordered one is unable to do so, leading to eruptive COMMENT MN.5,12,13,15,18,19,27 To support this concept, Piaserico et al15 recently described fading and disappearance of eruptive The development of eruptive MN is a rare event, and the MN on withdrawal of immunosuppressive therapy in a reporting of long-term follow-up of such a patient is unique. renal transplant recipient who was experiencing graft re- A key question about eruptive MN is whether they pre- jection. As other researchers25 have suggested, it seems

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1556 that immunodeficiency itself, not the type of immuno- 4. Kirby JD, Darley C. Eruptive melanocytic naevi following severe bullous disease. suppression, plays a pivotal role in the development of Br J Dermatol. 1978;99(5):575-580. 5. Kopf AW, Grupper C, Baer R, Mitchell J. Eruptive nevocytic nevi after severe bul- eruptive MN. lous disease. Arch Dermatol. 1977;113(8):1080-1084. It is possible that a dysfunctional immune system, un- 6. Shoji T, Cockerell C, Koff A, Bhawan J. Eruptive melanocytic nevi after Stevens- able to limit the proliferation of melanocytes, allows for Johnson syndrome. J Am Acad Dermatol. 1997;37(2 pt 2):337-339. the appearance of atypical cells, leading first to atypical/ 7. Goerz G. Eruptive nevocytic nevi after Lyell’s syndrome. Arch Dermatol. 1978;114 dysplastic MN and later to melanoma. It could be hy- (9):1400-1401. 8. Bauer JW, Schaeppi H, Kaserer C, Hantich B, Hintner H. Large melanocytic nevi pothesized that in immunosuppressed patients, erup- in hereditary epidermolysis bullosa. J Am Acad Dermatol. 2001;44(4):577- tive nevi may be at greater risk for undergoing malignant 584. degeneration. To our knowledge, no reports of malig- 9. Lanschuetzer CM, Emberger M, Hametner R, et al. Pathogenic mechanisms in nant degeneration of eruptive nevi in a patient with sys- epidermolysis bullosa naevi. Acta Derm Venereol. 2003;83(5):332-337. temic immunosuppression have been described. How- 10. Firooz A, Komeili A, Dowlati Y. Eruptive melanocytic nevi and cherry angiomas secondary to exposure to sulfur mustard gas. J Am Acad Dermatol. 1999;40 ever, patients who are immunosuppressed have a (4):646-647. 14,28,29 significantly increased risk of melanoma. Why only 11. Betlloch I, Amador C, Chiner E, Pasquau F, Calpe J, Vilar A. Eruptive melanocytic a small percentage of patients in these populations ex- nevi in human immunodeficiency virus infection. Int J Dermatol. 1991;30(4): perience eruptive MN remains to be determined. 303. In summary, we describe the long-term course of a pa- 12. Duvic M, Lowe L, Rapini R, Rodriguez S, Levy M. Eruptive dysplastic nevi associated with human immunodeficiency virus infection. Arch Dermatol. 1989; tient who developed eruptive MN after a bullous disor- 125(3):397-401. der. After 38 years of follow-up, his lesions have re- 13. Richert S, Bloom E, Flynn K, Seraly M. Widespread eruptive dermal and atypical mained stable, without signs of malignant degeneration. melanocytic nevi in association with chronic myelocytic leukemia: case report The etiology and natural course of eruptive MN may dif- and review of the literature. J Am Acad Dermatol. 1996;35(2 pt 2):326-329. fer between the 2 main populations of patients at risk for 14. Hollenbeak CS, Todd M, Billingsley E, Harper G, Dyer A, Lengerich E. Increased incidence of melanoma in renal transplantation recipients. Cancer. 2005;104 eruptive MN, with MN arising after bullous disorders (9):1962-1967. being likely to remain benign compared with those in pa- 15. Piaserico S, Alaibac M, Fortina A, Peserico A. Clinical and dermatoscopic fading tients with ongoing immunosuppression. However, this of post-transplant eruptive melanocytic nevi after suspension of immunosup- hypothesis has yet to be proved, and it will require long- pressive therapy. J Am Acad Dermatol. 2006;54(2):338-340. term surveillance of individuals who have developed erup- 16. Barker JN, MacDonald D. Eruptive dysplastic naevi following renal transplantation. Clin Exp Dermatol. 1988;13(2):123-125. tive MN to determine its merit. 17. Woodhouse J, Maytin E. Eruptive nevi of the palms and soles. J Am Acad Dermatol. 2005;52(5)(suppl 1):S96-S100. Accepted for Publication: June 4, 2007. 18. Belloni Fortina A, Piaserico S, Zattra E, Alaibac M. Dermoscopic features of erup- Correspondence: Jason K. Rivers, MD, FRCPC, Pacific tive melanocytic naevi in an adult patient receiving immunosuppressive therapy DermaAesthetics, 1790-1111 W Georgia St, Vancouver, for Crohn’s disease. Melanoma Res. 2005;15(3):223-224. 19. Bovenschen HJ, Tijoe M, Vermaat H, et al. Induction of eruptive benign mela- BC V6E 4M3, Canada ([email protected]). nocytic naevi by immune suppressive agents, including biologicals. Br J Dermatol. Author Contributions: Dr Rivers had full access to all 2006;154(5):880-886. the data in the study and takes responsibility for the in- 20. Hughes BR, Cunliffe W, Bailey C. Excess benign melanocytic naevi in children tegrity of the data and the accuracy of the data analysis. after chemotherapy for malignancy in childhood. BMJ. 1989;299(6691):88- Study concept and design: Rivers. Acquisition of data: 91. 21. Ibsen HH, Clemmensen O. Eruptive nevi in Addison’s disease. Arch Dermatol. Rivers. Analysis and interpretation of data: Gelfer and 1990;126(9):1239-1240. Rivers. Drafting of the manuscript: Gelfer and Rivers. Criti- 22. Cruz A, Sanchez J. Acral PUVA-induced pigmented macules. Bol Asoc Med P R. cal revision of the manuscript for important intellectual con- 1990;82(10):460-462. tent: Gelfer and Rivers. Administrative, technical, and ma- 23. Coskey R. Eruptive nevi [letter]. Arch Dermatol. 1975;111(12):1658. terial support: Gelfer. Study supervision: Rivers. 24. Eady RA, Gilkes J, Jones E. Eruptive naevi: report of two cases, with enzyme histochemical, light and electron microscopical findings. Br J Dermatol. 1977; Financial Disclosure: None reported. 97(3):267-278. Additional Contributions: A. Kopf, MD, provided the 25. Grob JJ, Bastuji-Garin S, Vaillant L, et al. Excess of nevi related to immunode- photograph of the original eruption from 1974. ficiency: a study in HIV-infected patients and renal transplant recipients. JIn- vest Dermatol. 1996;107(5):694-697. 26. Ross PM. Apparent absence of a benign precursor lesion: implications for the REFERENCES pathogenesis of malignant melanoma. J Am Acad Dermatol. 1989;21(3 pt 1): 529-538. 1. MacKie RM, English J, Aitchison T, Fitzsimons C, Wilson P. The number and dis- 27. Alaibac M, Piaserico S, Rossi C, et al. Eruptive melanocytic nevi in patients with tribution of benign pigmented moles (melanocytic naevi) in a healthy British renal allografts: report of 10 cases with dermoscopic findings. J Am Acad Dermatol. population. Br J Dermatol. 1985;113(2):167-174. 2003;49(6):1020-1022. 2. Hutchinson J. Outbreak of a large crop of pigmented moles: remarks as to pos- 28. Berg D, Otley C. Skin cancer in organ transplant recipients: epidemiology, patho- sible connection with melanosis. J Cutan Med Dis Skin. 1868:170-171. genesis, and management. J Am Acad Dermatol. 2002;47(1):1-17. 3. Soltani K, Bernstein J, Lorinez A. Eruptive nevocytic nevi following erythema 29. Le Mire L, Hollowood K, Gray D, Bordea C, Wojnarowska F. Melanomas in renal multiforme. J Am Acad Dermatol. 1979;1(6):503-505. transplant recipients. Br J Dermatol. 2006;154(3):472-477.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1557 EVIDENCE-BASED DERMATOLOGY: STUDY

SECTION EDITOR: MICHAEL BIGBY, MD; ASSISTANT SECTION EDITORS: DAMIANO ABENI, MD, MPH; ROSAMARIA CORONA, DSc, MD; URBÀ GONZA´ LEZ, MD, PhD; ABRAR A. QURESHI, MD, MPH; HYWEL WILLIAMS, MSc, PhD, FRCP Incidence and Risk Factors for Psoriasis in the General Population

Consuelo Huerta, MD, MPH; Elena Rivero, MD, MPH, FISPE; Luis A. Garcı´a Rodrı´guez, MD, MSc

Objectives: To study the clinical spectrum of psoria- dence interval (CI) for psoriasis as associated with se- sis and the incidence in the general population and to lected risk factors. identify risk factors associated with the occurrence of psoriasis. Results: The incidence rate of psoriasis was 14 per 10 000 person-years. Patients with antecedents of skin Design: Prospective cohort study with nested case- disorders and skin infection within the last year carried control analysis. the highest risk of developing psoriasis (OR, 3.6 [95% Setting: The data source was the United Kingdom Gen- CI, 3.2-4.1], and OR, 2.1 [95% CI, 1.8-2.4], respec- eral Practice Research Database containing computerized tively). Also, smoking was found to be an independent clinical information entered by general practitioners (GPs). risk factors for psoriasis (OR, 1.4 [95% CI, 1.3-1.6]). We did not find an association between risk of psoriasis Patients: The study population comprised patients re- and antecedents of stress, diabetes, hypertension, ceiving a first-ever diagnosis of psoriasis between Janu- hyperlipidemia, cardiovascular disease, or rheumatoid ary 1, 1996, and December 31, 1997, and free of cancer. arthritis.

Interventions: Diagnosis of psoriasis was validated in Conclusions: The incidence rate in our study was higher a random sample of 14% of all ascertained cases request- than those published in other studies, probably owing ing confirmation by the GPs. Nested case-control analy- to our case definition that considered cases recorded by sis included 3994 cases of psoriasis and a random sample the GPs independently of a specialist confirmation. Our of 10 000 controls frequency matched to cases by age, sex, results confirm the association between psoriasis, skin and calendar year. disorders, and smoking. Main Outcome Measures: Incidence rate of psoriasis and estimates of the odds ratio (OR) and 95% confi- Arch Dermatol. 2007;143(12):1559-1565

SORIASIS IS A CHRONIC, IMMU- its severity. The published studies on the nologically based, inflamma- natural history of psoriasis are scarce, have tory disease of the skin and inherent design limitations, and address few joints, which has been esti- aspects important to psoriasis. Fre- mated to affect 1% to 3% of quently, they are cross-sectional surveys Pthe population. The estimated preva- usually involving a large series of patients lence rates are mostly derived from gen- with psoriasis gathered from hospitals and eral population health surveys (rather than from dermatology clinics10-16 or patients from disease-specific studies)1-6 and from identified from large-population, non– specific registries.7,8 Studies providing in- disease-specific surveys. Nevertheless, some cidence rates of psoriasis are scarce. A studies provide data on specific aspects of Author Affiliations: study estimated an incidence rate of 60.4 the course of the disease, such as precipi- Spanish Center for per 100 000 person-years in a US general tating factors, comorbidity, incidence of Pharmacoepidemiologic population.9 cancer, and mortality.17-19 Research (CEIFE), Madrid, Spain Psoriasis is subject to flares and remis- We performed a prospective cohort (Drs Huerta and Garcı´a Rodrı´guez); and Department of sions and comes in many different varia- study with a nested case-control analysis Clinical Epidemiology, Novartis tions and degrees of severity. It may be using data from the General Practice Re- Farmace´utica SA, Barcelona, symptomatic throughout life and may be search Database (GPRD) in the United Spain (Dr Rivero). progressive with age or wax and wane in Kingdom with the aims of estimating the

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1559 incidence rate of psoriasis in the general population and over time, whether the patient had been hospitalized, and fi- identifying the risk factors associated with the occur- nally if there was a family history of psoriasis. We considered rence of psoriasis. a patient as a confirmed case of psoriasis if the diagnosis was confirmed by the GP in the questionnaire and no other exclusion criteria was found such as history of psoriasis according METHODS to the date of the first diagnosis provided in the questionnaire by the GP. The response rate was high (96%). Our computer- STUDY POPULATION based diagnosis of psoriasis was confirmed in 82% of patients. We excluded from the final list of psoriasis cases all individuals not confirmed by the GP in the validation study, resulting The GPRD contains computerized information entered by gen- in 3994 cases of psoriasis that were included in our analysis. eral practitioners (GPs) in the United Kingdom. Most of the UK population is registered with a GP. Currently, approximately 1500 GPs participate in the GPRD, covering a popula- COHORT AND NESTED tion of approximately 3 million individuals, who are broadly CASE-CONTROL ANALYSIS representative of the population of the United Kingdom as a whole.20 The information recorded in the database includes The incidence rate (IR) within each sex and age stratum was demographic data, medical diagnoses from GP visits, special- calculated as the ratio of the estimated number of cases over ist referrals and hospitalizations, results of laboratory tests as the total number of person-years of follow-up in each respec- well as a free-text section, and all written prescriptions. Pre- tive stratum, weighted by the confirmation rate obtained in the scriptions are generated directly from the computer and re- validation study for each stratum. We used all 3994 incident corded on the patient computerized file. An additional require- cases of psoriasis as cases for the nested case-control study, and ment is the recording of the indication for new courses of the date of the diagnosis was used as the index date. To select therapy. General practitioners send all this information anony- controls, a date during the study period was generated at ran- mously to the Medicines and Healthcare Products Regulatory dom for every member of the study cohort. If the random date Agency (MHRA).20 The MHRA organizes this information to of a study member was included in his or her eligible person- be used for research projects. Data from the GPRD on medical time (follow-up period), we marked that patient as an eligible diagnoses and drug use are of satisfactory quality for epide- control and used this random date as the index date. This in- miologic research.20-23 Previous studies have also confirmed the cidence density sampling method28 allows that the likelihood validity of using the GPRD for epidemiological research in the of being selected as a control is proportional to the person- field of psoriasis.24,25 time at risk. With this design, the odds ratio (OR) is an unbi- The study cohort comprised all persons who had been en- ased estimator of the IR ratio. Ten thousand controls free of rolled at least 2 years with a GP and who had at least 1 year psoriasis and cancer were frequency matched by sex, age (in- since the first-recorded prescription between January 1, 1996, terval of 1 year), and calendar year from the list of all eligible and December 31, 1997. All patients with cancer or who re- controls. For each variable, we estimated the OR of psoriasis ceived a diagnosis of psoriasis before the start date of the study and the corresponding 95% confidence interval (CI). To ac- were excluded. All study members were then followed from the count for the effects of potentially confounding factors, we cal- start date until the date of one of the following end points: a culated the OR using unconditional multiple logistic regres- recorded diagnosis of psoriasis, cancer, death, or December 31, sion. To test whether a model including an independent variable 1997, whichever came first. The study protocol was approved provides more information about the dependent variable than by the GPRD Scientific Ethical and Advisory Group. a similar model without this independent variable, we used the likelihood ratio statistic. Frequency-matching variables were PSORIASIS CASES ASCERTAINMENT included in the model as well as number of visits to the GP in AND VALIDATION the previous year, smoking, and body mass index (BMI). All statistical analyses were conducted using STATA software (version 8.2; StataCorp, College Station, Texas). For all patients identified with a first diagnostic code of psoriasis, we manually reviewed all their electronic medical records. We used the following algorithm to consider a patient as RISK FACTORS a possible case of psoriasis: referred to the specialist or hospitalized; receiving treatment recommended for psoriasis, in- Information on comorbidities and drug use was obtained from cluding topical (corticosteroids, retinoids, vitamin D ana- the database. We ascertained information any time prior to the logues, and anthralin) and/or systemic (methotrexate, index date on skin disorders (infectious and noninfectious), cyclosporine, acitretin, and phototherapy including psoralen- cardiovascular disease (heart failure, ischemic heart disease, and UV-A and UV-B) therapy; or with more than 1 entry of pso- hypertension), asthma, chronic obstructive pulmonary dis- riasis diagnosis in the computerized medical history. We con- ease, gastrointestinal diseases (inflammatory bowel diseases and sidered a patient as a case of psoriasis even when a specialist chronic liver disease), renal disease, diabetes, anemia, osteo- did not make the diagnosis because, based on the existing lit- arthritis, rheumatoid arthritis, systemic lupus erythematosus, erature, most cases in the United Kingdom are not referred for and various surgical procedures. We also ascertained informa- diagnosis to a specialist.26,27 Finally, after manual revision of tion, only in the last year, on pregnancy, stress, anxiety, or de- the computer medical profiles, 4110 patients were considered pression. Body mass index was calculated from recorded height as possible cases of psoriasis. We conducted a validation study and weight (weight in kilograms divided by height in meters to evaluate the accuracy of our psoriasis assessment and re- squared). Alcohol intake and smoking status was used as di- quested the confirmation of the diagnosis by the GPs in a ran- rectly recorded by the GP on computer files. We analyzed drug dom sample of 564 patients (approximately 14%). In the ques- use before the index date: this included anti-infectious drugs, tionnaire, we asked the GP to provide the confirmation of the acetylsalicylic acid, nonsteroidal anti-inflammatory drugs, ace- diagnosis, date of initial symptoms, whether the diagnosis had taminophen, antidepressants, antipsychotics, and antihyper- been confirmed by a specialist, type of psoriasis at onset, intensive agents. For each studied class of drugs, we defined 3 tensity of symptoms, whether the patient’s psoriasis worsened time windows of exposure: current use, past use, and nonuse.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1560 25.0

20.0

15.0 000 Person-years

10.0 IR per 10 5.0

0.0 Patients Male 11.0 11.1 17.4 12.8 16.1 18.6 22.4 17.3 Female 12.1 15.5 13.1 10.5 17.2 14.4 11.8 8.2 Overall 11.6 13.4 15.5 11.6 16.7 16.4 16.3 10.0 0-19 y 20-29 y 30-39 y 40-49 y 50-59 y 60-69 y 70-79 y ≥ 80 y Age Group

Figure. Incidence rate (IR) of psoriasis overall and by age group and sex.

Current use was categorized as use that lasted until the index older than 40 years, we did not find a clear association date or ended in the month prior to the index date based on (OR, 1.7 [95% CI, 0.7-1.9], and OR, 0.9 [95% CI, 0.6- the supply of drug therapy as prescribed by the GP. Past use 1.4], respectively). Diabetes was not associated with an was use that ended more than 1 month before the index date. increased risk of psoriasis (OR, 0.7 [95% CI, 0.6-0.9]). Finally, the time window of nonuse was defined as nonuse of each respective drug group at any time before the index date. No clear association was found between risk of pso- Duration of use was calculated as the period from the begin- riasis and osteoarthrosis, rheumatoid arthritis, inflam- ning of therapy with consecutive supplies (refill gap shorter than matory bowel diseases (neither Crohn syndrome dis- 2 months) among current users. eases nor ulcerative colitis), or chronic liver diseases. Pregnancy in the last year was associated with a de- RESULTS creased risk of psoriasis (OR, 0.7 [95% CI, 0.6-1.0]). No association was found with cardiovascular diseases (heart There were 3994 cases in 2 219 994 person-years. The failure or ischemic heart disease), hypertension, hyper- overall incidence of psoriasis in our study after being lipidemia, asthma, chronic obstructive airways disease, weighted by the confirmation rate obtained in the vali- thyroid disease, or surgery in the last year (data not dation study for each stratum was 14 per 10 000 person- shown). years. The Figure shows the IR of psoriasis in male pa- Table 2 presents use of drugs and its association with tients, female patients, and overall in different age groups. newly diagnosed psoriasis. Users of antibiotics had an OR The IR did not increase markedly with age after the age of 1.6 (95% CI, 1.3-1.8) compared with nonusers. We of 20 years. The IR was slightly higher in male patients did not find any association with use of antihyperten- after the age of 30 years. Of the psoriasis cases, 40% were sive agents (OR, 0.9 [95% CI, 0.8-1.0]). We also exam- first diagnosed before reaching the age of 40 years. ined the effect among various therapeutic groups of ␤ Table 1 gives the estimates of developing psoriasis antihypertensive agents ( -blockers, angiotensin- associated with selected risk factors. Visits to the GP in converting enzyme inhibitors, and calcium channel block- the last year were associated with an increased risk of pso- ers) and found that none was an independent risk factor riasis. Overweight individuals had only a slightly in- for psoriasis (data not shown). Nonsteroidal anti- creased risk. Patients with psoriasis were more likely to inflammatory drugs, acetaminophen, acetylsalicylic acid, be current smokers (OR, 1.5 [95% CI, 1.3-1.6]) com- or central nervous system drugs were not associated with pared with controls. History of any skin disorder diag- developing psoriasis. Respiratory drugs were not asso- nosis in the last year was associated with an OR of 3.6 ciated with the onset of psoriasis (data not shown). (95% CI, 3.2-4.1). Having an episode of infectious dis- Results after stratification according to history of skin ease in the last year increased the risk of psoriasis (OR, disorders were similar from the overall results (data not 1.6 [95% CI, 1.5-1.9]). Infectious skin disorders were as- shown). We also analyzed the effect of history of skin sociated with an OR of 2.1 (95% CI, 1.8-2.4). Of note, disorders using a lag time of 1 year before the diagnosis with regard to upper respiratory tract infections in the of psoriasis, since skin disorders diagnosed in the year month prior to psoriasis occurrence, there was an in- prior to the diagnosis of psoriasis could be related to that creased risk among patients aged 21 to 40 years (OR, 2.4 episode, and found no major difference with the main [95% CI, 1.5-3.9]); in patients younger than 21 years or analysis (data not shown).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1561 Table 1. Risk of Psoriasis Associated With Selected Risk Factorsa

Cases, No. (%) Controls, No. (%) Crude OR Adjusted OR Factor (n=3994) (n=10 000) (95% CI) (95% CI)b Body mass indexc 20-24 1034 (25.89) 2780 (27.80) 1 [Reference] 1 [Reference] Ͻ20 257 (6.43) 672 (6.72) 1.03 (0.88-1.21) 0.99 (0.84-1.17) 25-29 892 (22.33) 2165 (21.65) 1.11 (1.00-1.23) 1.11 (1.00-1.24) Ն30 452 (11.32) 883 (8.83) 1.38 (1.20-1.57) 1.33 (1.16-1.52) Smokingc Non/ex-smokers 1876 (46.97) 5080 (50.80) 1 [Reference] 1 [Reference] Smokers 1013 (25.36) 2008 (20.08) 1.37 (1.25-1.50) 1.45 (1.31-1.59) Alcohol (grams per week)c 0 1051 (26.31) 2475 (24.75) 1 [Reference] 1 [Reference] 1-20 1219 (30.52) 3169 (31.69) 0.91 (0.82-1.00) 0.96 (0.87-1.06) Ͼ20 312 (7.81) 688 (6.88) 1.07 (0.92-1.24) 1.06 (0.90-1.25) Visits to the GP in the year prior 0 477 (11.94) 2369 (23.69) 1 [Reference] 1 [Reference] 1-5 2211 (55.36) 5332 (53.32) 2.06 (1.84-2.3) 2.12 (1.89-2.37) Ͼ5 1306 (32.7) 2299 (22.99) 2.82 (2.5-3.18) 2.99 (2.64-3.39) Any skin disordersd,e 3372 (84.43) 7121 (71.21) 2.19 (1.99-2.41) 2.02 (1.83-2.23) Skin disorder within the last year 1827 (45.74) 2191 (21.91) 3.86 (3.47-4.29) 3.63 (3.24-4.06) Skin infections within the last yeard 559 (14.01) 674 (6.74) 2.40 (2.12-2.71) 2.08 (1.83-2.37) Osteoarthrosisd 572 (14.32) 1255 (12.55) 1.16 (1.05-1.3) 1.05 (0.93-1.19) Rheumatoid arthritisd 53 (1.33) 86 (0.86) 1.55 (1.10-2.19) 1.28 (0.90-1.83) Diabetesd 94 (2.35) 246 (2.46) 0.96 (0.75-1.22) 0.74 (0.58-0.95) Inflammatory bowel diseased 29 (0.73) 53 (0.53) 1.37 (0.87-2.16) 1.26 (0.80-2.00) Irritable bowel syndromed 202 (5.06) 373 (3.73) 1.37 (1.15-1.64) 1.18 (0.98-1.41) Chronic liver diseasesd 14 (0.14) 11 (0.28) 1.97 (0.89-4.34) 1.46 (0.66-3.26) Stress disorders any time befored Stress disorders within the last year 42 (1.05) 69 (0.69) 1.53 (1.04-2.25) 1.23 (0.83-1.82) Stress disorders before last year 104 (2.60) 237 (2.37) 1.11 (0.88-1.40) 0.95 (0.75-1.20) Pregnancy in the last yeard,f 88 (8.76) 204 (8.12) 1.09 (0.84-1.41) 0.73 (0.55-0.98)

Abbreviations: CI, confidence interval; GP, general practitioner; OR, odds ratio. a Values in bold are statistically significant (PՅ.05). b Estimates adjusted for sex, age, calendar year, body mass index, smoking, and visits to the GP in the last year. c Body mass index (calculated as weight in kilograms divided by height in meters squared) could not be calculated in 34% of the psoriasis cases and 35% of the controls; smoking status was unknown in 28% of the cases and 29% of the controls; and alcohol consumption was not recorded in 35% of the cases and 37% of the controls. d Reference category, “no.” e Skin disorders included any skin and subcutaneous tissue disease infections, skin and subcutaneous tissue inflammatory conditions, and any other skin and subcutaneous tissue disorders from systemic diseases affecting the skin. f Of the cases, 1005 were women 40 years or younger, and of the controls, 2513 were women 40 years or younger.

COMMENT GPs. Though it has been suggested that the ability of a primary care physician to diagnose skin complaints could 27 To our knowledge, there is only 1 study reporting inci- be poor compared with a dermatologist, psoriasis is one of the skin disorders best diagnosed by the GP accord- dence data of psoriasis, with an age- and sex-adjusted an- 27 nual incidence of psoriasis of 6 per 10 000 individuals9; ing to results from a study in the United Kingdom. our IR was 14 per 10 000 person-years. Because of the In line with the study conducted in Rochester, Min- 9 intrinsic difficulty in studying this disease and in par- nesota, we found the incidence to slightly increase gradu- ticular assessing the clinical onset, IRs would be ex- ally with age up to the seventh decade of life in men and pected to vary between different studies owing to differ- women. Our data also show, as suggested in some case ent operational case definitions and methods of case series of psoriasis, a bimodal curve in the age distribu- detection. Our case definition did not require cases to tion of the incidence of psoriasis.13 be confirmed by a specialist. If we had imposed that cri- Most previous reports on risk factors of psoriasis come terion, our estimate would have been substantially lower. from cross-sectional studies, or case-control studies using In our study, we manually reviewed all recorded clini- prevalent cases of psoriasis.29-32 There are 3 case-control cal information using an algorithm that included treat- studies that used newly diagnosed cases of psoriasis to ment indicated for psoriasis, recording of diagnosis in 2 study risk factors for the onset of psoriasis.33-35 or more different dates, or confirmation by a specialist. Smoking has been more consistently associated in pre- Furthermore, in the validation study requesting confir- vious studies with psoriasis compared with alcohol.30,36 mation of the diagnosis by the corresponding GP, we ob- Moreover, whereas increased ingestion of alcohol has been tained an 82% confirmation rate. Most cases were pa- described to be a factor triggering psoriasis, smoking in- tients with a diagnosis of psoriasis made directly by the creased the risk for the onset of the disease.33 Our study

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1562 Table 2. Risk of Psoriasis Associated With Selected Drugs

Cases, No. (%) Controls, No. (%) Crude OR Adjusted OR Drug Class (n=3994) (n=10 000) (95% CI) (95% CI)a Antibiotics Nonuse 465 (11.64) 1585 (15.85) 1 [Reference] 1 [Reference] Current use 446 (11.17) 734 (7.34) 2.07 (1.77-2.42) 1.56 (1.32-1.84) Past use 3083 (77.19) 7681 (76.81) 1.37 (1.22-1.53) 1.24 (1.10-1.39) Antihypertensive agents Never use 3081 (77.14) 7901 (79.01) 1 [Reference] 1 [Reference] Current use 507 (12.69) 1176 (11.76) 1.11 (0.99-1.24) 0.92 (0.81-1.05) Past use 406 (10.17) 923 (9.23) 1.13 (1.00-1.28) 0.99 (0.86-1.12) NSAIDs Never use 2101 (52.60) 5768 (57.68) 1 [Reference] 1 [Reference] Current use 243 (6.08) 461 (4.61) 1.45 (1.23-1.70) 1.19 (1.00-1.41) Duration, 0-30 d 87 (2.18) 191 (1.91) 1.25 (0.97-1.62) 1.03 (0.79-1.35) Duration, 31-365 d 82 (2.05) 136 (1.36) 1.66 (1.25-2.19) 1.31 (0.98-1.76) Duration, Ͼ1 y 74 (1.85) 134 (1.34) 1.52 (1.14-2.02) 1.29 (0.96-1.74) Past use 1650 (41.31) 3771 (37.71) 1.20 (1.11-1.30) 1.11 (1.02-1.20) Acetaminophen Never use 2187 (54.76) 6049 (60.49) 1 [Reference] 1 [Reference] Current use 294 (7.36) 566 (5.66) 1.44 (1.24-1.67) 1.07 (0.91-1.26) Duration, 0-30 d 83 (2.08) 197 (1.97) 1.17 (0.90-1.51) 0.92 (0.71-1.21) Duration, 31-365 d 115 (2.88) 176 (1.76) 1.81 (1.42-2.3) 1.30 (1.01-1.68) Duration, Ͼ1 y 96 (2.40) 193 (1.93) 1.38 (1.07-1.77) 1.02 (0.78-1.32) Past use 1513 (37.88) 3385 (33.85) 1.24 (1.14-1.34) 1.08 (0.99-1.17) Acetylsalicylic acid Never use 3730 (93.39) 9396 (93.96) 1 [Reference] 1 [Reference] Current use 138 (3.46) 311 (3.11) 1.12 (0.91-1.37) 0.92 (0.74-1.14) Past use 126 (3.15) 293 (2.93) 1.08 (0.88-1.34) 0.88 (0.71-1.10) Antipsychotics Never use 3507 (87.81) 8923 (89.23) 1 [Reference] 1 [Reference] Current use 43 (1.08) 99 (0.99) 1.11 (0.77-1.58) 0.90 (0.62-1.31) Past use 444 (11.12) 978 (9.78) 1.16 (1.03-1.30) 0.99 (0.87-1.12) Antidepressants Never use 3351 (83.90) 8630 (86.30) 1 [Reference] 1 [Reference] Current use 153 (3.83) 350 (3.50) 1.13 (0.93-1.37) 0.81 (0.66-0.99) Past use 490 (12.27) 1020 (10.20) 1.24 (1.10-1.39) 1.04 (0.92-1.17) Hypnotics and anxiolytics Never use 3320 (83.12) 8599 (85.99) 1 [Reference] 1 [Reference] Current use 108 (2.70) 245 (2.45) 1.14 (0.91-1.44) 0.89 (0.7-1.14) Past use 566 (14.17) 1156 (11.56) 1.27 (1.14-1.41) 1.10 (0.98-1.23)

Abbreviations: CI, confidence interval; NSAIDs, nonsteroidal anti-inflammatory drugs; OR, odds ratio. a Estimates were adjusted for sex, age, calendar year, body mass index, smoking, and visits to the general practitioner in the last year.

confirms smoking as a risk factor, whereas alcohol was betes has been associated with psoriasis, either studied not associated with the onset of psoriasis. Except for pre- as an independent risk factor31,39 or as part of the meta- vious skin disorders, infectious disorders, and obesity, bolic syndrome.32 Results of studies on the association we did not confirm any of the other studied risk factors between diabetes and psoriasis indicate that risk for dia- as risk factors for the onset of psoriasis. betes as well as for metabolic syndrome increases in pa- With respect to infectious disease, clinical and immu- tients according to duration and severity of the dis- nological evidence has traditionally supported a link be- ease.31,32 It has also been described that the risk increased tween an episode of streptococcal infection and the sub- when patients with severe disease were compared with sequent development of psoriasis, mainly in young those with moderate disease.32 people.35,37,38 We found an increased risk of psoriasis in pa- We did not find other cardiovascular diseases such as tients with recent infectious disease, and the risk was greater heart failure or ischemic heart disease, hypertension, or within the first month after an upper respiratory tract in- hyperlipidemia to be risk factors for a first episode of pso- fection, in particular among individuals aged 21 to 40 years. riasis. As for diabetes, studies have found that an asso- We did not have valid information to study the specific un- ciation with cardiovascular diseases could be restricted derlying infectious agent. As described by other authors,35 to severe forms of psoriasis.31,32,40 A possible explana- Streptococcal pyogenes has been isolated in a proportion of tion could be that cardiovascular risk factors could be patients with psoriasis ranging between 20% and 97%. more important once the disease is clearly established than Obesity has also been associated with psoriasis in dif- at the onset of the disease. It is likely that our newly di- ferent studies.36 On the other hand, in recent years dia- agnosed psoriasis cases probably involved patients with

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1563 a more moderate or mild form of the disease than the Accepted for Publication: April 20, 2007. prevalent cases included in prior studies. Correspondence: Consuelo Huerta MD, MPH, Spanish A number of drugs have been reported to precipitate Centre for Pharmacoepidemiologic Research (CEIFE), or exacerbate psoriasis in case reports and case series.41 Almirante 28 (2°), Madrid 28004, Spain (chuerta@ceife Other drugs reported as a potential risk factor for pso- .es). riasis include antibiotics, lithium, antihypertensive agents Author Contributions: Dr Huerta had full access to all (␤-blocking agents, angiotensin-converting enzyme in- of the data in the study and takes responsibility for the hibitors, and calcium channel blockers), and nonsteroi- integrity of the data and the accuracy of the data analy- dal anti-inflammatory drugs.41-43 sis. Study concept and design: Huerta, Rivero, and Garcıá Of all these drugs, we only found a small association Rodrı´guez. Acquisition of data: Garcıá Rodrı´guez. Analy- between psoriasis and antibiotic use. This adverse effect sis and interpretation of data: Huerta, Rivero, and Garcıá has been described previously as inducing pustular pso- Rodrı´guez. Drafting of the manuscript: Huerta and Gar- riasis.44 Based on our data, it is more likely that there is cıá Rodrı´guez. Critical revision of the manuscript for im- an association between psoriasis and infections rather than portant intellectual content: Huerta, Rivero, and Garcıá, with the drugs used to treat them. With respect to the Rodrı´guez. Statistical analysis: Huerta and Garcıá Rod- other aforementioned drugs, it is possible that the effect rı´guez. Obtained funding: Rivero. Administrative, techni- of these drugs is only observed on exacerbation and not cal, and material support: Huerta. Study supervision: Huerta initiation of psoriasis. In addition, differences in the ex- and Garcıá Rodrı´guez. posure ascertainment and definition between previous Financial Disclosure: Dr Rivero is employed by Novartis. studies with prevalent cases and our study may account Funding/Support: This study was supported in part by for the different associations found. an unrestricted grant from Novartis. A number of considerations need to be addressed in Additional Contributions: The general practitioners the interpretation of our study. A major strength is that provided excellent collaboration, and the Boston Col- we are studying incident cases of psoriasis, and efforts laborative Drug Surveillance Program provided access have been made to assure this. To determine the date of to the General Practice Research Database. Miguel Gil, onset of psoriasis is not a straightforward task. Given the MD, PhD, assisted in defining an algorithm for the case ascertainment. lack of valid diagnostic criteria developed for clinical and population-based studies on psoriasis, one could sur- mise that clinical psoriasis begins with a series of symp- REFERENCES toms that eventually lead to its diagnosis, but it is difficult to correctly identify the date the symptoms start. To 1. Braathen LR, Botten G, Bjerkedal T. Prevalence of psoriasis in Norway. Acta Derm determine whether this could have affected our results, Venereol Suppl (Stockh). 1989;142:5-8. first we stratified according to the presence of history of 2. Braathen LR, Botten G, Bjerkedal T. Psoriatics in Norway: a questionnaire study on health status, contact with paramedical professions, and alcohol and to- any skin disorders and observed similar results with this bacco consumption. Acta Derm Venereol Suppl (Stockh). 1989;142:9-12. subanalysis. Second, assuming that history of skin dis- 3. Barisic´-Drusko V, Paljan D, Kansky A, Vujasinovic S. Prevalence of psoriasis in orders in the year prior to the index date could be re- Croatia. Acta Derm Venereol Suppl (Stockh). 1989;146:178-179. lated to the diagnosis of psoriasis, we did not count any 4. Brandrup F, Green A. The prevalence of psoriasis in Denmark. Acta Derm Venereol. 1981;61(4):344-346. skin disorder diagnosed in the year prior and also found 5. Lomholt G. Psoriasis in the Faroe Islands. Acta Derm Venereol. 1954;34(1-2):92. no substantial change for any of the studied variables when 6. Nevitt GJ, Hutchinson PE. Psoriasis in the community: prevalence, severity and stratifying according to this new definition of history of patients’ beliefs and attitudes towards the disease. Br J Dermatol. 1996;135 skin disorders. Furthermore, after the case validation pro- (4):533-537. cess, we were not able to confirm 18% of patients as cases 7. Kavli G, Stenvold SE, Vandbakk Ø. Low prevalence of psoriasis in Norwegian Lapps. Acta Derm Venereol. 1985;65(3):262-263. of psoriasis. To avoid the possible misclassification bias, 8. Falk ES, Vandbakk Ø. Prevalence of psoriasis in Norwegian Lapp population. Acta data on incidence were corrected for by applying weights. Derm Venereol Suppl (Stockh). 1993;182:6-9. We studied only environmental risk factors associ- 9. Bell LM, Sedlack R, Beard CM, Perry HO, Michet CJ, Kurland LT. Incidence of ated with the onset of psoriasis. However, it is difficult psoriasis in Rochester, Minn, 1980-1983. Arch Dermatol. 1991;127(8):1184- 1187. to model causation in a disease such as psoriasis for which 10. Farber EM, Bright RD, Nall ML. Psoriasis: a questionnaire survey of 2,144 patients. one would need to study interactions between genetic pre- Arch Dermatol. 1968;98(3):248-259. disposition and environmental factors.30 We could not 11. Farber EM, Nall ML. The natural history of psoriasis in 5,600 patients. Dermatologica. study the effect of an important risk factor such as fam- 1974;148(1):1-18. 12. Brandrup F, Holm N, Grunnet N, Henningsen K, Hansen HE. Psoriasis in mono- ily history of psoriasis because this information was miss- zygotic twins: variation in expression in individuals with identical genetic ing for most of the study patients in the database. constitution. Acta Derm Venereol. 1982;62(3):229-236. In summary, our data confirmed that smoking, over- 13. Henseler T, Christophers E. Psoriasis of early and late onset: characterization of weight, and infectious diseases are moderate risk fac- two types of psoriasis vulgaris. J Am Acad Dermatol. 1985;13(3):450-456. 14. Ko¨no¨nen M, Torppa J, Lassus A. An epidemiological survey of psoriasis in the tors for the onset of psoriasis, while no association was greater Helsinki area. Acta Derm Venereol Suppl (Stockh). 1986;124:1-10. found with other characteristics previously described as 15. Nanda A, Kaur S, Kaur I, Kumar B. Childhood psoriasis: an epidemiologic survey risk factors in studies with prevalent cases. Psoriasis is a of 112 patients. Pediatr Dermatol. 1990;7(1):19-21. disease that may affect quality of life to a substantial de- 16. Swanbeck G, Inerot A, Martinsson T, et al. Age at onset and different types of psoriasis. Br J Dermatol. 1995;133(5):768-773. gree. Population-based studies focused on the inci- 17. Lindega˚rd B. Diseases associated with psoriasis in a general population of 159,200 dence of psoriasis are deemed necessary to know and con- middle-aged, urban, native Swedes. Dermatologica. 1986;172(6):298-304. firm factors related to the onset of the disease. 18. Stern RS, Lange R. Cardiovascular disease, cancer, and cause of death in pa-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1564 tients with psoriasis: 10 years prospective experience in a cohort of 1,380 patients. 32. Sommer DM, Jenisch S, Suchan M, Christophers E, Weichenthal M. Increased J Invest Dermatol. 1988;91(3):197-201. prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. 19. Roth PE, Grosshans E, Bergoend H. Psoriasis: development and fatal complications. Arch Dermatol Res. 2006;298(7):321-328. doi:10.1007/s00403-006-0703-z. Ann Dermatol Venereol. 1991;118(2):97-105. 33. Naldi L, Parazzini F, Brevi A, et al. Family history, smoking habits, alcohol con- 20. Garcı´a Rodrı´guez LA, Pe´rez Gutthann S. Use of the UK General Practice Re- sumption and risk of psoriasis. Br J Dermatol. 1992;127(3):212-217. search Database for pharmacoepidemiology. Br J Clin Pharmacol. 1998;45 34. Naldi L, Peli L, Parazzini F. Association of early-stage psoriasis with smoking (5):419-426. and male alcohol consumption: evidence from an Italian case-control study. Arch 21. Jick H, Jick S, Derby LE. Validation of information recorded on general practi- Dermatol. 1999;135(12):1479-1484. tioner based computerised data resource in the United Kingdom. BMJ. 1991; 35. Naldi L, Peli L, Parazzini F, Carrel CF. Family history of psoriasis, stressful life 302(6779):766-768. events, and recent infectious disease are risk factors for a first episode of acute 22. Jick H, Terris BZ, Derby LE, Jick SS. Further validation of information recorded guttate psoriasis: results of a case-control study. J Am Acad Dermatol. 2001; on a general practitioner based computerised data resource in the United Kingdom. 44(3):433-438. Pharmacoepidemiol Drug Saf. 1992;1:347-349. 36. Herron MD, Hinckley M, Hoffman MS, et al. Impact of obesity and smoking on 23. Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the General Practice psoriasis presentation and management. Arch Dermatol. 2005;141(12):1527- Research Database. Pharmacotherapy. 2003;23(5):686-689. 1534. 24. Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ. Lymphoma rates are low 37. Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection but increased in patients with psoriasis: results from a population-based cohort in the initiation of guttate psoriasis. Arch Dermatol. 1992;128(1):39-42. study in the United Kingdom. Arch Dermatol. 2003;139(11):1425-1429. 38. Horiuchi N, Aiba S, Ozawa H, et al. Peripheral blood lymphocytes from psoriatic 25. Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Preva- patients are hyporesponsive to beta-streptococcal superantigens. Br J Dermatol. lence and treatment of psoriasis in the United Kingdom: a population-based study. 1998;138(2):229-235. Arch Dermatol. 2005;141(12):1537-1541. 39. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol. 26. Gillard SE, Finlay AY. Current management of psoriasis in the United Kingdom: 1995;32(6):982-986. patterns of prescribing and resource use in primary care. Int J Clin Pract. 2005; 40. Mallbris L, Akre O, Granath F, et al. Increased risk for cardiovascular mortality in 59(11):1260-1267. psoriasis inpatients but not in outpatients. Eur J Epidemiol. 2004;19(3):225- 27. Basarab T, Munn SE, Jones RR. Diagnostic accuracy and appropriateness of gen- 230. eral practitioner referrals to a dermatology out-patient clinic. Br J Dermatol. 1996; 41. Dika E, Varotti C, Bardazzi F, Maibach HI. Drug-induced psoriasis: an evidence- 135(1):70-73. based overview and the introduction of psoriatic drug eruption probability score. 28. Kleinbaum DG, Kupper LL, Morgentern H. Epidemiologic Research: Principles Cutan Ocul Toxicol. 2006;25(1):1-11. and Quantitative Methods. New York, NY: John Wiley & Sons Inc; 1982. 42. Cohen AD, Bonneh DY, Reuveni H, Vardy DA, Naggan L, Halevy S. Drug expo- 29. Naldi L, Tognoni G, Cainelli T. Analytic epidemiology in psoriasis. J Invest Dermatol. sure and psoriasis vulgaris: case-control and case-crossover studies. Acta Derm 1994;102(6):19S-23S. Venereol. 2005;85(4):299-303. 30. Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3(2): 43. Cohen AD, Kagen M, Friger M, Halevy S. Calcium channel blockers intake and 121-128. psoriasis: a case-control study. Acta Derm Venereol. 2001;81(5):347-349. 31. Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence 44. Whittam LR, Wakelin SH, Barker JN. Generalized pustular psoriasis or drug- of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. induced toxic pustuloderma? the use of patch testing. Clin Exp Dermatol. 2000; 2006;55(5):829-835. 25(2):122-124.

Correction

Error in Text. In the Observation by Richmond et al titled “Nephrogenic Systemic Fibrosis: Relationship to Gado- linium and Response to Photopheresis,” published in the August issue of the Archives (2007;143[8]:1025-1030), in the second full paragraph in the first column on page 1029, “gadopentetate dimeglumine” was incorrectly listed in place of “gadopentetate ion.” The sentence should have read as follows: “It is possible that either free gadopentetate ion or the chelate itself could bind to endogenous ions in the tissues.30”

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Level of Agreement With the British Guidelines for the Use of Biological Therapies for Psoriasis

Tamar Nijsten, MD, PhD; Erasmus Medical Center, Rotterdam, the Netherlands

Commentary on: British Association riasis. Although the BAD group worked carefully to avoid of Dermatologists guidelines for use being hierarchical in their recommendation of which bio- of biological interventions in psoriasis 2005 logical agent to use, they observe that the tumor necrosis Smith CH, Anstey AV, Barker JN, et al factor (TNF) blockers are more effective than efaluz- Br J Dermatol. 2005;153(3):486-497 imab, and that of the TNF blockers, etanercept is the first choice in most eligible patients with stable disease with or without psoriatic arthritis when a decision has been made Question: When, who, and how to prescribe biological to treat with a TNF blocker. The group members suggest therapies for psoriasis in the United Kingdom? that the use of infliximab should be restricted to situa- Setting: British Association of Dermatologists (BAD) tions in which rapid clearing is required and that the use guideline working group. of efalizumab should be restricted to patients who are un- Design: The BAD group developed guidelines for the use responsive to anti–TNF therapies or in whom such thera- of biological interventions in psoriasis 2005. They used pies are contraindicated. BAD-recommended methodology and the AGREE (Ap- praisal of Guidelines for Research and Evaluation) instrument. A literature review was performed by search- Comment ing EMBASE and Medline (1990–early 2005) for clinical psoriasis trials involving efalizumab, etanercept, and in- The BAD guidelines are comprehensive regarding when, fliximab using an agreed-on protocol. Included manu- who, and how to prescribe etanercept, infliximab, and scripts were scored using the NICE (National Institute efaluzimab for psoriasis.1 The authors discuss some im- for Clinical Excellence) criteria for level of evidence and portant practical issues, such as eligibility criteria, exclu- strength of recommendation. The pharmacology, clini- sion criteria, efficacy, dosing, and monitoring of these 3 cal effectiveness, dosing regimens, and toxicity of the bio- agents. The BAD working group sends a strong signal to logical agents are reviewed. Three key questions (Which clinicians that biological therapy is not first-line treat- patients should be considered for biological therapy? Who ment and that etanercept is the drug of choice if biologi- should prescribe biological therapy? and How to pre- cal therapy is considered, except in some specific circum- scribe biological therapies?) are answered. stances, such as unstable psoriasis or increased risk of Results: The authors propose eligibility criteria for bio- tuberculosis or demyelineating disease. Although we may logical use in psoriasis. First, patients should have severe agree or disagree with this strong positioning of the bio- disease (defined as disease duration Ͼ6 months, candi- logical agents, especially etanercept, in the management date for UV or systemic therapy, Psoriasis Area and Se- of psoriasis, the guidelines are clear and informative for verity Index [PASI]Ͼ 10 and/or body surface area clinicians who would like to start introducing these newer [BSA]%Ͼ10, and Dermatology Quality of Life Index treatments into their psoriasis armamentarium. Other [DLQI]Ͼ10). Second, patients have to fulfill at least 1 of guidelines or consensus conferences may be less defini- 7 clinical minor criteria that are mainly related to UV and tive in ranking different systemic psoriasis treatments, in- systemic treatment (eg, unresponsiveness, intolerance or cluding the biological class of therapeutic agents.2,3 risk of toxic effects) and clinical disease characteristics (eg, erythrodermic, pustular psoriasis or psoriatic arthritis). See also page 1595 The authors recommend that the use of biological drugs should be restricted to dermatologists who have sufficient experience in managing difficult psoriasis, using The AGREE instrument was used in the develop- standard therapies, and assessing the severity of psoria- ment of the BAD guidelines (Figure).4,5 This frame- sis. The inclusion and exclusion criteria, clinical effec- work, which is widely accepted and commonly used in tiveness, important safety issues, and monitoring inves- the design of new guidelines, is used for assessing the qual- tigations of etanercept, infliximab, and efalizumab are ity of existing guidelines. Unfortunately, the authors are summarized in several tables. not explicit in how they used this instrument, nor do they Authors’ Conclusions: The biological agents should be re- show the domain scores for their guidelines. In my opin- served for a well-defined subgroup of patients with pso- ion, several AGREE items scored 2 or less on a 4-point

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1567 ten need to have moderate to severe disease (based on PASI, I. Scope and purpose percentage of body surface area, and/or health-related qual- Is (are) the overall objective(s) of the guideline specifically described? Is (are) the clinical question(s) covered by the guideline specifically described? ity-of-life impairment) and are not responsive to, have a Are the patients to whom the guideline is meant to apply specifically described? contraindication to, or are intolerant to other systemic II. Stakeholder involvement therapies, including cyclosporine, methotrexate, and pso- Does the guideline development group include individuals from all relevant professional groups? ralen–UV-A. However, because these eligibility criteria are Have the patients’ views and preferences been sought? Are the target users of the guideline clearly defined? based on low levels of evidence, such as expert opinion, Has the guideline been piloted among target users? more clinical research is needed to develop clear and valid III. Rigor of development measurements. To define severe psoriasis, Smith and col- Were systematic methods used to search for evidence? 7 Are the criteria for selecting the evidence clearly described? leagues have merged the Salford Psoriasis Index and “the 8 Are the methods used for formulating the recommendations clearly described? Rule of Tens.” Their definition includes outcome mea- Have the health benefits, side effects, and risks been considered in formulating the recommendations? sures that are often used in psoriasis research, such as the Is there an explicit link between the recommendations and the supporting PASI and the DLQI, but have several major practical and evidence? 9,10 Was the guideline externally reviewed by experts before its publication? methodological limitations. Most of the 7 minor crite- Is a procedure for updating the guideline provided? ria also have relatively low levels of evidence, and some IV. Clarity and presentation are ambiguous and not well defined. For example, crite- Are the recommendations specific and unambiguous? Are the different options for management of the condition clearly presented? rion 1, “...higher than average risk of developing clini- Are the key recommendations easily identifiable? cally important drug-related toxicity...”;criterion 2, “in- Is the guideline supported with tools for application? tolerant to or cannot receive standard systemic therapy”; V. Applicability Have the potential organizational barriers in applying the recommendations been and criterion 5, “significant, coexistent, unrelated comor- discussed? bidity....”Incontrast to responsiveness, intolerance is not Have the potential cost implications of applying the recommendations been considered? defined; eg, Is a patient who has methotrexate-induced nau- Does the guideline present key review criteria for monitoring and/or audit sea at a dosage of 20 mg/week orally, without the use of purposes? folic acid, intolerant to this drug? Epidemiological stud- VI. Editorial independence Is the guideline editorially independent from the funding body? ies show an association between psoriasis and obesity, dia- Have the conflict of interests of the guideline development members been betes, hypertension, and hyperlipidemia, suggesting that recorded? the first and fifth minor criteria are often met by patients Overall assessment 11 Would you recommend these guidelines for use in clinical practice? with psoriasis. A recent study that was conducted at the request of the European Agency for the Evaluation of Me- Figure. The domains of the Appraisal of Guidelines for Research and dicinal Products demonstrated that the efficacy of efali- Evaluation (AGREE) Instrument (adapted from reference 5). Items are scored zumab therapy in patients with psoriasis who are resis- from 4 (strongly agree) to 1 (strongly disagree), and independent scores can tant to at least 2 conventional therapies (ie, “high need” be calculated for each of the 6 domains (I-VI). A total score cannot be calculated for the AGREE instrument. An overall assessment can be scored patients) is comparable to that in more “naı¨ve” patients, as follows: strongly recommended, recommended (with provisions or suggesting that prior treatment experience does not affect alterations), not recommended, or unsure. the efficacy of efalizumab therapy (about 30% of patients have had 75% reduction in PASI score after 12 weeks).12 scale (items 5, 6, 7, 10, 13, 20, and 21), which may be The other question raised in Smith and colleagues’ ar- attributable to a lack of transparency as well as to other ticle is, “Who should prescribe biological therapy?” The inherent limitations of current approaches in the devel- question is answered, in part, by the eligibility criteria: der- opment of clinical guidelines.6 We may assume that the matologists who are experienced with standard UV and target users of the guidelines are dermatologists, but this systemic psoriasis therapies. However, a large proportion is not clearly stated. Moreover, the guidelines may also of dermatologists do not regularly prescribe methotrex- be useful for general physicians and rheumatologists. ate and cyclosporine for the treatment of psoriasis. Older Smith and colleagues restricted their literature search to US surveys and a recent Belgian survey reported that about EMBASE and MEDLINE and did not include all avail- 40% of the participating dermatologists indicated that they able data, nor were the Cochrane Library and clinical trial had little or no knowledge about methotrexate and cyclo- registers searched. Making the guidelines available on- sporine, and only 10% reported having good or excellent line for comments is not the same as testing among tar- experience with both drugs.13 Because many dermatolo- get users, seeking patients’ preferences, or having the gists are not comfortable using what are considered “stan- guidelines reviewed externally. The potential cost im- dard” therapies, including biological agents, patient care plications and the key review criteria for monitoring them can be affected. This observation is confirmed by the large are not well documented in the applicability domain (Fig- proportion of dissatisfied patients and the relatively in- ure). Despite these limitations, which are not likely to frequent use of systemic treatments.14,15 Therefore, to close have had a substantial impact on the published guide- the “knowledge-behavior gap,”additional efforts are needed lines, I would recommend the BAD guidelines for any- to educate physicians regarding the use of new and tradi- one who is considering or is now prescribing biological tional psoriasis therapies. Physician education is a key fac- therapy for psoriasis. tor in mastering the skills that are necessary to provide op- In response to the potential steep increment of costs timal patient care and to ensure that dermatologists, and of psoriasis care due to the biological drugs, several na- not rheumatologists, will continue to treat severe and re- tional regulatory agencies in Europe have, in contrast to sistant psoriasis. the United States, restricted reimbursement for biologi- In the United States, experience with traditional thera- cal drugs. Patients who are eligible for reimbursement of- pies may not be such an important issue because of the

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1568 lack of strict reimbursement criteria. Moreover, the bio- Additional Contributions: Phyllis Spuls, MD, PhD, and logical agents are promoted as drugs that are safe and easy Ellen de Haas, MD, provided comments and sugges- to use, with little or no end-organ damage, at least in the tions about the manuscript and the AGREE instrument. short term, suggesting a relatively simple follow-up. The recommended pretreatment and monitoring investiga- REFERENCES tions suggested by the BAD working group are indeed simple and are performed at wide intervals. Except for 1. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists guide- the complete blood cell count (eg, thrombocyte count) lines for use of biological interventions in psoriasis 2005. Br J Dermatol. 2005; 153(3):486-497. in patients using efalizumab, it is recommended that the 2. Callen JP, Krueger GG, Lebwohl M, et al. AAD consensus statement on psoria- investigations be performed before and at 3 and 6 months sis therapies. J Am Acad Dermatol. 2003;49(5):897-899. after the initiation of therapy. The evidence for these rec- 3. Kwaliteitsinstituut Web site. www.cbo.nl/product/richtlijnen/ folder20021023121843 ommendations and the frequency of follow-up is un- /rl_psoriasis_2005.pdf/view. Accessed September 21, 2006. 4. AGREE Electronic Library for Guideline Developers Web site. http://www clear and may be open for debate, but the authors do pro- .agreecollaboration.org/1/agreeguide/. Accessed May 25, 2006. vide an instructive table to which clinicians can refer. 5. AGREE Collaboration. Development and validation of an international appraisal However, the safety of the biological drugs is chal- instrument for assessing the quality of clinical practice guidelines: the AGREE lenged by a recent meta-analysis that showed a signifi- project. Qual Saf Health Care. 2003;12(1):18-23. cant increased risk for malignant neoplasms and serious 6. Raine R, Sanderson C, Black N. Developing clinical guidelines: a challenge to current methods. BMJ. 2005;331(7517):631-633. infections in patients with rheumatoid arthritis who were 7. Kirby B, Fortune DG, Bhushan M, Chalmers RJ, Griffiths CE. The Salford Pso- using tumor necrosis factor antibodies, a finding that re- riasis Index: an holistic measure of psoriasis severity. Br J Dermatol. 2000; confirms the need for caution in prescribing these agents.16 142(4):728-732. 8. Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol. 2005;152 (5):861-867. Bottom Line: Because of the financial implications, the 9. Nijsten T, Meads DM, McKenna SP. Dimensionality of the Dermatology Life Qual- use of biological drugs in the treatment of psoriasis ity Index (DLQI): a commentary. Acta Derm Venereol. 2006;86(3):284-285. should be reserved for a relatively small proportion of 10. van de Kerkhof PC. On the limitations of the psoriasis area and severity index patients in whom standard therapy has failed. These (PASI). Br J Dermatol. 1992;126(2):205. agents should be prescribed only by experienced der- 11. Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case- matologists, so more efforts are needed to educate der- control study. J Invest Dermatol. 2005;125(1):61-67. matologists regarding the administration of systemic 12. Dubertret L, Sterry W, Bos JD, et al. CLinical experience acquired with the efali- therapies. For now, etanercept appears to be the bio- zumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque pso- logical agent of choice in most cases. However, long- riasis: results from a phase III international randomized, placebo-controlled trial. Br J Dermatol. 2006;155(1):170-181. term postmarketing safety studies and comparative ran- 13. Nijsten T, Lambert J. Dermatologists’ views and opinions about photo(chemo) domized clinical trials between different types of therapy and conventional systemic psoriasis therapies: results from a Belgian biological drugs and between biological agents and survey. Dermatology. 2006;213(2):123-133. standard therapies are required to confirm the proposed 14. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, positioning of biological agents in psoriasis care. carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc. 2004;9(2): 136-139. Accepted for Publication: July 1, 2007. 15. Nijsten T, Margolis DJ, Feldman SR, Rolstad T, Stern RS. Traditional systemic Correspondence: Tamar Nijsten, MD, PhD, Depart- treatments have not fully met the needs of psoriasis patients: results from a na- ment of Dermatology, Erasmus Medical Center, Burge- tional survey. J Am Acad Dermatol. 2005;52(3 Pt 1):434-444. 16. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti– meester Jacobussenplein 51, PO Box 204, Rotterdam, the TNF antibody therapy in rheumatoid arthritis and the risk of serious infections Netherlands ([email protected]). and malignancies: systematic review and meta-analysis of rare harmful effects Financial Disclosure: None reported. in randomized controlled trials. JAMA. 2006;295(19):2275-2285.

Archives Feature

Free color publication if color illustrations enhance the didactic value of the article.

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The Role of Furry Pets in Eczema A Systematic Review

Sine´ad M. Langan, MRCP; Carsten Flohr, MRCPCH; Hywel C. Williams, PhD

Objective: To systematically search, summarize, and (pooled OR, 0.68; 95% CI, 0.53-0.87), or “any furry critically appraise the literature to examine whether pet pet” (pooled OR, 0.79; 95% CI, 0.74-0.84) is associated exposure in early life is associated with an increased risk with a lower risk of eczema. However, in the only co- of eczema. hort study adjusted for avoidance behavior, this “protective effect” disappeared (for cats: OR, 0.80; 95% CI, Data Sources and Study Selection: We searched 0.33-1.97). Stratified analysis by family history in MEDLINE (1950 to June 2006) supplemented by cita- 2 birth cohort studies showed that dog exposure was tion lists in retrieved articles and contact with research- protective in patients with atopic families. For cats, ers. No language restrictions were imposed. 1 study showed reduced risk in atopic families only; the other study showed no effect. Eight cross-sectional Data Extraction: Cohort studies were sufficiently simi- studies evaluated past pet exposure; a protective effect lar to allow pooled analysis. Meta-analysis was not pos- was seen in 3 studies for cat, dog, or any pet; no study sible for cross-sectional studies owing to differences in demonstrated an increased risk. methods and populations. Conclusions: There was no clear evidence that early pet Main Outcome Measures: Incidence or prevalence exposure is associated with increased risks of subse- of eczema. quent eczema. We found some evidence of a possible protective effect of early pet exposure, but this might be ex- Results: Evidence from longitudinal studies showed plained by avoidance behavior in high-risk families. that previous exposure to cats (pooled odds ratio [OR], 0.76; 95% confidence interval [CI], 0.62-0.92), dogs Arch Dermatol. 2007;143(12):1570-1577

EVERAL RESEARCHERS HAVE resulting in widely conflicting advice being suggested that early expo- given to parents. Some researchers7,8 rec- sure to animal allergens con- ommend prophylactic avoidance of pets tributes to the development in the perinatal period and early child- of eczema.1 Such assertions hood, whereas others advocate the re- haveS mainly been based on the finding of moval of pets from households after the high serum IgE levels to purified animal development of eczema in offspring. The allergen in children with eczema.2 Mak- opposite view has also been suggested by ing inferences about disease causation proponents of the hygiene hypothesis, that using allergic sensitization is potentially is, pet keeping in early life may increase misleading; specific serum IgE levels to cat exposure to endotoxins that provide a pro- or dog allergens cannot distinguish be- tective benefit against later development tween past or current pet exposure, and of eczema.9 To inform this lack of clarity the presence of such antibodies may sim- of clinical advice to parents, we con- ply be an epiphenomenon of the atopic ducted a systematic review of the litera- state. Pet allergens, especially for cat, have ture to determine whether keeping do- been shown to be ubiquitous in public mestic furry pets is associated with an places, in schools, and in families that increased risk of eczema. never owned a pet.3-5 The presence of a cat or dog in the house does not necessarily lead to allergic sensitization of the own- METHODS Author Affiliations: Centre of ers, and their direct contact with the ani- 6 Evidence-based Dermatology, mal may vary considerably. MEDLINE was searched for articles published Queen’s Medical Centre, The possible role of domestic animals between its inception in 1950 and June 30, 2006, Nottingham, England. in eczema development remains unclear, using the following search terms: domestic ani-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1570 mals, cats, dogs, horses, and pets combined with the following Coch- rane Skin Group search terms for atopic eczema10: Study or Odds Ratio (Random) Subcategory 95% CI 1. exp Dermatitis, Atopic/ 2. atopic dermatitis.mp. Cats 3. atopic eczema.mp. Zirngibl et al15 4. exp NEURODERMATITIS/ Nafstad et al6 5. neurodermatitis.mp. 6. infantile eczema.mp. Illi et al16 7. childhood eczema.mp. Hagendorens et al13 8. Besniers’ Prurigo.mp. Purvis et al14 9.1or2or3or4or5or6or7or8 10. domestic animals.mp. or exp Animals, Domestic/ Phipatanakul et al17 11. exp CATS/ or cats.mp. Kerkhof et al18

12. exp DOGS/ or dogs.mp. Gern et al9 13. horses.mp. or exp HORSES/ 14. pets.mp. Subtotal (95% CI) 15. 10 or 11 or 12 or 13 or 14 16. 9 and 15 Dogs Zirngibl et al15 The online search was supplemented by an extensive hand 6 search of citations in the retrieved articles, and researchers were Nafstad et al contacted for additional data as appropriate. We included longi- Illi et al16 tudinal and cross-sectional studies. We imposed no restrictions Purvis et al14 on participant age or study language. Each relevant article un- 17 derwent standardized data extraction by one of us (S.M.L.), and Phipatanakul et al all of the data were then assessed by the author panel. Kerkhof et al18 Studies were described in 2 categories: those that prospec- Gern et al9 tively followed cohorts of children from birth or before (in utero) Subtotal (95% CI) and all other designs. More weight was given to cohort than cross- sectional studies because of their ability to better separate the 0.2 0.5 1.0 2.0 5.0 chronological relationship between exposure (pets) and disease Exposure Increased (eczema). Meta-analysis using a random-effects model (a tech- Protective Odds nique described by DerSimonian and Laird11) (RevMan; The Coch- rane Collaboration, Oxfordshire, England) was planned if stud- Figure 1. Forest plot of cohort studies arranged by sample size for cats and ies were deemed to be sufficiently similar in terms of design, dogs separately. CI indicates confidence interval; diamonds, the overall participants, and age. We also looked carefully for adjusted analy- summary estimate for the analysis (width of the diamond represents the ses whereby the effects of avoidance behavior by atopic parents 95% CI). can be taken into account. Throughout this article, we use the 12 new World Allergy Association nomenclature for eczema. out an atopic family history (OR, 0.6; 95% CI, 0.3-1.2). Another study of 1128 Belgian children by Hagendo- RESULTS rens et al13 showed a 32% reduction in eczema with post- natal cat exposure (adjusted OR, 0.68; 95% CI, 0.47- The initial search retrieved 458 articles, of which 319 were 0.97). However, 6 additional longitudinal studies, 2 related to eczema in animals and, therefore, were ex- conducted in the United States,9,17 1 in New Zealand,14 1 cluded, leaving 139 articles. In the final analysis, 30 ar- in the Netherlands,18 and 2 in Germany,15,16 could not con- ticles6,9,13-40 were identified that specifically included data firm these results. For example, Zirngibl et al15 studied on the association between eczema and domestic ani- 4578 children up to age 2 years. At that age, cat expo- mals. No previous systematic reviews or randomized con- sure was not significantly associated with subsequent ec- trolled trials were identified. Results of cohort and cross- zema risk (adjusted OR, 1.03; 95 % CI, 0.70-1.51). Strati- sectional studies according to type of pet are summarized fied analysis by family history of atopy showed no herein. significant association with the outcome (positive family history: OR, 0.92; 95% CI, 0.58-1.47; and negative fam- CATS ily history: OR, 1.32; 95% CI, 0.65-2.68) (Joachim Hein- rich, PhD, written communication, June 2006).15 Illi et Cohort Studies al16 followed up 1314 children from birth to age 7 years. Eczema was determined by parental reporting of symp- Eight cohort studies6,9,13-18 examined the relationship be- toms, by a physician’s diagnosis, and by a dermatologist tween cat exposure and eczema (Figure 1 and Table 1 on physical examination. There was no association be- and Table 2). In a large cohort study, Nafstad et al6 fol- tween exposure to cats in early life and eczema at age 2 lowed up 2531 Norwegian children to age 4 years and years (adjusted OR, 0.83; 95% CI, 0.50-1.39) (Sabina Illi, found a 50% reduction in eczema risk with cat exposure MPH, written communication, October 2005).16 Pooled at birth (adjusted odds ratio [OR], 0.50; 95% confi- analysis for all cohort studies showed an overall statis- dence interval [CI], 0.30-0.90). Stratified analysis showed tically significant protective association between previ- that the reduced eczema risk was strongest in atopic fami- ous cat exposure and subsequent eczema (OR, 0.76; 95% lies (OR, 0.3; 95% CI, 0.1-0.9) compared with those with- CI, 0.62-0.92).6,9,13-18

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1571 Table 1. Summary of Data From Birth Cohort Studies Arranged by Sample Size

Source and Participants, Age at Diagnostic (D) and Outcome Measures: Confounders Adjusted Country No. Follow-up Exposure (E) Criteria OR (95% CI) for in Analysis Benn et al,19 24 341 18 mo Questionnaire and Any pet during pregnancy or first 6 mo: adj OR, Parental history of allergy, siblings, 2004, subgroup 0.87 (0.79-0.96) sex, maternal age and education, Denmark examination (D), and infections questionnaire (E) Zirngibl et al,15 4578 2 y Questionnaire (D), Any pet at 2 y: adj OR, 0.74 (0.57-0.97); family history Parental history of allergy, siblings, 2002, questionnaire (E) of atopy: adj OR, 0.74 (0.55-1.01); no family history sex, maternal age, smoke Germany of atopy: adj OR, 0.72 (0.43-1.20); cat at 2 y: adj OR, exposure, study area and group, 1.03 (0.70-1.51); family history of atopy: adj OR, and parental nationality 0.92 (0.58-1.47); no family history of atopy: adj OR, 1.32 (0.65-2.68); dog at 2 y: adj OR, 0.63 (0.40-0.98); family history of atopy: adj OR, 0.53 (0.30-0.93); no family history of atopy: adj OR, 0.88 (0.43-1.83); small furry pets at 1 and 2 y: adj OR, 0.57 (0.24-1.32) Nafstad et al,6 2531 4 y Questionnaire (D), Any pet at birth: adj OR, 0.70 (0.50-0.90); atopic Parental history of allergy, siblings, 2001, questionnaire (E) parents: adj OR, 0.60 (0.40-0.90); nonatopic parents: sex, maternal age and education, Norway adj OR, 0.80 (0.60-1.20); cat at birth: adj OR, infections, birth order and weight, 0.50 (0.30-0.90); atopic parents: adj OR, income, smoke exposure, 0.30 (0.10-0.90); nonatopic parents: adj OR, duration of breastfeeding, and 0.60 (0.30-1.20); dog at birth: adj OR, respiratory tract infections 0.70 (0.40-1.00); atopic parents: adj OR, 0.50 (0.20-1.00); nonatopic parents: adj OR, 0.80 (0.50-1.40) Illi et al,16 1314 7 y Questionnaire and Cat at 3 mo: adj OR, 2.33 (0.85-6.38); cat allergen Ն2 Atopic family members, 2004, physical concentration at 6 mo: adj OR, 1.23 (0.44-3.39); increased cord blood IgE level, Germany examination (D), dog at 3 mo: adj OR, 1.11 (0.62-2.00) and early wheezing questionnaire and cat allergen concentration at 6mo(E) Tariq et al,20 1218 4 y Physical examination Any pet at birth: OR, 0.77 (0.55-1.09) None 1998, (D), questionnaire United (E) Kingdom Arshad et al,21 1215 2 y Physical examination Any pet at birth: OR, 1.03 (0.71-1.51) None 1993, (D), questionnaire United (E) Kingdom Hagendorens 1128 1 y Questionnaire (D), Prenatal cat: adj OR, 0.90 (0.60-1.30); cat postnatally: Sex, mode of delivery, birth weight, et al,13 2005, questionnaire (E) adj OR, 0.68 (0.47-0.97); prenatal dog: adj OR, breastfeeding, siblings, day care, Belgium 0.60 (0.40-0.90); dog postnatally: adj OR, smoke exposure, parental 0.70 (0.50-1.10) education, parental atopy, and carpet in bedroom 14 Purvis et al, 871 31⁄2 y Questionnaire (D), Cat at 1 y: OR, 0.81 (0.44-1.49); cat at 31⁄2 y: adj OR, Parental history of allergy, siblings, 2005, New questionnaire (E) 0.45 (0.21-0.97); dog at 1 y: adj OR, smoke exposure, duration of Zealand 1.31 (0.66-2.62); dog at 31⁄2 y: adj OR, breastfeeding, early wheezing, 1.25 (0.63-2.46) antibiotic use in first year of life, and damp/mold Phipatanakul 498 1 y Questionnaire (D), Cat at 2-3 mo: adj OR, 1.01 (0.70-1.50); dog at 2-3 mo: Sex and income et al,17 2004, dust sampling adj OR, 0.48 (0.24-0.97) United for pet allergen States exposure (E) Kerkhof 76 patients 1 y Physical examination Cat at 3 or 12 mo: adj OR, 0.60 (0.30-1.10); dog at Sex, birth weight, gestational age, et al,18 with eczema; (D), questionnaire 3 or 12 mo: adj OR, 1.00 (0.40-2.40) maternal age, duration of 2003, the 228 controls (E) breastfeeding, siblings, day care, Netherlands and smoke exposure; borderline negative association for cat disappeared after adjusting for avoidance behavior Gern et al,9 285 1 y Questionnaire (D), Cat at birth and 1 y: OR, 1.10 (0.66-1.84); dog at birth None 2004, questionnaire (E) and 1 y: OR, 0.40 (0.24-0.68); adj OR not given United (although P values for confounders given) States

Abbreviations: adj, adjusted; CI, confidence interval; OR, odds ratio.

Cross-sectional Studies tweencurrenteczemaandahistoryofcatexposure(Figure 2 and Table 2 and Table 3). One study22 demonstrated a re- Four cross-sectional studies19-22 evaluated the association be- duced risk with past cat exposure during the first year of life

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1572 Table 2. Summary of Cohort and Cross-sectional Study or Odds Ratio (Random) Study Results Subcategory 95% CI

Studies, No. Eczema and Past Cat Exposure Hölscher et al23 Reduced No Increased Exposure Eczema Risk Association Eczema Risk Rönmark et al24 Cohort studies Bråbäck et al25 Cat 2 6 0 Wickens et al22 Dog 4 3 0 “Any pet” 3 2 0 Cross-sectional studies Eczema and Past Dog Exposure Past cat 1 3 0 Hölscher et al23 Past dog 1 3 0 Past any pet 1 4 0 Rönmark et al24 Bråbäck et al25

Wickens et al22 (adjustedOR,0.40;95%CI,0.20-0.80);theother3studies23-25 showed no significant association. 0.2 0.5 1.0 2.0 5.0 Reduced Increased DOGS Risk Risk

Cohort Studies Figure 2. Forest plot of cross-sectional studies of pet exposure in the past arranged by sample size for cats and dogs separately. CI indicates Four of 8 cohort studies6,9,13-18 demonstrated a protective confidence interval. effect of dog exposure with risk reductions of 30% to 60% (Figure 1 and Tables 1 and 2). Overall, pooled analysis for all cohort studies for past exposure to dogs showed a 36% SMALL FURRY PETS (HAMSTERS, reduction in eczema risk (OR, 0.68; 95% CI, 0.53-0.87). RABBITS, AND GUINEA PIGS) One of these studies17 reported that ownership of a dog as early as age 2 to 3 months provided significant protection The only cohort study15 that examined past exposure to against eczema until 1 year of age (adjusted OR, 0.48; 95% small furry pets other than cats or dogs found no signifi- CI, 0.24-0.97). These results were echoed by Gern et al,9 cant association with eczema (adjusted OR, 0.57; 95% CI, who found a 60% reduction in eczema risk at age 1 year if 0.24-1.32). No cross-sectional studies have systematically children had been exposed to a dog at the time of birth (ad- examined the role of small furry pets in eczema. justed OR, 0.40; 95% CI, 0.24-0.68). Zirngibl et al15 and Nafstad et al6 also demonstrated significant risk reduc- PETS UNSPECIFIED tions at 2 and 4 years of age with dog exposure in German and Norwegian children (adjusted OR, 0.63; 95% CI, 0.40- Cohort Studies 0.98; and adjusted OR, 0.70; 95% CI, 0.40-1.00, respectively). In the study by Zirngibl et al,15 the beneficial effect Three of 5 cohort studies6,15,19-21 reported a significant re- was seen only in patients with a family history of atopy (OR, duction in eczema risk, one of which was of borderline sig- 0.53; 95% CI, 0.30-0.93) compared with children without nificance, with “any pet exposure” ranging from 13% to a positive family history (OR, 0.88; 95% CI, 0.43-1.83) 30% (Tables 1 and 2). The largest of these was a Danish (Joachim Heinrich, PhD, written communication, June national birth cohort study with 24 341 infant-mother pairs 2006). Similarly, in the study by Nafstad et al,6 a signifi- that used a questionnaire to measure pet exposure before cant protective effect of dog exposure was seen only in atopic age 6 months. A randomly selected subgroup was also physi- families (atopic families: OR, 0.5; 95% CI, 0.2-1.0 vs no fam- cally examined for eczema using clearly defined diagnos- ily history: OR, 0.8; 95% CI, 0.5-1.4). Purvis et al14 did not tic criteria. Pet exposure remained in the final logistic re- find an association between past and current dog expo- gression model, suggesting that individuals exposed to a sure and eczema. A similar lack of association was re- pet before age 6 months had 13% less eczema until age 18 ported by Illi et al16 at 7 years (adjusted OR, 1.11; 95% CI, months (adjusted OR, 0.87; 95% CI, 0.79-0.96).19 The only 0.62-2.00). other study that used physical examination to determine eczema found a 23% risk reduction with pet exposure dur- Cross-sectional Studies ing the study period, but the results were not significant (adjusted OR, 0.77; 95% CI, 0.55-1.09).20 No association Four cross-sectional studies22-25 evaluated parent- was seen between eczema and any pet in another study by reported past dog exposure and current eczema. One large the Isle of Wight group,21 with follow-up of 2 years and survey23 of 5360 German children showed a significant diagnosis by questionnaire in relation to pet exposure at inverse association between eczema at ages 5 to 14 years birth (univariate OR, 1.03; 95% CI, 0.71-1.51). Pooled analy- and dog exposure in the first year of life (OR, 0.65; 95% sis combining the 5 cohort studies that included any pet CI, 0.48-0.87). Three other studies22,24,25 revealed no sig- exposure showed an overall protective effect (OR, 0.79; 95% nificant association (Tables 2 and 3 and Figure 2). CI, 0.74-0.84).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1573 Table 3. Summary of Data From Cross-sectional Studies Arranged by Sample Size

Source and Participants, Diagnostic (D) and Outcome Measures: Confounders Adjusted Country No. Age, y Exposure (E) Criteria OR (95% CI) for in Analysis Bornehag et al,26 2003, 14 077 1-6 Questionnaire (D), Any pet at time of birth: adj OR, Age, sex, smoke exposure, familial Sweden questionnaire (E) 0.73 (0.66-0.81); avoidance allergy, breastfeeding, type of behavior: adj OR, building, and avoidance behavior 0.87 (0.78-0.97) Zutavern et al,27 2005, 12 601 5-7; Physician examination (D), Authors report no increase in Age, sex, grade, parental allergy, Germany 9-11 questionnaire (E) eczema with pet exposure in parental education, antibiotic first year of life; unable to use, onset of antipyretic calculate OR from data medication, breastfeeding duration, dampness, and drafty rooms Ho¨lscher et al,23 2002, 5360 5-14 Questionnaire (D), Cat first year of life: adj OR, Age, sex, region, survey, parental Germany questionnaire (E) 1.08 (0.81-1.45); dog first year education, parental atopy, of life: adj OR, 0.65 (0.48-0.87) breastfeeding, day care, sharing bedroom, smoke exposure, and contact with rodents and birds Morales Sua´rez-Varela 4387 8-15 Questionnaire (D), Any pet (past): OR, None et al,28 2005, Spain questionnaire (E) 0.90 (0.70-1.10) Ro¨nmark et al,24 1998, 3431 7-8 Questionnaire (D), Cat (past): adj OR, 0.91 (0.63-1.33); SPTϩ, family history of asthma, Sweden questionnaire (E) cat (current): adj OR, sex, damp at home, 0.73 (0.46-1.18); dog (past): adj breastfeeding Ͻ 3 mo, smoking OR, 0.80 (0.56-1.15); dog mother, urban living, and birth (current): adj OR, order 0.58 (0.38-0.87); SPTϩ to cat: OR, 2.59 (2.10-3.19); SPTϩ to dog: OR, 2.75 (2.20-3.44) Anyo et al,29 2002, 2729 7-12 Questionnaire (D), Any pet (past): adj OR, Age, sex, parental nationality, the Netherlands questionnaire (E) 1.16 (0.86-1.56); any pet first parental allergy, parental 2 y: adj OR, 0.95 (0.79-1.15); any education, siblings, smoke cat/dog first 2 y: adj OR, exposure, day care, and area 1.01 (0.83-1.22) of residence Hesselmar et al,30 2481 in 1991; 7-9; Questionnaire (D), Any pet in first year: adj OR, Parental allergy, siblings, and 1999, Sweden 412 in subgroup 12-13 questionnaire (E) 0.91 (0.54-1.52) frequent colds; adjustment for avoidance behavior showed similar results Bra˚ba¨cketal,25 2001, 2108 10-11 Questionnaire (D), Cat (past): OR, 1.00 (0.70-1.50); None Sweden questionnaire (E) dog (past): OR, 1.20 (0.80-1.70); adj data not given Wickens et al,22 2002, 293 7-10 Questionnaire (D), Cat first year of life: adj OR, Farm abode, exposure to poultry or New Zealand questionnaire (E) 0.40 (0.20-0.80); dog first year pigs, sex, ethnicity, maternal of life: adj OR, 0.80 (0.40-1.50) education, family history of allergy, siblings, antibiotic use in first year, maternal smoking, fires, infections, and dairy food consumption

Abbreviations: adj, adjusted; CI, confidence interval; OR, odds ratio; SPT+, positive skin prick test.

Cross-sectional Studies or present) on study results (eTable; available at http: //www.archdermatol.com). Most cohort and cross- Five cross-sectional studies26-30 evaluated past pet expo- sectional studies used multiple logistic regression analy- sure and current eczema. A large Swedish postal sur- sis to control for potential confounding factors, but only vey,26 which recruited 14 077 children, found a protec- 3 studies18,26,30 directly adjusted for avoidance behavior (1 tive effect with exposure to furry pets at the time of birth cohort study and 2 cross-sectional studies). Two cohort (adjusted OR, 0.73; 95% CI, 0.66-0.81). The protective studies6,15 indirectly assessed avoidance behavior by using effect of early life exposure remained significant even af- stratified analysis of a family history of atopic disease. ter adjustment for avoidance behavior (adjusted OR, 0.87; Where avoidance behavior (ie, parents stating that fa- 95% CI, 0.78-0.97).26 Four additional studies27-30 showed milial atopy was the reason for not having pets) was di- no significant association between past exposure and ec- rectly taken into account, the protective effect of pet ex- zema risk (Tables 2 and 3). posure on eczema risk was either reduced or rendered insignificant.18,26,30 In the study by Kerkhof et al,18 after OTHER EFFECTS exclusion of babies where avoidance behavior was present, the borderline protective effect of cat exposure dis- Overall, there seemed to be no systematic effect of age to appeared (including avoidance behavior: OR, 0.6; 95% follow-up or timing of pet exposure measurement (past CI, 0.3-1.1; and excluding avoidance behavior: OR, 0.8;

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1574 95% CI, 0.3-2.0) (Marjan Kerkhof, MD, written commu- zema, despite dog allergy being less prevalent than cat nication, September 2006). In the cohort studies by Zirn- allergy and, therefore, less likely to trigger avoidance be- gibl et al15 and Nafstad et al,6 data were stratified by fa- havior. This finding suggests that avoidance behavior milial atopic disease. In the former study, the protective alone is unlikely to be a full explanation for these nega- effect was retained only for dog exposure in individuals tive associations. An alternative explanation for the stron- from atopic families (at 2 years only) and was no longer ger inverse association between pets and eczema in chil- seen with cat exposure in either atopic or nonatopic fami- dren with a family history of allergic disease (Nafstad et lies after stratification. In the latter study, the protective al6) is that any such effect is more likely to be detected effect of cat and dog exposure was preserved only in the in high-risk groups with high disease incidence than in stratum with atopic parents and was no longer seen in low-risk groups. those with no family history. In the 2 cross-sectional studies that directly assessed avoidance behavior, 1 study30 LIMITATIONS OF THIS REVIEW did not show any significant association between pet exposure and eczema, and stratification for avoidance be- Some of the differences in results seen between cross- havior did not alter this (avoidance behavior included: sectional and birth cohort studies could well be ex- OR, 0.91; 95% CI, 0.54-1.52; and avoidance behavior explained by methodological differences. For example, cross- cluded: OR, 0.93; 95% CI, 0.53-1.6). In the other cross- sectional studies that ask about antecedent events, such sectional study, Bornehag et al26 asked parents if they as pet exposure at birth, are prone to recall bias, and this avoided or got rid of pets because of allergy. The OR when may lead to a positive or negative association between avoidance behavior was present was 0.99 (95% CI, 0.81- eczema and pet exposure, depending on whether a par- 1.21) and when this behavior was not present was 0.80 ent believes that pets are harmful or otherwise. Parents (95% CI, 0.70-0.91). Formal adjustment for avoidance with children who have eczema may be less likely to ad- behavior did not significantly change the study results, mit to pet exposure than parents of other children be- with the overall protective effect seen with pet exposure cause of feelings of guilt. Studies used different ways of still being present (adjusted OR, 0.87; 95% CI, 0.78- defining eczema. Some used the UK Working Party re- 0.97). finement of the Hanifin and Rajka criteria,41 others used physician diagnosis, and many of the questionnaire stud- COMMENT ies used the International Study of Asthma and Aller- gies in Childhood questionnaire.42 The variety of definitions used is a source of heterogeneity between studies. This systematic review did not find any convincing evi- Using clinical history rather than skin prick test results dence of a positive association between past and current or specific IgE levels to define atopy is another possible pet exposure and eczema risk. The results of some well- source of heterogeneity among studies. conducted prospective studies suggest that exposure to A further difference between the studies was the tim- a pet, especially to a dog, may be protective against child- ing of pet exposure. Nine cohort studies6,9,13-19 exam- hood eczema. ined pet exposure in the first year of life. In that group of studies, 5 studies6,9,16-18 concentrated on the period from AVOIDANCE BEHAVIOR birth to age 3 months. Two studies20,22 assessed pet exposure up to age 4 years. However, pooling only the data Although longitudinal studies are generally seen as being for studies evaluating pet exposure to 1 year6,9,13-19 re- methodologically superior to cross-sectional studies, it sulted in a minimal change to the OR estimate (cat ex- was disappointing that most of the birth cohorts in- posure: pooled OR, 0.75; 95% CI, 0.61-0.91; and dog cluded in this review did not adjust for potential avoid- exposure: pooled OR, 0.73; 95% CI, 0.58-0.93). The cross- ance behavior. Such parents may also opt to get rid of an sectional studies,22-30 in contrast, studied pet exposure existing pet if their child develops eczema, illustrating either at birth or to the current age of the child. the importance of evaluating cohort studies that sepa- Although we attempted to be as comprehensive as pos- rate early exposure and subsequent disease.26,30 The 3 co- sible in the literature search, some relevant articles may hort studies18,26,30 that recognized avoidance behavior as have been missed, and some data could have been con- an important confounding factor noted either a weak- cealed in asthma or allergy articles that would not have ened or a nonsignificant association between pet expo- been picked up by the eczema search terms. We also ac- sure and eczema after adjustment. knowledge that publication bias (selective reporting of In the Prevention and Incidence of Asthma and Mite studies with positive results) may contribute to these find- Allergy study of high-risk births,18 parents were asked ings. Before formulation of the hygiene hypothesis, this at a 3-month visit whether allergy was the reason for not may have made publication of negative associations be- having a cat; excluding these participants removed a bor- tween pets and eczema less likely. derline nonsignificant protective effect. However, no study It is also important to emphasize that this review ad- has been performed in a birth cohort of high-risk fami- dressed only the question of keeping household pets at or lies stratifying by parental previous belief at birth to de- around the time of birth and the risk of subsequent ec- termine whether prospectively recorded avoidance be- zema development. The question of whether a cat or dog havior is the true explanation for the association between in the home is responsible for disease flares in those who pet exposure and eczema. At the same time, we found a already have eczema is a separate one, and we did not find similar negative association for dogs vs cats and ec- any high-quality studies that addressed such a notion.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1575 CLINICAL AND RESEARCH IMPLICATIONS 2. Bener A, Galadari I, Naser KA. Pets, allergy and respiratory symptoms in children living in a desert country. Allerg Immunol (Paris). 1995;27(6):190-195. 3. Adinoff AD, Tellez P, Clark RA. Atopic dermatitis and aeroallergen contact sensitivity. Parents of children with eczema frequently ask whether J Allergy Clin Immunol. 1988;81(4):736-742. keeping a cat or dog at home might increase the risk that 4. Almqvist C, Larsson PH, Egmar AC, Hedreń M, Malmberg P, Wickman M. School another child might develop eczema. This review sug- as a risk environment for children allergic to cats and a site for transfer for cat gests that pet exposure is not associated with an in- allergen to homes. J Allergy Clin Immunol. 1999;103(6):1012-1017. creased risk of eczema, a finding that does not support 5. Custovic A, Green R, Taggart SC, et al. Domestic allergens in public places, II: dog (Can f1) and cockroach (Bla g 2) allergens in dust and mite, cat, dog, and advising families to avoid pets in early life in the hope of cockroach allergens in the air in public buildings. Clin Exp Allergy. 1996;26 preventing subsequent eczema. A possible protective effect (11):1246-1252. is shown in a variety of studies, which is likely, in part, 6. Nafstad P, Magnus P, Gaarder PI, Jaakkola JJ. Exposure to pets and atopy- to be due to avoidance behavior. Future cohort studies related diseases in the first 4 years of life. Allergy. 2001;56(4):307-312. 7. Halken S, Høst A, Hansen LG, Osterballe O. Effect of an allergy prevention pro- exploring the association between pet exposure and sub- gramme on incidence of atopic symptoms in infancy: a prospective study of 159 sequent allergic disease need to record the timing and “high-risk” infants. Allergy. 1992;47(5):545-553. type of pet exposure and perform stratified analysis for 8. Braun-Falco O, Ring J. Therapy of atopic eczema [in German]. Hautarzt. 1984;35 atopic vs nonatopic families and according to previous (9):447-454. beliefs. A systematic review of the role of pets in asthma 9. Gern JE, Reardon CL, Hoffjan S, et al. Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol. 2004;113 has shown an increased risk in older children with pet (2):307-314. exposure but a possible protective effect in young chil- 10. Hoare C, Li Wan Po A, Williams H. Systematic review of treatments for atopic dren; these findings need to be considered in the formu- eczema. Health Technol Assess. 2000;4(37):1-191. lation of practical advice.43 New research is needed to as- 11. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; sess the roles of pets in disease flares in eczema. This 7(3):177-188. 12. Johansson SG, Bieber T, Dahl R, et al. Revised nomenclature for allergy for global evidence should ideally be obtained from direct experi- use: report of the Nomenclature Review Committee of the World Allergy Orga- mental provocation or cohort studies with objective ex- nization, October 2003. J Allergy Clin Immunol. 2004;113(5):832-836. posure and disease activity measurements. 13. Hagendorens MM, Bridts CH, Lauwers K, et al. Perinatal risk factors for sensitization, atopic dermatitis and wheezing during the first year of life (PIPO study). Accepted for Publication: July 1, 2007. Clin Exp Allergy. 2005;35(6):733-740. 14. Purvis DJ, Thompson JM, Clark PM, et al. Risk factors for atopic dermatitis in Correspondence: Sineád M. Langan, MRCP, Centre of New Zealand children at 3.5 years of age. Br J Dermatol. 2005;152(4):742- Evidence-based Dermatology, Queen’s Medical Centre, 749. Nottingham NG7 2UH, England (sinead.langan 15. Zirngibl A, Franke K, Gehring U, et al; GINI Study Group. Exposure to pets and @nottingham.ac.uk). atopic dermatitis during the first two years of life: a cohort study. Pediatr Allergy Immunol. 2002;13(6):394-401. Author Contributions: Dr Langan had full access to all 16. Illi S, von Mutius E, Lau S, et al; Multicenter Allergy Study Group. The natural of the data in the study and takes responsibility for the course of atopic dermatitis from birth to age 7 years and the association with integrity of the data and the accuracy of the data analy- asthma. J Allergy Clin Immunol. 2004;113(5):925-931. sis. Study concept and design: Langan and Williams. Ac- 17. Phipatanakul W, Celedoń JC, Raby BA, et al. Endotoxin exposure and eczema in quisition of data: Langan and Flohr. Analysis and inter- the first year of life. Pediatrics. 2004;114(1):13-18. 18. Kerkhof M, Koopman LP, van Strien RT, et al; PIAMA Study Group. Risk factors pretation of data: Langan and Flohr. Drafting of the for atopic dermatitis in infants at high risk of allergy: the PIAMA study. Clin Exp manuscript: Langan. Critical revision of the manuscript for Allergy. 2003;33(10):1336-1341. important intellectual content: Flohr and Williams. Study 19. Benn CS, Melbye M, Wohlfahrt J, Bjo¨rksteń B, Aaby P. Cohort study of sibling supervision: Williams. effect, infectious diseases, and risk of atopic dermatitis during first 18 months Financial Disclosure: None reported. of life. BMJ. 2004;328(7450):1223. doi:10.1136/bmj.38069.512245.FE. 20. Tariq SM, Matthews SM, Hakim EA, Stevens M, Arshad SH, Hide DW. The preva- Funding/Support: This study was supported by a grant lence of and risk factors for atopy in early childhood: a whole population birth from the BUPA Foundation (Dr Langan). cohort study. J Allergy Clin Immunol. 1998;101(5):587-593. Role of the Sponsor: The sponsor had no role in the de- 21. Arshad SH, Stevens M, Hide DW. The effect of genetic and environmental fac- sign and conduct of the study; in the collection, analy- tors on the prevalence of allergic disorders at the age of two years. Clin Exp Allergy. sis, and interpretation of data; or in the preparation, re- 1993;23(6):504-511. 22. Wickens K, Lane JM, Fitzharris P, et al. Farm residence and exposures and the view, or approval of the manuscript. risk of allergic diseases in New Zealand children. Allergy. 2002;57(12):1171- Additional Information: The eTable is available at 1179. http://archdermatol.com. 23. Ho¨lscher B, Frye C, Wichmann HE, Heinrich J. Exposure to pets and allergies in Additional Contributions: Sabina Illi, MPH, Lennart children. Pediatr Allergy Immunol. 2002;13(5):334-341. Bra˚ba¨ck, PhD, Bill Hesselmar, PhD, Wanda Phipatanakul, 24. Ro¨nmark E, Lundba¨ck B, Jo¨nsson E, Platts-Mills T. Asthma, type-1 allergy and related conditions in 7- and 8-year-old children in northern Sweden: prevalence MD, Joachim Heinrich, PhD, Margo Hagendorens, PhD, rates and risk factor pattern. Respir Med. 1998;92(2):316-324. Anne Zutavern, MPH, Marjan Kerkhof, MD, and Jane 25. Bra˚ba¨ck L, Kjellman NI, Sandin A, Bjo¨rksteń B. Atopy among schoolchildren in Austin, MD, provided unpublished data for this review. northern and southern Sweden in relation to pet ownership and early life events. Takeshi Kono, MD, translated Japanese-language ar- Pediatr Allergy Immunol. 2001;12(1):4-10. 26. Bornehag CG, Sundell J, Hagerhed L, Janson S; DBH Study Group. Pet-keeping ticles. Ignaçio Garcia-Doval, PhD, extracted data from a in early childhood and airway, nose and skin symptoms later in life. Allergy. 2003; Spanish-language article. No compensation was re- 58(9):939-944. ceived for contributions. 27. Zutavern A, Hirsch T, Leupold W, Weiland S, Keil U, von Mutius E. Atopic dermatitis, extrinsic atopic dermatitis and the hygiene hypothesis: results from a cross-sectional study. Clin Exp Allergy. 2005;35(10):1301-1308. REFERENCES 28. Morales Sua´rez-Varela MM, Jimeńez-Lope´z MC, Llopis-Gonza´lez A, Garcıá- Marcos L. Study of the presence of domestic animals: cats and dogs and their 1. Ruzicka T. Atopic eczema between rationality and irrationality. Arch Dermatol. role in asthma, allergic rhinitis and atopic dermatitis in children [in Spanish]. Aten 1998;134(11):1462-1469. Primaria. 2005;36(9):525.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1576 29. Anyo G, Brunekreef B, de Meer G, Aarts F, Janssen NA, van Vliet P. Early, cur- 36. Austin JB, Russell G. Wheeze, cough, atopy, and indoor environment in the Scot- rent and past pet ownership: associations with sensitization, bronchial respon- tish Highlands. Arch Dis Child. 1997;76(1):22-26. siveness and allergic symptoms in school children. Clin Exp Allergy. 2002; 37. Dotterud LK, Falk ES. Atopic disease among adults in Northern Russia, an area 32(3):361-366. with heavy air pollution. Acta Derm Venereol. 1999;79(6):448-450. 30. Hesselmar B, A˚ berg N, A˚ berg B, Eriksson B, Bjo¨rkste´n B. Does early exposure to 38. Scha¨fer T, Vieluf D, Behrendt H, Kra¨mer U, Ring J. Atopic eczema and other mani- cat or dog protect against later allergy development? Clin Exp Allergy. 1999; festations of atopy: results of a study in East and West Germany. Allergy. 1996; 29(5):611-617. 51(8):532-539. 31. Kurosaka F, Nakatani Y, Terada T, et al. Current cat ownership may be associ- 39. Kalyoncu AF, Selc¸uk ZT, Karakoca Y, et al. Prevalence of childhood asthma and ated with the lower prevalence of atopic dermatitis, allergic rhinitis and Japa- allergic diseases in Ankara, Turkey. Allergy. 1994;49(6):485-488. nese cedar pollinosis in schoolchildren in Himeji, Japan. Pediatr Allergy Immunol. 40. Sebo˜k B, Schneider I, Harangi F; Primary Care Paediatricians in Baranya County. 2006;17(1):22-28. Familiar and environmental factors influencing atopic dermatitis in the childhood. 32. Yemaneberhan H, Flohr C, Lewis SA, et al. Prevalence and associated factors of J Eur Acad Dermatol Venereol. 2006;20(4):418-422. atopic dermatitis symptoms in rural and urban Ethiopia. Clin Exp Allergy. 2004; 41. Williams HC, Burney PG, Hay RJ, et al. The UK Working Party’s Diagnostic Cri- 34(5):779-785. teria for Atopic Dermatitis, I: derivation of a minimum set of discriminators for 33. Miyake Y, Yura A, Iki M. Cross-sectional study of allergic disorders in relation to atopic dermatitis. Br J Dermatol. 1994;131(3):383-396. familial factors in Japanese adolescents. Acta Paediatr. 2004;93(3):380-385. 42. Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Aller- 34. Scha¨fer T, Heinrich J, Wjst M, et al. Indoor risk factors for atopic eczema in school gies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8(3): children from East Germany. Environ Res. 1999;81(2):151-158. 483-491. 35. Austin JB, Russell G, Adam MG, Mackintosh D, Kelsey S, Peck DF. Prevalence 43. Apelberg BJ, Aoki Y, Jaakkola JJ. Systematic review: exposure to pets and risk of asthma and wheeze in the Highlands of Scotland. Arch Dis Child. 1994;71 of asthma and asthma-like symptoms. J Allergy Clin Immunol. 2001;107(3): (3):211-216. 455-460.

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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1577 EDITORIAL Acute and Recurrent Vesicular Hand Dermatitis Not Pompholyx or Dyshidrosis

N THIS ISSUE,GUILLET ET AL1 DISCUSS THE POTEN- rare entities. The former is characterized by the sudden tial causes of pompholyx in 120 patients they development of small (1-2-mm) vesicles on nonery- studied during a 3-year period. For dermatolo- thematous skin, usually on the sides of the fingers or on gists interested in hand eczemas, this study high- the palms and soles. The vesicles itch a bit, last 1 to 2 lights issues that can confound any hand ec- weeks, desquamate, and then recur at unpredictable in- Izema study. tervals. Pompholyx is similar but more severe, explo- sive, includes bullae, and usually involves the palms but TERMINOLOGY rarely the soles. In both instances, the “usual suspects,” to be described later, have been eliminated and “idio- For starters, we confront the matter of terminology. The pathic” rules the day. I find these rigid definitions of value authors cite the description of “dysidrosis” given by Til- because giving these patients (especially the ones with a bury Fox2 in 1873 as being related to “difficult sweat- severe flare-up) 40 to 60 mg of prednisone on day 1 of ing” and characterized by recurrent crops of vesicles or the flare-up (if not too frequent) can stop the episodes. bullae (on nonerythematous skin) located on the lateral When hand eczemas sport constant bouts of vesicula- aspects of the fingers and on the palms and soles.2 tion on an erythematous base on the palms (or soles), I Hutchinson,3 describing the same entity in 1876, added call them chronic vesicular hand eczema. the term cheiro-pompholyx, or vesicular eruption of the The reason this terminology is so important is that un- hands, but discounted sweating. Ever since, the terms dys- less it is rigidly adhered to, it is almost impossible to com- hidrosis and pompholyx have been used by authors and pare causes and therapies from study to study. In 2004, practitioners to describe the same condition, different con- the European Dermato-Epidemiology Network7 re- ditions, or simply any chronic and often disabling ve- viewed 90 studies of treatments of hand eczema col- sicular hand eczema (despite the fact that episodic re- lected from 1977 to 2003 by reviewing electronic data- currences and absence of erythema are included in the bases, 17 dermatology journals, and 4 medical journals. classic definitions of both dyshidrosis or pompholyx). They concluded that “studies need to describe in more detail what they mean by hand eczema.”7(p451) “The over- See also page 1504 all recommendation is to ‘start again.’”7 In short, they believed that, with 1 or 2 exceptions, the 90 studies they Even the North American Contact Dermatitis Group reviewed were so inadequate “that physicians will con- (I admit I am a member) cannot make up its mind on tinue to use an array of treatments, many of which will 7(p451) this issue. Coding choices of allergic or irritant derma- be ineffective or even harmful.” titis, atopic dermatitis, psoriasis, nummular dermatitis, In a recent remarkably complete review of the therapy, epidemiology, and clinical characteristics of dyshidro- other dermatitis or dermatoses, contact urticaria, and pom- 8 2 pholyx are all offered as possible diagnoses to use in cod- sis, Lofgren and Warshaw cite the descriptions of Fox and Hutchinson3 of dysidrosis [sic] and pompholyx pre- ing hand eruptions. Dyshidrosis is not an option, nor is viously referenced and the description of Shelley9 in 1953, chronic vesicular hand eczema.4 Most members code which fully debunked the relationship of dysidrosis [sic] chronic vesicular hand eczemas as pompholyx (written 4 to eccrine sweat glands and again classically defined the communication from Warshaw et al, July 2007). condition. They review management strategies that ob- In the most recent published North American Con- 4 serve patients for months and cite the use of a Dyshi- tact Dermatitis Group data on contact dermatitis of the drotic Eczema Area and Severity Index that features ery- hands, pompholyx constitutes 1.7% of 3456 patients from thema in its calculations.10 They try hard to adhere to a 1994 to 2004 who were diagnosed as having only pom- description of dyshidrosis that features recurrences, tran- pholyx and 3.4% of 3456 patients with hand diagnoses sience, and no erythema, but the confusion over termi- who had pompholyx listed as 1 of 3 possible diagnostic nology in the literature makes it essentially impossible. codes. Of 1000 patients, 2.6% coded as having allergic For example, they cite (as do Guillet et al1 and oth- contact dermatitis were also coded as having pompho- ers) the work of de Boer et al,11 who note that dyshi- lyx.4 Either way, pompholyx is rare. drotic eczema can be associated with metal working flu- I have been down this controversial road before.5,6 It ids even in nonatopic patch test negative patients. is my view (I’m older than 60 years, so I’m entitled to a Dyshidrotic eczema in the article by de Boer et al in- view) that dyshidrosis and pompholyx are distinct but cludes the hands (the exact location is unknown) and

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1578 the forearms and has none of the classic features of “pure” though no one any longer considers sweating to have caus- dyshidrosis or pompholyx previously described. ative associations, it is often noted by these patients and Does any of this matter? Many textbooks and medi- has been cited in some therapies that successfully use ion- cal dictionaries have “thrown in the towel” and consid- tophoresis or botulinum toxin A injections.7 ered dyshidrosis, pompholyx, and often vesicular hand As a believer in dermatophytid reactions, I was pleased dermatitis as synonyms.12-14 A text on contact dermatitis to note that 5.0% of the controls in the study by Guillet states that “pompholyx (also referred to as dyshidrosis) et al,1 but 19 (15.8%) of their patients with pompholyx, is probably not a disease sui generis.”13(p80) In short, in had an interdigital dermatitis associated with a derma- this day of emphasis on evidence-based medicine, dis- tophyte or with Candida. They performed no trichophy- eases with natural histories strictly defined as lasting for tion intradermal injections. However, 13 of the 19 pa- weeks cannot have their outcomes evaluated by thera- tients who were treated with topical imidazole for 3 weeks pies administered for months.8 Precision is requisite if experienced clinical remissions without later recur- comparisons are to be made. rences of pompholyx symptoms. The subject of derma- Guillet et al,1 in the article in this issue, seemed to truly tophytids, like nickel allergy, is also viewed as rare and restrict their patient population to the rigid definitions controversial as an explanation for vesicular hand ecze- of pompholyx and dyshidrosis previously given. In par- mas. However, the recent review by Bryld et al,17 was un- ticular, they confine their patients to those with lesions able to associate nickel allergy with vesicular hand erup- on their palms or soles and they exclude erythema asso- tions, did find a statistically significant association with ciated with vesicles, “thus eliminating contact ecze- tinea pedis. I agree. mas.”1 They insist on a “cyclic pattern of recurrent short- Of the patients studied by Guillet et al,1 48.3% smoked, term attacks.” The frequency of recurrences is not vs 28.0% of their controls. Also, 24.1% of their patients documented, nor is the clarity of the skin between at- suspected stress as causative. The authors believed smok- tacks. They provide 100 age- and sex-matched control ing triggered symptoms in 2 patients but did not ana- patients, a most unusual addition. We do not know where lyze stress. They did, however, note high credibility in the controls came from or if they had any dermatitis. These 3 patients with ingested drug-related stories and 3 with restrictions allow them to clearly focus on potential causes food-related stories. of pompholyx and dyshidrosis. Perhaps the portion of the study by Guillet et al1 that will be accepted with the greatest difficulty by derma- CAUSES tologists who perform patch testing is their set of conclusions about “contact pompholyx.” After selecting pa- Like all hand eczemas, pompholyx and dyshidrosis may tients with no vesicles associated with erythema, thus result from several factors. Allergens, irritants, infec- eliminating contact eczemas, they concluded that a con- tions, friction, drugs, atopy, foods, and various ingested tact allergy was found in 74.2% of their patients. Oth- items have been indicted as causal agents.12-14 The ar- ers8,13 writing about pompholyx and dyshidrosis have cited ticle by Guillet et al1 reviews associations of hyperhidro- studies aligning positive patch test results with this con- sis, smoking, stress, atopy, foot fungal infections, in- dition, but mostly only a few allergens other than met- gested metals, food or drugs, and contact allergens in 120 als are discussed with much credence. The results by Guil- patients with pompholyx, as defined by them. let et al allow for comments on the methods used for patch The term pompholyx had almost been abandoned by testing, how these tests are interpreted, and how rel- authors before the work of Veien and Kaaber15 and some evance is determined. others in the late 1970s, attaching the association of in- In addition to nickel, shower gels, fragrance, sham- gested metals (especially nickel), balsam of Peru, and foods poos, lauryl sulfate, fresh tobacco, and octyl gallate are with pompholyx-type hand eczemas in allergic pa- listed, among others, as causing positive reactions. In fact, tients.15 Veien and Menne´ 14 often diagnosed their pa- the relevance of positive test results for shower gel is said tients as having “vesicular hand eczemas (pompholyx)” to have been confirmed 28 of 30 times; and shampoos, but did not adhere to the classic definitions of pompho- 14 of 17 times. The allergens in the shower gels and sham- lyx. The association of these ingested substances and ve- poos were said to be fragrances in 14 instances. Overall, sicular hand eczemas is highly controversial.5,6,8,12 An im- relevance for contact pompholyx is stated as being 67.5% portant observation of the relationship of ingested metals (81 of 120 patients). This relevance was confirmed by is that of Veien et al,16 who found that a metal-restricted an “eviction test.” diet seemed to improve vesicular hand eczemas even in The separation of irritant from allergic patch test re- patients with negative patch test results. In the study by sults can be difficult. Guillet et al1 relied on the diminu- Guillet et al,1 none of the patients with negative patch tion of erythema at the second 96-hour reading as an in- test results experienced a flare-up after oral doses of 2.5 dication of irritation. In fact, this is not always the case, mg of nickel sulfate or 1 mg of cobalt sulfate using the particularly with detergents, as shown by Rietschel.18 Fur- methods of Veien et al. Only 2 of the 25.0% of their pa- thermore, patch testing with soaps and detergents at any tients who had positive results to metal had flare-ups with concentration is so subject to misinterpretation that many oral metal challenges. This failure to tie nickel allergy to patch testers (like me) do not test soaps at all. When it vesicular hand eruptions has been recently confirmed by is done, standard texts recommend cautious interpreta- others.17 The controversy, however, is not at rest. tion with the addition of controls.13 We know nothing Of the patients studied by Guillet et al,1 40.0% noted about the intensity of the reactions of Guillet et al or how hyperhidrosis, compared with 7.0% of their controls. Al- relevance was determined. It is unclear what the “evic-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1579 tion test” is that was used to determine allergen “involve- use in our own patients’ care, but in studies and reviews ment.” Furthermore, the nature of “disease recurrence” such rigidity seldom prevails. Until a more concise label with external application of a suspect allergen is not de- can be agreed on, I propose the use of “acute and recur- scribed. Were shower gels and shampoos applied to the rent vesicular hand dermatitis,” given by Veien and hands only, or was a shower taken and the hair sham- Menne,14 for discussion. This will not include feet-only pooed? When did the recurrence occur, and what did it situations, but dermatologists caring for these patients look like? How could the face or eyelids have remained know that feet can be included in this primarily hand con- clear in such exposures in allergic patients? And, fi- dition. It is time for pompholyx and dyshidrosis to exit. nally, how did the authors know that fragrances were the guilty shampoo or shower gel ingredient? Did they test Frances J. Storrs, MD individual soap ingredients and did they discover if the fragrance mix ingredients were actually in the soap fra- Correspondence: Dr Storrs, Department of Dermatol- grances? None of these questions are answered in this ogy, Oregon Health & Science University, 3303 SW Bond article. No data or description of their “relevance analy- Ave, Mail Code CH 16D, Portland, OR 97239 (storrsf sis” is provided to allow us to answer these questions. @ohsu.edu). We do not know what relevance means in this study. Fra- Financial Disclosure: None reported. grances and other allergens are often found guilty of causation in allergic contact dermatitis, with little or no docu- REFERENCES mented proof.19 The evaluation of patients with contact dermatitis by 1. Guillet MH, Wierzbicka E, Guillet S, Dagregorio G, Guillet G. A 3-year causative patch testing involves the following: (1) the selection of study of pompholyx in 120 patients. Arch Dermatol. 2007;143(12):1504-1508. 2. Fox T. Dysidrosis: an undescribed eruption. BMJ. 1873;2:365-366. standardized allergens, as much as possible, to allow 3. Hutchinson J. Cheiro-pompholyx: notes of a clinical lecture. Lancet. 1876;1:630- comparisons from study to study (this is not done with 631. soaps); (2) the critical and sometimes cynical assess- 4. Warshaw EM, Ahmed RL, Belsito DV, et al; North American Contact Dermatitis ment of the patch test reaction itself (is it replicable, Group. Contact dermatitis of the hands: cross-sectional analyses of North Ameri- can Contact Dermatitis Group Data, 1994-2004 [published online ahead of print strong, and negative in controls?); and (3) the defini- June 5, 2007]. J Am Acad Dermatol. 2007;57(2):301-314. tion of how relevance is determined and strict adher- 5. Fowler JF, Storrs FJ. Nickel allergy and dyshidrotic eczema: are they related? ence to this definition. Am J Contact Dermat. 2001;12(2):119-121. When all the avenues for causation were investigated 6. Warshaw E, Lee G, Storrs FJ. Hand dermatitis: a review of clinical features, thera- by these authors, 15.0% of their patients had no expla- peutic options, and long-term outcomes. Am J Contact Dermat. 2003;14(3): 119-137. nation. These patients were “atopic,” although we do not 7. Van Coevorden AM, Coenraads PJ, Svensson A, et al; European Dermato- know if this was respiratory or cutaneous atopy. In this Epidemiology Network (Eden). Overview of studies of treatments for hand ec- study, 46.7% of the patients had an atopic condition (vs zema: the EDEN hand eczema survey. Br J Dermatol. 2004;151(2):446-451. 20.0% of the controls). The authors1 suggest that pom- 8. Lofgren SM, Warshaw EM. Dyshidrosis: epidemiology, clinical characteristics and therapy. Dermatitis. 2006;17(4):165-181. pholyx could represent an equivalent of atopic palmar 9. Shelley WB. Dysidrosis (pompholyx). AMA Arch Derm Syphilol. 1953;68(3):314- plantar dermatitis. The literature notes conflict on the 319. association of atopy and pompholyx or dyshidrosis, and 10. Vocks E, Plo¨tz SG, Ring J. The Dyshidrotic Eczema Area and Severity Index: a Bryld et al17 found no association. score developed for the assessment of dyshidrotic eczema. Dermatology. 1999; 198(3):265-269. 11. de Boer EM, Bruynzeel DP, van Ketel WG. Dyshidrotic eczema as an occupa- CONCLUSIONS tional dermatitis in metal workers. Contact Dermatitis. 1988;19(3):184-188. 12. Burns T, Breathnach S, Cox N, Griffiths C, eds. Rook’s Textbook of Dermatology. So now do we know what pompholyx is and what causes 7th ed. Oxford, England: Blackwell; 2004. it? I’m afraid not. I join the European Dermato- 13. Rietschel RL, Fowler JF, eds. Fisher’s Contact Dermatitis. 5th ed. New York, NY: Lippincott Williams & Wilkins; 2001:80, 89, 273. Epidemiology Network study’s lament that we use inex- 14. Veien NK, Menne´T.Acute and recurrent vesicular hand dermatitis (pompholyx). 7 act terminology in defining all kinds of hand eczema. In: Menne´ T, Maibach HI, eds. Hand Eczema. 2nd ed. New York, NY: CRC Press; This lack of precision in definition has rendered accu- 2000. rate analysis of causation and comparisons of therapeu- 15. Veien NK, Kaaber K. Nickel, cobalt, and chromium sensitivity in patients with pom- tic strategies impossible. Thorough descriptions of meth- pholyx (dyshidrotic eczema). Contact Dermatitis. 1979;5(6):371-374. 16. Veien NK, Hattel T, Justesen O, Norholm A. Oral challenge with metal salts, I: ods and definitions of interpretations and relevance are vesicular patch-test–negative hand eczema. Contact Dermatitis. 1983;9(5): lacking or are simply not adhered to. In short, as the Eu- 402-406. ropean Dermato-Epidemiology Network study sug- 17. Bryld LE, Agner T, Menne´ T. Relation between vesicular eruptions on the hands gests, we should “start again.” Clearly, the terms pom- and tinea pedis, atopic dermatitis and nickel allergy. Acta Derm Venereol. 2003; 83(3):186-188. pholyx and dyshidrosis are obsolete in that really no 18. Rietschel RL. Advances and pitfalls in irritant allergen testing. J Soc Cosmet Chem. modern investigators use them as originally defined. Some 1982;33:309-314. dermatologists (old ones like me) define them rigidly for 19. Storrs FJ. Fragrance. Dermatitis. 2007;18(1):3-7.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1580 EDITORIAL Teledermatology Extending Specialty Care Beyond Borders

ELEMEDICINE IS THE “USE OF TELECOMMU- way and Canada, and in US state-sponsored telemedi- nications technology for medical diagnos- cine programs. tic, monitoring and therapeutic purposes Teledermatology is an established tool for delivering when distance and/or time separate the specialty care. In a review of the teledermatology litera- participants”1(p11) and includes distance ture, Whited2 reported that the agreement rate between Tlearning. Practitioners of telemedicine in the dermatol- clinic-based dermatologists and store-and-forward tele- ogy community have created a body of research litera- dermatologists ranged from 57% to 95% when both the ture that is unsurpassed by any other specialty. These telediagnosis and differential diagnoses were considered.4 In dermatologists reported enhanced patient access to a study that compared the diagnostic reliability of tele- specialty care with decreased waiting time for consulta- dermatologists with clinic-based dermatologists, diag- tion, good diagnostic reliability, and high patient satis- nostic reliability was found to be comparable between faction.2 Two types of telemedicine delivery platforms have these 2 examiner groups. Interestingly, in-person, face- been studied: (1) real-time teleconsultations using vid- to-face evaluation of 100 consecutive patients by 5 board- eoconferencing equipment and (2) store-and-forward tele- certified dermatologists demonstrated an 80% diagnos- consultations, in which patient information and digital tic concordance rate.5 images are electronically sent to the specialist who at a In this issue of the Archives, Binder et al6 demon- later time evaluates the data and submits comments elec- strate the feasibility of remote monitoring and care of leg tronically to the referring physician. Each delivery plat- ulcers by wound care experts using digital images. High form has its strengths and weaknesses in terms of cost, patient satisfaction and acceptance by home care nurses ease of use, and time to complete the teleconsultation. and wound experts were noted, reinforcing the results Although a dermatologist cannot touch or smell a le- of other store-and-forward wound care studies.7-9 Braun sion at a distant location, the physician extender who pre- et al10 and Tsai et al11 reported the feasibility of treating sents the patient during a live interactive or a store-and- wounds at a distance based on images captured by cell forward consultation can be trained to provide this phone cameras. Agreement on treatment recommenda- information. tions by remote evaluation vs face-to-face evaluation of ulcers was reported at 73%.12,13 See also page 1511 The American Academy of Dermatology Association (AADA) “supports the use of telemedicine to deliver der- The first wave of telemedicine in the 1970s was marked matologic expertise to populations who would not oth- by custom-made systems using microwave technology erwise have access to dermatologists.”14(p1) that were slow, expensive, and large. One setup re- The AADA, like the American College of Radiology and quired 2 flatbed trailers and 2 days for a 5-person crew the American Psychiatric Association, has developed guide- to assemble.3 The second wave of telemedicine in the mid lines for conducting telemedicine consultations. The AADA 1990s was driven by digital cameras, cheaper telecom- Task Force on Dermatology provides information on tech- munications and technology, and the Internet. Remote nical standards that are applicable worldwide and state- monitoring of dermatologic conditions is increasing now ments on credentialing, licensure, and reimbursement that owing to lowered costs of digital cameras with excellent are applicable to the United States. The recent summer “hands-on” teledermatology workshop and the annual AAD resolution and videoconferencing equipment, cheaper teledermatology forum offered opportunities for derma- telecommunications line costs, and widespread Inter- tologists to familiarize themselves with this technology. net access. Patient expectations to be seen by a special- The American Telemedicine Association Teledermatol- ist based on more patient involvement in their health care ogy Working Group recently developed “Practice Guide- decisions and access to online medical information are lines for Teledermatology” for clinical, technical, and ad- driving the demand for teledermatology consultations. ministrative issues that are available online.15 Just as using a bank automated teller machine and pay- Regulation of a technology is an indication of the gov- ing for gasoline with a credit card were once novel tech- ernment’s perception of or need to manage a growing ac- nologies, so is telemedicine on its way to becoming a fa- tivity. Malaysia has ruled that physicians providing care miliar way to administering health care. It already is to patients in their country must hold Malaysian medi- familiar to patients and practitioners in countries that have cal licenses.16 Other countries have similar require- national or regional telemedicine networks, such as Nor- ments. In the United States, a physician is required to have

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1581 a medical license in the state where the patient is lo- Correspondence: Dr Burdick, Department of Dermatol- cated. The US Joint Commission on Accreditation of ogy, University of Miami Miller School of Medicine, 1600 Health Care Organizations requires that physicians who NW 10th Ave, Room 2023A, Miami, FL 33136 (aburdick provide real-time, live interactive consultations must be @med.miami.edu). credentialed at the originating site where they provide Financial Disclosure: None reported. direct patient care. However, store-and-forward consultants who provide recommendations to referring physicians and do not provide direct patient care are consid- REFERENCES ered consultants and do not require this credentialing.17 A detailed analysis of federal and state laws are available 1. US DHHS Agency for Healthcare Research and Quality Web site. http://www from the American Health Lawyers Association.18 .ahrq.gov. Accessed September 25, 2007. As telemedicine has become more widely used and its 2. Whited JD. Teledermatology research review. Int J Dermatol. 2006;45(3):220-229. 3. Preston J. The Telemedicine Handbook, Improving Health Care With Interac- usefulness better understood by insurance providers, re- tive Video. Austin, TX: Telemedical Interactive Consultative Services Inc; imbursement has improved and expanded. In the United 1993. States, teleradiology has been reimbursed by Medicare 4. Whited JD, Hall RP, Simel DL, Foy ME, Stechuchak KM, Drugge RJ. Reliability for many years because the medical services provided are and accuracy of dermatologists’ and clinic-based and digital image consultations. not typically delivered face-to-face by a radiologist to a J Am Acad Dermatol. 1999;41(5, pt 1):693-702. 5. Lowitt MH, Kessler II, Kauffman CL, Hooper FJ, Siegel E, Burnett JW. Teleder- patient. Currently, Medicare reimburses for live inter- matology and in-person examinations. Arch Dermatol. 1998;134(4):471-476. active teleconsultations, and in 18 states Medicaid reim- 6. Binder B, Hofmann-Wellenhof R, Salmhofer W, Okcu A, Kerl H, Soyer HP. Tele- burses live teleconsultations.19 Several private payers, such dermatological monitoring of leg ulcers in cooperation with home health care as Blue Cross, pay for telemedicine consultations in some nurses. Arch Dermatol. 2007;143(12):1511-1514. 20 7. Hofmann-Wellenhof R, Salmhofer W, Binder B, Okcu A, Kerl H, Soyer HP. Fea- states. Outcomes of the Medicare demonstration project sibility and acceptance of telemedicine for wound care in patients with chronic for teledermatology in Alaska and Hawaii are pending. leg ulcers. J Telemed Telecare. 2006;12(suppl 1):15-17. California law requires all insurance companies to pay 8. Wilkins EG, Lowery JC, Goldfarb S. Feasibility of virtual wound care: a pilot study. for clinical services regardless of the method of deliver- Adv Skin Wound Care. 2007;20(5):275-278. ing the care, including telemedicine. 9. Kim HM, Lowery JC, Hamill JB, Wilkins EG. Patient attitudes toward web-based system for monitoring chronic wounds. Telemed J E Health. 2004;10(2):S26- Dermatologists can participate in teledermatology con- S34. 21 sultations through the Swinfen Charitable Trust, which 10. Braun RP, Vecchietti JL, Thomas L, et al. Telemedical wound care using a new supports health care practitioners around the world using generation of mobile telephones. Arch Dermatol. 2005;141(2):254-258. a store-and-forward system and was highlighted during 11. Tsai HH, Pong YP, Liang CC, Lin PY, Hsieh CH. Teleconsultation by using the mobile camera phone for remote management of the extremity wound: a pilot the 2007 Society of Pediatric Dermatology teledermatol- study. Ann Plast Surg. 2004;53(6):584-587. 22 ogy forum. In addition, the Office for the Advance- 12. Kim HM, Lowery JC, Hamill JB, Wilkins EG. Accuracy of a web-based system for ment of Telehealth has established regional telemedi- monitoring chronic wounds. Telemed J E Health. 2003;9(2):129-140. cine resource centers to provide education and training.23 13. Salmhofer W, Hofmann-Wellenhof R, Gabler G, et al. Wound teleconsultation in Telemedicine is a way to address the maldistribution patients with chronic leg ulcers. Dermatology. 2005;210(3):211-217. 14. Position Statement on Telemedicine. American Academy of Dermatology of dermatologists and shortage of medical dermatolo- Association Web site. http://www.aad.org/NR/rdonlyres/D3BC8497-02CA gists. Teledermatology has been shown to substantially -4647-B085-C50B91580A49/0/Telemedicine.pdf. Accessed September 25, shorten the time between referral date and definitive clini- 2007. cal intervention compared with traditional clinic-based 15. American Telemedicine Association Special Interest Group in Teledermatology 24 Web site. http://atmeda.org/ICOT/sigtelederm.htm. Accessed September 25, consultation. Part-time, disabled, and retired derma- 2007. tologists may use teledermatology to provide specialty 16. Laws of Malaysia, Telemedicine Act of 1997, Act 564. http://www.parlimen.gov care to patients both locally and around the world. .my/actindexbi/pdf/ACT-564.pdf. Accessed September 25, 2007. Resident training in teledermatology is an estab- 17. Joint Commission. Education makes volunteers part of the team. The Source. lished part of some programs. All dermatology resi- 2003;1(10):1-12 http://www.jcrinc.com/ppdf/pubs/pdfs/TS/TS1003.pdf. Ac- cessed September 25, 2007. dency programs must document that they are assessing 18. Mayo TW, Kepler T. Telemedicine: Survey Analysis of Federal and State Laws. and improving the 6 core competencies of the American Washington, DC: American Health Lawyers Association; 2007. College of Graduate of Medical Education. A store-and- 19. US DHHS Centers for Medicare and Medicaid Services. http://www.cms.hhs.gov forward teledermatology system enables documenta- /home/medicaid.asp. Accessed September 25, 2007. 20. Burdick AE, Hu S. Telemedicine reimbursement surveys. In: Pak HS, Edison K, tion of each of these core competencies in the areas of Whited J, eds. Teledermatology: A User’s Guide. New York, NY: Cambridge Uni- patient care, medical knowledge, practice-based learn- versity Press; 2008. ing, interpersonal and communication skills, profession- 21. Swinfen Charitable Trust Web site. http://www.uq.edu.au/swinfen. Accessed Sep- alism, and systems-based practice.25 tember 25, 2007. It can be envisioned that, in a few years, the Ameri- 22. Teledermatology Forum Events and News, 19th Annual Pre-American Academy of Dermatology Meeting; February 1, 2007; Washington, DC. Society of Pediat- can Board of Dermatology will require telemedicine tech- ric Dermatology Web site. http://www.pedsderm.net/preAAD2007.htm. Ac- nology to be taught during residency training. First, the cessed September 25, 2007. faculty who train these residents will need to learn and 23. US DHHS Health Resources and Services Administration, Office for the Advance- familiarize themselves with this technology. Then they ment of Telehealth Web site. http://www.hrsa.gov/telehealth. Accessed Septem- ber 25, 2007. can model the effectiveness and ease with which remote 24. Whited JD, Hall RP, Foy ME, et al. Teledermatology’s impact on time to inter- diagnosis and management for skin disease can be per- vention among referrals to a dermatology consult service. TelemedJEHealth. formed for the next generation of dermatologists. 2002;8(3):313-321. 25. Perez OA, Berman B, Hodson DS, et al. Teledermatology: an educational tool for Anne E. Burdick, MD, MPH resident training. Telemed J E Health. 2007;13(2):220-236.

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SECTION EDITOR: JAMES M. GRICHNIK, MD, PhD; ASSISTANT SECTION EDITORS: ASHFAQ A. MARGHOOB, MD; ALON SCOPE, MD A Dermoscopy Subpattern of Plaque-Type Psoriasis Red Globular Rings

Francisco Va´zquez-Lo´pez, MD; Pedro Zaballos, MD; Alejandro Fueyo-Casado, MD; Jesus Sańchez-Martıń, MD; Asturias Central University Hospital, Oviedo (Drs Va´zquez-Lo´pez, Fueyo-Casado, and Sańchez-Martıń), and Hospital Sant Pau y Santa Tecla, Tarragona (Dr Zaballos), Spain

HE LESIONS SHOWN ARE FROM THE LEG OF capillary appearance. Histologically, the red globules a 55-year-old man (Figure 1), the leg of represent the view from the top of the tortuous, plenti- a 34-year-old woman (Figure 2), the ful, coiled, ectatic, and elongated capillaries within the arm of a 45-year-old man (Figure 3), thin, elongated, psoriatic dermal papillae, which are the and the trunk of a 40-year-old man vascular basis of the Auspitz sign. Characteristically, the (TFigure 4). All of these lesions reveal a similar dermo- dilated red globules are regularly and uniformly distrib- scopic subpattern (original magnification ϫ10): pres- uted along the psoriatic plaque. The ring pattern illus- ence of round capillaries (red globules) arranged in trated herein is infrequent and represents a dermo- irregular circles or rings with a beaded, lacelike scopic subpattern of plaque-type psoriasis.

Figure 1. Figure 2.

Figure 3. Figure 4.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1612 OFF-CENTER FOLD

SECTION EDITOR: MICHAEL E. MING, MD, MSCE; ASSISTANT SECTION EDITORS: CARRIE ANN R. CUSACK, MD; SENAIT W. DYSON, MD; JACQUELINE M. JUNKINS-HOPKINS, MD; VINCENT LIU, MD; KARLA S. ROSENMAN, MD

Solitary Cutaneous Nodule in an Immunocompromised Patient

Minal N. Singh, MRCP; Susan Andrew, MRCPath; David Fitzgerald, MRCP; Hope Hospital, National Health Services Trust, Manchester, England (Drs Singh and Fitzgerald), and Ysbyty Gwynedd, Bangor, Wales (Dr Andrew) REPORT OF A CASE oral tacrolimus, oral prednisolone, and atorvastatin cal- liver function screening test, erythrocyte sedimentation cium trihydrate. rate, and chest radiograph were within reference range. A A 47-year-old woman who had undergone renal trans- Physical examination revealed a single cutaneous wedge biopsy sample was obtained from the lesion and plantation presented with a 3-month history of a persis- nodule measuring 1.0ϫ2.8 cm overlying the left medial sent for histologic analysis (Figure 2 and Figure 3) tent ulcerating nodule on the left ankle. She had no his- malleolus (Figure 1). The patient had no lymphade- and culture. tory of travel abroad and was systemically well. Her nopathy and no hepatosplenomegaly. Findings from a What is your diagnosis? medications included lansoprazole, doxazosin mesylate, complete blood cell count, urea and electrolyte levels,

Figure 1. Figure 2. Figure 3.

Generalized Papules in a Patient With Acute Myeloid Leukemia

Kyoko Nakahigashi, MD; Miki Tanioka, MD, PhD; Yoshiki Miyachi, MD, PhD; Kyoto University, Kyoto, Japan REPORT OF A CASE increased circulating blast cell count (58% of WBCs). day. These papules were 5 to 10 mm in diameter and some He had received fluconazole as antifungal prophylaxis. appeared purpuric. He had been in nadir with WBC counts A 58-year-old Japanese man, who had been followed up He commenced chemotherapy via a central venous lower than 100 cells/µL for 7 days. A skin biopsy speci- and received blood transfusions regularly for myelodys- catheter. On day 11, he had a high fever, and a blood cul- men was obtained from a papule on the trunk (Figure 2 plastic syndrome (refractory anemia with an excess of ture was taken. On day 13, he presented with asymp- and Figure 3 [hematoxylin-eosin]). blast cells) for 1 year, developed acute myeloid leuke- tomatic papules on the upper limbs (Figure 1), which What is your diagnosis? mia. He had pancytopenia, with a white blood cell spread over the trunk, face, and lower limbs on the next (WBC) count of 800 cells/µL (to convert to ϫ109/L, multiply by 0.001), neutropenia (7.0 % of WBCs), and

Figure 1. Figure 2. Figure 3.

A Firm Papule on the Lateral Tongue

Pitiporn Suwattee, MD, FRCPC; Matthew C. McClelland, MD; Brian C. Berg, MD; University of Minnesota Medical School (Drs Suwattee, McClelland, and Berg) and the Veterans Affairs Medical Center (Drs Suwattee and Berg), Minneapolis REPORT OF A CASE increased in size. He denied any history of trauma to was tender to palpation (Figure 1). The lesion was the area. His medical history was remarkable for type biopsied for histologic examination (Figure 2 and A 39-year-old male presented with a firm, tender pap- 1 diabetes mellitus. Physical examination revealed a Figure 3). ule on the dorsal surface of his tongue of 6 months’ 5-mm, well-circumscribed, firm, mucosal-colored pap- What is your diagnosis? duration. Prior to evaluation, the papule had slowly ule on the left lateral dorsal surface of the tongue that

Figure 1. Figure 2. Figure 3.

Soft Papules and Nodules on the Buttock

Marlyanne M. Pol-Rodriguez, MD; Kristin M. Nord, MD; Danielle E. Engler, MD; The Permanente Medical Group, Oakland, California (Dr Pol-Rodriguez), and Columbia University Medical Center, New York, New York (Drs Nord and Engler) REPORT OF A CASE in size, but after 5 years, the masses stopped growing of the sacrum and right buttock (Figure 1). The plaques and changing. There was no family history of similar had a wrinkled, cerebriform surface. Two nodules were A 24-year-old healthy African American woman pre- lesions. excised for histologic evaluation (Figure 2 and sented with a 10-year history of “growths” on her right Physical examination revealed multiple soft, sessile, Figure 3). buttock that had started as a single lump over the skin-colored to hyperpigmented grouped papules and What is your diagnosis? sacrum. Over time, new lesions developed and increased nodules coalescing into plaques over a 16ϫ10-cm area

Figure 1. Figure 2. Figure 3.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1583-1588 THE CUTTING EDGE

SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: MICHAEL P. HEFFERNAN, MD; CHRISTIE AMMIRATI, MD Fractional Resurfacing A New Therapeutic Modality for Becker’s Nevus

Adrienne S. Glaich, MD; Leonard H. Goldberg, MD, FRCP; Tianhong Dai, PhD; Joy H. Kunishige, MD; Paul M. Friedman, MD; DermSurgery Associates, Houston, Texas (Drs Glaich, Goldberg, and Friedman); and Departments of Dermatology, Weill Cornell Medical College, Methodist Hospital, Houston (Drs Goldberg and Friedman), Harvard Medical School, Boston, Massachusetts (Dr Dai), and The University of Texas Medical School, Houston (Drs Goldberg, Kunishige, and Friedman)

The Cutting Edge: Challenges in Medical and Surgical Therapeutics

REPORT OF CASES ment area was cleansed before the procedure using a mild soap. A topical lidocaine cream, 4% (LMX; Ferndale Labo- ratories Inc, Ferndale, Michigan), was applied under oc- PATIENT 1 clusion to the treatment area for 1 hour before treatment. A water-soluble tint certified by the US Food and A 26-year-old white man presented with a pigmented le- Drug Administration (OptiGuide Blue; Reliant Tech- sion on the right upper chest that developed at 15 years nologies Inc) was applied to the treatment area to allow of age. Results of physical examination showed mul- the laser’s Intelligent Optical Tracking System (Reliant tiple light brown macules coalescing into patches with Technologies Inc) to adjust the treatment pattern with terminal hairs (Figure 1A). The patient’s medical history was unremarkable. No previous treatment to the area respect to handpiece velocity. An ointment (LipoThene had been administered. Inc, Pacific Grove, California) was applied over the water- soluble tint so that the laser handpiece could glide PATIENT 2 smoothly over the treatment area. Treatment variables were selected to target the pig- A 16-year-old white male adolescent was referred for treatment in the papillary dermis and adjusted for pain tol- ment of a pigmented patch with terminal hairs on the right erance. In each treatment session, patients were treated cheek (Figure 2A). His mother reported that the pig- with energy levels from 6 to 10 mJ, with final densities mented patch first developed at 5 years of age, and ter- of 2000 to 3048 microscopic treatment zones per square 2 minal hairs developed within the lesion during puberty. centimeter (MTZs/cm ). Patients underwent 8 to 10 passes 2 The patient’s medical history was unremarkable. No pre- at a density of 250 or 254 MTZs/cm per pass (Table). vious treatment to the area had been administered. A cold-air cooling system (Cryo 5; Zimmer MedizinSys- Based on the history and clinical presentation, both tems, Irvine, California) was used to cool the skin dur- patients were diagnosed as having Becker’s nevus. ing the treatment and to mitigate patient discomfort (fan power 2, 10-14 cm from the skin surface). Treatment sessions were performed at 4-week intervals. Patient 1 un- THERAPEUTIC CHALLENGE derwent 6 treatment sessions; patient 2, 5 treatment sessions. Patient 1 exhibited mild erythema before treatment Traditional laser treatment of Becker’s nevus may involve 1,2 1-3 5, so the energy level was decreased to 6 mJ. the use of ablative and Q-switched lasers. Ablative la- Photographic documentation and clinical improve- sers remove the entire epidermis of the treatment area and 1,2 ment scores were determined at each treatment visit, at 1 are clinically effective. However, patients experience a month after the last treatment, and at 3 or 6 months after high incidence of significant adverse effects. Q-switched the last treatment. A medical evaluation was indepen- lasers are effective in the treatment of cutaneous pig- dently performed using the following well-established quar- mented lesions. The major disadvantage of this modality tile grading scale: grade 1 (Ͻ25%) indicates minimal to is that complete clearing of the lesion is rarely achieved, 1 no improvement; grade 2 (25%-50%), moderate improve- and many treatment sessions are usually required. ment; grade 3 (51%-75%), marked improvement; and grade 4(Ͼ75%), near total improvement. SOLUTION During treatment, the patients experienced mild pain. Moderate to severe postprocedure erythema and edema typi- Both patients were treated with the 1550-nm wave- cally resolved within 24 to 48 hours. No additional ad- length erbium-doped fiber laser (Fraxel; Reliant Tech- verse effects were observed. Based on independent clini- nologies Inc, Mountain View, California). The treat- cal assessment by comparison with baseline photographs,

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1488 A B

Figure 1. Becker’s nevus on the right chest of patient 1 before (A) and after (B) 6 treatments with fractional resurfacing.

A B

Figure 2. Becker’s nevus on the right cheek of patient 2 before (A) and after (B) 5 treatments with fractional resurfacing. both patients achieved grade 4 improvement, indicating that patch with a sharply outlined but irregular border.6,7 In greater than 75% of the pigment had faded by the 1-month male patients, the lesion may develop increased hairi- follow-up (Figures 1B and 2B). This improvement was ness after puberty.7 Histopathologically, the melanin con- maintained at the final follow-up visit, which was per- tent of the keratinocytes is increased, whereas the num- formed at 6 months for patient 1 and at 3 months for pa- ber of melanocytes is normal or only slightly increased. tient 2. There was no improvement in hypertrichosis. The basal cell layer is hyperpigmented, and melanophages may be present in the papillary dermis.7 Beck- COMMENT er’s nevus is fairly common: a study of 19 302 adolescents and men aged 17 to 26 years revealed a prevalence Becker’s nevus (pigmented hairy epidermal nevus)5 is of 0.52%.8 Becker’s nevus is a benign condition, and there characterized by the presence of a light or dark brown have been no reports of malignant transformation.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1489 ment. There has also been a report of using the long- Table. Treatment Settingsa pulsed ruby laser for Becker’s nevus to decrease both pigmentation and hair density.4 With Q-switched lasers, Patient 1 Patient 2 complete clearing of the lesions is rarely achieved, and many 1 Total Total treatment sessions are necessary. Treatment Energy Density, Energy Density, These 2 cases demonstrate marked lightening of a Beck- Session Level, mJ MTZs/cm2 Level, mJ MTZs/cm2 er’s nevus on the chest and face after a series of frac- 1 8 2000 10 2500 tional resurfacing treatments. Fractional resurfacing is 2 8 2000 10 2500 a promising new treatment modality for Becker’s nevus. 3 8 2500 10 3048 No adverse effects were observed, and the safety profile 4 8 2500 10 3048 appears to be fairly broad.15 Additional controlled stud- 5 6 2000 10 3048 6 10 2500 NA NA ies are warranted to better understand the efficacy of fractional resurfacing for the treatment of Becker’s nevus and Abbreviations: MTZs, microscopic treatment zones; NA, not applicable. to determine optimal treatment settings. a A 15-mm spot size was used. Accepted for Publication: January 3, 2007. Correspondence: Paul M. Friedman, MD, DermSurgery Fractional resurfacing creates hundreds to thou- Associates, 7515 S Main St, Ste 210, Houston, TX 77030 sands of dense MTZs while sparing surrounding tis- ([email protected]). sue.9-12 The epidermis and dermis are coagulated but only Author Contributions: Dr Friedman had full access to all within the MTZs. A density of 2500 MTZs/cm2 at 10 mJ the data in the study and takes responsibility for the in- results in approximately 25% cross-sectional area of ther- tegrity of the data and the accuracy of the data analysis. mal damage. As a result, epidermal repair is rapid be- Study concept and design: Glaich, Dai, and Friedman. Ac- cause of the relatively small area of injury and short mi- quisition of data: Glaich, Dai, and Friedman. Analysis and gratory paths for keratinocytes. Twenty-four hours after interpretation of data: Glaich, Goldberg, Dai, Kunishige, fractional resurfacing, the continuity of the epidermal basal and Friedman. Drafting of the manuscript: Glaich, Dai, and layer is restored.13 Complete epidermal regeneration is Kunishige. Critical revision of the manuscript for impor- obtained by day 7.13 tant intellectual content: Goldberg, Kunishige, and Fried- The 1550-nm wavelength, which targets tissue wa- man. Study supervision: Goldberg and Friedman. ter, penetrates to a depth of approximately 1000 µm into Financial Disclosure: None reported. the skin (absorption coefficient penetration, approxi- −1 14 mately 9.6 cm in water at 1550 nm). By adjusting the REFERENCES optical focal length and/or the energy of the laser, high local radiant exposure can be achieved at various intra- 1. Trelles MA, Allones I, Moreno-Arias GA, Ve´lez M. Becker’s naevus: a compara- dermal depths. Thus, different compartments of vari- tive study between erbium:YAG and Q-switched neodymium:YAG: clinical and ous depths can be arbitrarily selected as the targets of pho- histopathological findings. Br J Dermatol. 2005;152(2):308-313. tothermolysis. The stratum corneum remains intact during 2. Trelles MA, Allones I, Ve´lez M, Moreno-Arias GA. Becker’s nevus: erbium:YAG versus Q-switched neodimium:YAG? Lasers Surg Med. 2004;34(4):295-297. exposure to 1550-nm irradiation because it contains less 3. Kopera D, Hohenleutner U, Landthaler M. Quality-switched ruby laser treatment 13 water. This dramatically reduces the risk of infection of solar lentigines and Becker’s nevus: a histopathological and immunohisto- compared with more complete ablative techniques. chemical study. Dermatology. 1997;194(4):338-343. Only a limited number of the keratinocytes within the 4. Nanni CA, Alster TS. Treatment of a Becker’s nevus using a 694-nm long-pulsed ruby laser. Dermatol Surg. 1998;24(9):1032-1034. lesion are removed in a single treatment session (lim- 5. Copeman PWM, Jones EW. Pigmented hairy epidermal nevus (Becker). Arch ited to the MTZs). This results in rapid and complete epi- Dermatol. 1965;92(3):249-251. dermal healing between treatment sessions. With mul- 6. Becker SW. Concurrent melanosis and hypertrichosis in a distribution of nevus tiple treatment sessions, however, thermal damage over unius lateris. Arch Dermatol. 1949;60(2):155-160. the whole treatment area can be achieved. Fractional re- 7. Danarti R, Ko¨nig A, Salhi A, Bittar M, Happle R. Becker’s nevus syndrome revisited. J Am Acad Dermatol. 2004;51(6):965-969. surfacing may improve Becker’s nevus by removing ac- 8. Tymen R, Forestier JF, Boutet B, Colomb D. Late Becker’s nevus: one hundred anthotic and pigmented epidermis. cases [in French]. Ann Dermatol Venereol. 1981;108(1):41-46. Laser treatment of Becker’s nevus has included abla- 9. Manstein D, Herron GS, Sink RK, Tanner H, Anderson RR. Fractional photother- tive and Q-switched techniques. Ablative lasers, such as molysis: a new concept for cutaneous remodeling using microscopic patterns of thermal injury. Lasers Surg Med. 2004;34(5):426-438. the 2940-nm erbium:YAG lasers, target tissue water and 10. Geronemus RG. Fractional photothermolysis: current and future applications. La- remove the entire epidermis and varying thicknesses of sers Surg Med. 2006;38(3):169-176. the dermis. Patients frequently experience posttreat- 11. Behroozan DS, Goldberg LH, Glaich AS, Dai T, Friedman PM. Fractional photo- ment edema, erythema, burning, and crusting. Ery- thermolysis for the treatment of poikiloderma of Civatte. Dermatol Surg. 2006; thema can last several months.2 Pigmentary changes, acne 32(2):298-301. 12. Behroozan DS, Goldberg LH, Dai T, Geronemus RG, Friedman PM. Fractional pho- flares, herpes simplex infection, scars, and milia forma- tothermolysis for the treatment of surgical scars: a case report. J Cosmet Laser tion may also occur with ablative techniques. Ther. 2006;8(1):35-38. Q-switched lasers, such as the 694-nm Q-switched ruby, 13. Laubach HJ, Tannous Z, Anderson RR, Manstein D. Skin responses to fractional 1064-nm Q-switched Nd:YAG, and 755-nm Q-switched photothermolysis. Lasers Surg Med. 2006;38(2):142-149. 14. Irvine WM, Pollack JB. Infrared optical properties of water and ice spheres. Icarus. alexandrite lasers, selectively damage epidermal and der- 1968;8(1-3):324-360. mal melanin without removing the entire epidermis. This 15. Fisher GH, Geronemus RG. Short-term side effects of fraction photothermolysis. modality decreases the adverse effects associated with treat- Dermatol Surg. 2005;31(9, pt 2):1245-1249.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1490 ARCHIVES A CENTURY AGO

SECTION EDITOR: MARK BERNHARDT, MD

THE JOURNAL OF CUTANEOUS DISEASES

VOL. XXV. DECEMBER, 1907. NO.12.

THE OPSONIC METHOD IN SKIN DISEASES.

By ARTHUR WHITFIELD, M.D., F.R.C.P. Professor of Dermatology in King’s College, London; Physician to the Skin Department, King’s College and Great Northern Central Hospitals. *** CONCLUSIONS I may state that I believe that the opsonic method foreshadows an enormous advance in our control over infective disorders, but that at present there exists a great hiatus in our knowledge which renders the results uncertain in some cases. The following conclusions are, however, based on long and steady work at the method and are, I hope, stated with reasonable impartiality. 1. The opsonic treatment of boils is uniformly successful and is the only form of treatment for general furunculosis which is in the slightest degree reliable. 2. In sycosis the treatment is a valuable aid, but must be continued for long periods in proportion to the duration of the disease, and it is best combined with X-ray depilation. 3. In acne the treatment is uncertain, in some cases being most brilliant, in others without the slightest avail. J Cutan Dis. December 1907;25(12):529-537.

Don’t show me what’s new—show me what’s left of the old! Mark Bernhardt to Hannah and Morris Bernhardt Atlantic Station, Atlanta, GA, October 20, 2006

I have to admit, half the fun of writing this column is the opportunity to sneeringly look down my century-long nose at the obsolete and archaic methodologies of my predecessors. This is only en- joyable when the chasm—both temporal and medical—is so great that I literally cannot relate to what was written 100 years ago in the Archives. But, boy oh boy, this month the tables were turned on me! I can remember when dermatologists actually used opsonic therapy for acne! Though I dismissed these hacks as therapeutic troglodytes, we were nonetheless contemporaries! It’s like living next door to a Neanderthal! Even as I write these words, I feel my joints stiffen, my muscle tone flabben, and my sense of scientific superiority wilten. It’s not just bacterial vaccines: I remember typewriters, carbon paper, cathode-ray TVs—all of which were not only perfectly adequate, but in some ways superior to their technological descendants. Come on, have you ever tried to pile patient charts on the top of a flat-screen monitor? Hate to admit it, but this first draft—like all my first drafts—is being written with a pen (fountain!!!) on paper. It’s not that I’m a Luddite, it’s just that I don’t necessarily see progress as a positive thing. I mean, my 50-year-old, slate-roofed, plaster-walled, brass-balustraded house in New Jersey was in so many ways superior to my newer, tar-papered, dry-walled manse in South Florida. My audiophile friends insist that nothing beats vacuum tubes and turntables for sonic fidelity. Any automobile enthusiast will still stick with a stick. I personally rue the day when my beloved, irreplaceable, yet obsolete can- tharidin and papaverine become extinct. As I lay me down to nap, I must confess that my solo, cash- or-check-only, paper-records practice is also fast becoming a relic. Peace.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1484 CORRESPONDENCE

glutinin.2 Furthermore, R-salbutamol inhibits superox- RESEARCH LETTERS ide generation and peroxidase release from stimulated human granulocytes.3,4 These effects might have therapeutic potential in cutaneous lupus. Nine consecutive patients entered this prospective Discoid and Subacute Lupus Erythematosus explorative investigation, 5 with treatment-resistant Treated With 0.5% R-Salbutamol Cream DLE and 4 with SCLE. Patients were asked to discon- tinue treatment with topical glucocorticosteroid and reatment of discoid lupus erythematosus (DLE) use R-salbutamol cream twice daily on affected skin and subacute lupus erythematosus (SCLE) in- areas or parts thereof. Photographic documentation T cludes topical or systemic glucocorticosteroid, was performed before and during treatment. The pa- chloroquine, methotrexate, retinoids, and even thalido- tients were seen every 2 to 3 weeks. The treatment effi- mide.1 In severe cases, these treatments may be ineffec- cacy was evaluated by the physician using assessment of tive or not well tolerated leading to cessation of therapy symptoms and disease grade. The physician graded the or lack of compliance. Alternative treatments to modify effect of the treatment on a 4-point scale: 0, no effect; the autoimmune response in the skin would therefore be ϩ, slight improvement; ϩϩ, some improvement; and useful.1,2 ϩϩϩ, pronounced effect. The adverse effect of dermatitis was graded in the same way (Table). Methods. We investigated the effect of ASF-1096 (As- tion Pharma, Copenhagen, Denmark) in an explorative Results. Results and patient data are listed in the Table. study. The active substance is a sulfate salt of R-salbuta- Images of patients before and after treatment are pre- mol in 0.5% concentration in an oil-in-water emulsion. sented in the Figure. R-Salbutamol has various anti-inflammatory effects and The 4 patients treated for SCLE all responded within inhibits proliferation and secretion of IL-2 and inter- a few days and had pronounced effect after 2 to 3 weeks. feron ␥ in human T cells stimulated with phytohemag- After “healing,” some patients reported that the skin re-

Table. Results of Treatment With 0.5% R-Salbutamol Cream (RSC)

Duration of Years Earlier RSC Treatment Adverse Diagnosis Age, y With LE Treatments (Doses/d, No.)a Effectsb Effectsb Comments DLE 48 4 TG, HC, MTX 4 wk (2); ϩϩϩ Breast and ϩϩ back; 0; Antipruritic, dermatitis 3mo(1) NR ϩϩϩ DLE 66 21 TG, SG, HC 5 wk (2); ϩ; ϩ Mild irritation; Inflammation and thickness 1 y (1) ϩ NR diminished (Figure, D) DLE 47 34 TG, HC, MTX, TL 6 wk (2); ϩϩϩ New elements; 0; Inflammation and thickness 6mo(1) ϩ Old thickened elements ϩ Mild irritation diminished, antipruritic DLE 35 16 TG, SG, HC, AZ 3-4 wk (2); ϩ Effect on thin old elements 0 Compliance not good None DLE 56 29 TG, HC 5 wk (2); 0 on Hypertrophic elements 0 No effect, antipruritic None SCLE 51 10 TG, HC 6 wk (2); ϩϩ; 0; Skin on fingers healed, and 1 y (1) ϩϩ 0 the patient could work again SCLE 82 18 TG, HC, MTX, 4 wk (2); ϩϩϩ Face and ϩback ϩϩ Face Dermatitis AZ, RT, TL None (Figure, A) SCLE 35 20 TG, SG, HC 2 wk (2); ϩϩϩ Face and arms, ϩ fingers; 0; Antipruritic 2mo(2) ϩϩϩ Face and arms, ϩ fingers 0 SCLE 11 1 TG, SG, HC, AZ 2 wk (2); ϩϩ Face and arm; 0; SG was lowered during 2mo(1) ϩϩ Face and arm 0 treatment (Figures B and C)

Abbreviations: AZ, azathioprine; DLE, discoid LE; HC, hydroxychloroquine; LE, lupus erythematosus; MTX, methotrexate; NR, not reported; RT, retinoid; SCLE, subacute LE; SG, systemic glucocorticosteroid; TG, topical glucocorticosteroid; TL, thalidomide; 0, no effect; ϩ, slight effect; ϩϩ, some effect; ϩϩϩ, pronounced effect. aData are reported as short-term treatment; maintenance treatment. bData are reported as short-term effects; long-term effects.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1589 the lupus. Thereafter, treatment was resumed in 1 of the Before After patients using a different cream vehicle, which was tolerated. A The 5 patients with DLE underwent treatment on hypertrophic lesions as well as relatively new and nonhypertrophic lesions. Some minor effect was seen on the hypertrophic elements beginning after 2 months of treatment (Figure, D). The relatively new and nonhypertrophic lesions responded well but to a lesser degree than the SCLE. Two patients reported excellent effect, while B 2 others reported no effect. However, 1 of the latter had bad compliance. The skin lesions fluctuated in severity over time, especially in SCLE. We can assume that these fluctuations were not related to the time of year because treatment was initiated at different times of the year. The fluctuations give a risk of bias; however, the effect of the treatment on new and nonhypertrophic lesions was very fast and was sustained during the treatment period, though without 100% clearance (Table). Old hypertrophic lesions are difficult to treat, and it was therefore positive to see a slow improvement over time even in these cases.

Comment. When salbutamol is used in a powder formulation for inhalation in patients with asthma, irrita- C tion of the mucosa is a known adverse effect, as are tremor and tachycardia.5 It was therefore interesting to notice that a dermatitis could be seen after dermal application as well, although different vehicle formulations were involved. Contact allergy could not be anticipated, since the dermatitis when present was not seen in all the treated areas, and the drug was reapplied without recurrence of the dermatitis in 1 of the patients. Even when treating areas up to 2000 cm2 twice daily, no signs of tremor or tachycardia were observed. No other adverse effects were reported. D An explorative investigation does not have the proper controls used in a controlled clinical trial. However, the results from this investigation seem very promising.

Hans Christian Wulf, MD, DSc Susanne Ullman, MD

Correspondence: Dr Wulf, Department of Dermatol- Figure. Subacute lupus erythematosus (SCLE) (A-C) and discoid lupus ogy, Copenhagen University Hospital, Bispebjerg Bakke erythematosus (DLE) (D). A-C, Patient with SCLE before and after 2 to 4 weeks of twice-daily treatment with ASF-1096 (Astion Pharma, Copenhagen, 23, 2400 Copenhagen NV, Denmark (hcw01@bbh Denmark). D, Patient with DLE before and after 11 months of twice-daily .regionh.dk). treatment with ASF-1096. Financial Disclosure: Dr Wulf is member of the advisory board of Astion Pharma. action could change from day to day from totally cleared to slightly erythematous. After each application, 1. Kuhn A, Lehmann P, Ruzicka T, eds. Cutaneous Lupus Erythematosus. Berlin and Heidelberg, Germany: Springer; 2005. some patients experienced diminished itch within min- 2. Baramki D, Koester J, Anderson AJ, Borish L. Modulation of T-cell function utes and complete relief from itch after a few days by (R)- and (S)-isomers of albuterol: anti-inflammatory influence of (R)- (Table). isomers are negated in the presence of the (S)-isomer. J Allergy Clin Immunol. 2002;109(3):449-454. After experiencing a primary beneficial effect, 2 of 3. Volcheck GW, Kelkar P, Bartemes KR, Gleich GJ, Kita H. Effects of (R)- and the patients developed an adverse event in the form of (S)-isomers of ␤-adrenergic agonists on eosinophil response to interleukin-5. Clin Exp Allergy. 2005;35(10):1341-1346. dermatitis in parts of the treated area, one in the face 4. Leff AR, Herrnreiter A, Naclerio RM, Baroody FM, Handley DA, Mun˜ oz NM. and the other on the back. This reaction started after 4 Effect of enantiomeric forms of albuterol on stimulated secretion of granular to 6 weeks of use and after the full effect had been ob- protein from human eosinophils. Pulm Pharmacol Ther. 1997;10(2):97-104. 5. Pinto Pereira LM, Clement YN, Pereira SMP. Comparison of innovator and tained. The dermatitis ceased within 4 to 6 days of topi- generic salbutamol inhalers: a double-blind randomized study of efficacy and cal glucocorticosteroid application, leaving no flare in tolerance. Int J Clin Pharmacol Res. 2002;22(3-4):73-80.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1590 High Procalcitonin Levels in Patients Quality of Dermatologic Care With Severe Drug Reactions Delivered by Physician Assistants: An Analysis of Prescribing Behavior lthough procalcitonin (PCT) serum level is still for the Combination Antifungal Agent considered to be a highly specific and sensitive Clotrimazole-Betamethasone A biologic marker of severe bacterial infections, it can be increased in noninfectious situations such as dif- 1 ost patients with skin disease do not see a der- fuse metastatic solid cancers, C-cell carcinoma of the thy- 1 roid gland,2 major trauma or surgery,3,4 or after cardio- matologist. In an effort to better meet pa- pulmonary bypass.5 Herein we show that PCT level tients’ needs, there is growing use of physi- M 2 increases in some patients with severe drug reactions. Cli- cian assistants in dermatology. The quality of nicians should therefore not rely on PCT values to dis- dermatologic care offered by physician assistants is not criminate between infectious and immunoallergic erup- well characterized. Our group has used clotrimazole- tions in patients who present with fever and a rash. betamethasone dipropionate prescribing behavior as a measure of the quality of dermatologic services pro- 3,4 Methods. We investigated 8 consecutive patients with a vided by practitioners in different specialties. Herein, severe cutaneous drug eruption. Four patients had to assess the quality of dermatologic care provided by phy- Stevens-Johnson syndrome (SJS); 2 had drug rash, eo- sician assistants, we analyze clotrimazole-betametha- sinophilia, and systemic symptoms syndrome (DRESS); sone prescribing behavior of 4 practitioner groups: der- 1 had acute generalized exanthematous pustulosis; and matologists, dermatology physician assistants, primary 1 had Lyell syndrome. The diagnosis of drug eruption care providers, and primary care physician assistants. was based on clinical, biologic, and histologic findings. In all cases, investigations including routine biology tests, Methods. Data on the use of the combination antifungal blood cultures, urinary bacterial examination, pulmo- agent clotrimazole-betamethasone were obtained from the 1995-2004 National Ambulatory Medical Care Sur- nary radiography, and serology failed to identify any bac- 5 3,4 terial or viral agent. vey and analyzed as previously described. First, we identified the 5 most common diagnoses that were treated with Results. Procalcitonin levels were significantly elevated in clotrimazole-betamethasone at least some of the time. 2 patients, one with DRESS (3.96 µg/L) and the other with Then we determined the percentage of visits for those 5 SJS (0.53 µg/L). All patients healed within a mean of 25 days conditions at which clotrimazole-betamethasone was pre- (range, 15-45 days) without any antibiotic treatment. scribed. Each patient visit was analyzed according to whether a physician, physician assistant, or both were Comment. Our findings suggest that in some patients with involved in the visit. Direct supervision is defined as vis- severe drug eruptions, PCT level can be elevated in the its where patients were seen by both the physician as- absence of bacterial infection. Thus, elevated PCT lev- sistant and the physician. els neither predict infection in patients with severe drug rashes nor allow discrimination between infectious and Results. There were an estimated 301 million outpa- noninfectious eruptions. tient visits for inflammatory or fungal skin conditions for which clotrimazole-betamethasone was sometimes pre- Mehdi Sfia, MD scribed. Most of the visits for these skin diseases were to Peggy Boeckler, MD primary care physicians (44.7%) and dermatologists Dan Lipsker, MD, PhD (38.8%) (Table 1). Other subspecialty physicians accounted for 16.5% of these visits. In 95% of the visits, a Correspondence: Dr Lipsker, Clinique Derma- physician was the only provider to see the patient. Both tologique, Hopitaux Universitaites, 1 Place de l’Hopital, 67091 Strasbourg CEDEX, France (dan.lipsker@gmail .com). Table 1. Proportion of Outpatient Visits Managed by Different Financial Disclosure: None reported. Specialties for Inflammatory or Fungal Skin Conditions for Which Clotrimazole-Betamethasone a 1. Matzaraki V, Alexandraki KI, Venetsanou K, et al. Evaluation of serum pro- Was Sometimes Prescribed calcitonin and interleukin-6 levels as markers of liver metastasis. Clin Biochem. 2007;40(5-6):336-342. Estimated Visits, % 2. Bertagna XY, Nicholson WE, Pettengill OS, Sorenson GD, Mount CD, Orth Medical Care Provider (NϷ301 million) DN. Ectopic production of high molecular weight calcitonin and corticotro- pin by human small cell carcinoma cells in tissue culture: evidence for sepa- Primary care physician 44.7 rate precursors. J Clin Endocrinol Metab. 1978;47(6):1390-1393. Dermatologist 38.8 3. Meisner M, Tschaikowsky K, Hutzler A, Schick C, Schuttler J. Postoperative plasma concentrations of procalcitonin after different types of surgery. Inten- Other subspecialty physician 16.5 sive Care Med. 1998;24(7):680-684. Physician only 95.0 4. Mimoz O, Benoist JF, Edouard AR, Assicot M, Bohuon C, Samii K. Procalci- Physician assistant only 0.9 tonin and C-reactive protein during the early posttraumatic systemic inflam- Physician assistant and physician 1.4 matory response syndrome. Intensive Care Med. 1998;24(2):185-188. Other provider 2.7 5. Meisner M, Tschaikowsky K, Schmidt J, Schu¨ ttler J. Procalcitonin (PCT)— indications for a new diagnostic parameter of severe bacterial infection and a 5 sepsis in transplantation, immunosuppression, and cardiac assist devices. Car- Data are from the 1995-2004 National Ambulatory Medical Care Survey. diovasc Eng. 1996;1(1):67-76. Betamethasone was betamethasone dipropionate.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1591 When clotrimazole-betamethasone prescribing behav- Table 2. Multivariate Analysis Examining Predictors a ior is used as the measure of quality, physician assistants of Clotrimazole-Betamethasone Prescription provide dermatologic care more comparable to that of primary care physicians than to that of dermatologists. How- Clotrimazole-Betamethasone Dipropionate Prescription, ever, these are pilot data that only begin to assess a very Prescription Predictor OR (95% CI)a complex issue. The growing demand for dermatologic care and the limited availability of dermatologists require that Health care provider characteristic Primary care physician 20.3 (10.5-39.3) additional attention be paid to the quality of care offered 6 Other physician 6.4 (3.0-13.6) by physician extenders. Physician assistant only 4.3 (0.7-25.6) Other provider 0.3 (0.1-1.2) Anita Satyaprakash, BS Physician assistant and physician 1.8 (0.4-8.0) Rajesh Balkrishnan, PhD Patient characteristic Fabian T. Camacho, MS Younger than 5 y 0.3 (0.1-0.6) Sujata S. Jayawant, MS Age 5-18 y 0.5 (0.3-0.8) Age Ͼ18-30 y 0.4 (0.2-0.8) Alan B. Fleischer Jr, MD Male 1.0 (0.7-1.5) Steven R. Feldman, MD, PhD White 0.6 (0.4-0.9) Correspondence: Dr Feldman, Department of Derma- Abbreviations: CI, confidence interval; OR, odds ratio. tology, Wake Forest University School of Medicine, Medi- a Data are from the 1995-2004 National Ambulatory Medical Care Survey cal Center Boulevard, Winston-Salem, NC 27157-1071 (NAMCS).5 Results are weighted by NAMCS sample weights. Regression ([email protected]). model is logistic. Reference categories (dropped) in the logistic regression include dermatologists, visits where only physicians were seen, and patient Financial Disclosure: None reported. age older than 30 years. Reported ORs are relative to the value for adult patients seen by dermatologists. 1. Feldman SR, Fleischer AB Jr, Williford PM, White R, Byington R. Increasing uti- lization of dermatologists by managed care: an analysis of the National Ambu- latory Medical Care survey, 1990-1994. J Am Acad Dermatol. 1997;37(5 pt 1): 784-788. a physician and physician assistant were seen during 1.4% 2. Clark AR, Monroe JR, Feldman SR, Fleischer AB Jr, Hauser DA, Hinds MA. of these visits, and a physician assistant was the sole health The emerging role of physician assistants in the delivery of dermatologic health care. Dermatol Clin. 2000;18(2):297-302. care provider during 0.9% of visits. 3. Smith ES, Fleischer AB Jr, Feldman SR. Nondermatologists are more likely In multivariate logistic regression analyses of clotrima- than dermatologists to prescribe antifungal/corticosteroid products: an analysis of office visits for cutaneous fungal infections, 1990-1994. J Am Acad zole-betamethasone prescriptions, primary care provid- Dermatol. 1998;39(1):43-47. ers prescribed clotrimazole-betamethasone at a rate of 4. Balkrishnan R, Cook JM, Shaffer MP, Saltzberg FB, Feldman SR, Fleischer 4.9% compared with the dermatologist prescription rate AB Jr. Analysis of factors associated with prescription of a potentially inap- propriate combination dermatological medication among US outpatient of 0.2%; other subspecialty physicians prescribed the drug physicians. Pharmacoepidemiol Drug Saf. 2004;13(3):133-138. at a rate of 1.7%. Clotrimazole-betamethasone was more 5. Centers for Disease Control and Prevention; National Center for Health Sta- likely to be prescribed at visits to physician assistants (re- tistics. National Ambulatory Medical Care Survey. http://www.cdc.gov/nchs /about/major/ahcd/namcsdes.htm [registration required]. Accessed August 28, gardless of specialty) when the physician assistant was 2007. the sole provider of dermatologic care vs when the phy- 6. Resneck J Jr, Kimball AB. The dermatology workforce shortage. J Am Acad sician assistant was under direct supervision by a phy- Dermatol. 2004;50(1):50-54. sician (odds ratio [OR], 4.3; 95% confidence interval [CI], 0.7-25.6 vs OR, 1.8; 95% CI, 0.4-8.0) (Table 2). The highest rate of clotrimazole-betamethasone use, Quality of Care 16.9%, was by physician assistants practicing in primary From a Patient’s Perspective care and seeing patients without direct supervision. Phy- sician assistants practicing under dermatologists and see- growing number of measures, such as physi- ing patients without direct supervision prescribed clotrima- cian performance incentives, aim to improve the zole-betamethasone at a much lower rate of 3.8% compared A quality of health care in the United States. Pa- with their primary care counterparts. For both primary care tients and physicians, however, differ in their determi- physician assistants and dermatology physician assis- nation of quality of care and patient satisfaction.1,2 The tants, however, seeing patients under physician supervi- 2001 Institute of Medicine’s Crossing the Quality Chasm: sion decreased the rate of clotrimazole-betamethasone pre- A New Health System for the 21st Century3 established scription to 8.3% and 1.1%, respectively. guidelines for improving the current health care system to better meet patient needs. These guidelines Comment. Physician assistants practicing in a dermatol- provided a basis to define quality of care from a ogy office are much less likely to prescribe clotrimazole- patient’s perspective in an outpatient, university- betamethasone than are physician assistants working in based, dermatology setting. primary care specialties. Even without direct supervision, dermatology physician assistants’ clotrimazole- Methods. Our survey, as approved by the institutional betamethasone prescribing behavior is no worse than that review board, was administered to patients older than 18 of primary care physicians. When supervised by a derma- years who were waiting for their appointment in the der- tologist, physician assistants’ clotrimazole-betametha- matology outpatient clinic at the Penn State Milton S. Her- sone prescribing behavior comes closer to that of the shey Medical Center. The survey asked participants to dermatologists. indicate what they considered to be most important to

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1592 Table. The 6 Most Important Patient-Rated Aspects of Medical Care

Respondents Ranking as Aspect of Care Category of Care “Very Important,” % P Valuea Physician’s thorough explanation of your problem or condition Professional interactions 88.9 Referent Physician’s concern for your questions or worries Professional interactions 85.4 Ͼ.99 Discussion of all available treatment options Treatment 81.2 Ͼ.99 Physician includes you in decisions about your treatment Treatment 79.8 Ͼ.99 Detailed instructions of the treatment Treatment 79.3 Ͼ.99 Personalized care for your individual situation Professional interactions 75.6 .12

a Compared with the most important aspect. the quality of their care and to rate the importance of 28 pects above the length of time spent with the physician— aspects of their overall care. Level of importance was rated clearly showing that the content of the visit, not its on a 5-point scale: 1, not important; 2, of little impor- duration, is most important to a patient’s definition of tance; 3, no opinion; 4, important; and 5, very impor- quality of care. Perhaps, as has been shown in other spe- tant. The 28 aspects of care were grouped into 5 catego- cialties, dermatology patients may be willing to forgo a ries: treatment, access to care, professional interactions, treatment outcome in favor of other aspects of care.4 Qual- follow-up care, and environment of care. Participants were ity goals can then be focused toward these ideals, and im- asked to also use a 5-point scale to rank these 5 catego- provement in these aspects should yield an overall im- ries of care from 1, most important, to 5, least important provement in quality of care as determined by patients. to the quality of their health care. Christie G. Regula, BA Results. A total of 220 patients were asked to partici- Jeffrey J. Miller, MD pate in the study. Of these, 212 (96.4%) agreed to par- David T. Mauger, PhD ticipate, and 174 of the surveys (82.1%) were fully com- James G. Marks, MD pleted. The mean±SD age of participants was 52.5±16.8 Correspondence: Ms Regula, Penn State University Col- years. Nearly 60% of respondents were women; 22% of lege of Medicine, Milton S. Hershey Medical Center, 78 all participants were between ages 18 and 39 years; 38% University Manor E, Hershey, PA 17033 (cregula@hmc were between ages 40 and 59 years; and 37% were 60 years .psu.edu). or older. Most respondents had completed high school Financial Disclosure: None reported. or college as their highest level of education (38.2% each), while 21% had completed graduate (postcollege) 1. Ersser SJ, Surridge H, Wiles A. What criteria do patients use when judging education. the effectiveness of psoriasis management? J Eval Clin Pract. 2002;8(4):367- 376. The Table lists the percentages of patients who ranked 2. Zandbelt LC, Smets EM, Oort FJ, Godfried MH, de Haes HC. Satisfaction with each of the top 6 aspects of care as “5, very important” the outpatient encounter. J Gen Intern Med. 2004;19(11):1088-1095. 3. Institute of Medicine. Crossing the Quality Chasm: A New Health System for on the 5-point scale. The 22 aspects of care not included the 21st Century. Washington, DC: National Academy Press; 2004:61-63. in the Table were proven to be statistically less impor- 4. Ryan M. Using conjoint analysis to take account of patient preferences and tant (PϽ.05) than the top-ranked aspect of care. Three go beyond health outcomes: an application to in vitro fertilization. Soc Sci of the 6 top-ranking aspects of care were categorized as Med. 1999;48(4):535-546. professional interactions, and 3 as treatment. Demo- graphic variables were not associated with a difference in ranking of these individual aspects of care. COMMENTS AND OPINIONS Of the 5 categories of care, treatment ranked as most important to most patients (58.9%). Most open-ended responses cited an aspect of either treatment or professional interactions as most important to the quality of Psoriasiform Eruptions During Anti–TNF-␣ health care. These included a knowledgeable physician Treatment: Psoriasis or Not? (21.9%), concern/caring of physician (15.7%), and a physician who listens (10.1%). e read with interest the report by de Gannes et al1 concerning psoriasis triggered by tu- Comment. Our patients believe that treatment is most W mor necrosis factor ␣ (TNF-␣) inhibitors. important to the quality of their health care. The most The paradoxical induction of psoriasislike eruption in pa- important aspects of treatment were the patient’s inclu- tients treated with anti–TNF-␣ agents was first de- sion in the treatment process, discussion of treatment op- scribed by Verea et al2 in 2004. Since that time, more than tions, and instruction on the chosen treatment—not the 70 cases of psoriasiform eruptions have been reported treatment’s speed or outcome. Patients seek quality in their in patients with autoinflammatory diseases who are un- personal interactions with a knowledgeable, thorough dergoing treatment with anti–TNF-␣ agents. The major physician who listens, communicates well, and is fo- clinical presentation is palmoplantar pustulosis some- cused on individualized care. Patients ranked such as- times accompanied by guttate or plaquelike psoriasis. In

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1593 A B

Figure. Psoriasiform eruption triggered by tumor necrosis factor ␣ inhibitor. A, Delayed distant positive reading showing a lesion consistent with an erythematous and squamous plaque. B, Histological features include mixed lichenoid and spongiotic patterns.

20 cases, histologic findings were consistent with pso- chenoid or spongiotic psoriasiform drug eruptions. Nega- riasis. In other reports, skin biopsy findings were not typi- tive local patch test results can be explained by the fact cal of psoriasis or showed a lichenoid2 pattern. How- that only 43% of patch test findings are positive in in- ever, psoriasiform eruptions were not always analyzed vestigating cutaneous drug eruption.4 Moreover, the strong histologically. inhibitory effect of anti–TNF-␣ on local patch test re- Our research group3 has described 8 patients (3 women sponses could be compared with the usual results of the and 5 men; mean age, 45 years) who experienced pso- corticosteroid patch tests.5 riasiform eruptions during anti–TNF-␣ treatment.3 In that It is now known that anti–TNF-␣ agents increase lev- report, we provided clinical, histopathologic, and im- els of interferon ␣, which plays a major role in psoriasis munohistochemical arguments that the psoriasiform erup- induction but is also essential in the pathogenesis of cy- tions do not represent true psoriasis.3 The psoriasiform totoxic skin reactions such as lichen planus or lichen- eruptions developed 2 to 26 months after the initiation oid eruptions.6 Interferon ␣ induces the expression of CXC of the treatment for long-standing rheumatoid arthritis chemochine receptor 3 on activated T cells, facilitating (etanercept and adalimumab), ankylosing spondylitis (in- homing to the skin. Moreover, anti–TNF-␣ agents can fliximab), and psoriatic arthritis (infliximab). Only 1 pa- promote the activation of autoreactive T cells, and the tient had a history of psoriasis. All patients developed predominantly lichenoid or spongiotic autoreactivity to plaque-type psoriasis accompanied in 3 cases by pustu- keratinocytes might be mediated by theCD8ϩ T cells that lar lesions of the palms and/or soles. Histologic findings we have detected in the lesions. Although true psoriasis in 6 patients showed epidermal hyperplasia, parakera- may arise in the context of anti–TNF-␣ therapy, we think tosis, and spongiosis. A lichenoid pattern was observed that most psoriasiform eruptions induced by anti– in 3 samples with an infiltrate showing a predominant TNF-␣ agents, puzzling phenomenon for both derma- CD8ϩ cytotoxic T-cell phenotype. tologists and rheumatologists, constitute rather a new Patients were patch tested with the European stan- model of adverse drug reaction. dard series and 2 anti–TNF-␣ molecules (etanercept and infliximab). Tests were read at 48 hours and at day 8. Only Julien Seneschal, MD 1 patient reacted to the etanercept patch test at 48 hours Se´bastien Lepreux, MD with edema and vesicles. Readings at day 8 showed a flare Brigitte Milpied, MD of dermatitis in 4 of the 8 patients (Figure). Histologic and immunohistochemical studies showed features com- Thierry Schaeverbeke, MD, PhD parable with the initial psoriasiform lesions. Moreover, Alain Taı¨eb, MD, PhD the biopsy specimen of 1 patient contained a moderate number of eosinophils. All skin eruptions improved with Correspondence: Dr Taı¨eb, Department of Dermatol- topical steroid treatment but recurred after reinitiation ogy, Hoˆpital St Andre´, 1 rue Jean Burguet, 33075 Bor- of the same anti–TNF-␣ agents in 4 patients. deaux CEDEX, France ([email protected]). In contrast to the conclusions of de Gannes et al1 that Financial Disclosure: None reported. psoriasiform eruptions induced by anti–TNF-␣ agents are Funding/Support: The patient follow-up was sup- true psoriasis, we propose that psoriasiform eruptions are ported by a regional Programme Hospitalier de Recher- “class effect” lesions, compatible histologically with li- che Clinique grant (Dr Schaeverbeke).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1594 1. de Gannes GC, Ghoreishi M, Pope J, et al. Psoriasis and pustular dermatitis ␣ dritic cells have also been implicated in the pathogenesis of triggered by TNF- inhibitors in patients with rheumatologic conditions. Arch 7 Dermatol. 2007;143(2):223-231. atopic dermatitis. 2. Verea MM, Del Pozo J, Yebra-Pimentel MT, et al. Psoriasiform eruption in- The patch test results and the description of lichenoid and duced by infliximab. Ann Pharmacother. 2004;38(1):54-57. eczematous features of the eruptions noted by Seneschal et 3. Seneschal J, Lepreux S, Bouyssou-Gauthier ML, et al. Psoriasiform drug eruptions under anti-TNF treatment of arthritis are not true psoriasis. Acta Derm al are consistent with the theme of local type 1 interferon Venereol. 2007;87(1):77-80. up-regulation by TNF-α antagonism. Type 1 interferons 4. Barbaud A, Goncalo M, Bruynzeel D, et al. Guidelines for performing skin tests with drugs in the investigation of cutaneous adverse drug reactions. Con- are clearly associated with the cytotoxic inflammation 8 tact Dermatitis. 2001;45(6):321-328. noted in lichen planus, for example. Cytotoxic T cells are 5. Reitamo S, Lauerma AI, Stubb S, et al. Delayed hypersensitivity to topical also implicated in the pathogenesis of psoriasis.9 The ac- corticosteroids. J Am Acad Dermatol. 1986;14(4):582-589. 6. Wenzel J, Scheler M, Proelss J, et al. Type I interferon-associated cytotoxic cess to tissue for examination of cytokines and T-cell sub- inflammation in lichen planus. J Cutan Pathol. 2006;33(10):672-678. sets that the skin offers will allow us to learn how and why TNF-α inhibition may result in such varied cutaneous manifestations. In reply We thank Seneschal et al for their interest in our article. Gillian C. de Gannes, MD They agree with our observation that most psoriasiform erup- Mehran Ghoreishi, MD, PhD tions occurring during anti–TNF-α therapy are reported to Janet Pope, MD, FRCPC show histologic findings consistent with psoriasis. How- Anthony Russell, MA, MB, BChir, FRCP(C) ever, the authors point out a report of a patient treated with David Bell, MD, FRCPC infliximab who developed a symmetrical papular eruption Stewart Adams, MD, FRCPC with lichenoid features.1 They further review 8 cases origi- Kamran Shojania, MD, FRCPC nally described by their own research group2 with histo- Magdalena Martinka, MD, FRCPC logic findings atypical for psoriasis despite a morphologic Jan P. Dutz, MD, FRCPC description of the lesions as “plaque-type psoriasis” with “pustular lesions of the palms and/or soles.” They propose the Correspondence: Dr Dutz, Department of Dermatology term lichenoid or spongiotic psoriasiform drug eruption and Skin Science, The Skin Care Centre, 835 W 10th for the reaction. They state that this is likely a new model Ave, Vancouver BC, V5Z 4E8, Canada (dutz@interchange for an adverse drug reaction, unrelated to psoriasis, and chal- .ubc.ca). lenge our association of anti–TNF-α treatment with pso- Financial Disclosure: Dr Shojania has received re- riasis induction. They base this conclusion on 3 of 8 biopsy search funding and speaking honoraria from Abbott, results from their patients with psoriasiform eruptions Amgen, Schering, and Centocor. + demonstrating a lichenoid pattern with CD8 T-cell pre- 1. Verea MM, Del Pozo J, Yebra-Pimentel MT, Porta A, Fonseca E. Psoriasiform dominance. Furthermore, 4 of 8 patients responded to topi- eruption induced by infliximab. Ann Pharmacother. 2004;38(1):54-57. α 2. Seneschal J, Lepreux S, Bouyssou-Gauthier ML, et al. Psoriasiform drug erup- cal anti–TNF- application (using a protein patch test pro- tions under anti-TNF treatment of arthritis are not true psoriasis. Acta Derm tocol) by developing delayed psoriasiform lesions with the Venereol. 2007;87(1):77-80. presence of eosinophils, suggestive of a drug eruption. 3. Ritchlin C, Tausk F. A medical conundrum: onset of psoriasis in patients receiving anti-tumour necrosis factor agents. Ann Rheum Dis. 2006;65(12): The histologic features of our cases and many of the cases 1541-1544. we reviewed in the literature were consistent with 1 of 3 forms 4. Dutz JP. Tumor necrosis factor-␣ inhibition and palmoplantar pustulosis: Janus- of cutaneous psoriasis: psoriasis vulgaris, guttate psoria- faced therapy? J Rheumatol. 2007;34(2):247-249. 5. Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G. Palmoplantar pustu- sis, and/or palmoplantar pustulosis. We proposed, based on losis: a clinical and immunohistological study. Br J Dermatol. 1998;138(3): an understanding of cytokine regulation in vivo and of our 390-398. 6. Lee HH, Song IH, Friedrich M, et al. Cutaneous side-effects in patients with demonstrated increased myxovirus-resistance protein A stain- rheumatic diseases during application of tumour necrosis factor-alpha ing, that the cutaneous eruptions were due in part to the lo- antagonists. Br J Dermatol. 2007;156(3):486-491. cal up-regulation of type 1 interferons. This possibility has 7. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, et al. Major differences 3 in inflammatory dendritic cells and their products distinguish atopic derma- been proposed independently by others. Our group has re- titis from psoriasis. J Allergy Clin Immunol. 2007;119(5):1210-1217. cently emphasized that palmoplantar psoriasis has clinical 8. Wenzel J, Scheler M, Proelss J, Bieber T, Tuting T. Type I interferon- and genetic features that are distinct from psoriasis vul- associated cytotoxic inflammation in lichen planus. J Cutan Pathol. 2006; 4 5 33(10):672-678. garis. Eosinophils may be detected in such lesions. Fur- 9. Austin LM, Coven TR, Bhardwaj N, Steinman R, Krueger JG. Intraepidermal thermore, the eruptions noted in patients undergoing anti– lymphocytes in psoriatic lesions are activated GMP-17(TIA-1) α ϩCD8ϩCD3ϩ CTLs as determined by phenotypic analysis. J Cutan Pathol. TNF- therapy tend to resolve, not unlike a relatively rare 1998;25(2):79-88. psoriasis variant called acute palmoplantar pustular psoriasis of Andrews. This condition has been called a bac- terid, implying a response to a remote bacterial infection, which is consistent with our proposal that these eruptions British Guidelines on the Use of Biological derive from the local dysregulation of type 1 interferons. Therapies for Psoriasis: A Note Since the publication of our review, another report has of Clarification on the Role of Etanercept been published, describing a series of patients with rheumatic diseases who were treated with TNF-α antagonists e are pleased that the British Association of and subsequently developed cutaneous manifestations.6 Again, Dermatologists guidelines on use of biologi- psoriasislike skin lesions were prominent. Interestingly, W cal therapies in psoriasis1 have been high- an equal incidence of eczematous eruptions was reported. lighted and summarized so succinctly. We are also glad Of note, type 1 interferon–producing plasmacytoid den- that the reviewing author, Dr Nijsten,2 found them to be

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1595 “clear and informative” and that he recommends their use. matologists Subcommittee on Biological Therapy for However, we are concerned that his conclusion (as stated Psoriasis. in the abstract and in the commentary) that “etanercept 1. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists is the biological drug of choice in most eligible patients guidelines on biological interventions in psoriasis. Br J Dermatol. 2005;153 with stable disease with or without psoriatic arthritis” is (3):486-497. a misrepresentation of what is stated in the guidelines. In- 2. Nijsten T. Level of agreement with the British guidelines for the use of biological therapies for psoriasis. Arch Dermatol. 2007;143(12):1567-1569. deed, we were very careful not to provide explicit guid- ance as to which of the agents covered (etanercept, infliximab, and efalizumab) should be the preferred choice given VIGNETTES the lack of evidence available at the time. See also page 1567 Multiple Subcutaneous Lipomas The specific recommendations in the guidelines in re- Induced by HAART in the Absence lation to etanercept are as follows1: (1) etanercept should of Protease Inhibitors be considered first choice for patients with significant uncontrolled psoriatic arthritis (according to the British So- ciety of Rheumatology guidelines at the time of guide- e report herein a case of atypical lipodystro- line development), and (2) etanercept should be used in phy manifesting as multiple subcutaneous cases of stable psoriasis in which a decision to treat with W lipomas in a patient with human immunode- an anti–tumor necrosis factor has been made, unless there ficiency virus (HIV) undergoing highly active antiretro- are reasons not to do so. The reasoning behind this state- viral therapy (HAART) lacking a protease inhibitor. ment was based on the fact that infliximab was unli- censed for psoriasis in the United Kingdom at the time Report of a Case. A 50-year-old white man presented for that the guidelines were published. However, in cases in evaluation of multiple subcutaneous tumors on his back, which there are no compelling reasons to use an anti– chest (Figure 1), neck, abdomen, forearms, and left heel. tumor necrosis factor (eg, stable chronic plaque psoria- He was diagnosed 10 months earlier as having HIV in- sis without joint disease), based on the evidence that has fection concurrently with HIV-related non-Hodgkin lym- been collated on clinical efficacy and safety, efalizumab phoma of the diffuse large B-cell type. He stated that the might equally well be the treatment of choice. lesions first appeared shortly after the initiation of his We strongly concur with Dr Nijsten’s concluding re- HAART, which consisted of the nonnucleoside reverse- marks that the appropriate positioning of these agents in transcriptase inhibitor (NNRTI) efavirenz along with the context of the overall therapeutic armamentarium for tenofovir and lamivudine (2 nucleoside reverse- the treatment of psoriasis requires detailed long-term safety transcriptase inhibitors [NRTIs]). He received 6 cycles studies and further comparative studies on efficacy and safety between the different biological therapies as well as standard therapies. Biological therapy is a rapidly moving field of drug development and clinical practice, and we are in the process of revising our 2005 guidelines to include recently published randomized clinical trial data on the safety and efficacy of the various agents and on changes in the licensing status of certain drugs (eg, infliximab), thereby ensuring that the guidelines continue to provide up-to- date, evidence-based recommendations. Catherine H. Smith, MD, FRCP Anthony D. Ormerod, FRCP Correspondence: Dr Smith, St John’s Institute of Derma- tology, St Thomas Hospital, Lambeth Palace Rd, London Lo SE1 7EH, England ([email protected]). Financial Disclosure: Dr Smith has served as a consultant to Novartis and has received honoraria from Wyeth and Serono and grants from Serono, Wyeth, and Schering- Plough. Dr Ormerod has received honoria from Merck- Serono and Wyeth for invited lectures and has acted as a consultant for Schering-Plough. Role of the Sponsors: The sponsors had no role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation of the manuscript, review, or approval of the manuscript. Additional Information: Drs Smith and Ormerod wrote Figure 1. Multiple subcutaneous lipomas from nonnucleoside and this article on behalf of the British Association of Der- nucleoside reverse transcriptase inhibitors.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1596 to decrease visceral and dorsocervical fat, but it is also associated with a high rate of adverse events.4 The formation of subcutaneous lipomas as part of lipodystrophy syndrome is rare. In 2000, Bo¨rnhovd et al5 published the first report to our knowledge of multiple circumscribed subcutaneous lipomas following initiation of HAART. The patient was being treated with the protease inhibitor indinavir and the NNRTI efavirenz. The researchers postulated that the lipomatosis was caused by indinavir exerting its known effects on lipid metabolism. To our knowledge, the finding of multiple subcutaneous lipomas in our patient is unique in that he was never treated with a protease inhibitor. Therefore, dermatolo- Figure 2. Histopathologic section revealing a lipoma with focal spindle cell gists should become aware of this atypical lipodystro- features (hematoxylin-eosin, original magnification ϫ10). phy reaction to NNRTI and NRTI medications. of lymphoma chemotherapy using dose-adjusted infu- Elena Balestreire, BS sional etoposide, prednisone, vincristine, cyclophospha- Justin M. Haught, MD mide, and doxorubicin. Over the year, his HAART regi- Joseph C. English III, MD men remained the same except that lamivudine was Correspondence: Dr English, Department of Dermatol- replaced with emtricitabine (an NRTI). The patient gained ogy, University of Pittsburgh, 190 Lothrop St, Ste 145, 59 pounds (27 kg) over this period. Lothrop Hall, Pittsburgh, PA 15213 (englishjc@upmc On physical examination, the lesions measured 1.0 .edu). to 6.0 cm in diameter, and most were localized on the Financial Disclosure: None reported. patient’s trunk (Figure 1) and upper extremities. A tu- ϫ Additional Contributions: Jon Ho, MD, and Sourva Ray, mor on the patient’s left heel measuring 1.2 1.5 cm MD, provided the histopathologic photograph forFigure 2. was excised owing to its interference with his wearing of shoes. Histopathologic analysis showed a lipoma 1. Chen D, Misra A, Garg A. Clinical review 153: lipodystrophy in human im- Figure 2 munodeficiency virus-infected patients. J Clin Endocrinol Metab. 2002;87 with focal spindle cell features ( ). Serum tests (11):4845-4856. revealed elevated levels of fasting glucose (103 mg/dL), 2. Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on overall cholesterol (368 mg/dL), low-density lipo- serum lipids in men. JAMA. 2003;289(22):2978-2982. 3. Barragan P, Fisac C, Podzamczer D. Switching strategies to improve lipid pro- protein (LDL) cholesterol (273 mg/dL), triglycerides file and morphologic changes. AIDS Rev. 2006;8(4):191-203. (338 mg/dL), and very-low-density lipoprotein (VLDL) 4. Wohl DA. Diagnosis and management of body morphology changes and lipid cholesterol (54 mg/dL). These were reported to his pri- abnormalities associated with HIV infection and its therapies. Top HIV Med. 2004;12(3):89-93. mary physician for management. (To convert fasting 5. Bornho¨vd E, Sakrauski AK, Bruhl H, et al. Multiple circumscribed subcuta- glucose to millimoles per liter, multiply by 0.0555; neous lipomas associated with use of human immunodeficiency virus prote- overall, LDL, and VLDL cholesterol to millimoles per li- ase inhibitors? Br J Dermatol. 2000;143(5):1113-1114. ter, multiply by 0.0259; triglycerides to millimoles per liter, multiply by 0.0113.) Clinical Improvement of Pityriasis Rubra Comment. Highly active antiretroviral therapy has be- Pilaris With Combination Etanercept come the mainstay of treatment for HIV-positive pa- and Acitretin Therapy tients. However many patients experience dermatologic adverse effects such as the lipodystrophy syndrome, which ityriasis rubra pilaris (PRP) is a rare chronic papu- manifests as disruptions in serum lipid levels (hypercho- losquamous disorder of unknown cause charac- lesterolemia, hypertriglyceridemia, and reduced levels of P terized by erythematous scaly plaques, palmo- high-density lipoprotein cholesterol), insulin resis- plantar keratoderma, and keratotic follicular papules. The tance, central fat redistribution, increased dorsocervical disease can be intensely painful, disabling, and difficult fat (“buffalo hump”), and/or peripheral lipoatrophy.1 to treat. We report the first case of PRP treated success- While the abundance of circulating lipids increases the fully with combination etanercept and acitretin therapy. risk of cardiovascular disease, the importance of main- taining a low viral load and normal CD4 cell count may Report of a Case. A 55-year-old man presented with a outweigh this adverse reaction to HAART.2 large erythematous scaly patch on his right temple and Protease inhibitors (eg, indinavir) have been strongly scalp. Clinical appearance and skin biopsy findings led associated with lipodystrophy syndrome. Patients under- to the diagnosis of adult-onset type 1 PRP. Over the next going treatment with protease inhibitors have been 8 months, the plaques gradually spread to cover his chest, switched to NNRTI regimens (eg, efavirenz) and shown back, arms, legs, palms, and the soles of his feet, even- improvement in their fasting serum lipid levels.3 Treat- tually covering an estimated 90% of his body surface area ment of the cutaneous manifestations of lipodystrophy syn- (Figure 1). drome have largely comprised the use of intralesional filler The patient was treated with calcipotriene ointment substances for lipoatrophy and systemic recombinant hu- and clobetasol propionate cream twice a day. The pa- man growth hormone therapy. The latter has been shown tient continued to experience severe burning and itch-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1597 Figure 1. Plaques gradually spread to cover an estimated 90% of the patient’s Figure 2. After 7 months of combination etanercept and acitretin therapy, body surface area, including his face, head, neck, shoulders, and chest. 85% to 90% of his plaques had resolved completely. ing and developed more widespread disease. Five months Tumor necrosis factor ␣ is a cytokine believed to be later, he began treatment with acitretin, 25 mg/d, and UV-B involved in the pathogenesis of several inflammatory and light therapy 2 to 3 times per week for 2 weeks, which autoimmune disorders by eliciting multiple proinflam- failed to provide any clinical improvement. Acitretin matory responses such as induction of IL-1, leuko- therapy was discontinued, and a cyclosporine regimen, trienes, and neutrophil migration and activation.2 Inflix- 100 mg/d, was initiated. Nevertheless, the patient’s con- imab, a chimeric monoclonal antibody that binds to dition worsened. The patient then began prednisone TNF-␣, has been shown to dramatically improve PRP in monotherapy, 20 mg/d. After 2 weeks of prednisone selected cases.2-5 Etanercept binds to both TNF-␣ and monotherapy, the patient’s condition had not im- TNF-␤ receptors, rendering TNF biologically inactive and proved, and he began to complain of joint pain. The pred- likely interrupting a significant step in a critical PRP path- nisone treatment was discontinued. way. The US Food and Drug Administration (FDA) in- Finally, the patient began treatment with a combina- dications for etanercept include ankylosing spondylitis, tion of etanercept, 50 mg subcutaneously twice a week, and rheumatoid arthritis, juvenile rheumatoid arthritis, plaque acitretin, 25 mg/d, and he began to show clinical improve- psoriasis, and psoriasis with arthropathy. While etaner- ment. After 7 months of this combination treatment 85% cept is not currently approved by the FDA for use in PRP, to 90% of his plaques had resolved completely (Figure 2). further studies to investigate the safety and efficacy of He currently receives maintenance etanercept therapy at etanercept in the treatment of PRP are warranted. 50 mg subcutaneously every other week. Kristy F. Davis, BS Comment. Several agents are used for the treatment of Jashin J. Wu, MD PRP, including topical corticosteroids, emollients, reti- Jenny E. Murase, MD noids, antimetabolites, cyclosporine, and photo- Fredric R. Rosenberg, MD therapy; however, none has been shown to be univer- Erik P. Sorenson, PA sally remittive.1 One difficulty in developing a targeted Azin Meshkinpour, MD treatment is the lack of a clearly elucidated cause. How- ever, PRP shares clinical and histologic features with pso- Correspondence: Dr Wu, Department of Dermatology, riasis and responds to many of the same treatments. Tu- University of California, Irvine, 101 The City Drive South, mor necrosis factor (TNF) inhibitors have been proven Bldg 53, Room 302A, Rt 81, Orange, CA 92868-3201 (jjwu successful in the treatment of psoriasis, and off-label use @uci.edu). of these agents has recently been successful in PRP treat- Financial Disclosure: None reported. 2-5 ␣ ment. This anecdotal evidence suggests that TNF- plays 1. Cohen PR, Prystowsky JH. Pityriasis rubra pilaris: a review of diagnosis and a role in the pathogenesis of PRP as well as in psoriasis. treatment. J Am Acad Dermatol. 1989;20(5, pt 1):801-807.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1598 2. Drosou A, Kirsner RS, Welsh E, Sullivan TP, Kerdel FA. Use of infliximab, an progressive pigmented capillaropathy. Our case had a anti-tumor necrosis alpha antibody, for inflammatory dermatoses. J Cutan Med Surg. 2003;7(5):382-386. more unusual clinical presentation, ie, eruptions with a 3. Alexis AF, Strober BE. Off-label dermatologic uses of anti-TNF-␣ therapies. zosteriform distribution of L1/L2. J Cutan Med Surg. 2005;9(6):296-302. 4. Liao WC, Mutasim DF. Infliximab for the treatment of adult-onset pityriasis rubra pilaris. Arch Dermatol. 2005;141(4):423-425. 5. Manoharan S, White S, Gumparthy K. Successful treatment of type I adult- onset pityriasis rubra pilaris with infliximab. Australas J Dermatol. 2006;47 (2):124-129.

A Case of Zosteriform Pigmented Purpuric Dermatosis

Report of a Case. A 61-year-old Japanese woman was referred to us with a 6-month history of gradually spreading, asymptomatic, irregularly shaped, red-brown purpuric papules and plaques with tiny petechiae on her left lower abdomen, back, and femoral regions (Figure 1). The lesions had a zosteriform distribution of L1/L2. She had no history of a bleeding disorder, and the medical and family histories were unremarkable. Histopathologic examination revealed a perivascular and interstitial lymphocytic infiltrate with extravasation of erythrocytes and mild liquefactive degeneration of the basal layer (Figure 2). There was no evidence of vasculitis. Results of laboratory investigations were within normal range, including those of complete blood cell count, biochemical examinations, prothrombin time, and activated partial thromboplastin time. Test results for cryo- globulins and cryofibrinogen were negative. Hepatitis C antibody was not detected. The diagnosis of pigmented purpuric dermatosis was confirmed. Topical steroid therapy was administered for a few months without any apparent benefit.

Comment. Pigmented purpuric dermatoses are a group of chronic skin disorders of unknown cause characterized by petechiae, lichenoid papules, telangiectasia, and later development of pigmentation. They are traditionally divided into 5 clinical entities: Schamberg disease, Figure 1. Red-brown purpuric papules and plaques with tiny petechiae on itching purpura, pigmented purpuric lichenoid derma- the left lower abdomen and femoral regions. Lesions had a zosteriform titis of Gougerot and Blum, lichen aureus, and purpura distribution of L1/L2. annularis telangiectodes. Each shares similar clinical and histopathologic features, and the eruptions commonly have a symmetrical distribution on the lower extremities. In early lesions, there is perivascular and interstitial lymphocytic inflammation and extravasation of erythrocytes with endothelial swelling of superficial small vessels in the papillary dermis. In older lesions, there is less inflammation, and hemosiderin deposits are found in macrophages. Pigmented purpuric dermatosis may per- sist for many years, and treatment is often ineffective. The present case did not seem to fit any of the 5 classic entities of pigmented purpuric dermatoses owing to the unusual clinical presentation. However, although rarely seen, some cases of chronic pigmented purpuric eruptions with a linear distribution on a unilateral lower limb have been described.1-4 These cases are considered to be a subgroup of pigmented purpuric dermatoses and Figure 2. Skin biopsy specimen from the left lower abdomen reveals a perhaps are compatible with Schamberg disease. They perivascular and interstitial lymphocytic infiltrate with extravasation of have been referred to as a unilateral progressive pigmen- erythrocytes in the upper dermis and mild vacuolar degeneration of the basal tary purpura, unilateral linear capillaritis, or unilateral layer (hematoxylin-eosin, original magnification ϫ100).

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1599 Many skin disorders with a zosteriform distribution centrically, become darker, and filled the entire nail have been reported. The commonly recognized diseases plate. include lichen planus, infectious exanthemas, mycoses, On physical examination, we found a dark brown mac- urticaria, scleroderma, dermatitis herpetiformis, and seg- ule and brown and black longitudinal streaks that filled the mental neurofibromatosis.5 In most cases, the reason for the localization of skin lesions in certain areas is unknown. The pathomechanism of zosteriform lichen planus has been discussed by a few authors, who have suggested that the specific manifestation was due to Koebner phenomenon or a previous herpes zoster eruption within the affected nerve segments.5 We believe that our patient is the first distinct case reported of zosteriform pigmented purpuric dermatosis. This condition should be included in the list of disorders with a zosteriform distribution pattern in the skin. Takahiro Hamada, MD Yoshihiko Inoue, MD Takekuni Nakama, MD Takashi Hashimoto, MD Correspondence: Dr Hamada, Department of Dermatol- ogy, Kurume University School of Medicine, 67 Asahi- machi, Kurume, Fukuoka 830-0011, Japan (hamataka @med.kurume-u.ac.jp). Financial Disclosure: None reported. Funding/Support: This work was supported by a Grant- in-Aid for Scientific Research (Dr Hamada) and an Open Research Center Project (Dr Hashimoto) from the Min- istry of Education, Culture, Sports, Science and Technol- ogy of Japan and by Health Science Grants for Research on Scientific Disease from the Ministry of Health, Labor and Welfare of Japan (Dr Hashimoto), Tokyo.

1. Hersh CS, Shwayder TA. Unilateral progressive pigmentary purpura (Scham- berg’s disease) in a 15-year-old boy. J Am Acad Dermatol. 1991;24(4):651. 2. Riordan CA, Darley C, Markey AC, Murphy G, Wilkinson JD. Unilateral linear capillaritis. Clin Exp Dermatol. 1992;17(3):182-185. 3. Filo V, Galbavy S, Filova A, Borecka D, Novotna V. Unilateral progressive pigmented capillaropathy (Schamberg’s disease?) of the arm. Br J Dermatol. 2001; 144(1):190-191. 4. Taketuchi Y, Chinen T, Ichikawa Y, Ito M. Two cases of unilateral pigmented purpuric dermatosis. J Dermatol. 2001;28(9):493-498. 5. Fink-Puches R, Hofmann-Wellenhof R, Smolle J. Zosteriform lichen planus. Dermatology. 1996;192(4):375-377. Figure 1. A brown macule with black longitudinal streaks and Hutchinson sign on the right thumb.

Subungual Melanoma In Situ in a Hispanic Girl Treated With Functional Resection and Reconstruction With Onychocutaneous Toe Free Flap

elanoma of the ungual apparatus represents less than 3% of all cases of cutaneous melanoma.1 To our knowledge, the medical literature re- M 2 ports only 6 cases of subungual melanomas in children, and we report the first case of a subungual melanoma in a child treated with slow Mohs surgery and reconstructive surgery with a free flap to restore function.

Report of a Case. An asymptomatic, 12-year-old His- panic girl, skin phototype III, had a brown spot under Figure 2. Atypical melanocytes with huge hyperchromatic nuclei distributed the lunula of her right thumb first noticed at the age of 3 in all epidermal layers (pagetoid dissemination) (hematoxylin-eosin, original years. A year before her visit, the spot had extended ec- magnification ϫ10.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1600 Figure 3. Right thumb following tumor excision.

Figure 5. Excision of the nail apparatus from the hallux with corresponding artery, vein, and nerve.

lateral and distal edges (Figure 3). The surgical specimen confirmed the findings of the previous biopsy: no dermal invasion was present, and all lateral and deep margins were disease free. One week after tumor excision, the plastic surgeon har- vested a microvascular composite onychocutaneous free flap from the right first toe (Figures 4, 5, and 6) and transferred it to the thumb defect using microvascular anastomoses of the artery, vein, and nerve. At 3-month follow-up, normal nail growth and full mobility of the Figure 4. Arterial plexus marked on the right foot for donor nail apparatus. interphalangeal thumb joint were present. entirenailplate.Blackpigmentationwaspresentintheproxi- Comment. According to Mendonc¸a et al,1 subungual mela- mal nailfold (Figure 1). The remaining fingers and toe- noma, a rare variety of acral melanoma, was first de- nails were normal. No axillary lymph nodes were involved. scribed by Hutchinson in 1886. Peak incidence of acral Histologic studies revealed atypical melanocytes with melanoma among the low-income patients treated at the large and irregular hyperchromatic nuclei distributed National Cancer Institute of Colombia occurs at around throughout all epidermis layers. Melanophages were found age 60 years and accounts for 46% of all melanoma cases.3 in the upper dermis (Figure 2). Subungual melanoma Whether all reported cases of longitudinal melano- in situ was diagnosed. nychia in children are true melanomas is a matter of some We used slow Mohs micrographic surgery (paraffin controversy because benign longitudinal melanonychia embedded) to excise the tumor with 1-cm lateral mar- can include a certain degree of cellular atypias and me- gins at the proximal nailfold and 0.5-cm margins at the lanocytic migration, making diagnosis difficult.4 Never-

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1601 Correspondence: Dr Motta, Department of Dermatol- ogy, Universidad El Bosque, Calle 134 No. 13 7B-83, Of- fice 1021, Bogota´, Colombia ([email protected]). Financial Disclosure: None reported. Additional Contributions: Mariam Rolo´n, MD, provided the histologic diagnosis.

1. Mendonc¸a I, Kac B, Silva R, Spinelli L, Orofino R, Franc¸a J. Nail apparatus melanoma. An Bras Dermatol. 2004;79(5):575-580. 2. Antonovich DD, Grin C, Grant-Kels J. Childhood subungual melanoma in situ in diffuse nail melanosis beginning as expanding longitudinal melanonychia. Pediatr Dermatol. 2005;22(3):210-212. 3. Acosta AE. Melanoma in Colombia. Poster presented at the Sixth World Con- gress on Melanoma; September 2005; Vancouver, British Columbia, Canada. 4. Goettmann-Bonvallot S, Andre´ J, Belaich S. Longitudinal melanonychia in children: a clinical and histopathologic study of 40 cases. J Am Acad Dermatol. 1999;41(1):17-22. 5. Banfield CC, Dawber RPR. Nail melanoma: a review of the literature with recommendations to improve patient management. Br J Dermatol. 1999;141 (4):628-632. 6. Moehrle M, Metzger S, Schippert W, Garbe C, Rassner G, Breuninger H. “Functional” surgery in subungual melanoma. Dermatol Surg. 2003;29(4): 366-374.

Docetaxel Monotherapy for Angiosarcoma in an Elderly Patient

reatment of angiosarcoma (AS) of the scalp in elderly patients remains difficult owing to the high frequency of local recurrence and lung me- T 1 tastasis. Recently, weekly low-dose docetaxel therapy has proven effective for treating local recurrences and lung metastases of AS of the scalp2,3 and radiation-induced AS of the breast.4 Herein, we describe a patient with AS of the scalp and face treated with docetaxel alone who Figure 6. Three month follow-up. showed a partial response. theless, our case showed severe cellular atypias and mel- Report of a Case. A 91-year-old woman presented with anocyte migration in all epidermis layers with no nest a 9-week history of facial edema and progressively en- formations accompanied by rapid and progressive ex- larging violaceous plaques with dark purple dissemi- pansion of the lesion, which filled the entire nail appa- nated nodules on her face. She had no history of trauma ratus and partial proximal nailfold. to the face, bleeding, or treatment with corticosteroids Amputation has been considered the treatment of or anticoagulation drugs. Nine weeks before her admis- choice for these lesions.5 However, this approach war- sion, she had noticed thumb-sized purpura on her right rants caution because melanomas in situ can be success- cheek, which grew rapidly and spread over her scalp (fron- fully treated with conservative surgery. A study of pa- tal and right temporal), her glabella, and both cheeks with tients with subungual melanoma in situ or with minimal extension to the mandible (Figure 1). local infiltration compared the results obtained be- A biopsy specimen of her cheek revealed extensive tween amputation and functional surgery.6 Patient fol- hemorrhaging and the presence of irregular anastomos- low-up showed no significant survival differences being vascular channels lined by atypical, enlarged endo- tween them, but the functional surgery led to superior thelial cells permeated by collagen bundles. Neck and aesthetic, functional, and psychological results. This type chest computed tomographic scans revealed no meta- of surgery has shown positive results with regard to the static lesions in the cervical lymph nodes or lungs. function of the fingers related to the preservation of the Owing to the extensive involvement of her scalp, gla- nail. The knowledge gained about the safety of this pro- bella, and cheeks, surgical excision and wide-field irra- cedure will contribute to the ability of the parents of these diation therapy were excluded as treatment options. Mono- patients to make an informed decision. We recommend therapy with docetaxel (Taxotere; Sanofi-Aventis, Tokyo, that functional resection followed by reconstruction with Japan) was administered intravenously at a dose of 25 onychocutaneous toe free flap be considered for treat- mg/m2 for 1 hour per week over a period of 8 weeks. No ing subungual melanoma. treatment was administered on the fourth and eighth weeks. Eight weeks after docetaxel administration began, the Adriana Motta, MD violaceous plaques resolved, and the facial edema im- Carlos Lo´pez, MD proved (Figure 2). Biopsy specimens revealed the dis- Alvaro Acosta, MD appearance of atypical endothelial cells and irregular anas- Camilo Pen˜aranda, MD tomosing vessels. The patient experienced no severe

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1602 higher potency.5 Paclitaxel has also been reported to have unique activity in the treatment of AS of the scalp and AIDS-related Kaposi sarcoma.6,7 However, in studies conducted in Europe,8 it was concluded that docetaxel was rather ineffective for soft tissue sarcomas, including AS, and could not be recommended for further use. There- after, the application of docetaxel for AS was discontinued. In addition, owing to the severe and progressive nature of this disease, combination therapy (surgical excision, irradiation, and chemotherapy) has been performed. To our knowledge, this is the first report to show the effectiveness of docetaxel monotherapy for primary lesions of AS of the scalp. We describe a case of docetaxel monotherapy used successfully to treat AS in an elderly patient. As a caveat, we should add that good response in the neoplastic lesion does not mean longer survival. Moreover, the randomized European study8 included only 6 patients with AS. Figure 1. Clinical appearance before treatment with docetaxel. Facial edema At present, the effect of docetaxel on disease-free or over- and widespread violaceous plaques with disseminated dark purple nodules all survival of patients with AS is not well known. Fu- were seen on her cheek with extension to the mandible. ture clinical observations should explore the efficacy of docetaxel in the treatment of AS. Tohru Nagano, MD, PhD Yukimasa Tai, MD Yuka Higashida, MD Norihiro Fujiwara, MD Masahiro Oka, MD, PhD Chikako Nishigori, MD, PhD Correspondence: Dr Nagano, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan ([email protected] .ac.jp). Financial Disclosure: None reported.

1. Mark RJ, Poen JC, Tran LM, et al. Angiosarcoma: a report of 67 patients and a review of literature. Cancer. 1996;77(11):2400-2406. 2. Yamada M, Hatta N, Mizuno M, et al. Weekly low-dose docetaxel in the treatment of lung metastases from angiosarcoma of the head. Br J Dermatol. 2005; 152(4):811-812. Figure 2. Clinical appearance 8 weeks after beginning weekly docetaxel 3. Isogai R, Kawada A, Aragane Y, et al. Successful treatment of pulmonary me- regimen. tastasis and local recurrence of angiosarcoma with docetaxel. J Dermatol. 2004; 31(4):335-341. 4. Mano MS, Fraser G, Kerr J, et al. Radiation-induced angiosarcoma of the breast adverse effects such as high-grade neutropenia, liver or shows major response to docetaxel after failure of anthracycline-based renal dysfunction, or peripheral neuropathy. chemotherapy. Breast. 2006;15(1):117-118. Because the patient experienced only partial remis- 5. Pazdur R, Newman RA, Newman BM, et al. Phase I trial of Taxotere: five-day schedule. J Natl Cancer Inst. 1992;84(23):1781-1788. sion, additional treatment was administered. She main- 6. Fata F, O’Reilly E, Ilson D, et al. Paclitaxel in the treatment of patients with tained partial remission after 6 months of docetaxel mono- angiosarcoma of the scalp or face. Cancer. 1999;86(10):2034-2037. 7. Tulpule A, Groopman J, Saville MW, et al. Multicenter trial of low-dose pa- therapy. clitaxel in patients with advanced AIDS-related Kaposi sarcoma. Cancer. 2002; 95(1):147-154. Comment. Like paclitaxel, docetaxel promotes micro- 8. Verweij J, Lee SM, Ruka W, et al. Randomized phase II study of docetaxel versus doxorubicin in first and second line chemotherapy for locally ad- tubule assembly and inhibits the depolymerization of tu- vanced or metastatic soft tissue sarcomas in adults. J Clin Oncol. 2000;18 bulin, thus stabilizing microtubules; but docetaxel has (10):2081-2086.

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1603 ANNUAL REVIEWERS LIST

We thank all of the reviewers who have generously and thoughtfully assisted the Editorial Board, our authors, and our readers during 2007. June K. Robinson, MD Editor Jeffrey P. Callen, MD Associate Editor

A. Bernard Ackerman Paula Andrea Boggio Ponciano D. Cruz Matthew G. Fleming David R. Adams Melissa A. Bogle Brittney Culp Joseph F. Fowler Fatma Sule Afsar Erin Boh Clara Curiel- Lindy Fox Necmettin Akdeniz Renan Rangel Bonamigo Lewandrowski Michael Joseph Franzblau Hirotaka Akita Mathieu Boniol Patricia Ramos Cury Adam Friedman Ayse Akman J. Bouwes Bavinck Carrie Ann Cusack Thilo Gambichler Mauro Alaibac Glen Montrose Bowen Maurice Joseph Dahdah Carlos Garcia Murad Alam Valeria Brazzelli Mark V. Dahl Jerome M. Garden Afsaneh Alavi Sarah Brenner Paul I. Dantzig Amit Garg Jorg G. Albert Nooshin Brinster Mark D. P. Davis Maria Cecilia Garzon Joseph Alcalay Robert T. Brodell Stephen C. Davis Anthony A. Gaspari Merce Alsina-Gibert Martin L. Brown Dipankar De Joel M. Gelfand Davide Altamura Barbara A. Brown-Elliott Fernando deCastro Alan C. Geller Christie Ammirati Amanda Swantje Buchau Robert Paul Dellavalle Roy G. Geronemus Alfred Ammoury Walter H. C. Burgdorf Marie-France Demierre Larisa J. Geskin Attila Stephan Antal Susan Burgin Cuyan Demirkesen Samer Ghosn Richard J. Antaya Cynthia Jane Burk Olivier Dereure Jason Giacomel M. Ara Craig Garrett Burkhart John J. DiGiovanna Anita Gilliam Giuseppe Argenziano David F. Butler Jeffrey S. Dover Robert Gniadecki Myrna L. Armstrong H. Randolph Byers,PhD Yahya Dowlati Kenneth B. Gordon Kenneth A. Arndt Jean-Claude Bystryn Zoe Draelos U. Graeven Amber Reck Atwater Pier Giacomo Calzavara David Drews Sergei A. Grando Robert Auerbach Pinton Reinhard Dummer Jane M. Grant-Kels Philippe Autier Charles Camisa Cory A. Dunnick Malcolm W. Greaves Marie-Francoise Avril Ruggero Caputo Alain Dupuy James M. Grichnik Renato Marchiori Bakos Paolo Carli Stephen William Dusza Pearl E. Grimes Elma D. Baron Jean D. A. Carruthers William H. Eaglstein Frederick Grinnell Terry L. Barrett Daniel Cassuto Ximena del Pilar Thomas Grobner Aviv Barzilai Julide Tok Celebi Echeverria Edward Gross Eulalia Baselga Lorenzo Cerroni Thomas Kurt Eigentler Douglas Grossman Ioannis D. Bassukas Robert J. G. Chalmers Boni E. Elewski Lorenzo Gualandri Boris C. Bastian Sarah Lynn Chamlin Charles N. Ellis Fabrizio Guarneri Juergen Bauer Henry H. L. Chan Craig A. Elmets Joan Guitart I. Bellinghausen Lawrence S. Chan Dirk M. Elston Erhard Holzle Donald V. Belsito Mary W. Chang Lennart Emtestam Smail Hadj-rabia Peter T. Berg Shyue-luen Chang Deborah Englert Rebat M. Halder Timothy G. Berger M. Shane Chapman Joseph C. English Allan C. Halpern Wilma F. Bergfeld Chan Choi Odile Enjolras Takahiro Hamada Reuven Bergman Joe A. Chorny Emel Erkek John Gibson Hancox Wilma Bergman Brenda Chrastil Giuseppe Fabrizi Eckart Haneke David R. Berk Chia-Yu Chu Anna Falabella Jon M. Hanifin Joshua Matthew Berlin Jin Ho Chung Rafael Falabella Rudolf Happle Brian Berman Lorinda Chung Matthew E. Falagas Takashi Hashimoto Marianne Berwick Nancy M. Chung Giovanni Fava Naohito Hatta Ashish C. Bhatia Vinh Quoc Chung Daniel Federman John L. M. Hawk Jag Bhawan Loren Emory Clarke Steven R. Feldman Harley Haynes Premanshu Bhushan Clay J. Cockerell James Ferguson Adelaide A. Hebert Michael E. Bigby Lisa M. Cohen Jo-David Fine Michael P. Heffernan Robert Bissonnette Vilma Cokkinides David F. Fiorentino Yolanda Rosi Helfrich Alexa Boer Kimball Edward West Cowen Alan B. Fleischer Klaus F. Helm

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM E1 Warren R. Heymann Craig L. Leonardi Luigi Naldi Thomas G. Salopek Whitney A. High Jack L. Lesher Jr Audrey M. Nelson Francesca Sampogna Wolfram Hoetzenecker Stuart R. Lessin Amy Elaine Newburger Robert Sarkany Rainer Hofmann- Moise L. Levy Brian J. Nickoloff Pamela L. Scheinman Wellenhof Kevan G. Lewis Tamar Nijsten Andrew Scheman Kristen E. Holland Lin-feng Li James J. Nordlund Max Simon Schlaak Thomas D. Horn Anita Licata C. Norwood Chrysalyne Schmults George J. Hruza Olivier Lidove Keyvan Nouri Paul Ira Schneiderman Sylvia Hsu Bernt Lindelof David L. O’Riordan Robert A. Schwartz Shasa Hu Peter A. Lio N. Oleinick Alon Scope Matilde Iorizzo Dan Lipsker Elise Olsen Peggy Sekula Akira Ishiko Wendy Liu Arnold P. Oranje Thomas Serena J. Mark Jackson A. Livneh Tony Ormerod John T. Seykora Sharon E. Jacob T. Lombardi Anthony Oro Kara Noelle Shah William D. James Daniel S. Loo Jeffrey S. Orringer Christopher Richard Shea Yiannias A. James Torello M. Lotti Clark C. Otley Hiroshi Shimizu A. Janecke Pierre Loulergue Fezal Ozdemir Katherine A. Short T. Jelinek Lori Lowe Amy S. Paller Daniel M. Siegel Marie-Louise T. Johnson Markham C. Luke Michael Paltiel Simon Silver Marcel F. Jonkman Peter J. Lynch Amit G. Pandya Sanjay Singh Joseph L. Jorizzo Rona M. MacKie Kim A. Papp Andrzej T. Slominski Jean Kanitakis Robert J. MacNeal David Michael Pariser Robert Jay Snyder Yoko Kano Amit Kumar Malhotra Lawrence Charles Parish Arthur J. Sober Matthew H. Kanzler Anthony J. Mancini P. Parola Keyoumars M. Soltani J. Scott Kasteler Sahar Mansour Asha R. Patel Vernon Sondak Andreas D. Katsambas Boby Varkey Maramatton Ben Peirce H. Peter Soyer Kenneth A. Katz Ashfaq A. Marghoob Giovanni Pellacani James M. Spencer Joely Kaufman David J. Margolis Claudio Pelucchi A. Srivastava David Kelsell William Marston Ketty Peris Jerod Stapleton Francisco A. Kerdel Ludovic Martin Cesare Perotti Sarah L. Stein Jonette Keri Angelo Valerio Marzano Tania J. Phillips Kurt S. Stenn Helmut Kerl Jose M. Mascaro W. M. Porter Robert S. Stern Kiarash Khosrotehrani Cesare Massone Lisa Prosser Wolfram Sterry Isil Kilinc-Karaarslan Zirwas Mathew Lluis Puig Seth R. Stevens Ellen J. Kim Eric Matteson Susana Puig Jon Stone Marvin Herman Klapman Lester Mayers Claudia C. Ramirez Erik Stratman Rebecca Kleinerman Calvin O. McCall Marcia Ramos-e-Silva Bruce E. Strober Caroline Scott Koblenzer Joseph McCulloch Didier Raoult Richard A. Sturm Heidi H. Kong John A. McGrath Marvin J. Rapaport Lyndon D. Su John Y. M. Koo Jennifer M. McNiff Allison Beckworth James W. Swan Steven Kossard Silvia Anett Mejia Readinger David L. Swanson Alexander Kreuter Rodriguez Alfredo Enrico Rebora Robert A. Swerlick Anne Kricker Patricia M. Mertz Pedro Redondo Alain Taieb Annegret Kuhn Gita Meshkat Razavi George Reizner Risa Tamagawa-Mineoka Pramod Kumar Alexander Meves Cristina Renzi Fernanda Teixeira I. Kurokawa Jeffrey J. Miller Luis Requena Michael D. Tharp Joseph C. Kvedar Oliver Fred Miller Jack Resneck Martin Thornhill Oh Sang Kwon Matthias Mohrenschlager Lesley E. Rhodes Antonio Torrelo Christine Labreze L. Montella Vincent M. Riccardi Hensin Tsao Mario Lacouture Angela Yen Moore Phoebe A. Rich Stephen K. Tyring Michael E. Landthaler Warwick L. Morison Robert L. Rietschel Tien-Yi Tzung Alfred T. Lane Eliot N. Mostow Jason K. Rivers Hisashi Uhara Sean W. Lanigan Ronald L. Moy Randy K. Roenigk Jochen Utikal Charles M. Lapiere Sanjeev Vishnu Mulekar Thomas E. Rohrer Abby S. Van Voorhees Anne Laumann J. B. Mulliken Paolo Romanelli Erika Varga Robert Lavker Colin Munro Amy Simon Ross Francisco Vazquez-Lopez Clifford M. Lawrence Dedee Murrell Jean Roujeau Lisette Verhoeven Andrew Lazar Diya F. Mutasim Thomas M. Ruenger Javier Vicente Mark Gabriel Lebwohl Patricia L. Myskowski Thomas Ruzicka Miikka Vikkula Edith Rachel Lederman Jean-Marie Marie Naeyaert Berthold Rzany Eric Carl Vonderheid Delphine J. Lee Eduardo Nagore Amar Safdar Richard F. Wagner Lela A. Lee Geore T. Nahass Toshiaki Saida Hobart W. Walling

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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM E3 tients with psoriasis: 10 years prospective experience in a cohort of 1,380 patients. 32. Sommer DM, Jenisch S, Suchan M, Christophers E, Weichenthal M. Increased J Invest Dermatol. 1988;91(3):197-201. prevalence of the metabolic syndrome in patients with moderate to severe psoriasis. 19. Roth PE, Grosshans E, Bergoend H. Psoriasis: development and fatal complications. Arch Dermatol Res. 2006;298(7):321-328. doi:10.1007/s00403-006-0703-z. Ann Dermatol Venereol. 1991;118(2):97-105. 33. Naldi L, Parazzini F, Brevi A, et al. Family history, smoking habits, alcohol con- 20. Garcı´a Rodrı´guez LA, Pe´rez Gutthann S. Use of the UK General Practice Re- sumption and risk of psoriasis. Br J Dermatol. 1992;127(3):212-217. search Database for pharmacoepidemiology. Br J Clin Pharmacol. 1998;45 34. Naldi L, Peli L, Parazzini F. Association of early-stage psoriasis with smoking (5):419-426. and male alcohol consumption: evidence from an Italian case-control study. Arch 21. Jick H, Jick S, Derby LE. Validation of information recorded on general practi- Dermatol. 1999;135(12):1479-1484. tioner based computerised data resource in the United Kingdom. BMJ. 1991; 35. Naldi L, Peli L, Parazzini F, Carrel CF. Family history of psoriasis, stressful life 302(6779):766-768. events, and recent infectious disease are risk factors for a first episode of acute 22. Jick H, Terris BZ, Derby LE, Jick SS. Further validation of information recorded guttate psoriasis: results of a case-control study. J Am Acad Dermatol. 2001; on a general practitioner based computerised data resource in the United Kingdom. 44(3):433-438. Pharmacoepidemiol Drug Saf. 1992;1:347-349. 36. Herron MD, Hinckley M, Hoffman MS, et al. Impact of obesity and smoking on 23. Jick SS, Kaye JA, Vasilakis-Scaramozza C, et al. Validity of the General Practice psoriasis presentation and management. Arch Dermatol. 2005;141(12):1527- Research Database. Pharmacotherapy. 2003;23(5):686-689. 1534. 24. Gelfand JM, Berlin J, Van Voorhees A, Margolis DJ. Lymphoma rates are low 37. Telfer NR, Chalmers RJ, Whale K, Colman G. The role of streptococcal infection but increased in patients with psoriasis: results from a population-based cohort in the initiation of guttate psoriasis. Arch Dermatol. 1992;128(1):39-42. study in the United Kingdom. Arch Dermatol. 2003;139(11):1425-1429. 38. Horiuchi N, Aiba S, Ozawa H, et al. Peripheral blood lymphocytes from psoriatic 25. Gelfand JM, Weinstein R, Porter SB, Neimann AL, Berlin JA, Margolis DJ. Preva- patients are hyporesponsive to beta-streptococcal superantigens. Br J Dermatol. lence and treatment of psoriasis in the United Kingdom: a population-based study. 1998;138(2):229-235. Arch Dermatol. 2005;141(12):1537-1541. 39. Henseler T, Christophers E. Disease concomitance in psoriasis. J Am Acad Dermatol. 26. Gillard SE, Finlay AY. Current management of psoriasis in the United Kingdom: 1995;32(6):982-986. patterns of prescribing and resource use in primary care. Int J Clin Pract. 2005; 40. Mallbris L, Akre O, Granath F, et al. Increased risk for cardiovascular mortality in 59(11):1260-1267. psoriasis inpatients but not in outpatients. Eur J Epidemiol. 2004;19(3):225- 27. Basarab T, Munn SE, Jones RR. Diagnostic accuracy and appropriateness of gen- 230. eral practitioner referrals to a dermatology out-patient clinic. Br J Dermatol. 1996; 41. Dika E, Varotti C, Bardazzi F, Maibach HI. Drug-induced psoriasis: an evidence- 135(1):70-73. based overview and the introduction of psoriatic drug eruption probability score. 28. Kleinbaum DG, Kupper LL, Morgentern H. Epidemiologic Research: Principles Cutan Ocul Toxicol. 2006;25(1):1-11. and Quantitative Methods. New York, NY: John Wiley & Sons Inc; 1982. 42. Cohen AD, Bonneh DY, Reuveni H, Vardy DA, Naggan L, Halevy S. Drug expo- 29. Naldi L, Tognoni G, Cainelli T. Analytic epidemiology in psoriasis. J Invest Dermatol. sure and psoriasis vulgaris: case-control and case-crossover studies. Acta Derm 1994;102(6):19S-23S. Venereol. 2005;85(4):299-303. 30. Naldi L. Epidemiology of psoriasis. Curr Drug Targets Inflamm Allergy. 2004;3(2): 43. Cohen AD, Kagen M, Friger M, Halevy S. Calcium channel blockers intake and 121-128. psoriasis: a case-control study. Acta Derm Venereol. 2001;81(5):347-349. 31. Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence 44. Whittam LR, Wakelin SH, Barker JN. Generalized pustular psoriasis or drug- of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. induced toxic pustuloderma? the use of patch testing. Clin Exp Dermatol. 2000; 2006;55(5):829-835. 25(2):122-124.

Correction

(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1565 29. Anyo G, Brunekreef B, de Meer G, Aarts F, Janssen NA, van Vliet P. Early, cur- 36. Austin JB, Russell G. Wheeze, cough, atopy, and indoor environment in the Scot- rent and past pet ownership: associations with sensitization, bronchial respon- tish Highlands. Arch Dis Child. 1997;76(1):22-26. siveness and allergic symptoms in school children. Clin Exp Allergy. 2002; 37. Dotterud LK, Falk ES. Atopic disease among adults in Northern Russia, an area 32(3):361-366. with heavy air pollution. Acta Derm Venereol. 1999;79(6):448-450. 30. Hesselmar B, A˚ berg N, A˚ berg B, Eriksson B, Bjo¨rkste´n B. Does early exposure to 38. Scha¨fer T, Vieluf D, Behrendt H, Kra¨mer U, Ring J. Atopic eczema and other mani- cat or dog protect against later allergy development? Clin Exp Allergy. 1999; festations of atopy: results of a study in East and West Germany. Allergy. 1996; 29(5):611-617. 51(8):532-539. 31. Kurosaka F, Nakatani Y, Terada T, et al. Current cat ownership may be associ- 39. Kalyoncu AF, Selc¸uk ZT, Karakoca Y, et al. Prevalence of childhood asthma and ated with the lower prevalence of atopic dermatitis, allergic rhinitis and Japa- allergic diseases in Ankara, Turkey. Allergy. 1994;49(6):485-488. nese cedar pollinosis in schoolchildren in Himeji, Japan. Pediatr Allergy Immunol. 40. Sebo˜k B, Schneider I, Harangi F; Primary Care Paediatricians in Baranya County. 2006;17(1):22-28. Familiar and environmental factors influencing atopic dermatitis in the childhood. 32. Yemaneberhan H, Flohr C, Lewis SA, et al. Prevalence and associated factors of J Eur Acad Dermatol Venereol. 2006;20(4):418-422. atopic dermatitis symptoms in rural and urban Ethiopia. Clin Exp Allergy. 2004; 41. Williams HC, Burney PG, Hay RJ, et al. The UK Working Party’s Diagnostic Cri- 34(5):779-785. teria for Atopic Dermatitis, I: derivation of a minimum set of discriminators for 33. Miyake Y, Yura A, Iki M. Cross-sectional study of allergic disorders in relation to atopic dermatitis. Br J Dermatol. 1994;131(3):383-396. familial factors in Japanese adolescents. Acta Paediatr. 2004;93(3):380-385. 42. Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Aller- 34. Scha¨fer T, Heinrich J, Wjst M, et al. Indoor risk factors for atopic eczema in school gies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995;8(3): children from East Germany. Environ Res. 1999;81(2):151-158. 483-491. 35. Austin JB, Russell G, Adam MG, Mackintosh D, Kelsey S, Peck DF. Prevalence 43. Apelberg BJ, Aoki Y, Jaakkola JJ. Systematic review: exposure to pets and risk of asthma and wheeze in the Highlands of Scotland. Arch Dis Child. 1994;71 of asthma and asthma-like symptoms. J Allergy Clin Immunol. 2001;107(3): (3):211-216. 455-460.

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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1577 primary cutaneous B-cell lymphomas of follicle center cell origin: a clinical fol- WHO) and prognostic factors. J Clin Oncol. 2007;25(12):1581-1587. low-up study of 55 patients treated with radiotherapy or polychemotherapy. doi:10.1200/JCO.2006.09.6396. J Clin Oncol. 1996;14(2):549-555. 14. Santucci M, Pimpinelli N, Arganini L. Primary cutaneous B-cell lymphoma: a unique 5. Willemze R, Meijer CJ, Sentis HJ, et al. Primary cutaneous large cell lymphomas type of low-grade lymphoma: clinicopathologic and immunologic study of 83 of follicular center cell origin: a clinical follow-up study of nineteen patients. cases. Cancer. 1991;67(9):2311-2326. J Am Acad Dermatol. 1987;16(3, pt 1):518-526. 15. Willemze R, Meijer CJ, Scheffer E, et al. Diffuse large cell lymphomas of follicu- 6. Bekkenk MW, Vermeer MH, Geerts ML, et al. Treatment of multifocal primary lar center cell origin presenting in the skin: a clinicopathologic and immunologic cutaneous B-cell lymphoma: a clinical follow-up study of 29 patients. J Clin Oncol. study of 16 patients. Am J Pathol. 1987;126(2):325-333. 1999;17(8):2471-2478. 16. Willemze R. Primary cutaneous B-cell lymphoma: classification and treatment. 7. Eich HT, Eich D, Micke O, et al. Long-term efficacy, curative potential, and prog- Curr Opin Oncol. 2006;18(5):425-431. nostic factors of radiotherapy in primary cutaneous B-cell lymphoma. Int J Ra- 17. Kodama K, Massone C, Chott A, Metze D, Kerl H, Cerroni L. Primary cutaneous diat Oncol Biol Phys. 2003;55(4):899-906. large B-cell lymphomas: clinicopathologic features, classification, and prognos- 8. Piccinno R, Caccialanza M, Berti E, Baldini L. Radiotherapy of cutaneous B cell tic factors in a large series of patients. Blood. 2005;106(7):2491-2497. lymphomas: our experience in 31 cases. Int J Radiat Oncol Biol Phys. 1993; 18. Kurtin PJ, DiCaudo DJ, Habermann TM, Chen MG, Su WP. Primary cutaneous 27(2):385-389. large cell lymphomas: morphologic, immunophenotypic, and clinical features of 9. Piccinno R, Caccialanza M, Berti E. Dermatologic radiotherapy of primary cuta- 20 cases. Am J Surg Pathol. 1994;18(12):1183-1191. neous follicle center cell lymphoma. Eur J Dermatol. 2003;13(1):49-52. 19. Grange F, Bekkenk MW, Wechsler J, et al. Prognostic factors in primary cuta- 10. Smith BD, Glusac EJ, McNiff JM, et al. Primary cutaneous B-cell lymphoma treated neous large B-cell lymphomas: a European multicenter study. J Clin Oncol. 2001; with radiotherapy: a comparison of the European Organization for Research and 19(16):3602-3610. Treatment of Cancer and the WHO classification systems. J Clin Oncol. 2004; 20. Hoefnagel JJ, Vermeer MH, Jansen PM, et al. Primary cutaneous marginal zone 22(4):634-639. B-cell lymphoma: clinical and therapeutic features in 50 cases. Arch Dermatol. 11. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous 2005;141(9):1139-1145. lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the Eu- 21. Cozzio A, Kempf W, Schmid-Meyer R, et al. Intra-lesional low-dose interferon ropean Organization for Research and Treatment of Cancer. Blood. 1997;90 alpha2a therapy for primary cutaneous marginal zone B-cell lymphoma. Leuk (1):354-371. Lymphoma. 2006;47(5):865-869. 12. Jaffe ES, Harris NL, Stein H, et al. World Health Organization Classification of 22. Kerl K, Prins C, Saurat JH, French LE. Intralesional and intravenous treatment of Tumours: Pathology and Genetics of Tumours of Hematopoietic and Lymphoid cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: Tissues. Lyon, France: IARC Press; 2001. report and follow-up of eight cases. Br J Dermatol. 2006;155(6):1197-1200. 13. Senff NJ, Hoefnagel JJ, Jansen PM, et al. Reclassification of 300 primary 23. Kyrtsonis MC, Siakantaris MP, Kalpadakis C, et al. Favorable outcome of pri- cutaneous B-cell lymphomas according to the new WHO-EORTC classification mary cutaneous marginal zone lymphoma treated with intralesional rituximab. for cutaneous lymphomas: comparison with previous classifications (EORTC; Eur J Haematol. 2006;77(4):300-303.

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(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 12), DEC 2007 WWW.ARCHDERMATOL.COM 1526 lack of strict reimbursement criteria. Moreover, the bio- Additional Contributions: Phyllis Spuls, MD, PhD, and logical agents are promoted as drugs that are safe and easy Ellen de Haas, MD, provided comments and sugges- to use, with little or no end-organ damage, at least in the tions about the manuscript and the AGREE instrument. short term, suggesting a relatively simple follow-up. The recommended pretreatment and monitoring investiga- REFERENCES tions suggested by the BAD working group are indeed simple and are performed at wide intervals. Except for 1. Smith CH, Anstey AV, Barker JN, et al. British Association of Dermatologists guide- the complete blood cell count (eg, thrombocyte count) lines for use of biological interventions in psoriasis 2005. Br J Dermatol. 2005; 153(3):486-497. in patients using efalizumab, it is recommended that the 2. Callen JP, Krueger GG, Lebwohl M, et al. AAD consensus statement on psoria- investigations be performed before and at 3 and 6 months sis therapies. J Am Acad Dermatol. 2003;49(5):897-899. after the initiation of therapy. The evidence for these rec- 3. Kwaliteitsinstituut Web site. www.cbo.nl/product/richtlijnen/ folder20021023121843 ommendations and the frequency of follow-up is un- /rl_psoriasis_2005.pdf/view. Accessed September 21, 2006. 4. AGREE Electronic Library for Guideline Developers Web site. http://www clear and may be open for debate, but the authors do pro- .agreecollaboration.org/1/agreeguide/. Accessed May 25, 2006. vide an instructive table to which clinicians can refer. 5. AGREE Collaboration. Development and validation of an international appraisal However, the safety of the biological drugs is chal- instrument for assessing the quality of clinical practice guidelines: the AGREE lenged by a recent meta-analysis that showed a signifi- project. Qual Saf Health Care. 2003;12(1):18-23. cant increased risk for malignant neoplasms and serious 6. Raine R, Sanderson C, Black N. Developing clinical guidelines: a challenge to current methods. BMJ. 2005;331(7517):631-633. infections in patients with rheumatoid arthritis who were 7. Kirby B, Fortune DG, Bhushan M, Chalmers RJ, Griffiths CE. The Salford Pso- using tumor necrosis factor antibodies, a finding that re- riasis Index: an holistic measure of psoriasis severity. Br J Dermatol. 2000; confirms the need for caution in prescribing these agents.16 142(4):728-732. 8. Finlay AY. Current severe psoriasis and the rule of tens. Br J Dermatol. 2005;152 (5):861-867. Bottom Line: Because of the financial implications, the 9. Nijsten T, Meads DM, McKenna SP. Dimensionality of the Dermatology Life Qual- use of biological drugs in the treatment of psoriasis ity Index (DLQI): a commentary. Acta Derm Venereol. 2006;86(3):284-285. should be reserved for a relatively small proportion of 10. van de Kerkhof PC. On the limitations of the psoriasis area and severity index patients in whom standard therapy has failed. These (PASI). Br J Dermatol. 1992;126(2):205. agents should be prescribed only by experienced der- 11. Naldi L, Chatenoud L, Linder D, et al. Cigarette smoking, body mass index, and stressful life events as risk factors for psoriasis: results from an Italian case- matologists, so more efforts are needed to educate der- control study. J Invest Dermatol. 2005;125(1):61-67. matologists regarding the administration of systemic 12. Dubertret L, Sterry W, Bos JD, et al. CLinical experience acquired with the efali- therapies. For now, etanercept appears to be the bio- zumab (Raptiva) (CLEAR) trial in patients with moderate-to-severe plaque pso- logical agent of choice in most cases. However, long- riasis: results from a phase III international randomized, placebo-controlled trial. Br J Dermatol. 2006;155(1):170-181. term postmarketing safety studies and comparative ran- 13. Nijsten T, Lambert J. Dermatologists’ views and opinions about photo(chemo) domized clinical trials between different types of therapy and conventional systemic psoriasis therapies: results from a Belgian biological drugs and between biological agents and survey. Dermatology. 2006;213(2):123-133. standard therapies are required to confirm the proposed 14. Stern RS, Nijsten T, Feldman SR, Margolis DJ, Rolstad T. Psoriasis is common, positioning of biological agents in psoriasis care. carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction. J Investig Dermatol Symp Proc. 2004;9(2): 136-139. Accepted for Publication: July 1, 2007. 15. Nijsten T, Margolis DJ, Feldman SR, Rolstad T, Stern RS. Traditional systemic Correspondence: Tamar Nijsten, MD, PhD, Depart- treatments have not fully met the needs of psoriasis patients: results from a na- ment of Dermatology, Erasmus Medical Center, Burge- tional survey. J Am Acad Dermatol. 2005;52(3 Pt 1):434-444. 16. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti– meester Jacobussenplein 51, PO Box 204, Rotterdam, the TNF antibody therapy in rheumatoid arthritis and the risk of serious infections Netherlands ([email protected]). and malignancies: systematic review and meta-analysis of rare harmful effects Financial Disclosure: None reported. in randomized controlled trials. JAMA. 2006;295(19):2275-2285.

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Index to Volume 143 January through December 2007

Editor June K. Robinson, MD Archives of Dermatology 132 E Delaware Pl, #5806 Chicago, IL 60611

Associate Editor Jeffrey P. Callen, MD Louisville, Kentucky

Editorial Assistant Mark D. Matthews Chicago, Illinois

Editorial Board

Murad Alam, MD Chicago, Illinois Moise L. Levy, MD Houston, Texas Ashish C. Bhatia, MD Naperville, Illinois Michael E. Ming, MD, MSCE Philadelphia, Pennsylvania Michael Bigby, MD Boston, Massachusetts Ronald L. Moy, MD Los Angeles, California Mary-Margaret Chren, MD San Francisco, California Anthony E. Oro, MD, PhD Stanford, California Robert P.Dellavalle, MD, PhD, MSPH Denver, Colorado Darrell S. Rigel, MD New York, New York Alan B. Fleischer Jr, MD Winston-Salem, North Carolina Lawrence A. Schachner, MD Miami, Florida James M. Grichnik, MD, PhD Durham, North Carolina Kathryn Schwarzenberger, MD Burlington, Vermont Thomas D. Horn, MD Little Rock, Arkansas Maria L. Chanco Turner, MD Bethesda, Maryland George J. Hruza, MD St Louis, Missouri Gary S. Wood, MD Madison, Wisconsin AUTHOR INDEX TO VOLUME 143

In this index in alphabetical order are listed names of authors of all articles and letters. Full citation is given under first author only; reference is made from joint authors. Names which begin with a prefix are entered under the prefix. The month is given as a two-letter notation in parentheses.

A linked immunosorbent assay index of a bul- Balestreire E, Haught JM, English JC III: Mul- lous pemphigoid antigen noncollagenous tiple subcutaneous lipomas induced by HAART Abad ME see Larralde M domain, 1168 (Se) in the absence of protease inhibitors (letter) Abdelmalek M, Han J, Allen H: Diffuse cuta- Aractingi S see de Fonclare A-L 1596 (De) neous nodules, 937 (Jy) Arai E, Shimizu M, Tsuchida T, Izaki S, Ogawa Balkrishnan R see Ali SM; Fosse K; Abdulla FR, Adams BB: Ortho-phthalalde- F, Hirose T: Lymphomatoid keratosis: an epi- Satyaprakash A hyde causing facial stains after cystoscopy (let- dermotropic type of cutaneous lymphoid Balme B see Dalle S ter) 670 (My) hyperplasia: clinicopathological, immuno- Bandow GD see Xu LY Ackermann F, Levy A, Daugas E, Schartz N, histochemical, and molecular biological study Bangert S see Vu J Riaux A, Derancourt C, Urena P, LebbeĆ: of 6 cases, 53 (Ja) Bansal A see Jain K Sodium thiosulfate as first-line treatment for Arbiser JL see Bhandarkar SS; Perry B Ban˜ uls J see Mataix J calciphylaxis (letter) 1336 (Oc) Argenziano G see Altamura D; Giacomel J; Banyard J see Perry B Acosta A see Motta A Zaballos P; Zalaudek I Barnea Y see Mashiah J Adams BB see Abdulla FR Argenziano G, Zalaudek I, Ferrara G: Fast- Baron E see Evers M Adams S see de Gannes GC growing and slow-growing melanomas (let- Barzilai DA, Weinstock MA: Accessible evi- Adams WB, Becknell CA: Rare manifestation ter) 802 (Je) dence-based medicine: critically appraised top- of scalp necrosis in temporal arteritis (letter) Argenziano G, Zalaudek I, Ferrara G, Lorenzoni ics, 1189 (Se) 1079 (Au) A, Soyer HP: Involution: the natural evolu- Bassoli S see Longo C Adams-McDonnell R see Sariya D tion of pigmented Spitz and Reed nevi? (let- Bastida J, Camacho-Galań R, Armesto- Adrian R see Karsai S ter) 549 (Ap) Fernańdez MA, Dıáz-Cascajo C: Adult dis- Agarwal S see Thakuria M Armesto-Fernańdez MA see Bastida J seminated primary papular xanthoma treated Agero ALC see Benvenuto-Andrade C; Arndt KA see Bogle MA with doxycycline (letter) 667 (My) Changchien L; Scope A Arnulf B see Asli B Bauman JE, Eaton KD, Martins RG: Treat- Aggarwal K see Jain K Arranz I see Vagace JM ment of recurrent squamous cell carcinoma of Aguado L see Espanã A Arseculeratne G, Berroeta L, Meiklejohn D, the skin with cetuximab, 889 (Jy) Ahmadi H see Toossi P Mountain RE, Ryan JC, Spinou C, Das SN, Bayliss SJ see Berk DR Akalin T see Gencoglan G; Ozdemir F Evans AT, Lowe JG: Bleomycin-induced Bazex J see Ammoury AF; El Sayed F Akdeniz N, Ko¨sem M, Ç alka O¨ , Bilgili SG, Metin “flagellate dermatitis” (letter) 1461 (No) Beaugerie L see de Fonclare A-L A, Gelincik I: Intralesional bleomycin for Arseculeratne G, Wong AKC, Goudie DR, Becker JC see Otto K angiolymphoid hyperplasia, 841 (Jy) Ferguson J: Trimethylaminuria (fish-odor syn- Becknell CA see Adams WB Al Eisa A see Mulekar SV drome): a case report, 81 (Ja) Be´dard M-S, Gilbert M: Telithromycin- Al Issa A see Mulekar SV Asaad M see Mulekar SV induced TEN: report of a case (letter) 427 (Mr) Alaee Z see Toossi P Asai K see Aoyama Y Beddingfield FC III see Losina E Alam M see Bhatia AC; Rashid RM Asgari MM, Cockerell CJ, Weitzul S: Head-tilt Begon E see Bachmeyer C Alavian C see Garg A maneuver: a clinical aid in recognizing head Beissert S, Werfel T, Frieling U, Bo¨hm M, Ali SM, Brodell RT, Balkrishnan R, Feldman and neck angiosarcomas, 75 (Ja) Sticherling M, Stadler R, Zillikens D, Rzany SR: Poor adherence to treatments: a funda- Ashcroft DM see Seston EM B, Hunzelmann N, Meurer M, Gollnick H, mental principle of dermatology, 912 (Jy) Askari SK see Wenner R Ruzicka T, Pillekamp H, Junghans V, Allen H see Abdelmalek M Asli B, Bienvenu B, Cordoliani F, Brouet J-C, Bonsmann G, Luger TA: Comparison of oral Alomar A see Vidal D Uzunhan Y, Arnulf B, Malphettes M, Rybojad methylprednisolone plus azathioprine or Alonso N see Vagace JM M, Fermand J-P: Chronic urticaria and mono- mycophenolate mofetil for the treatment of Alsdurf H see Noe R clonal IgM gammopathy (Schnitzler bullous pemphigoid, 1536 (De) Altamura D see Lozzi GP syndrome): report of 11 cases treated with Bell D see de Gannes GC Altamura D, Zalaudek I, Sera F, Argenziano G, pefloxacin, 1046 (Au) Bellucci KS see Szyfelbein K Fargnoli MC, Rossiello L, Peris K: Dermo- Augustin A see Hammes S Benitez J see Vagace JM scopic changes in acral melanocytic nevi during Augustine JJ see Robinson MR Benoit BM see Newton SB digital follow-up, 1372 (No) Avril M-F see Grange F Benouni S, Kos L, Ruggeri SY, North PE, Drolet Ambros-Rudolph CM, Glatz M, Trauner M, Kerl BA: Clear cell papulosis in Hispanic siblings, H, Mu¨ llegger RR: Importance of serum bile B 358 (Mr) acid level analysis and treatment with urso- Bentley DD see Heffernan MP deoxycholic acid in intrahepatic cholestasis of Baccaglini L see Thornhill MH Benvenuto-Andrade C, Dusza SW, Agero ALC, pregnancy: a case series from Central Europe, Bachelet H see Chaby G Scope A, Rajadhyaksha M, Halpern AC, 757 (Je) Bachmann I see Rhodes LE Marghoob AA: Differences between polar- Amini S see Weiss E Bachmeyer C, Begon E, Blum L, Cerf I, Petitjean ized light dermoscopy and immersion con- Ammoury AF see El Sayed F B, Vignon-Pennamen M-D, Pertuiset E: Over- tact dermoscopy for the evaluation of skin Ammoury AF, El Sayed F, Bazex J: Delayed lapping neutrophilic dermatosis in a patient lesions, 329 (Mr) wound healing following treatment with low- with SAPHO syndrome (letter) 275 (Fe) Benvenuto-Andrade C see Scope A dose interferon alfa-2b for cutaneous mela- Badenas C see Herrero C Berends MAM, van Oijen MGH, Snoek J, van noma (letter) 1339 (Oc) Bagel J see Pariser DM de Kerkhof PCM, Drenth JPH, van Krieken Anadkat MJ see Heffernan MP Bagot M see Grange F JH, de Jong EMGJ: Reliability of the Roenigk Anastasopoulou N see Janssens AS Bajo R see Vagace JM classification of liver damage after metho- Andrew S see Singh MN Baker BL, Fitzgibbons CA, Buescher LS: Cal- trexate treatment for psoriasis: a clinicopatho- Annest NM see Grekin SJ ciphylaxis responding to sodium thiosulfate logic study of 160 liver biopsy specimens, 1515 Anstey A see Rhodes LE therapy (letter) 269 (Fe) (De) Antille C see Sorg O Bakos L, Bakos RM: Focal acne during topical Berg BC see Suwattee P Antoniou C see Janssens AS tacrolimus therapy for vitiligo (letter) 1223 (Se) Bergman W, Gruis NA: Phenotypic variation in Aoki V see Rocha-Alvarez R Bakos L see Bakos RM familial melanoma: consequences for predic- Aoyama Y, Asai K, Hioki K, Funato M, Kondo Bakos RM, Bakos L: Dermoscopic diagnosis of tive DNA testing, 525 (Ap) N, Kitajima Y: Herpes gestationis in a mother furuncular myiasis (letter) 123 (Ja) Berk DR, Spector EB, Bayliss SJ: Familial acan- and newborn: immunoclinical perspectives Bakos RM see Bakos L thosis nigricans due to K650T FGFR3 muta- based on a weekly follow-up of the enzyme- Baldassano M see Sariya D tion, 1153 (Se)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E2 Berk DR, Tapia B, Lind A, Bayliss SJ: Sock- Bruce A, Rogers RS III: New and old therapeu- Cesinaro AM see Longo C line hyperpigmentation: case series and tics for oral ulcerations, 519 (Ap) Chaby G see Vaneau M literature review (letter) 428 (Mr) Buell C, Tobinick E, Lamp K: Resolution of Chaby G, Senet P, Vaneau M, Martel P, Berneburg M see Yazdi AS chronic pain and fingertip ulceration due to Guillaume J-C, Meaume S, Teót L, Debure Berroeta L see Arseculeratne G hand-arm vibration syndrome following com- C, Dompmartin A, Bachelet H, Carsin H, Matz Bertenthal D see Chen T bination pharmacotherapy (letter) 1343 (Oc) V, Richard JL, Rochet JM, Sales-Aussias N, Berwick M see Stitzenberg KB Buescher LS see Baker BL Zagnoli A, Denis C, Guillot B, Chosidow O: Bessis D see Du-Thanh A Burdick AE: Teledermatology: extending spe- Dressings for acute and chronic wounds: a sys- Betlloch I see Mataix J cialty care beyond borders, 1581 (De) tematic review, 1297 (Oc) Beylot-Barry M see Grange F Burkhardt DL see McLaughlin JA Chakrabarti S, Williamson D: Rapidly enlarging Beynon TA see LeBon B Busam KJ see Scope A necrotic ulcer on the right calf, 791 (Je) Bhandarkar SS, Cohen C, Kuruvila M, Rea TH, Bystryn J-C: Cham PMH see Wenner R MacKelfresh JB, Lee DJ, Modlin RL, Arbiser Confusing message will not improve the detec- Chamaillard M, Heliot-Hosten I, Constans J, JL: Angiogenesis in cutaneous lesions of lep- tion of melanoma (letter) 806 (Je) Taıëb A: Bosentan as a rescue therapy in sclero- rosy: implications for treatment, 1527 (De) Increasing ratio of thin to thick melanoma derma refractory digital ulcers (letter) 125 (Ja) Bhatia AC, Alam M: Archives of Dermatology lesions: pathogenesis and early detection of this Chamlin SL, Lai J-S, Cella D, Frieden IJ, Web site: adding new dimensions to the lit- cancer (letter) 804 (Je) Williams ML, Mancini AJ, Chren M-M: Child- erature, 1320 (Oc) Bystryn J-C see Weitz D hood atopic dermatitis impact scale: reliability, discriminative and concurrent validity, and Bhushan P see Sardana K C Bianchi F see Patrizi A responsiveness, 768 (Je) Chan LS see Peterson JD Bianchi T see Romanelli M Cabo H, Kolm I, Puig S, Malvehy J: Palmar basal Bidegain E see Moreno-Ramirez D Chan P see MacGregor JL cell carcinoma in a patient with Gorlin-Goltz Chandra P see Schaffer JV Bienvenu B see Asli B syndrome (letter) 813 (Je) Bigby M: Chang AJ see Peterson JD Cabo H see Zaballos P; Zalaudek I Chang Y-C see Lu C-I Evidence-based dermatology section welcomes Caeiro JP see Martinez LC Changchien L, Dusza SW, Agero ALC, a new feature: critically appraised topics, 1185 Caetano R see Werlinger KD Korzenko AJ, Braun RP, Sachs D, Usman (Se) Calcaterra R see Carducci M MHU, Halpern AC, Marghoob AA: Age- and Use of antibiotic ointment after clean cutane- Calduch L see Martıń JM; Martin JM site-specific variation in the dermoscopic pat- ous surgery, 1180 (Se) Ç alka O¨ see Akdeniz N terns of congenital melanocytic nevi: an aid Bigby M see Corona R Callaly EL, Mulligan N, Powell FC: Multiple to accurate classification and assessment of Bilgili SG see Akdeniz N painless papules on the wrists, 791 (Je) melanocytic nevi, 1007 (Au) Billingsley EM see Fang SH Callen JP see Frazier TH; Kalajian AH Checcucci V see de Giorgi V Binder B, Hofmann-Wellenhof R, Salmhofer W, Camacho FM see Moreno-Ramirez D Chen SC see Pennie ML; Pressley ZM; Swetter Okcu A, Kerl H, Soyer HP: Teledermatologi- Camacho FT see Fosse K; Satyaprakash A SM cal monitoring of leg ulcers in cooperation with Camacho-Galań R see Bastida J Chen T, Bertenthal D, Sahay A, Sen S, Chren home care nurses, 1511 (De) Campbell I see Rocha-Alvarez R M-M: Predictors of skin-related quality of life Birk TJ see Pieper B Cannon-Albright LA see Eliason MJ after treatment of cutaneous basal cell carci- Bitzer M see Yazdi AS Cantley LC see Perry B noma and squamous cell carcinoma, 1386 (No) Blalock WK see Forman SB Cardenas TCP see Mertz PM Chen TH-H see Su L-H Blanco FP see Gonzalez ME Carducci M, Calcaterra R, Rinaldi M, Mussi A, Chen W see Eliason MJ Blaschke S see Ziemer M Viola G, Venturo I, Perracchio L, Franco G, Cheng L-C see Yang C-Y Blum A see Zalaudek I Lopez M, Morrone A: Paraneoplastic Raynaud Chenoweth C see Hutchin M Blum L see Bachmeyer C phenomenon with digital necrosis associated Chiang MP see Colbert RL Blumetti BL, Gilliam AC, Cooper KD, Helms with hyperhomocysteinemia and antiphos- Cho S see Breedlove J; Kafi R SE: Persistent violaceous papules on the ears, pholipid antibodies (letter) 1342 (Oc) Chodick G see Heymann AD 417 (Mr) Carli P: Chorny JA, Stephens FV, Cohen JL: Eruptive Bodemer C see Cazes A Dermoscopy not yet shown to increase sensitivity of melanoma diagnosis in real practice keratoacanthomas in a new tattoo (letter) 1457 Boeckler P see Sfia M (No) Bogle MA, Arndt KA, Dover JS: Evaluation of (letter) 664 (My) Chosidow O see Chaby G; Vaneau M plasma skin regeneration technology in low- Identification of incipient tumors by means of Chrastil B, Glaich AS, Goldberg LH, Friedman energy full-facial rejuvenation, 168 (Fe) sequential dermoscopy imaging: a new way to PM: Fractional photothermolysis: a novel treat- Bo¨hm M see Beissert S inflate the “epidemic” of melanoma? (letter) ment for disseminated superficial actinic poro- Bonsmann G see Beissert S 805 (Je) Carlin CS see Colbert RL keratosis (letter) 1450 (No) Borer M, Smith J, White B, Sheehan D: Scaly Chren M-M see Chamlin SL; Chen T plaque on the scalp, 1067 (Au) Carrasco R see Moreno-Ramirez D Chrusciak-Talhari A, Talhari C, de Souza Borghi A see Zampino MR Carraux P see Sorg O Carrera C see Segura S Santos MN, Ferreira LC, Talhari S: Nodular Botella R see Mataix J lesions on the arm, 1323 (Oc) Bottini S see Cavicchini S Carrera C, Segura S, Palou J, Puig S, Segura J, Martı´ RM, Malvehy J: Seborrheic keratosis- Chua SL, Kulkarni K, Saihan E: Hyper- Bowe WP, Nguyen VH, Elenitsas R, Katz KA: like melanoma with folliculotropism, 373 (Mr) pigmented keratotic nodules, 1201 (Se) Keratotic papules on the right side of the neck Carrington PR see Soderberg KI Chuang Y-H see Lu C-I and back, 535 (Ap) Carsin H see Chaby G Chung JH see Kwon OS Bowen G see Eliason MJ Caselli E see Zampino MR Chung L, Genovese MC, Fiorentino DF: Pilot Braathen LR see Hassan AS Cash SH, Dever TT, Hyde P, Lee JB: Epider- trial of rituximab in the treatment of patients Braun RP, Gaide O, Skaria AM, Kopf AW, molysis bullosa nevus: an exception to the with dermatomyositis, 763 (Je) Saurat J-H, Marghoob AA: Exclusively benign clinical and dermoscopic criteria for mela- Cianchini G, Corona R, Frezzolini A, Ruffelli dermoscopic pattern in a patient with acral noma, 1164 (Se) M, Didona B, Puddu P: Treatment of severe melanoma (letter) 1213 (Se) Cassai E see Zampino MR pemphigus with rituximab: report of 12 cases Braun RP see Changchien L; Scope A Cave H see Du-Thanh A and a review of the literature, 1033 (Au) Bray DW see Redd MA Cavicchini S, Tourlaki A, Bottini S: Dermo- Cicale L see Dalle S Breedlove J, Cho S, Gunning S: Erythematous scopic vascular patterns in nodular “pure” Clarke CA see Huang KP papules and plaques involving the groin and amelanotic melanoma, 556 (Ap) Clarke JT see George R scrotum, 1067 (Au) Cazes A, Prost-Squarcioni C, Bodemer C, Heller Clarke PJ see Sladden MJ Brenner S see Mashiah J M, Brousse N, Fraitag S: Histologic cutane- Cockerell CJ see Asgari MM Brier SE see Stitzenberg KB ous modifications after the use of EMLA cream, Cohen AL see Noe R Brindley DN see Perry B a diagnostic pitfall: review of 13 cases (re- Cohen C see Bhandarkar SS; Perry B Brockow T see Schiener R search letter) 1074 (Au) Cohen JL see Chorny JA Brodell RT see Ali SM; Poulos GA Cazzaniga AL see Davis SC Cohen PR: Paraneoplastic relapsing polychon- Broshtilova VK see Gantcheva ML Cecalupo AJ see Fiala KH dritis (letter) 949 (Jy) Brouet J-C see Asli B Cella D see Chamlin SL Cohen PR, Tschen JA, Schulze KE, Martinelli Brousse N see Cazes A Cerf I see Bachmeyer C PT, Nelson BR: Dermal plaques of the face and Brownell I see Irizarry E; Rao S Cerroni L see Pizzichetta MA scalp, 109 (Ja)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E3 Colbert RL, Chiang MP, Carlin CS, Fleming M: azathioprine hypersensitivity in patients with E Progressive extragenital lichen sclerosus suc- inflammatory bowel disease, 744 (Je) cessfully treated with narrowband UV-B pho- de Gannes GC, Ghoreishi M, Pope J, Russell Eaglstein WH, Ravis SM: Allergic contact der- totherapy, 19 (Ja) A, Bell D, Adams S, Shojania K, Martinka M, matitis: another adverse effect of over-the- Collado-Mesa F see Ma F Dutz JP: countertopicalhydrocortisone(letter)1217(Se) Constans J see Chamaillard M Psoriasiform eruptions during anti–TNF-␣ treat- Eaglstein WH see Davis SC; Ravis SM Cooper K: National Eczema Association and ment: psoriasis or not? (letter) 1595 (De) Eaton KD see Bauman JE topical calcineurin inhibitor labeling (letter) Psoriasis and pustular dermatitis triggered by Ebran N see Maire G 546 (Ap) TNF-␣ inhibitors in patients with rheumato- Eguino P see Lo´pez-Pestanã A Cooper KD see Blumetti BL; Doshi DN logic conditions, 223 (Fe) Eimpunth S see Manuskiatti W Cooperative Group on Fogo Selvagem Research de Giorgi V, Massi D, Mannone F, Checcucci El Sayed F, Dhaybi R, Ammoury A, Bazex J: see Rocha-Alvarez R V, De Magnis A, Sestini S, Papi F, Lotti T: Black tongue and Enterobacter cloacae (let- Corazza M see Zampino MR Dermoscopy in vulvar basal cell carcinoma (letter) 815 (Je) Corden T see Maronn ML ter) 426 (Mr) El Sayed F see Ammoury AF Cordoliani F see Asli B de Gruijl F see Janssens AS Elenitsas R see Bowe WP; Sariya D Corona R, Bigby M: What are the risks of seri- de Haas ERM see Nijsten T Eliason MJ, Hansen CB, Hart M, Porter-Gill P, ous infections and malignancies for patients de Haas ERM, Sterenborg HJCM, Neumann Chen W, Sturm RA, Bowen G, Florell SR, treated with anti-tumor necrosis factor anti- HAM, Robinson DJ: Response of Bowen dis- Harris RM, Cannon-Albright LA, Swinyer L, bodies? 405 (Mr) ease to ALA-PDT using a single and a 2-fold Leachman SA: Multiple primary melanomas Corona R see Cianchini G; Zalaudek I illumination scheme (research letter) 264 (Fe) in a CDKN2A mutation carrier exposed to ion- Cosnes J see de Fonclare A-L de Jong EMGJ see Berends MAM izing radiation, 1409 (No) Coto-Segura P see Va´zquez-Lo´pez F De Lacerda D see Farhi D Eming R see Niedermeier A Cottoni F see Satta R De Magnis A see de Giorgi V Emmert S see Thoms K-M Courville P see Grange F de Prost Y see Maire G Engler DE see Pol-Rodriguez MM Crawford GH see Quain RD de Rie MA see Rhodes LE English JC III see Balestreire E; Whalen JG Crawford RI see Somani N de Rooij MJM see Heinen MM Enrı´quez-Salamanca R see Herrero C Creamer D, Martyn-Simmons CL, Osborne G, de Souza Santos MN see Chrusciak-Talhari A Erben P see Utikal J Kenyon M, Salisbury JR, Devereux S, Pagliuca Esler-Brauer L, Rothman I: Tender nodules on Debure C see Chaby G A, Ho AY, Mufti GJ, du Vivier AWP: Eczematoid the palms and soles, 1201 (Se) Delaporte E see Grange F graft-vs-host disease: a novel form of chronic Espan˜ a A, Garcıá-Amigot F, Aguado L, Garcıá- Delaunay M see Grange F cutaneous graft-vs-host disease and its response Foncillas J: Novel missense mutation in the Dellavalle RP see Johnson KR; McLaughlin JA to psoralen–UV-A therapy, 1157 (Se) CYLD gene in a Spanish family with multiple Demierre M-F, Ferzli P, Miller D: Measuring Creech J see Davis SC familial trichoepithelioma (research letter) HRQOL in patients with cutaneous T-cell lym- Criscione VD, Weinstock MA: Incidence of cuta- 1209 (Se) phoma undergoing therapy with oral bexaro- neous T-cell lymphoma in the United States, Esteve E see Grange F tene and extracorporeal photopheresis 1973-2002, 854 (Jy) Eun HC see Kwon OS (research letter) 659 (My) Cue´llar A, Garcıá E, Rodrı´guez A, Halpert E, Evans AT see Arseculeratne G Go´mez A: Functional dysregulation of den- Demierre M-F see Taverna JA Evers AWM see Heinen MM dritic cells in patients with papular urticaria Deng A see Markowski TR Evers M, Baron E, Zaim MT, Han A: Papules caused by fleabite, 1415 (No) Denis C see Chaby G and plaques on the nose, 535 (Ap) Culler SD see Pennie ML Derancourt C see Ackermann F Cusack C see Sariya D Dereure O see Du-Thanh A F Descamps V: Evidence insufficient to recom- D mend melanoma surveillance following pho- Fabre´ VC see Frazier TH totherapy for jaundice (letter) 1216 (Se) Fang SH, Ioffreda MD, Miller JJ, Helm KF, Dagregorio G see Guillet MH Dever TT see Cash SH Billingsley EM: Bilateral symmetrical nod- Dahl MV: Granuloma annulare: long-term fol- Devereux S see Creamer D ules on the feet, 417 (Mr) low-up (research letter) 946 (Jy) Dhaybi R see El Sayed F Fantini F see Longo C Dai T see Glaich AS Di Stefani A see Zalaudek I Fargnoli MC see Altamura D Dalac S see Grange F Diaz LA see Rocha-Alvarez R Farhi D, De Lacerda D, Palangie´ A, Dupin N, Dalle S, Ronger-Savle S, Cicale L, Balme B, Dıáz-Cascajo C see Bastida J Wallach D: Burgeoning nodule on the scalp Thomas L: Blue-gray subungual discolora- Didona B see Cianchini G of a 65-year-old man, 653 (My) tion, 937 (Jy) Diepgen T see Janssens AS Feldman SR see Ali SM; Fosse K; Satyaprakash Dalle S see Grange F Dimon NS, Fullen DR, Helfrich YR: Goose- A Dalton K see Stitzenberg KB fleshlike lesions and hypohidrosis, 1323 (Oc) Ferguson J see Arseculeratne G Dapprich DC, Roenigk RK: Nodule on the toe, Dini V see Romanelli M Fermand J-P see Asli B 1067 (Au) Doerries K see Inhoff O Ferrandiz L see Moreno-Ramirez D Das SN see Arseculeratne G Doerries R see Inhoff O Ferrara G see Argenziano G; Giacomel J; Dasher D see Rocha-Alvarez R Zalaudek I Dompmartin A see Chaby G Daufı´ C see Zaballos P Ferreira LC see Chrusciak-Talhari A Donovan KO see Kalajian AH Daugas E see Ackermann F Ferzli P see Demierre M-F Doshi DN, Hanneman KK, Cooper KD: Smok- Davis KF, Wu JJ, Murase JE, Rosenberg FR, Fiala KH, Wells MJ, Stetson CL, Cecalupo AJ: ing and skin aging in identical twins, 1543 (De) Sorenson EP, Meshkinpour A: Clinical When a bump can be a hole (letter) 1083 (Au) Dover JS see Bogle MA improvement of pityriasis rubra pilaris with Fierlbeck G see Hoetzenecker W combination etanercept and acitretin therapy Drenth JPH see Berends MAM Figl A, Thirumaran RK, Ugurel S, Gast A, (letter) 1597 (De) Dresden G: Atrial tachycardia associated with Hemminki K, Kumar R, Schadendorf D: Mul- Davis MDP, Nakamura KJH: Peristomal pyo- isotretinoin use (letter) 1084 (Au) tiple melanomas after treatment for Hodgkin derma gangrenosum associated with collag- Drolet BA see Benouni S; Maronn ML; Webber lymphoma in a non-Dutch p16-Leiden muta- enous colitis (letter) 669 (My) KA tion carrier with 2 MC1R high-risk variants, Davis MDP see Soares TF du Vivier AWP see Creamer D 495 (Ap) Davis SC, Cazzaniga AL, Ricotti C, Zalesky P, Du-Thanh A, Cave H, Bessis D, Puso C, Guilhou Fimiani M see De Aloe G Hsu L-C, Creech J, Eaglstein WH, Mertz PM: J-J, Dereure O: Novel PTPN11 gene muta- Fincher EF see Marra DE Topical oxygen emulsion: a novel wound tion in a patient with LEOPARD syndrome (re- Fiorentino DF: Yin and yang of TNF-␣ inhibi- therapy, 1252 (Oc) search letter) 1210 (Se) tion, 233 (Fe) Davis SC see Mertz PM Dunn M see Tyring S Fiorentino DF see Chung L; Richmond H Davison M see Garcia C Dupin N see Farhi D Fischer E see Hammes S Dayal S see Jain K Duriez P see de Fonclare A-L Fischer J, Metzler G, Schaller M: Cosmetic per- De Aloe G, Poggiali S, Rubegni P, Miracco C, Dusza SW see Benvenuto-Andrade C; manent fillers for soft tissue augmentation: a Fimiani M: Nodule on a boy’s back, 417 (Mr) Changchien L new contraindication for interferon thera- de Argila D see Vagace JM Dutch Cutaneous Lymphoma Group see Senff pies, 507 (Ap) de Fonclare A-L, Khosrotehrani K, Aractingi S, NJ Fischer MA see Qureshi A Duriez P, Cosnes J, Beaugerie L: Erythema Dutz JP see de Gannes GC; Somani N Fisher GJ see Kafi R; Wang F nodosum–like eruption as a manifestation of Duvic M see Lambert TJ Fitzgerald D see Singh MN

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E4 Fitzgibbons CA see Baker BL Gelfer A, Rivers JK: Long-term follow-up of a Grichnik JM: Monthly final page: skINsight, Fleischer AB Jr see Satyaprakash A patient with eruptive melanocytic nevi after 1433 (No) Fleming M see Colbert RL Stevens-Johnson syndrome, 1555 (De) Grichnik JM see Thomas MW Flohr C see Langan SM Gelincik I see Akdeniz N Griffiths CEM see Seston EM Florell SR see Eliason MJ Geller AC see Loo DS; Losina E Groden C see Inhoff O Fontas E see Passeron T Gencoglan G, Gerceker-Turk B, Kilinc- Grossman ME see MacGregor JL; Weiser JA Forman SB, Hudgins EM, Blalock WK: Lichen Karaarslan I, Akalin T, Ozdemir F: Dermo- Gruis NA see Bergman W spinulosus: excellent response to tretinoin gel scopic findings in Laugier-Hunziker syndrome, Guevara IL see Werlinger KD and hydroactive adhesive applications (let- 631 (My) Guijarro J see Mataix J ter) 122 (Ja) Genovese MC see Chung L Guilhou J-J see Du-Thanh A Fosse K, Kurtz E, Khanna V, Camacho FT, George R, Fulchiero GJ Jr, Marks JG Jr, Clarke Guillaume J-C see Chaby G Balkrishnan R, Feldman SR: Practice bro- JT: Neurovascular instability syndrome: a uni- Guillet G see Guillet MH chure: complement to, not supplement for, fying term to describe the coexistence of Guillet MH, Wierzbicka E, Guillet S, Dagregorio good physician-patient interaction (research temperature-related vascular disorders in G, Guillet G: 3-year causative study of pom- letter) 1447 (No) affected patients (letter) 274 (Fe) pholyx in 120 patients, 1504 (De) Foster JK see Pressley ZM Gerceker-Turk B see Gencoglan G Guillet S see Guillet MH Fraitag S see Cazes A; Maire G Gervasini G see Vagace JM Guillot B see Chaby G; Vaneau M Francis SO see McLaughlin JA Ghersi MM, Ricotti C, Nousari CH, Newman Guitart J, Magro C: Cutaneous T-cell lym- Franco G see Carducci M MI: Negative pressure dressing in the man- phoid dyscrasia: a unifying term for idio- Franke A see Schiener R agement of pyoderma gangrenosum ulcer, pathic chronic dermatoses with persistent Frazier TH, Richardson JB, Fabre´ VC, Callen 1249 (Oc) T-cell clones, 921 (Jy) JP: Fluoroscopy-induced chronic radiation Ghersi MM see Ricotti C Gunning S see Breedlove J skin injury: a disease perhaps often over- Ghoreishi M see de Gannes GC Gwinn M, Khoury MJ: Dermatology and the looked, 637 (My) Ghwish B see Mulekar SV human genome: an epidemiologic approach, Freedberg KA see Losina E Giacomel J, Zalaudek I, Ferrara G, Argenziano 1194 (Se) Freeman SR see Johnson KR G: Dermoscopy patterns of eczemalike mela- Frezzolini A see Cianchini G noma (letter) 1081 (Au) H Frieden IJ see Chamlin SL Giacomini F see Patrizi A Friedman H see Rocha-Alvarez R Gilaberte M see Martinez-De Pablo MI Haas AF: Teens and tans: implementing behav- Friedman PC, Husain S, Silvers DN, Garzon Gilbert M see Be´dard M-S ioral change, 1058 (Au) Haberkorn U see Utikal J MC: Subcutaneous nodule and diffuse lymph- Gilchrest BA see Loo DS; Losina E Haley RW see Werlinger KD adenopathy in a 6-month-old boy from Africa, Gill M see Scope A Halpern AC see Benvenuto-Andrade C; 1323 (Oc) Gilliam AC see Blumetti BL Changchien L; Scope A Friedman PM see Chrastil B; Glaich AS Gimeńez E see Pascual JC Halpert E see Cue´llar A Frieling U see Beissert S Glaich AS, Goldberg LH, Dai T, Kunishige JH, Hamada T, Inoue Y, Nakama T, Hashimoto T: Fueyo-Casado A see Va´zquez-Lo´pez F Friedman PM: Fractional resurfacing: a new Case of zosteriform pigmented purpuric der- Fujiwara N see Nagano T therapeutic modality for Becker’s nevus, 1488 matosis (letter) 1599 (De) Fulchiero GJ Jr see George R (De) Hamada T, Kimura Y, Hayashi S, Nakama T, Fullen DR see Dimon NS Glaich AS see Chrastil B Funato M see Aoyama Y Hashimoto T: Hypereosinophilic syndrome Glatz M see Ambros-Rudolph CM with peripheral circulatory insufficiency and G Goerdt S see Inhoff O; Utikal J cutaneous microthrombi (letter) 812 (Je) Goldberg L see Taverna JA Hamilton TA see Helfrich YR; Kafi R Gaide O see Braun RP Goldberg LH see Chrastil B; Glaich AS; Wang Hammes S, Augustin A, Raulin C, Ockenfels Galdeano R see Moreno-Ramirez D SQ H-M, Fischer E: Pupil damage after peri- Galmiche L see Maire G Gollnick H see Beissert S orbital laser treatment of a port-wine stain, Galvan M see Zampino MR Go´mez A see Cue´llar A 392 (Mr) Gambichler T: Balneophototherapy for psoriasis Go´mez-Dıéz S see Va´zquez-Lo´pez F Hammes S see Karsai S using saltwater baths and UV-B irradiation, Gonza´lez CM see Werlinger KD Han A see Evers M revisited, 647 (My) Gonzalez ME, Blanco FP, Garzon MC: Verru- Han J see Abdelmalek M Gambichler T see Kreuter A cous papules and plaques in a pediatric patient, Hanafusa T, Yamaguchi Y, Kitaba S, Katayama Gantcheva ML, Broshtilova VK, Lalova AI: 1201 (Se) I: Intractable wounds from a herpes simplex Necrolytic migratory erythema: the outer- Gonzalez S see Scope A infection in an immunosuppressed patient with most marker for glucagonoma syndrome (let- Gonza´lez U: Cloud over sentinel node biopsy: rheumatoid arthritis (letter) 1340 (Oc) ter) 1221 (Se) unlikely survival benefit in melanoma, 775 (Je) Hanft VN see Kafi R Garcia C, Davison M: Awareness of genera- Gonza´lez-Ensen˜ at MA see Martinez-De Pablo Hanneman KK see Doshi DN tional differences is the first step (letter) 120 MI Hansen CB see Eliason MJ (Ja) Goodfield M see Usmani N Happel C see Niedermeier A Garcia C, Poletti E: Scalp biopsy specimens: Gordon KB see Tyring S Harman KE see Sladden MJ transverse vs vertical sections (research let- Gottlieb AB see Tyring S Harrington CR see Swetter SM ter) 268 (Fe) Goudie DR see Arseculeratne G Harris RM see Eliason MJ Garcıá E see Cue´llar A Gould LH see Noe R Harrison-Balestra C see Martinez LC Garcıá-Amigot F see Espanã A Goulden V see Rhodes LE Hart M see Eliason MJ Garcıá-Foncillas J see Espanã A Grabbe J see Shimanovich I Hashimoto T see Hamada T Garg A, Mahalingam M, Alavian C: Pruritic Grange F, Beylot-Barry M, Courville P, Maubec Hashino S see Yanagi T patches on the back and papules on the legs, E, Bagot M, Vergier B, Souteyrand P, Machet Hassan AS, Simon D, Simon H-U, Braathen LR, 255 (Fe) L, Dalac S, Esteve E, Templier I, Delaporte Yawalkar N: Efalizumab-associated papular Garg VK see Sardana K E, Avril M-F, Robert C, Dalle S, Laroche L, psoriasis, 900 (Jy) Garibaldinos TM see Yones SS Delaunay M, Joly P, Wechsler J, Petrella T: Haught JM see Balestreire E Garza LA see Wang F Primary cutaneous diffuse large B-cell lym- Hawk JLM see Yones SS Garzon MC see Friedman PC; Gonzalez ME phoma, leg type: clinicopathologic features Hayashi S see Hamada T Gaspari AA see Markowski TR and prognostic analysis in 60 cases, 1144 (Se) Hebert AA see Vu J Gast A see Figl A Green A see McBride P Heffernan MP see Xu LY Gat A see Mashiah J Green M see Heymann AD Heffernan MP, Anadkat MJ, Smith DI: Adali- Gelfand JM: Long-term treatment for severe pso- Green WH, Yosipovitch G, Pichardo RO: Recur- mumab treatment for pyoderma gangreno- riasis: we’re halfway there, with a long way to rent, pruritic dermal plaques and bullae, 791 sum, 306 (Mr) go, 1191 (Se) (Je) Heffernan MP, Bentley DD, Tapia B, Klekotka Gelfand JM see Pariser DM Greenway HT Jr, Twersky JM, Meads SB, Kelley P: Painful nodule on the knee, 937 (Jy) Gelfand JM, Troxel AB, Lewis JD, Kurd SK, BF: Melanoma of the foot and ankle: a case Heinen MM, van der Vleuten C, de Rooij MJM, Shin DB, Wang X, Margolis DJ, Strom BL: series of an underrecognized entity (research Uden CJT, Evers AWM, van Achterberg T: Risk of mortality in patients with psoriasis: letter) 543 (Ap) Physical activity and adherence to compres- results from a population-based study, 1493 Grekin SJ, Annest NM, Madison KC: Beefy red sion therapy in patients with venous leg ulcers, (De) plaque in the popliteal fossa, 1323 (Oc) 1283 (Oc)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E5 Helfrich YR see Dimon NS Inoue Y see Hamada T Katz KA see Bowe WP Helfrich YR, Yu L, Ofori A, Hamilton TA, Inoue Y, Matui T, Ono T: Outbreak of Vibrio Kedrowski DA see Wenner R Lambert J, King A, Voorhees JJ, Kang S: Effect vulnificus infection in Kumamoto, Japan, 2001, Keegan BR see Schaffer JV of smoking on aging of photoprotected skin: 140:888 (Jy); correction, 143:391 (Mr) Kelley BF see Greenway HT Jr evidence gathered using a new photo- Ioffreda MD see Fang SH Kelly JW, McArthur GA, Wolfe R, Thompson numeric scale, 397 (Mr); correction, 633 (My) Irizarry E, Brownell I, Pomeranz MK: “Louse JF, Liu W: Heliot-Hosten I see Chamaillard M blouse” as a cause of erythroderma, 682 (My) Confusing message will not improve the detec- Heller M see Cazes A Ishay A, Ziv M, Kerner M, Luboshitzky R: Sup- tion of melanoma (letter) 806 (Je) Heller P see Schaffer JV pression of the HPA axis in pediatric patients Fast-growing and slow-growing melanomas Helm KF see Fang SH with atopic dermatitis (letter) 1449 (No) (letter) 803 (Je) Helms SE see Blumetti BL Isseroff RR see Margolis DJ Kempf VA see Hoetzenecker W Hemminki K see Figl A Izaki S see Arai E Kenyon M see Creamer D Herrero C, To-Figueras J, Badenas C, Me´ndez Izatt JA see Thomas MW Kerl H see Ambros-Rudolph CM; Binder B; M, Serrano P, Enrı´quez-Salamanca R, Lecha Legat FJ; Zalaudek I M: Clinical, biochemical, and genetic study of J Kerner M see Ishay A 11 patients with erythropoietic protopor- Keslair F see Maire G phyria including one with homozygous dis- Jahreis A see Tyring S Khanna V see Fosse K ease, 1125 (Se) Jain K, Dayal S, Jain VK, Aggarwal K, Bansal Khosrotehrani K see de Fonclare A-L Hertl M see Niedermeier A A: Blaschko linear nodular morphea with der- Khoury MJ see Gwinn M Hexsel CL see Lim HW mal mucinosis (letter) 953 (Jy) Kilinc-Karaarslan I see Gencoglan G Heydendael VMR, Hoekzema R: Acute blue Jain VK see Jain K Kim MH see Kwon OS patch on the forearm, 937 (Jy) James WD: Sponsorship of graduate medical Kim YC see Kim YJ Heymann AD, Chodick G, Kramer E, Green M, education: one successful model (letter) 1211 Kim YH see Huang KP; Richmond H Shalev V: Pemphigus variant associated with (Se) Kim YJ, Kim YC: Successful treatment of pity- penicillin use: a case-cohort study of 363 James WD see Treat J riasis versicolor with 5-aminolevulinic acid patients from Israel, 704 (Je) Janer V see Sorg O photodynamic therapy (letter) 1218 (Se) Higashida Y see Nagano T Janssens AS, Pavel S, Ling T, Winhoven SM, Kimball AB see Turner E High WA see Lu LK Anastasopoulou N, Stratigos A, Antoniou C, Kimura Y see Hamada T Hildenbrand R see Utikal J Diepgen T, de Gruijl F, Rhodes LE: Suscep- King AL see Helfrich YR; Kafi R Hillhouse J, Turrisi R, Shields AL: Patterns of tibility to UV-A and UV-B provocation does Kinney MA see Mertz PM indoor tanning use: implications for clinical not correlate with disease severity of poly- Kirkland F see Winfield HL interventions, 1530 (De) morphic light eruption, 599 (My) Kirsner RS: Wound healing, 1318 (Oc) Hillman JD see Kappel ST Jaworsky C see Thakuria M Kirsner RS see Ma F; Pieper B Hioki K see Aoyama Y Jayawant SS see Satyaprakash A Kitaba S see Hanafusa T Hiraga H see Yanagi T Jee S-H see Yang C-Y Kitajima Y see Aoyama Y Hirose T see Arai E Johnson KR, Freeman SR, Dellavalle RP: Wikis: Kittler H, Menzies SW: Identification of incipient Ho AY see Creamer D the application of Web 2.0, 1065 (Au) tumors by means of sequential dermoscopy Hochhaus A see Utikal J Johr R see Zalaudek I imaging: a new way to inflate the “epidemic” Hoefnagel JJ see Senff NJ Joly P see Grange F of melanoma? (letter) 805 (Je) Hoekzema R see Heydendael VMR Jones-Caballero M, Unaeze J, Pen˜ as PF, Stern Klekotka P see Heffernan MP Hoetzenecker W, Ulmer A, Klingel K, Kempf RS: Use of biological agents in patients with Klingel K see Hoetzenecker W VA, Schanz S, Metzler G, Fierlbeck G: moderate to severe psoriasis: a cohort-based Koga H see Saida T Dissemination of a localized cutaneous infec- perspective, 846 (Jy) Koh HK: Melanoma screening: focusing the tion with Mycobacterium chelonae under immu- Jorda´ E see Martı´n JM; Martin JM public health journey, 101 (Ja) nosuppressive treatment (letter) 951 (Jy) Jorizzo JL see Torti DC Kolm I see Cabo H; Zalaudek I Hofer A see Legat FJ Junghans V see Beissert S Kolm P see Pressley ZM Hoffstad O see Margolis DJ Junkins-Hopkins J see Quain RD Kondo N see Aoyama Y Hofmann-Wellenhof R see Binder B; Zalaudek Kopf AW see Braun RP I K Korman BD see Robinson MR Holland KE see Webber KA Korman NJ see Pariser DM; Robinson MR Hoppe RT see Huang KP Kafi R, Kwak HSR, Schumacher WE, Cho S, Korzenko AJ see Changchien L Horn EJ see Pariser DM Hanft VN, Hamilton TA, King AL, Neal JD, Kos L see Benouni S; Webber KA Horn TD see Winfield HL Varani J, Fisher GJ, Voorhees JJ, Kang S: Ko¨sem M see Akdeniz N Hruza GJ: Cutting edge, 1062 (Au) Improvement of naturally aged skin with vita- Kovach RF see Williams JM Hsu L-C see Davis SC min A (retinol) 606 (My) Kowalczyk JP see Ricotti C Hu S see Ma F Kalajian AH, Turpen KB, Donovan KO, Malone Kramer E see Heymann AD Huang C-C see Lu C-I JC, Callen JP: Phenylephrine-induced micro- Kreuter A, Gambichler T: Narrowband UV-B Huang KP, Weinstock MA, Clarke CA, vascular occlusion syndrome in a patient with phototherapy for extragenital lichen sclero- McMillan A, Hoppe RT, Kim YH: Second lym- a heterozygous factor V Leiden mutation, 1314 sus (letter) 1213 (Se) phomas and other malignant neoplasms in (Oc) Kulkarni K see Chua SL patients with mycosis fungoides and Se´zary Kamekura R see Yanagi T Kumar R see Figl A syndrome: evidence from population-based Kang S see Helfrich YR; Kafi R; Wang F Kunishige JH see Glaich AS and clinical cohorts, 45 (Ja) Kanzler MH: Current status of evaluation and Kuo H-C see Lu C-I Hudgins EM see Forman SB treatment of high-risk cutaneous melanoma: Kurd SK see Gelfand JM Huerta C, Rivero E, Rodrı´guez LA: Incidence therapeutic breakthroughs remain elusive, 785 Kurtz E see Fosse K and risk factors for psoriasis in the general (Je) Kuruvila M see Bhandarkar SS population, 1559 (De) Kao GF see Markowski TR Kurzen H see Utikal J Hunzelmann N see Beissert S Kappel ST, Wu JJ, Hillman JD, Linden KG: Kwak HSR see Kafi R Husain S see Friedman PC Histopathologic findings of disseminated coc- Kwon OS, Kim MH, Park SH, Chung JH, Eun Hutchin M, Chenoweth C, Ma L, McClean K: cidioidomycosis with hyphae (letter) 548 (Ap) HC, Oh JK: Staged hair transplantation in cica- Auricular erythema with nodules and scale, Karaarslan IK see Ozdemir F tricial alopecia after carbon dioxide laser– 1441 (No) Karanikola E see Rallis E assisted scar tissue remodeling, 457 (Ap) Hyde P see Cash SH Karsai S, Adrian R, Hammes S, Thimm J, Raulin C: Randomized double-blind study of the effect L I of Botox and Dysport/Reloxin on forehead wrinkles and electromyographic activity (re- Lacour J-P see Passeron T Idoate M see Redondo P search letter) 1447 (No) Lacouture M see Montella L Inhoff O, Doerries K, Doerries R, Scharf J, Kartono F, Lee EW, Lanum D, Pham L, Maibach Lai J-S see Chamlin SL Groden C, Goerdt S, Schadendorf D: Dis- HI: Crusted Norwegian scabies in an adult with Lalova AI see Gantcheva ML seminated cutaneous Kaposi sarcoma and pro- Langerhans cell histiocytosis: mishaps lead- Lambert J see Helfrich YR gressive multifocal leukoencephalopathy in a ing to systemic chemotherapy, 626 (My) Lambert TJ, Prieto VG, Duvic M: Multiple patient with idiopathic CD4ϩ T lymphocyto- Katayama I see Hanafusa T plaques on the hands and feet, 109 (Ja) penia (letter) 673 (My) Kato N see Yanagi T Lamp K see Buell C

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E6 Langan SM, Flohr C, Williams HC: Role of furry cally characterized by reticular depigmenta- Martinez LC, Harrison-Balestra C, Caeiro JP, pets in eczema: a systematic review, 1570 (De) tion (letter) 808 (Je) Nousari CH: Role of the quantiFERON-TB Langford D see Zalaudek I Lu C-I, Huang C-C, Chang Y-C, Tsai Y-T, Kuo gold test as screening prior to administration Langley RGB see Propperova I; Tyring S H-C, Chuang Y-H, Shih T-S: Short-term thal- of tumor necrosis factor inhibitors (letter) 809 Lanum D see Kartono F lium intoxication: dermatological findings cor- (Je) Laroche L see Grange F related with thallium concentration, 93 (Ja) Martıńez-Cuesta A see Redondo P Larralde M, Abad ME, Santos Mun˜ oz A, Luna Lu LK, High WA: Acute generalized exanthema- Martinez-De Pablo MI, Gonza´lez-Ensen˜ at MA, P: Childhood flexural comedones: a new entity, tous pustulosis caused by illicit street drugs? Vicente A, Gilaberte M, Mascaro´ JM Jr: Child- 909 (Jy) (letter) 430 (Mr) hood bullous pemphigoid: clinical and immu- Lawrence CM see Wahie S Luboshitzky R see Ishay A nological findings in a series of 4 cases, 215 Leachman SA see Eliason MJ Lucky AW see Sluzevish JC (Fe) Lebbe´ C see Ackermann F Luger TA see Beissert S Martinka M see de Gannes GC; Somani N LeBon B, Beynon TA, Whittaker SJ: Palliative Luna P see Larralde M Martins RG see Bauman JE care in patients with primary cutaneous lym- Lutz L see Markowski TR Martyn-Simmons CL see Creamer D phoma: symptom burden and characteristics Mascaro´ JM Jr see Martinez-De Pablo MI of hospital palliative care team input (re- M Masgrau E see Sorg O search letter) 423 (Mr) Mashiah J, Wohl Y, Barnea Y, Schneebaum S, Ma F, Collado-Mesa F, Hu S, Kirsner RS: Skin Lebwohl MG see Pariser DM Gat A, Misonzhnik-Bedny F, Brenner S: cancer awareness and sun protection behaviors Immunohistochemical expression of platelet Lecha M see Herrero C in white Hispanic and white non-Hispanic high Lederman E see Noe R growth factor and vascular endothelial growth school students in Miami, Florida, 983 (Au) factor in patients with melanoma with and Lee DJ see Bhandarkar SS Ma L see Hutchin M Lee EW see Kartono F without redness (Brenner sign) 1001 (Au) MacGregor JL, Chan P, Schneiderman PI, Massi D see de Giorgi V Lee JB see Cash SH Grossman ME: Diabetic muscle infarction (let- Leemans E see Sorg O Massone C see Pizzichetta MA ter) 1456 (No) Mataix J, Botella R, Ban˜ uls J, Guijarro J, Pastor Legat FJ, Hofer A, Wackernagel A, Salmhofer Machet L see Grange F N, Betlloch I: Asymptomatic nodule of the W, Quehenberger F, Kerl H, Wolf P: Narrow- MacKelfresh JB see Bhandarkar SS tongue, 653 (My) band UV-B phototherapy, alefacept, and clear- Madison KC see Grekin SJ ance of psoriasis, 1016 (Au) Matıás-Guiu X see Vidal D Magro C see Guitart J Matsumura T see Yanagi T Leifsdottir R see Rhodes LE Mahalingam M see Garg A Mattingly D see Stitzenberg KB Lepreux S see Seneschal J Maibach HI see Kartono F Matui T see Inoue Y Lerner A see Taverna JA Maire G, Fraitag S, Galmiche L, Keslair F, Ebran Matz V see Chaby G Lesesky EB, Pelle MT, O’Grady TC: Diffuse nod- N, Terrier-Lacombe M-J, de Prost Y, Pedeutour Maubec E see Grange F ules in a woman with renal failure, 1201 (Se) F: Clinical, histologic, and molecular study of Mauger DT see Regula CG Lessin SR: Cutaneous T-cell lymphoma epide- 9 cases of congenital dermatofibrosarcoma pro- McArthur GA see Kelly JW miology: patients providing the power, 916 (Jy) tuberans, 203 (Fe) McBride P, Neale R, Pandeya N, Green A: Sun- Lessin SR see Sariya D Maisels MJ see Newman TB related factors, Betapapillomavirus, and actinic Levy A see Ackermann F Malone JC see Kalajian AH keratoses: a prospective study, 862 (Jy) Levy AL, Wilkin N, Poh-Fitzpatrick MB, Malphettes M see Asli B McCarty MA see Torti DC Rasberry RD: Verrucous nodules on the toes Malvehy J see Cabo H; Carrera C; Scope A; McClain SA see Scope A of a renal transplant recipient, 653 (My) Segura S; Zaballos P; Zalaudek I McClean K see Hutchin M Lewis JD see Gelfand JM Mancini AJ see Chamlin SL McClelland MC see Suwattee P Mannone F see de Giorgi V Li N see Rocha-Alvarez R McLaughlin ER see Perry B ManuskiattiW,EimpunthS,Wanitphakdeedecha Lim HW, Hexsel CL: Vitiligo: to treat or not to McLaughlin JA, Francis SO, Burkhardt DL, R: Effect of cold air cooling on the incidence treat, 643 (My) Dellavalle RP: Indoor UV tanning youth access of postinflammatory hyperpigmentation after Lin JY see Szyfelbein K laws: update 2007, 529 (Ap) Q-switched Nd:YAG laser treatment of Lin T-L see Yang C-Y McMillan A see Huang KP acquired bilateral nevus of Ota–like macules, Lind A see Berk DR Meads SB see Greenway HT Jr Linden KG see Kappel ST 1139 (Se) Marghoob AA see Benvenuto-Andrade C; Braun Meaume S see Chaby G Ling T see Janssens AS Meiklejohn D see Arseculeratne G Lipsker D: Increasing ratio of thin to thick mela- RP; Changchien L; Scope A; Zaballos P Margolis DA see Webber KA Meńdez M see Herrero C noma lesions: pathogenesis and early detec- Menzies SW: Dermoscopy not yet shown to tion of this cancer (letter) 804 (Je) Margolis DJ, Hoffstad O, Isseroff RR: Associa- tion between the use of ␤-adrenergic recep- increase sensitivity of melanoma diagnosis in Lipsker D see Sfia M real practice (letter) 665 (My) Liu A see Wenner R tor agents and the development of venous leg ulcers, 1275 (Oc) Menzies SW see Kittler H Liu C see Loo DS Margolis DJ see Gelfand JM Merlini G see Satta R Liu W see Kelly JW Mertz PM, Cardenas TCP, Snyder RV, Kinney ´ Markowski TR, Martin DB, Kao GF, Lutz L, Llambrich Asee Zaballos P Deng A, Gaspari AA: Leukemia cutis: a pre- MA, Davis SC, Plano LRW: Staphylococcus Lobo C see Lo´pez-Pestanã A senting sign in acute promyelocytic leukemia aureus virulence factors associated with Longo C, Fantini F, Cesinaro AM, Bassoli S, (letter) 1220 (Se) infected skin lesions: influence on the local Seidenari S, Pellacani G: Pigmented mammary Marks JG Jr see George R immune response, 1259 (Oc) Paget disease: dermoscopic, in vivo reflectance- Marks JG see Regula CG Mertz PM see Davis SC mode confocal microscopic, and immuno- Markus R see Rao S Meshkinpour A see Davis KF histochemical study of a case, 752 (Je) Maronn ML, Corden T, Drolet BA: Pneumocystis Metin A see Akdeniz N Loo DS, Liu C, Geller AC, Gilchrest BA: Aca- carinii pneumonia in infant treated with oral Metzler G see Fischer J; Hoetzenecker W; Yazdi demic dermatology manpower: issues of steroids for hemangioma (letter) 1224 (Se) AS recruitment and retention, 341 (Mr) Marra DE, Pourrabbani S, Fincher EF, Moy RL: Meurer M see Beissert S Looman CWN see Nijsten T Fractional photothermolysis for the treat- Micantonio T see Lozzi GP Lo´pez C see Motta A ment of adult colloid milium, 572 (My) Michaels BD, Mullinax KA, Wells MJ, Stetson Lopez M see Carducci M Martel P see Chaby G; Vaneau M CL: Tuberous necrobiosis lipoidica (letter) 546 Lo´pez-Pestan˜ a A, Tuneu A, Lobo C, Zubizarreta Martı´ RM see Carrera C (Ap) J, Eguino P: Blue-black pigmentation of legs Martin DB see Markowski TR Militello G see Quain RD and arms in a 68-year-old woman, 1441 (No) Martıń JM, Calduch L, Molina I, Ruiz C, Miller D see Demierre M-F Lorenzoni A see Argenziano G Monteagudo C, JordaÉ:Ulceronecrotic naso- Miller JJ see Fang SH; Regula CG Losina E, Walensky RP, Geller A, Beddingfield paranasal lesion, 653 (My) Millikan RC see Stitzenberg KB FC III, Wolf LL, Gilchrest BA, Freedberg KA: Martin JM, Monteagudo C, Calduch L, Villaloń Milpied B see Seneschal J Visual screening for malignant melanoma: a G, JordaÉ:Dermatoscopic changes in acquired Ming ME: The Off-Center Fold 935 (Jy) cost-effectiveness analysis, 21 (Ja) melanocytic nevi and seborrheic keratoses after Miracco C see De Aloe G Lotti T see de Giorgi V the application of a self-tanning airbrush (let- Misciali C see Patrizi A Lowe JG see Arseculeratne G ter) 1453 (No) Misery L see Schollhammer M Lozzi GP, Piccolo D, Micantonio T, Altamura Martinelli PT see Cohen PR Misonzhnik-Bedny F see Mashiah J D, Peris K: Early melanomas dermoscopi- Martinez A see Pascual JC Miyachi Y see Nakahigashi K

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E7 Mockenhaupt M see Ziemer M molysis bullosa acquisita to combined treat- Passeron T, Lacour J-P, Fontas E, Ortonne J-P: Modlin RL see Bhandarkar SS ment with immunoadsorption and rituximab Treatment of oral erosive lichen planus with 1% Mohr RE, Takashima A: Epidermal Langerhans (anti-CD20 monoclonal antibodies) 192 (Fe) pimecrolimus cream: a double-blind, random- cell movement in situ: a model for under- Nieto-Garcia A see Moreno-Ramirez D ized, prospective trial with measurement of standing immunologic function in the skin, Nijsten T: Level of agreement with the British pimecrolimus levels in the blood, 472 (Ap) 1352 (Oc); correction, 1438 (No) guidelines for the use of biological therapies Passeron T, Ortonne J-P: Effect of tacrolimus Molina I see Martıń JM for psoriasis, 1567 (De) on vitiligo in absence of UV radiation expo- Monteagudo C see Martıń JM; Martin JM Nijsten T, de Haas ERM, Neumann MHA: sure (letter) 120 (Ja) Montella L, Palmieri G, Lacouture M: Era of tar- Question the obvious, 1429 (No) Pastor N see Mataix J geted therapies: increasing role for novel onco- Nijsten T, Looman CWN, Stern RS: Clinical Patrizi A, Giacomini F, Bianchi F, Misciali C, logic drugs in dermatology, 788 (Je) severity of psoriasis in last 20 years of PUVA Neri I: Recurrent calcified cutaneous nodule Morais F see Vagace JM study, 1113 (Se) of the perianal region, 1441 (No) Mordente I see Zalaudek I Nishigori C see Nagano T Pavel S see Janssens AS Moreno-Alvarez P see Moreno-Ramirez D Noe R, Cohen AL, Lederman E, Gould LH, Pearson GW see Rao S Moreno-Ramirez D, Ferrandiz L, Nieto- Alsdurf H, Vranken P, Ratard R, Morgan J, Pedeutour F see Maire G Garcia A, Carrasco R, Moreno-Alvarez P, Norton SA, Mott J: Skin disorders among con- Pellacani G see Longo C Galdeano R, Bidegain E, Rios-Martin JJ, struction workers following Hurricane Katrina Pelle MT see Lesesky EB Camacho FM:Store-and-forward telederma- and Hurricane Rita: an outbreak investiga- Pemberton MN see Thornhill MH tology in skin cancer triage: experience and tion in New Orleans, Louisiana, 1393 (No) Pen˜ aranda C see Motta A evaluation of 2009 teleconsultations, 479 (Ap); Noordijk EM see Senff NJ Pen˜ as PF see Jones-Caballero M correction, 886 (Jy) Nord KM see Pol-Rodriguez MM Pennie ML, Soon SL, Risser JB, Veledar E, Moreno-Ramı´rez D see Zaballos P Norgauer J see Ziemer M Culler SD, Chen SC: Melanoma outcomes for Morgan J see Noe R North PE see Benouni S Medicare patients: association of stage and sur- Morrone A see Carducci M Norton AB see Williams JM vival with detection by a dermatologist vs a Moscarella E see Zalaudek I Norton SA see Noe R nondermatologist, 488 (Ap) Mott J see Noe R Nousari CH see Ghersi MM; Martinez LC; Perez AL, Werchniak AE: Antemortem diag- Motta A, Lo´pez C, Acosta A, Pen˜ aranda C: Sub- Ricotti C nosis of rabies via nuchal skin biopsy (letter) ungual melanoma in situ in a Hispanic girl 663 (My) treated with functional resection and recon- O Pe´rez-Oliva N see Va´zquez-Lo´pez F struction with onychocutaneous toe free flap Peris K see Altamura D; Lozzi GP (letter) 1600 (De) Obata T see Perry B Perracchio L see Carducci M Mountain RE see Arseculeratne G Obici L see Satta R Perry B, Banyard J, McLaughlin ER, Watnick Moy RL see Marra DE Ockenfels H-M see Hammes S R, Sohn A, Brindley DN, Obata T, Cantley Mufti GJ see Creamer D Ofori A see Helfrich YR LC, Cohen C, Arbiser JL: AKT1 overexpres- Mulekar SV, Asaad M, Ghwish B, Al Issa A, Al Ogawa F see Arai E sion in endothelial cells leads to the develop- Eisa A: Koebner phenomenon in vitiligo: not O’Grady TC see Lesesky EB ment of cutaneous vascular malformations in always an indication of surgical failure (re- Oh JK see Kwon OS vivo, 504 (Ap) search letter) 801 (Je) Oka M see Nagano T Pertuiset E see Bachmeyer C Mu¨ llegger RR see Ambros-Rudolph CM Okcu A see Binder B Peter RU see Schiener R Mu¨ ller-Hermelink H-K see Yazdi AS Olerud JE: Academic workforce in dermatol- Peterson JD, Chang AJ, Chan LS: Clinical evi- Mulligan N see Callaly EL ogy, 409 (Mr) dence of an intermolecular epitope spreading Mullinax KA see Michaels BD Ollila DW see Stitzenberg KB in a patient with pemphigus foliaceus convert- Mully TW see Whalen JG Ondo AL see Shanler SD ing into bullous pemphigoid (letter) 272 (Fe) Murase JE see Davis KF Ono T see Inoue Y Peterson JD, Wirges ML: Equinology, 438 (Mr) Mussi A see Carducci M Ormerod AD see Smith CH Petitjean B see Bachmeyer C N Orringer JS see Wang F Petrella T see Grange F Ortega-Loayza AG see Rocha-Alvarez R Pfu¨ tze M see Niedermeier A Nabai L see Toossi P Ortonne J-P see Passeron T Pham L see Kartono F Nachamkin I see Treat J Osawa R see Yanagi T Piccolo D see Lozzi GP Nagano T, Tai Y, Higashida Y, Fujiwara N, Oka Osborne G see Creamer D Pichardo RO see Green WH M, Nishigori C: Docetaxel monotherapy for Otto K, Starz H, Becker JC, Schrama D: Over- Pieper B, Kirsner RS, Templin TN, Birk TJ: angiosarcoma in an elderly patient (letter) 1602 expression of matrix metalloproteinases, Injection drug use: an understudied cause of (De) chemokines, and chemokine receptors rel- venous disease, 1305 (Oc) Nakahigashi K, Tanioka M, Miyachi Y: Gener- evant for metastasis in experimental models Pillekamp H see Beissert S alized papules in a patient with acute myeloid not an indication of lymph node metastases Pizzichetta MA, Soyer HP, Massone C, Cerroni leukemia, 1583 (De) in human melanoma (research letter) 947 (Jy) L: Clinical and dermoscopic features of agmi- Nakama T see Hamada T Ozdemir F see Gencoglan G nated blue nevus (letter) 1225 (Se) Nakamura KJH see Davis MDP Ozdemir F, Karaarslan IK, Akalin T: Varia- Plano LRW see Mertz PM National Psoriasis Foundation see Pariser DM tions in the dermoscopic features of acquired Poggiali S see De Aloe G Neal JD see Kafi R acral melanocytic nevi, 1378 (No) Poh-Fitzpatrick MB see Levy AL Neale R see McBride P Pol-Rodriguez MM, Nord KM, Engler DE: Soft Nebe T see Utikal J P papules and nodules on the buttock, 1583 (De) Neelis KJ see Senff NJ Poletti E see Garcia C Nelson BR see Cohen PR Pagliuca A see Creamer D Pomeranz MK see Irizarry E Neri I see Patrizi A Palangie´ A see Farhi D Pope J see de Gannes GC Neumann CR see Niedermeier A Palmer RA see Yones SS Porter-Gill P see Eliason MJ Neumann HAM see de Haas ERM Palmieri G see Montella L Poulin Y see Tyring S Neumann MHA see Nijsten T Palou J see Carrera C; Segura S Poulos GA, Brodell RT: Perioral dermatitis asso- Newman MI see Ghersi MM Pandeya N see McBride P ciated with an inhaled corticosteroid (letter) Newman TB, Maisels MJ: Evidence insuffi- Pandya AG see Werlinger KD 1460 (No) cient to recommend melanoma surveillance Papi F see de Giorgi V Pourrabbani S see Marra DE following phototherapy for jaundice (letter) Pariser DM, Bagel J, Gelfand JM, Korman NJ, Powell FC see Callaly EL 1216 (Se) Ritchlin CT, Strober BE, Van Voorhees AS, Pressley ZM, Foster JK, Kolm P, Zhao L, Warren Newton SB, Yoon JS, Benoit BM, Wysocka M, Young M, Rittenberg S, Lebwohl MG, Horn F, Weintraub W, Sumpio BE, Chen SC: Digi- Rook AH: Apoptotic responses to all-trans reti- EJ, National Psoriasis Foundation: National tal image analysis: a reliable tool in the quan- noic acid of targretin-resistant, malignant, CD4ϩ Psoriasis Foundation clinical consensus on dis- titative evaluation of cutaneous lesions and peripheral blood T cells from patients with Se´- ease severity, 239 (Fe) beyond (research letter) 1331 (Oc) zary syndrome (research letter) 661 (My) Park SH see Kwon OS Prieto VG see Lambert TJ Nguyen VH see Bowe WP Pascual JC, Gimeńez E, Sivera F, Martinez A: Propperova I, Langley RGB: Reflectance- Niedermeier A, Eming R, Pfu¨ tze M, Neumann Atrophic macules and soft papules in a 24-year- mode confocal microscopy for the diagnosis CR, Happel C, Reich K, Hertl M: Clinical old woman, 109 (Ja) of sebaceous hyperplasia in vivo, 134 (Ja) response of severe mechanobullous epider- Pasha T see Sariya D Prost-Squarcioni C see Cazes A

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E8 Puddu P see Cianchini G Risser JB see Pennie ML Sańchez-Martıń J see Va´zquez-Lo´pez F Puig S see Cabo H; Carrera C; Scope A; Segura Ritchlin CT see Pariser DM Sandoval-Tress C see Sańchez-Castellanos ME S; Zaballos P; Zalaudek I Rittenberg S see Pariser DM Santos Mun˜ oz A see Larralde M Puso C see Du-Thanh A Rivero E see Huerta C Sarasombath P, Young PK: Unusual presenta- Rivers JK see Gelfer A; Somani N tion of cutaneous larva migrans (letter) 955 Q Rivitti EA see Rocha-Alvarez R (Jy) Robert C see Grange F Sardana K, Bhushan P, Garg VK: Effect of tacro- Quain RD, Militello G, Junkins-Hopkins J, Yan Robinson DJ see de Haas ERM limus on vitiligo in absence of UV radiation AC, Crawford GH: Erythematous atrophic Robinson JK: Next frontier of dermatologic exposure (letter) 119 (Ja) macules and papules following the lines of research, 1195 (Se) Sariya D, Ruth K, Adams-McDonnell R, Cusack Blaschko, 109 (Ja) Robinson JK, Turrisi R, Stapleton J: Efficacy of C, Xu XW, Elenitsas R, Seykora J, Pasha T, Quehenberger F see Legat FJ a partner assistance intervention designed to Zhang P, Baldassano M, Lessin SR, Wu H: Quetglas EG see Redondo P increase skin self-examination performance, Clinicopathologic correlation of cutaneous Qureshi A, Fischer MA: Topical calcineurin 37 (Ja) metastases: experience from a cancer center, inhibitors revisited (letter) 545 (Ap) Robinson MR, Augustine JJ, Korman NJ: 613 (My) Cinacalcet for the treatment of calciphylaxis, 152 R Sartori M see Rashid RM (Fe) Sasaki N see Yanagi T Sodium thiosulfate as first-line treatment for cal- Rajadhyaksha M see Benvenuto-Andrade C Satta R, Obici L, Merlini G, Cottoni F: Late- ciphylaxis (letter) 1338 (Oc) Rallis E, Karanikola E, Verros C: Successful onset familial Mediterranean fever: an atypical Robinson MR, Korman BD, Korman NJ: Com- treatment of Favre-Racouchot disease with presentation of dermatologic interest (letter) bination immunosuppressive therapies: the 0.05% tazarotene gel (letter) 810 (Je) 1080 (Au) promise and the peril, 1053 (Au) Satyaprakash A, Balkrishnan R, Camacho FT, Ramı´rez-Ba´rcena P see Sańchez-Castellanos ME Rocha-Alvarez R, Ortega-Loayza AG, Friedman Ramos-Ceballos FI see Winfield HL Jayawant SS, Fleischer AB Jr, Feldman SR: H, Campbell I, Aoki V, Rivitti EA, Dasher D, Quality of dermatologic care delivered by phy- Rao S, Tschen JA, Pearson GW, Markus R, Li N, Diaz LA, Cooperative Group on Fogo Brownell I: Comparison of treatment options sician assistants: an analysis of prescribing Selvagem Research: Endemic pemphigus vul- behavior for the combination antifungal agent for a Monsel tattoo (letter) 1452 (No) garis, 895 (Jy) Rapaport M: Rebound vasodilation from long- clotrimazole-betamethasone (research let- Rochet JM see Chaby G ter) 1591 (De) term topical corticosteroid use (letter) 268 (Fe) Ro¨cken M see Yazdi AS Rasberry RD see Levy AL Saurat J-H see Braun RP; Sorg O Rodrı´guez A see Cue´llar A Schadendorf D see Figl A; Inhoff O; Utikal J Rashid RM, Sartori M, White LE, Villa MT, Yoo Rodrı´guez LA see Huerta C Schaeverbeke T see Seneschal J SS, Alam M: Breaking strength of barbed poly- Roenigk RK see Dapprich DC Schaffer JV, Chandra P, Keegan BR, Heller P, propylene sutures: rater-blinded, controlled Rogers HD see Weiser JA Shin HT: Widespread granulomatous derma- comparison with nonbarbed sutures of vari- Rogers RS III see Bruce A titis of infancy: an early sign of Blau syndrome, ous calibers, 869 (Jy); correction, 1186 (Se) Romanelli M, Dini V, Bianchi T, Romanelli P: 386 (Mr) Ratard R see Noe R Wound assessment by 3-dimensional laser Raulin C see Hammes S; Karsai S scanning (research letter) 1333 (Oc) Schaller M see Fischer J Ravis SM, Eaglstein WH: Topical hydrocorti- Romanelli M, Dini V, Romanelli P: Hydroxy- Schanz S see Hoetzenecker W sone from prescription to over-the-counter urea-induced leg ulcers treated with a protease- Scharf J see Inhoff O sale: a past controversy: a cautionary tale, 413 modulating matrix, 1310 (Oc) Schartz N see Ackermann F (Mr) Romanelli P see Romanelli M Scheinfeld N: Glistening brown nodule, 255 (Fe) Ravis SM see Eaglstein WH Ronger-Savle S see Dalle S Scher RK see Weiser JA Rea TH see Bhandarkar SS Rook AH see Newton SB Schiener R, Brockow T, Franke A, Salzer B, Redd MA, Bray DW, Royer M: Asymptomatic Rose C see Shimanovich I Peter RU, Resch KL: Bath PUVA and saltwa- cutaneous lip plaque, 791 (Je) Rosenberg FR see Davis KF ter baths followed by UV-B phototherapy as Redondo P, Martıńez-Cuesta A, Quetglas EG, Rossiello L see Altamura D treatments for psoriasis: a randomized con- Idoate M: Active angiogenesis in an exten- Rothman I see Esler-Brauer L trolled trial, 586 (My) sive arteriovenous vascular malformation: a Royer M see Redd MA Schifferli JA see Trendelenburg M possible therapeutic target? 1043 (Au) Rubegni P see De Aloe G Schneebaum S see Mashiah J Reece AS: Hair graying in substance addiction Ruffelli M see Cianchini G Schneiderman PI see MacGregor JL (research letter) 116 (Ja) Ruggeri SY see Benouni S Schollhammer M, Misery L: Treatment of hyper- Regula CG, Miller JJ, Mauger DT, Marks JG: Ruiz C see Martıń JM hidrosis with oxybutynin (letter) 544 (Ap) Quality of care from a patient’s perspective Russell A see de Gannes GC Schrama D see Otto K (research letter) 1592 (De) Ruth K see Sariya D Schulze KE see Cohen PR Reich K see Niedermeier A Ruzicka T see Beissert S Schumacher WE see Kafi R Reiter A see Utikal J Ryan JC see Arseculeratne G Schupp P see Thoms K-M Resch KL see Schiener R Rybojad M see Asli B Scope A, Benvenuto-Andrade C, Agero A-LC, Reynolds O: Ambiguous igneous rocks (letter) Rzany B see Beissert S 118 (Ja) Halpern AC, Gonzalez S, Marghoob AA: Cor- relation of dermoscopic structures of melano- Rhodes LE see Janssens AS S Rhodes LE, de Rie MA, Leifsdottir R, Yu RC, cytic lesions to reflectance confocal microscopy, 176 (Fe) Bachmann I, Goulden V, Wong GAE, Richard Saatee S see Toossi P M-A, Anstey A, Wolf P: Five-year follow-up Sachs D see Changchien L Scope A see Benvenuto-Andrade C of a randomized, prospective trial of topical Saffold OE see Thakuria M Scope A, Busam KJ, Malvehy J, Puig S, McClain methyl aminolevulinate photodynamic therapy Sahay A see Chen T SA, Braun RP, Marghoob AA: Ex vivo der- vs surgery for nodular basal cell carcinoma, Saida T: Exclusively benign dermoscopic pat- moscopy of melanocytic tumors: time for der- 1131 (Se) tern in a patient with acral melanoma (letter) matopathologists to learn dermoscopy, 1548 Riaux A see Ackermann F 1215 (Se) (De) Richard JL see Chaby G Saida T, Koga H: Dermoscopic patterns of acral Scope A, Gill M, Benvenuto-Andrade C, Richard M-A see Rhodes LE melanocytic nevi: their variations, changes, and Halpern AC, Gonzalez S, Marghoob AA: Cor- Richardson JB see Frazier TH significance, 1423 (No) relation of dermoscopy with in vivo reflec- Richmond H, Zwerner J, Kim Y, Fiorentino D: Saihan E see Chua SL tance confocal microscopy of streaks in mela- Nephrogenic systemic fibrosis: relationship to Sales-Aussias N see Chaby G nocytic lesions, 727 (Je) gadolinium and response to photopheresis, Salisbury JR see Creamer D Segura J see Carrera C 1025 (Au); correction, 1565 (De) Salmhofer W see Binder B; Legat FJ Segura S see Carrera C Ricotti C, Kowalczyk JP, Ghersi M, Nousari CH: Salomon D see Sorg O Segura S, Puig S, Carrera C, Palou J, Malvehy Diagnostic yield of histopathologic sampling Salsench E see Zaballos P J: Dendritic cells in pigmented basal cell car- techniques in PAN-associated cutaneous ulcers Salter S see Turner E cinoma: a relevant finding by reflectance- (research letter) 1334 (Oc) Salzer B see Schiener R mode confocal microscopy, 883 (Jy) Ricotti C see Davis SC; Ghersi MM Sańchez J see Va´zquez-Lo´pez F Seidenari S see Longo C Rinaldi M see Carducci M Sańchez-Castellanos ME, Sandoval-Tress C, Sen S see Chen T Rincoń ET see Werlinger KD Ramı´rez-Ba´rcena P: Subungual exostosis, 1234 Seneschal J, Lepreux S, Milpied B, Rios-Martin JJ see Moreno-Ramirez D (Se) Schaeverbeke T, Taıëb A: Psoriasiform erup-

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E9 tions during anti–TNF-␣ treatment: psoriasis oxides and thymine dimers in human skin in Thornhill MH, Baccaglini L, Theaker E, or not? (letter) 1593 (De) vivo, 363 (Mr) Pemberton MN: Randomized, double-blind, Senet P see Chaby G; Vaneau M Souteyrand P see Grange F placebo-controlled trial of pentoxifylline for Senff NJ, Hoefnagel JJ, Neelis KJ, Vermeer MH, Soyer HP see Argenziano G; Binder B; the treatment of recurrent aphthous stomati- Noordijk EM, Willemze R, Dutch Cutaneous Pizzichetta MA; Zalaudek I tis, 463 (Ap); correction, 716 (Je) Lymphoma Group: Results of radiotherapy in Spector EB see Berk DR To-Figueras J see Herrero C 153 primary cutaneous B-cell lymphomas clas- Spinou C see Arseculeratne G Tobinick E see Buell C sified according to the WHO-EORTC classi- Stadler R see Beissert S Toossi P, Nabai L, Alaee Z, Ahmadi H, Saatee fication, 1520 (De) Stapleton J see Robinson JK S: Prevalence of skin diseases and cutaneous Sera F see Altamura D; Zalaudek I Starz H see Otto K manifestations among Iranian children: a sur- Serrano P see Herrero C Stephens FV see Chorny JA vey of 1417 children (research letter) 115 (Ja) Sestini S see de Giorgi V Sterenborg HJCM see de Haas ERM Torti DC, Jorizzo JL, McCarty MA: Oral lichen Seston EM, Ashcroft DM, Griffiths CEM: Bal- Stern RS: Methotrexate and risk for lymphoma planus: a case series with emphasis on therapy, ancing the benefits and risks of drug treat- (letter) 664 (My) 511 (Ap) ment: a stated-preference, discrete choice Stern RS see Jones-Caballero M; Nijsten T Tourlaki A see Cavicchini S experiment with patients with psoriasis, 1175 Stetson CL see Fiala KH; Michaels BD Trauner M see Ambros-Rudolph CM (Se) Sticherling M see Beissert S Treat J, James WD, Nachamkin I, Seykora JT: Seykora JT see Sariya D; Treat J Stitzenberg KB, Thomas NE, Dalton K, Brier Growth inhibition of Trichophyton species by Sfia M, Boeckler P, Lipsker D: High procalci- SE, Ollila DW, Berwick M, Mattingly D, Pseudomonas aeruginosa 61 (Ja) tonin levels in patients with severe drug reac- Millikan RC: Distance to diagnosing pro- Trendelenburg M, Schifferli JA: Rituximab in tions (research letter) 1591 (De) vider as a measure of access for patients with a patient with hyper-IgE syndrome (letter) 807 Sgambato A see Zalaudek I melanoma, 991 (Au) (Je) Shalev V see Heymann AD Storrs FJ: Acute and recurrent vesicular hand Troxel AB see Gelfand JM Shanler SD, Ondo AL: Successful treatment of dermatitis not pompholyx or dyshidrosis, 1578 Tsai KY: Systemic adjuvant therapy for patients the erythema and flushing of rosacea using a (De) with high-risk melanoma, 779 (Je) topically applied selective ␣1-adrenergic recep- Stratigos A see Janssens AS Tsai Y-T see Lu C-I tor agonist, oxymetazoline, 1369 (No) Strober BE see Pariser DM Tschen JA see Cohen PR; Rao S Sharp M see Soderberg KI Strom BL see Gelfand JM Tsuchida T see Arai E Sheehan D see Borer M Sturm RA see Eliason MJ Tuneu A see Lo´pez-Pestanã A Sheth AP see Sluzevish JC Su L-H, Chen TH-H: Association of androge- Turner E, Yoo J, Salter S, Kimball AB: Leader- Shields AL see Hillhouse J netic alopecia with smoking and its preva- ship workforce in academic dermatology (re- Shih T-S see Lu C-I lence among Asian men: a community-based search letter) 948 (Jy) Shimanovich I, Rose C, Zillikens D, Grabbe J: survey, 1401 (No) Turpen KB see Kalajian AH Erythema and blistering of the left leg, 535 (Ap) Sumpio BE see Pressley ZM Turrisi R see Hillhouse J; Robinson JK Shimizu M see Arai E Suwattee P, McClelland MC, Berg BC: Firm Twersky JM see Greenway HT Jr Shin DB see Gelfand JM papule on the lateral tongue, 1583 (De) Tyring S, Gordon KB, Poulin Y, Langley RG, Shin HT see Schaffer JV Swetter SM, Soon S, Harrington CR, Chen SC: Gottlieb AB, Dunn M, Jahreis A: Long-term Shojania K see de Gannes GC Effect of health care delivery models on mela- safety and efficacy of 50 mg of etanercept twice Siegfried EC: Long-term follow-up of a child noma thickness and stage in a university- weekly in patients with psoriasis, 719 (Je) treated with efalizumab for atopic dermatitis based referral center: an observational pilot Tzung T-Y see Yang C-Y (letter) 1077 (Au) study, 30 (Ja) U Silvers DN see Friedman PC Swick BL, Walling HW: Papular eruption in an Simon D see Hassan AS HIV-infected man, 255 (Fe) Ubriani R, Van Voorhees AS: Onset of psoriasis Simon H-U see Hassan AS Swinyer L see Eliason MJ during treatment with TNF-␣ antagonists: a Singh MN, Andrew S, Fitzgerald D: Solitary Szyfelbein K, Lin JY, Bellucci KS, Williams JM: report of 3 cases (letter) 270 (Fe) cutaneous nodule in an immunocompro- Tender erythema of the left lower extremity, Uden CJT see Heinen MM mised patient, 1583 (De) 535 (Ap) Ugurel S see Figl A; Utikal J Sivera F see Pascual JC T Ullman S see Wulf HC Skaria AM see Braun RP Ulmer A see Hoetzenecker W Sladden MJ, Clarke PJ, Wettenhall J: Infliximab- Unaeze J see Jones-Caballero M induced palmoplantar pustulosis in a patient Tai Y see Nagano T Taıëb A see Chamaillard M; Seneschal J Urena P see Ackermann F with Crohn disease (letter) 1449 (No) Usman MHU see Changchien L Sladden MJ, Harman KE: What is the chance Takashima A see Mohr RE Talhari C see Chrusciak-Talhari A Usmani N, Goodfield M: Efalizumab in the treat- of a normal pregnancy in a woman whose fetus ment of discoid lupus erythematosus, 873 (Jy) Talhari S see Chrusciak-Talhari A has been exposed to isotretinoin? 1187 (Se) Utikal J, Ugurel S, Kurzen H, Erben P, Reiter Tanioka M see Nakahigashi K Sluzevish JC, Sheth AP, Lucky AW: Persistent A, Hochhaus A, Nebe T, Hildenbrand R, Tapia B see Berk DR; Heffernan MP eosinophilia as a presenting sign of scabies in Haberkorn U, Goerdt S, Schadendorf D: Ima- Taverna JA, Lerner A, Goldberg L, Werth S, patients with disorders of keratinization (let- tinib as a treatment option for systemic non- Demierre M-F: Infliximab as a therapy for idio- ter) 670 (My) Langerhans cell histiocytoses, 736 (Je) pathic hypereosinophilic syndrome, 1110 (Se) Smith CH, Ormerod AD: British guidelines on Uzunhan Y see Asli B the use of biological therapies for psoriasis: a Templier I see Grange F note of clarification on the role of etanercept Templin TN see Pieper B V (letter) 1595 (De) Teót L see Chaby G; Vaneau M Smith DI see Heffernan MP Terrier-Lacombe M-J see Maire G Vagace JM, Gervasini G, Morais F, Benitez J, Smith J see Borer M Thakuria M, Agarwal S, Saffold OE, Jaworsky Alonso N, de Argila D, Arranz I, Bajo R: Reti- Snoek J see Berends MAM C: Fulminant cutaneous eruption in a 51-year- nal toxic reactions following photopheresis, Snyder RV see Mertz PM old man, 255 (Fe) 622 (My) Soares TF, Davis MDP: Success of Goeckerman Theaker E see Thornhill MH van Achterberg T see Heinen MM treatment in 2 patients with psoriasis not Thimm J see Karsai S van de Kerkhof PCM see Berends MAM responding to biological drugs (letter) 950 (Jy) Thirumaran RK see Figl A van der Vleuten C see Heinen MM Soderberg KI, Sharp M, Carrington PR: Brown Thomas L see Dalle S van Krieken JH see Berends MAM and black scaly patches on the lower leg, 1441 Thomas MW, Grichnik JM, Izatt JA: Three- van Oijen MGH see Berends MAM (No) dimensional images and vessel rendering using Van Voorhees AS see Pariser DM; Ubriani R Sohn A see Perry B optical coherence tomography, 1468 (No) Vaneau M see Chaby G Somani N, Martinka M, Crawford RI, Dutz JP, Thomas NE see Stitzenberg KB Vaneau M, Chaby G, Guillot B, Martel P, Senet Rivers JK: Treatment of atypical nevi with imi- Thompson JF see Kelly JW P, Teót L, Chosidow O: Consensus panel rec- quimod 5% cream, 379 (Mr) Thoms K-M, Zimmermann O, Schupp P, Thoms ommendations for chronic and acute wound Soon SL see Pennie ML; Swetter SM S, Emmert S: Nocardia otitidiscaviarum: cause dressings, 1291 (Oc) Sorenson EP see Davis KF of long-term cutaneous abscesses on the leg Varani J see Kafi R; Wang F Sorg O, Janer V, Antille C, Carraux P, Leemans of an immunocompetent man (letter) 1086 Va´zquez-Lo´pez F, Coto-Segura P, Fueyo- E, Masgrau E, Saurat J-H, Salomon D: Effect (Au) Casado A, Pe´rez-Oliva N: Dermoscopy of port- of intense pulsed-light exposure on lipid per- Thoms S see Thoms K-M wine stains, 962 (Jy)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E10 Va´zquez-Lo´pez F, Go´mez-Dıéz S, Sańchez J, Weitz D, Bystryn J-C: Frequency of shifts over festation of Erdheim-Chester disease (letter) Pe´rez-Oliva N: Dermoscopy of active lichen time in the profile of antidesmoglein antibod- 952 (Jy) planus, 1092 (Au) ies in pemphigus vulgaris (research letter) 1073 Yanagi T, Matsumura T, Kamekura R, Sasaki Va´zquez-Lo´pez F, Zaballos P, Fueyo-Casado A, (Au) N, Hashino S: Relapsing polychondritis and Sańchez-Martıń J: Dermoscopy subpattern of Weitzul S see Asgari MM malignant lymphoma: is polychondritis para- plaque-type psoriasis: red globular rings, 1612 Wells MJ see Fiala KH; Michaels BD neoplastic? 89 (Ja) (De) Wenner R, Askari SK, Cham PMH, Kedrowski Yang C-Y, Lin T-L, Tzung T-Y, Cheng L-C, Veledar E see Pennie ML DA, Liu A, Warshaw EM: Duct tape for the Wang J-T, Jee S-H: Direct identification of der- Venturo I see Carducci M treatment of common warts in adults: a double- matophyte DNA from clinical specimens by Vergier B see Grange F blind randomized controlled trial, 309 (Mr) a nested polymerase chain reaction assay (re- Verma SB see Wollina U Werchniak AE see Perez AL search letter) 799 (Je) Vermeer MH see Senff NJ Werfel T see Beissert S Yawalkar N see Hassan AS Verros C see Rallis E Werlinger KD, Guevara IL, Gonza´lez CM, Yazdi AS, Metzler G, Weyrauch S, Berneburg Vetter R see Ziemer M Rincoń ET, Caetano R, Haley RW, Pandya M, Bitzer M, Mu¨ ller-Hermelink H-K, Ro¨cken Vicente A see Martinez-De Pablo MI AG: Prevalence of self-diagnosed melasma M: Lymphomatoid granulomatosis induced by Vidal D, Matıás-Guiu X, Alomar A: Fifty-five among premenopausal Latino women in Dal- imatinib treatment (letter) 1222 (Se) basal cell carcinomas treated with topical imi- las and Fort Worth, Tex (research letter) 424 Yones SS, Palmer RA, Garibaldinos TM, Hawk quimod: outcome at 5-year follow-up (re- (Mr) JLM:Randomized double-blind trial of treat- search letter) 266 (Fe) Werth S see Taverna JA ment of vitiligo: efficacy of psoralen–UV-A Vignon-Pennamen M-D see Bachmeyer C Wettenhall J see Sladden MJ therapy vs narrowband–UV-B therapy, 578 Villa MT see Rashid RM Weyrauch S see Yazdi AS (My); correction, 906 (Jy) Villaloń G see Martin JM Whalen JG, Mully TW, English JC III: Spon- Yoo J see Turner E Viola G see Carducci M taneous Citrobacter freundii infection in an Yoo SS see Rashid RM immunocompetent patient (letter) 124 (Ja) Virgili A see Zampino MR Yoon JS see Newton SB White B see Borer M Voorhees JJ see Helfrich YR; Kafi R; Wang F Yosipovitch G see Green WH White LE see Rashid R; Rashid RM Vranken P see Noe R Young M see Pariser DM Vu J, Bangert S, Hebert AA: Skin cancer pre- Whitmore SE: Methotrexate and risk for lymphoma (letter) 663 (My) Young PK see Sarasombath P senting as a nonhealing wound: the associa- Yu L see Helfrich YR tion of polio and skin cancer (letter) 1338 (Oc) Whittaker SJ see LeBon B Wierzbicka E see Guillet MH Yu RC see Rhodes LE W Wiesend CL see Ziemer M Wilkin N see Levy AL Z Willemze R see Senff NJ Wackernagel A see Legat FJ Zaballos P see Va´zquez-Lo´pez F Wahie S, Lawrence CM: Wound complica- Williams HC see Langan SM Zaballos P, Daufı´ C, Puig S, Argenziano G, tions following diagnostic skin biopsies in der- Williams JM see Szyfelbein K Moreno-Ramı´rez D, Cabo H, Marghoob AA, matology inpatients, 1267 (Oc) Williams JM, Norton AB, Kovach RF: Petechial Llambrich A´ , Zalaudek I, Malvehy J: Der- Walensky RP see Losina E and red-brown papular lesions in a 2-year- moscopy of solitary angiokeratomas: a mor- Wallach D see Farhi D old girl, 1067 (Au) phological study, 318 (Mr) Walling HW see Swick BL Williams ML see Chamlin SL Zaballos P, Salsench E, Puig S, Malvehy J: Wang F, Garza LA, Kang S, Varani J, Orringer Williamson D see Chakrabarti S Dermoscopy of pyogenic granulomas, 824 (Je) JS, Fisher GJ, Voorhees JJ: In vivo stimula- Winfield HL, Kirkland F, Ramos-Ceballos FI, Zagnoli A see Chaby G tion of de novo collagen production caused by Horn TD: Osteopontin expression in Spitz nevi cross-linked hyaluronic acid dermal filler injec- (research letter) 1076 (Au) Zaim MT see Evers M tions in photodamaged human skin, 155 (Fe) Winhoven SM see Janssens AS Zalaudek I: Dermoscopy not yet shown to increase sensitivity of melanoma diagnosis in Wang J-T see Yang C-Y Wirges ML see Peterson JD real practice (letter) 666 (My) Wang SQ, Goldberg LH: Pulsed-dye laser treat- Wohl Y see Mashiah J ment of nonhealing chronic ulcer with hyper- Wolf LL see Losina E Zalaudek I, Argenziano G, Mordente I, granulation tissue, 700 (Je) Wolf P see Legat FJ; Rhodes LE Moscarella E, Corona R, Sera F, Blum A, Cabo Wang X see Gelfand JM Wolfe R see Kelly JW H, Di Stefani A, Hofmann-Wellenhof R, Johr Wanitphakdeedecha R see Manuskiatti W Wollina U, Verma SB: Acute digital gangrene R, Langford D, Malvehy J, Kolm I, Sgambato A, Puig S, Soyer HP, Kerl H: Nevus type in Warren F see Pressley ZM in a newborn (letter) 121 (Ja) dermoscopy is related to skin type in white Warshaw EM see Watsky KL; Wenner R Wong AKC see Arseculeratne G persons, 351 (Mr) Watnick R see Perry B Wong GAE see Rhodes LE Zalaudek I see Altamura D; Argenziano G; Watsky KL, Warshaw EM: Allergic contact der- Wood GS: Call for papers for On the Horizon 253 Giacomel J; Zaballos P matitis: another adverse effect of over-the- (Fe) Zalaudek I, Ferrara G, Argenziano G: Dermos- counter topical hydrocortisone (letter) 1217 Woodley DT: Role of IgE anti–basement mem- copy insights into nevogenesis: “abtropfung” (Se) brane zone autoantibodies in bullous vs “hochsteigerung” 284 (Fe) Webber KA, Kos L, Holland KE, Margolis DA, pemphigoid, 249 (Fe) Drolet BA: Intertriginous eruption associ- Wu H see Sariya D Zalesky P see Davis SC ated with chemotherapy in pediatric patients, Wu JJ see Davis KF; Kappel ST Zampino MR, Borghi A, Caselli E, Galvan M, 67 (Ja) Wulf HC, Ullman S: Discoid and subacute lupus Corazza M, Cassai E, Virgili A: Virologic safety Webster GF: Skin microecology: the old and the erythematosus treated with 0.5% r-salbuta- of polyvinyl chloride film in dermoscopic new, 105 (Ja) mol cream (research letter) 1589 (De) analysis of mucosal areas (research letter) 945 Wysocka M see Newton SB Wechsler J see Grange F (Jy) Zhang P see Sariya D Weinfeld PK: Successful treatment of notalgia X paresthetica with botulinum toxin type A, 980 Zhao L see Pressley ZM Ziemer M, Wiesend CL, Vetter R, Weiss J, (Au) Xu LY, Bandow GD, Heffernan MP: Crusted vio- Blaschke S, Norgauer J, Mockenhaupt M: Weinstock MA see Barzilai DA; Criscione VD; laceous plaques on an immunocompromised Cutaneous adverse reactions to valdecoxib dis- Huang KP host, 417 (Mr) tinct from Stevens-Johnson syndrome and Weintraub W see Pressley ZM Xu XW see Sariya D Weiser JA, Rogers HD, Scher RK, Grossman toxic epidermal necrolysis, 711 (Je) ME: Signs of a “broken heart”: suspected Y Zillikens D see Beissert S; Shimanovich I Muehrcke lines after cardiac surgery (letter) Zimmermann O see Thoms K-M 815 (Je) Yamaguchi Y see Hanafusa T Zirwas MJ: Role of filaggrin mutations as an etio- Weiss E, Amini S: Novel treatment for knuckle Yamane N see Yanagi T logic factor in atopic dermatitis, 1437 (No) pads with intralesional fluorouracil (letter) Yan AC see Quain RD Ziv M see Ishay A 1458 (No) Yanagi T, Kato N, Yamane N, Osawa R, Hiraga Zubizarreta J see Lo´pez-Pestanã A Weiss J see Ziemer M H: Verruca plana–like papules as a new mani- Zwerner J see Richmond H

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E11 SUBJECT INDEX TO VOLUME 143

The following index is an alphabetical list of significant subjects presented in this volume.

A Teens and tans: implementing behavioral change Hair graying in substance addiction (research let- [Haas] 1058 (Au) ter) [Reece] 116 (Ja) Abnormalities Adrenal Cortex Hormones Melanoma outcomes for Medicare patients: asso- What is the chance of a normal pregnancy in a Allergic contact dermatitis: another adverse effect ciation of stage and survival with detection by woman whose fetus has been exposed to of over-the-counter topical hydrocortisone (let- a dermatologist vs a nondermatologist [Pennie] isotretinoin? [Sladden] 1187 (Se) ter) [Watsky] 1217 (Se) 488 (Ap) Abortion, Spontaneous Comparison of oral methylprednisolone plus aza- Primary cutaneous diffuse large B-cell lym- What is the chance of a normal pregnancy in a thioprine or mycophenolate mofetil for the phoma, leg type: clinicopathologic features and woman whose fetus has been exposed to treatment of bullous pemphigoid [Beissert] prognostic analysis in 60 cases [Grange] 1144 isotretinoin? [Sladden] 1187 (Se) 1536 (De) (Se) Abscess Hypereosinophilic syndrome with peripheral cir- Visual screening for malignant melanoma: a cost- Nocardia otitidiscaviarum: cause of long-term culatory insufficiency and cutaneous micro- effectiveness analysis [Losina] 21 (Ja) cutaneous abscesses on the leg of an immuno- thrombi (letter) [Hamada] 812 (Je) akt-Oncogene Protein see Oncogene Protein v-akt competent man (letter) [Thoms] 1086 (Au) New and old therapeutics for oral ulcerations Albuterol Acanthoma [Bruce] 519 (Ap) Discoid and subacute lupus erythematosus Glistening brown nodule [Scheinfeld] 255 (Fe) Perioral dermatitis associated with an inhaled treated with 0.5% r-salbutamol cream (re- Acanthosis Nigricans corticosteroid (letter) [Poulos] 1460 (No) search letter) [Wulf] 1589 (De) Familial acanthosis nigricans due to K650T Pneumocystis carinii pneumonia in infant treated Alefacept FGFR3 mutation [Berk] 1153 (Se) with oral steroids for hemangioma (letter) Narrowband UV-B phototherapy, alefacept, and [Maronn] 1224 (Se) Acitretin clearance of psoriasis [Legat] 1016 (Au) Rebound vasodilation from long-term topical Clinical improvement of pityriasis rubra pilaris Alginates corticosteroid use (letter) [Rapaport] 268 (Fe) with combination etanercept and acitretin Consensus panel recommendations for chronic Suppression of the HPA axis in pediatric patients therapy (letter) [Davis] 1597 (De) and acute wound dressings [Vaneau] 1291 with atopic dermatitis (letter) [Ishay] 1449 (No) (Oc) Acne Vulgaris Vitiligo: to treat or not to treat [Lim] 643 (My) Atrial tachycardia associated with isotretinoin Dressings for acute and chronic wounds: a sys- Adrenergic Agonists use (letter) [Dresden] 1084 (Au) tematic review [Chaby] 1297 (Oc) Successful treatment of the erythema and flush- Childhood flexural comedones: a new entity All-trans Retinoic Acid ing of rosacea using a topically applied selec- [Larralde] 909 (Jy) Apoptotic responses to all-trans retinoic acid of tive ␣1-adrenergic receptor agonist, oxy- ϩ Focal acne during topical tacrolimus therapy for targretin-resistant, malignant, CD4 periph- metazoline [Shanler] 1369 (No) vitiligo (letter) [Bakos] 1223 (Se) eral blood T cells from patients with Se´zary Adrenergic ␤-Agonists What is the chance of a normal pregnancy in a syndrome (research letter) [Newton] 661 (My) Association between the use of ␤-adrenergic woman whose fetus has been exposed to Leukemia cutis: a presenting sign in acute pro- receptor agents and the development of venous isotretinoin? [Sladden] 1187 (Se) myelocytic leukemia (letter) [Markowski] leg ulcers [Margolis] 1275 (Oc) Acquired Hyperostosis Syndrome 1220 (Se) Adrenergic ␤-Antagonists Overlapping neutrophilic dermatosis in a patient Alopecia Association between the use of ␤-adrenergic with SAPHO syndrome (letter) [Bachmeyer] Association of androgenetic alopecia with smok- receptor agents and the development of venous 275 (Fe) ing and its prevalence among Asian men: a leg ulcers [Margolis] 1275 (Oc) community-based survey [Su] 1401 (No) Actinic Keratosis see Keratosis, Actinic Adrenergic ␤-Receptors see Receptors, Activated Charcoal see Charcoal ␤ Staged hair transplantation in cicatricial alope- Adrenergic, cia after carbon dioxide laser–assisted scar tis- Adalimumab Adverse Reaction sue remodeling [Kwon] 457 (Ap) Adalimumab treatment for pyoderma gangreno- Delayed wound healing following treatment with Alopecia, Androgenetic see Alopecia sum [Heffernan] 306 (Mr) low-dose interferon alfa-2b for cutaneous mela- Alternaria What are the risks of serious infections and noma (letter) [Ammoury] 1339 (Oc) Solitary cutaneous nodule in an immunocom- malignancies for patients treated with anti- Pupil damage after periorbital laser treatment of promised patient [Singh] 1583 (De) tumor necrosis factor antibodies? [Corona] a port-wine stain [Hammes] 392 (Mr) 405 (Mr) Wound complications following diagnostic skin Ambulatory Care Adenocarcinoma biopsies in dermatology inpatients [Wahie] Quality of care from a patient’s perspective (re- Clinicopathologic correlation of cutaneous 1267 (Oc) search letter) [Regula] 1592 (De) metastases: experience from a cancer center Adynamic Bone Syndrome see Renal 5-Aminolevulinate Synthetase [Sariya] 613 (My) Osteodystrophy Successful treatment of pityriasis versicolor with Adjuvants, Pharmaceutic Africa 5-aminolevulinic acid photodynamic therapy Systemic adjuvant therapy for patients with high- Subcutaneous nodule and diffuse lymphade- (letter) [Kim] 1218 (Se) risk melanoma [Tsai] 779 (Je) nopathy in a 6-month-old boy from Africa Aminolevulinic Acid Administration, Inhalation [Friedman] 1323 (Oc) Response of Bowen disease to ALA-PDT using Perioral dermatitis associated with an inhaled Age Factors a single and a 2-fold illumination scheme (re- corticosteroid (letter) [Poulos] 1460 (No) Age- and site-specific variation in the dermoscopic search letter) [de Haas] 264 (Fe) Administration, Topical patterns of congenital melanocytic nevi: an aid Aminolevulinic Acid Synthetase see 5- National Psoriasis Foundation clinical consen- to accurate classification and assessment of me- Aminolevulinate Synthetase sus on disease severity [Pariser] 239 (Fe) lanocytic nevi [Changchien] 1007 (Au) Amyloidosis Adnexal Tumors see Neoplasms, Adnexal and Age of Onset Papules and plaques on the nose [Evers] 535 Skin Appendage Late-onset familial Mediterranean fever: an atypi- (Ap) Adolescent cal presentation of dermatologic interest (let- Pruritic patches on the back and papules on the Childhood flexural comedones: a new entity ter) [Satta] 1080 (Au) legs [Garg] 255 (Fe) [Larralde] 909 (Jy) Aged, 80 and over Analytic Sample Preparation Methods Indoor UV tanning youth access laws: update Docetaxel monotherapy for angiosarcoma in an Diagnostic yield of histopathologic sampling 2007 [McLaughlin] 529 (Ap) elderly patient (letter) [Nagano] 1602 (De) techniques in PAN-associated cutaneous ulcers Recurrent calcified cutaneous nodule of the peri- Aging (research letter) [Ricotti] 1334 (Oc) anal region [Patrizi] 1441 (No) Clinical severity of psoriasis in last 20 years of Anetoderma see Atrophy, Macular Skin cancer awareness and sun protection behav- PUVA study [Nijsten] 1113 (Se) Angiogenesis Inhibitors iors in white Hispanic and white non- Efficacy of a partner assistance intervention Angiogenesis in cutaneous lesions of leprosy: Hispanic high school students in Miami, designed to increase skin self-examination per- implications for treatment [Bhandarkar] 1527 Florida [Ma] 983 (Au) formance [Robinson] 37 (Ja) (De)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E12 Angiogenesis, Pathologic see Neovascularization, Antineoplastic Agents Arthrodermataceae Pathologic Era of targeted therapies: increasing role for novel Direct identification of dermatophyte DNA from Angiokeratoma oncologic drugs in dermatology [Montella] 788 clinical specimens by a nested polymerase Dermoscopy of solitary angiokeratomas: a mor- (Je) chain reaction assay (research letter) [Yang] phological study [Zaballos] 318 (Mr) Antiphospholipid Antibodies see Antibodies, 799 (Je) Angiolymphoid Hyperplasia with Eosinophilia Antiphospholipid Asia Intralesional bleomycin for angiolymphoid Antiphospholipid Syndrome Association of androgenetic alopecia with smok- hyperplasia [Akdeniz] 841 (Jy) Acute digital gangrene in a newborn (letter) ing and its prevalence among Asian men: a Angiosarcoma see Hemangiosarcoma [Wollina] 121 (Ja) community-based survey [Su] 1401 (No) Animals, Domestic Antiretroviral Therapy, Highly Active Asian Continental Ancestry Group Role of furry pets in eczema: a systematic review Multiple subcutaneous lipomas induced by Effect of cold air cooling on the incidence of [Langan] 1570 (De) HAART in the absence of protease inhibitors postinflammatory hyperpigmentation after Ankle (letter) [Balestreire] 1596 (De) Q-switched Nd:YAG laser treatment of Hydroxyurea-induced leg ulcers treated with a Anus Diseases acquired bilateral nevus of Ota–like macules protease-modulating matrix [Romanelli] 1310 Recurrent calcified cutaneous nodule of the peri- [Manuskiatti] 1139 (Se) (Oc) anal region [Patrizi] 1441 (No) Aspergillus fumigatus Melanoma of the foot and ankle: a case series Aphthae see Stomatitis, Aphthous Tender erythema of the left lower extremity of an underrecognized entity (research let- Apoptosis [Szyfelbein] 535 (Ap) ter) [Greenway] 543 (Ap) Apoptotic responses to all-trans retinoic acid of Aspirin ϩ Anthracyclines targretin-resistant, malignant, CD4 periph- Resolution of chronic pain and fingertip ulcer- Primary cutaneous diffuse large B-cell lymphoma, eral blood T cells from patients with Se´zary ation due to hand-arm vibration syndrome fol- leg type: clinicopathologic features and prog- syndrome (research letter) [Newton] 661 (My) lowing combination pharmacotherapy (let- nostic analysis in 60 cases [Grange] 1144 (Se) ARCHIVES A CENTURY AGO (Bernhardt M, ed) ter) [Buell] 1343 (Oc) Anti-Asthmatic Agents Book review, 1366 (No) Atrophy, Macular Perioral dermatitis associated with an inhaled Book reviews. Conference on the moral phi- Atrophic macules and soft papules in a 24-year- corticosteroid (letter) [Poulos] 1460 (No) losophy of medicine, 699 (Je) old woman [Pascual] 109 (Ja) Anti-Bacterial Agents Cancer, the prevention of, regarded as a prac- Erythematous atrophic macules and papules fol- Skin microecology: the old and the new tical question ripe for solution, 302 (Mr) lowing the lines of Blaschko [Quain] 109 (Ja) [Webster] 105 (Ja) Commemorative medals, 1247 (Oc) Atypical Fibroxanthoma Use of antibiotic ointment after clean cutane- Correspondence: a remarkable photo-physical Burgeoning nodule on the scalp of a 65-year- ous surgery [Bigby] 1180 (Se) discovery, 571 (My) old man [Farhi] 653 (My) Antibiotic Resistance see Drug Resistance Discussion on radiotherapy by the Chicago Der- Autoantibodies matological Society, 978 (Au) Antibiotics see Anti-Bacterial Agents Role of IgE anti–basement membrane zone auto- Hydroa pruriginosum, 838 (Jy) Antibodies antibodies in bullous pemphigoid [Woodley] Multiple cancer of the skin and keratosis fol- Frequency of shifts over time in the profile of 249 (Fe) antidesmoglein antibodies in pemphigus vul- lowing the long-continued use of arsenic: mul- Autoimmune Diseases garis (research letter) [Weitz] 1073 (Au) tiple ulcerations of the skin after the pro- Clinical evidence of an intermolecular epitope Herpes gestationis in a mother and newborn: tracted use of the same drug, 16 (Ja) spreading in a patient with pemphigus folia- immunoclinical perspectives based on a weekly Opsonic method in skin diseases, 1484 (De) ceus converting into bullous pemphigoid (let- follow-up of the enzyme-linked immuno- Significance of indican in the urine of those ter) [Peterson] 272 (Fe) sorbent assay index of a bullous pemphigoid afflicted with certain diseases of the skin, 454 Pilot trial of rituximab in the treatment of patients antigen noncollagenous domain [Aoyama] (Ap) with dermatomyositis [Chung] 763 (Je) 1168 (Se) Some further observations on the treatment of What are the risks of serious infections and pigmented hairy naevi with liquid air; three Azathioprine malignancies for patients treated with anti- additional case reports, 1108 (Se) Comparison of oral methylprednisolone plus aza- tumor necrosis factor antibodies? [Corona] Superficial multiple epithelioma, 150 (Fe) thioprine or mycophenolate mofetil for the 405 (Mr) ARCHIVES OF DERMATOLOGY treatment of bullous pemphigoid [Beissert] Antibodies, Antinuclear Archives of Dermatology Web site: adding new 1536 (De) Psoriasis and pustular dermatitis triggered by dimensions to the literature [Bhatia] 1320 (Oc) Erythema nodosum–like eruption as a manifes- TNF-␣ inhibitors in patients with rheumato- Call for papers for On the Horizon [Wood] 253 tation of azathioprine hypersensitivity in logic conditions [de Gannes] 223 (Fe) (Fe) patients with inflammatory bowel disease [de Fonclare] 744 (Je) Antibodies, Antiphospholipid Cutting edge [Hruza] 1062 (Au) Atrophic macules and soft papules in a 24-year- Evidence-based dermatology section wel- old woman [Pascual] 109 (Ja) comes a new feature: critically appraised top- B Paraneoplastic Raynaud phenomenon with digi- ics [Bigby] 1185 (Se) Bacillus Calmette Guerin Vaccine see BCG tal necrosis associated with hyperhomocys- Monthly final page: skINsight [Grichnik] 1433 Vaccine teinemia and antiphospholipid antibodies (let- (No) ter) [Carducci] 1342 (Oc) The Off-Center Fold [Ming] 935 (Jy) Back Keratotic papules on the right side of the neck Antibodies, Monoclonal Wound healing [Kirsner] 1318 (Oc) and back [Bowe] 535 (Ap) Clinical response of severe mechanobullous epi- Arm dermolysis bullosa acquisita to combined treat- Nodular lesions on the arm [Chrusciak-Talhari] Back Pain ment with immunoadsorption and ritux- 1323 (Oc) Successful treatment of notalgia paresthetica with imab (anti-CD20 monoclonal antibodies) Arteriovenous Malformations botulinum toxin type A [Weinfeld] 980 (Au) [Niedermeier] 192 (Fe) Active angiogenesis in an extensive arteriove- Bacteria Antifungal Agents nous vascular malformation: a possible thera- Skin microecology: the old and the new Growth inhibition of Trichophyton species by peutic target? [Redondo] 1043 (Au) [Webster] 105 (Ja) Pseudomonas aeruginosa [Treat] 61 (Ja) Arteritis, Temporal see Temporal Arteritis Bacterial Infections Quality of dermatologic care delivered by phy- Arthritis, Psoriatic Skin disorders among construction workers fol- sician assistants: an analysis of prescribing National Psoriasis Foundation clinical consen- lowing Hurricane Katrina and Hurricane Rita: behavior for the combination antifungal agent sus on disease severity [Pariser] 239 (Fe) an outbreak investigation in New Orleans, clotrimazole-betamethasone (research let- Arthritis, Rheumatoid Louisiana [Noe] 1393 (No) ter) [Satyaprakash] 1591 (De) Intractable wounds from a herpes simplex infec- Spontaneous Citrobacter freundii infection in an Antigens, CD20 tion in an immunosuppressed patient with immunocompetent patient (letter) [Whalen] Clinical response of severe mechanobullous epi- rheumatoid arthritis (letter) [Hanafusa] 1340 124 (Ja) dermolysis bullosa acquisita to combined treat- (Oc) Balneology ment with immunoadsorption and rituximab Psoriasis and pustular dermatitis triggered by Balneophototherapy for psoriasis using saltwa- (anti-CD20 monoclonal antibodies) TNF-␣ inhibitors in patients with rheumato- ter baths and UV-B irradiation, revisited [Niedermeier] 192 (Fe) logic conditions [de Gannes] 223 (Fe) [Gambichler] 647 (My) Antigens, CD34 What are the risks of serious infections and Bath PUVA and saltwater baths followed by UV-B Clinical, histologic, and molecular study of 9 malignancies for patients treated with anti- phototherapy as treatments for psoriasis: a ran- cases of congenital dermatofibrosarcoma pro- tumor necrosis factor antibodies? [Corona] domized controlled trial [Schiener] 586 (My) tuberans [Maire] 203 (Fe) 405 (Mr) Balneotherapy see Balneology

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E13 Bandages Biopsy, Sentinel Lymph Node see Sentinel Buttocks Consensuspanelrecommendationsforchronicand Lymph Node Biopsy Intractable wounds from a herpes simplex infec- acute wound dressings [Vaneau] 1291 (Oc) Bites and Stings tion in an immunosuppressed patient with rheu- Dressings for acute and chronic wounds: a sys- Functional dysregulation of dendritic cells in matoid arthritis (letter) [Hanafusa] 1340 (Oc) tematic review [Chaby] 1297 (Oc) patients with papular urticaria caused by flea- Recurrent calcified cutaneous nodule of the peri- Negative pressure dressing in the management bite [Cue´llar] 1415 (No) anal region [Patrizi] 1441 (No) of pyoderma gangrenosum ulcer [Ghersi] 1249 Blastomyces Soft papules and nodules on the buttock (Oc) Beefy red plaque in the popliteal fossa [Grekin] [Pol-Rodriguez] 1583 (De) Wound healing [Kirsner] 1318 (Oc) 1323 (Oc) Bandages, Hydrocolloid Blastomycosis C Consensus panel recommendations for chronic Verrucous nodules on the toes of a renal trans- and acute wound dressings [Vaneau] 1291 plant recipient [Levy] 653 (My) Calcineurin (Oc) Blau Syndrome Vitiligo: to treat or not to treat [Lim] 643 (My) Dressings for acute and chronic wounds: a sys- Widespread granulomatous dermatitis of infancy: Calcineurin Inhibitors tematic review [Chaby] 1297 (Oc) an early sign of Blau syndrome [Schaffer] 386 National Eczema Association and topical calci- Basal Cell Cancer see Neoplasms, Basal Cell (Mr) neurin inhibitor labeling (letter) [Cooper] 546 Basal Cell Nevus Syndrome Bleomycin (Ap) Palmar basal cell carcinoma in a patient with Bleomycin-induced “flagellate dermatitis” (let- Topical calcineurin inhibitors revisited (letter) Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) ter) [Arseculeratne] 1461 (No) [Qureshi] 545 (Ap) Basement Membrane Intralesional bleomycin for angiolymphoid Calcinosis Role of IgE anti–basement membrane zone auto- hyperplasia [Akdeniz] 841 (Jy) Recurrent calcified cutaneous nodule of the peri- antibodies in bullous pemphigoid [Woodley] Blister anal region [Patrizi] 1441 (No) 249 (Fe) Erythema and blistering of the left leg Calciphylaxis Baths [Shimanovich] 535 (Ap) Calciphylaxis responding to sodium thiosul- Balneophototherapy for psoriasis using salt- Blood fate therapy (letter) [Baker] 269 (Fe) water baths and UV-B irradiation, revisited Importance of serum bile acid level analysis and Cinacalcet for the treatment of calciphylaxis [Gambichler] 647 (My) treatment with ursodeoxycholic acid in intra- [Robinson] 152 (Fe) Bath PUVA and saltwater baths followed by UV-B hepatic cholestasis of pregnancy: a case series Rapidly enlarging necrotic ulcer on the right calf phototherapy as treatments for psoriasis: a ran- from Central Europe [Ambros-Rudolph] 757 [Chakrabarti] 791 (Je) domized controlled trial [Schiener] 586 (My) (Je) Sodium thiosulfate as first-line treatment for cal- BCG Vaccine Treatment of oral erosive lichen planus with 1% ciphylaxis (letter) [Ackermann] 1336 (re- Subcutaneous nodule and diffuse lymph- pimecrolimus cream: a double-blind, random- ply) [Robinson] 1338 (Oc) adenopathy in a 6-month-old boy from Africa ized, prospective trial with measurement of Calcipotriene [Friedman] 1323 (Oc) pimecrolimus levels in the blood [Passeron] Vitiligo: to treat or not to treat [Lim] 643 (My) Behavior 472 (Ap) Calmette-Guerin Bacillus see Mycobacterium Patterns of indoor tanning use: implications for Blood Vessels bovis clinical interventions [Hillhouse] 1530 (De) AKT1 overexpression in endothelial cells leads Candida krusei Benefit-Risk Assessment see Risk Assessment to the development of cutaneous vascular mal- Generalized papules in a patient with acute Betamethasone formations in vivo [Perry] 504 (Ap) myeloid leukemia [Nakahigashi] 1583 (De) Quality of dermatologic care delivered by phy- Dermoscopic vascular patterns in nodular Cannabis sician assistants: an analysis of prescribing “pure” amelanotic melanoma [Cavicchini] Acute generalized exanthematous pustulosis behavior for the combination antifungal agent 556 (Ap) caused by illicit street drugs? (letter) [Lu] 430 clotrimazole-betamethasone (research let- Blue Nevus see Nevus, Blue (Mr) ter) [Satyaprakash] 1591 (De) Body Image Capillaries Betapapillomavirus Teens and tans: implementing behavioral change Phenylephrine-induced microvascular occlu- Sun-related factors, Betapapillomavirus, and [Haas] 1058 (Au) sion syndrome in a patient with a heterozy- actinic keratoses: a prospective study Trimethylaminuria (fish-odor syndrome): a case gous factor V Leiden mutation [Kalajian] 1314 [McBride] 862 (Jy) report [Arseculeratne] 81 (Ja) (Oc) Bexarotene Body Surface Area Carcinogens Measuring HRQOL in patients with cutaneous National Psoriasis Foundation clinical consen- Teens and tans: implementing behavioral change T-cell lymphoma undergoing therapy with oral sus on disease severity [Pariser] 239 (Fe) [Haas] 1058 (Au) bexarotene and extracorporeal photo- Bone Syndrome, Adynamic see Renal Carcinoma pheresis (research letter) [Demierre] 659 (My) Osteodystrophy Clinicopathologic correlation of cutaneous Bile Acids and Salts Bosentan metastases: experience from a cancer center Importance of serum bile acid level analysis and Bosentan as a rescue therapy in scleroderma [Sariya] 613 (My) treatment with ursodeoxycholic acid in intra- refractory digital ulcers (letter) [Chamaillard] Carcinoma, Adenoid Cystic hepatic cholestasis of pregnancy: a case series 125 (Ja) Novel missense mutation in the CYLD gene in from Central Europe [Ambros-Rudolph] 757 Botulinum Toxin Type A a Spanish family with multiple familial tricho- (Je) Randomized double-blind study of the effect of epithelioma (research letter) [Espan˜ a] 1209 Biofilms Botox and Dysport/Reloxin on forehead (Se) Skin microecology: the old and the new wrinkles and electromyographic activity (re- Carcinoma, Basal Cell [Webster] 105 (Ja) search letter) [Karsai] 1447 (No) Dendritic cells in pigmented basal cell carci- Biological Markers Successful treatment of notalgia paresthetica noma: a relevant finding by reflectance- Necrolytic migratory erythema: the outermost with botulinum toxin type A [Weinfeld] mode confocal microscopy [Segura] 883 (Jy) marker for glucagonoma syndrome (letter) 980 (Au) Dermoscopy in vulvar basal cell carcinoma (let- [Gantcheva] 1221 (Se) Bowen Disease ter) [de Giorgi] 426 (Mr) Biopsy Response of Bowen disease to ALA-PDT using Differences between polarized light dermos- Antemortem diagnosis of rabies via nuchal skin a single and a 2-fold illumination scheme (re- copy and immersion contact dermoscopy for biopsy (letter) [Perez] 663 (My) search letter) [de Haas] 264 (Fe) the evaluation of skin lesions [Benvenuto- Identification of incipient tumors by means of Brazil Andrade] 329 (Mr) sequential dermoscopy imaging: a new way to Endemic pemphigus vulgaris [Rocha-Alvarez] Fifty-five basal cell carcinomas treated with topi- inflate the “epidemic” of melanoma? (letter) 895 (Jy) cal imiquimod: outcome at 5-year follow-up [Carli] (reply) [Kittler] 805 (Je) Breast (research letter) [Vidal] 266 (Fe) Reliability of the Roenigk classification of liver Dissemination of a localized cutaneous infec- Five-year follow-up of a randomized, prospec- damage after methotrexate treatment for pso- tion with Mycobacterium chelonae under tive trial of topical methyl aminolevulinate riasis: a clinicopathologic study of 160 liver immunosuppressive treatment (letter) photodynamic therapy vs surgery for nodu- biopsy specimens [Berends] 1515 (De) [Hoetzenecker] 951 (Jy) lar basal cell carcinoma [Rhodes] 1131 (Se) Scalp biopsy specimens: transverse vs vertical Bullous Skin Diseases see Skin Diseases, Palmar basal cell carcinoma in a patient with sections (research letter) [Garcia] 268 (Fe) Vesiculobullous Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) Wound complications following diagnostic skin Burns Predictors of skin-related quality of life after treat- biopsies in dermatology inpatients [Wahie] Topical oxygen emulsion: a novel wound therapy ment of cutaneous basal cell carcinoma and 1267 (Oc) [Davis] 1252 (Oc) squamous cell carcinoma [Chen] 1386 (No)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E14 Reflectance-mode confocal microscopy for the Childhood flexural comedones: a new entity Cocaine-Related Disorders diagnosis of sebaceous hyperplasia in vivo [Larralde] 909 (Jy) Ulceronecrotic nasoparanasal lesion [Martı´n] 653 [Propperova] 134 (Ja) Clinical, histologic, and molecular study of 9 (My) Carcinoma, Basal Cell, Pigmented see Carcinoma, cases of congenital dermatofibrosarcoma pro- Coccidioidomycosis Basal Cell tuberans [Maire] 203 (Fe) Histopathologic findings of disseminated coc- Carcinoma, Microcystic Adnexal Dermoscopic changes in acral melanocytic nevi cidioidomycosis with hyphae (letter) [Kappel] Asymptomatic cutaneous lip plaque [Redd] 791 during digital follow-up [Altamura] 1372 (No) 548 (Ap) (Je) Evidence insufficient to recommend mela- Cold Carcinoma, Renal Cell noma surveillance following phototherapy for Effect of cold air cooling on the incidence of Nodule on the toe [Dapprich] 1067 (Au) jaundice (letter) [Newman] (reply) postinflammatory hyperpigmentation after Carcinoma, Squamous Cell [Descamps] 1216 (Se) Q-switched Nd:YAG laser treatment of Predictors of skin-related quality of life after treat- Intertriginous eruption associated with chemo- acquired bilateral nevus of Ota–like macules ment of cutaneous basal cell carcinoma and therapy in pediatric patients [Webber] 67 (Ja) [Manuskiatti] 1139 (Se) squamous cell carcinoma [Chen] 1386 (No) Lichen spinulosus: excellent response to treti- Neurovascular instability syndrome: a unify- Skin cancer presenting as a nonhealing wound: noin gel and hydroactive adhesive applica- ing term to describe the coexistence of tem- the association of polio and skin cancer (let- tions (letter) [Forman] 122 (Ja) perature-related vascular disorders in affected ter) [Vu] 1338 (Oc) Long-term follow-up of a child treated with efali- patients (letter) [George] 274 (Fe) Treatment of recurrent squamous cell carci- zumab for atopic dermatitis (letter) [Siegfried] Colectomy noma of the skin with cetuximab [Bauman] 1077 (Au) Peristomal pyoderma gangrenosum associated 889 (Jy) Nodule on a boy’s back [De Aloe] 417 (Mr) with collagenous colitis (letter) [Davis] 669 Carcinoma, Transitional Cell Petechial and red-brown papular lesions in a (My) Erythematous papules and plaques involving the 2-year-old girl [Williams] 1067 (Au) Colitis, Collagenous groin and scrotum [Breedlove] 1067 (Au) Prevalence of skin diseases and cutaneous mani- Peristomal pyoderma gangrenosum associated Cardiac Surgical Procedures festations among Iranian children: a survey of with collagenous colitis (letter) [Davis] 669 Signs of a “broken heart”: suspected Muehrcke 1417 children (research letter) [Toossi] 115 (My) lines after cardiac surgery (letter) [Weiser] 815 (Ja) Collagen (Je) Role of furry pets in eczema: a systematic review Bilateral symmetrical nodules on the feet [Fang] Cartilage [Langan] 1570 (De) 417 (Mr) Asymptomatic nodule of the tongue [Mataix] Sock-line hyperpigmentation: case series and lit- In vivo stimulation of de novo collagen produc- 653 (My) erature review (letter) [Berk] 428 (Mr) tion caused by cross-linked hyaluronic acid CD4-Positive T-Lymphocytes Suppression of the HPA axis in pediatric patients dermal filler injections in photodamaged Apoptotic responses to all-trans retinoic acid of with atopic dermatitis (letter) [Ishay] 1449 human skin [Wang] 155 (Fe) targretin-resistant, malignant, CD4ϩ periph- (No) Collagen Diseases eral blood T cells from patients with Se´zary Verrucous papules and plaques in a pediatric Hyperpigmented keratotic nodules [Chua] 1201 syndrome (research letter) [Newton] 661 (My) patient [Gonzalez] 1201 (Se) (Se) CD20 Antigens see Antigens, CD20 Chlorhexidine Collagen Type VII CD30-Positive Anaplastic Large-Cell Lymphoma Black tongue and Enterobacter cloacae (letter) [El Clinical response of severe mechanobullous epi- see Lymphoma, Large-Cell, Ki-1 Sayed] 815 (Je) dermolysis bullosa acquisita to combined treat- CD34 Antigens see Antigens, CD34 Cholestasis, Intrahepatic ment with immunoadsorption and ritux- CD4-Positive T-Lymphocytopenia, Idiopathic Importance of serum bile acid level analysis and imab (anti-CD20 monoclonal antibodies) see T-Lymphocytopenia, Idiopathic CD4- treatment with ursodeoxycholic acid in intra- [Niedermeier] 192 (Fe) Positive hepatic cholestasis of pregnancy: a case series Colloids CDKN2 Genes see Genes, p16 from Central Europe [Ambros-Rudolph] 757 Fractional photothermolysis for the treatment Cell Movement (Je) of adult colloid milium [Marra] 572 (My) Epidermal Langerhans cell movement in situ: a Choristoma Color model for understanding immunologic func- Asymptomatic nodule of the tongue [Mataix] Differences between polarized light dermos- tion in the skin [Mohr] 1352 (Oc); correc- 653 (My) copy and immersion contact dermoscopy for tion, 1438 (No) Chromosomes, Human, Pair 9 the evaluation of skin lesions Cellulitis Palmar basal cell carcinoma in a patient with [Benvenuto-Andrade] 329 (Mr) Recurrent, pruritic dermal plaques and bullae Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) Comedones see Acne [Green] 791 (Je) Chromosomes, Human, Pair 16 Communicable Diseases Cetuximab Novel missense mutation in the CYLD gene in What are the risks of serious infections and Treatment of recurrent squamous cell carci- a Spanish family with multiple familial tricho- malignancies for patients treated with anti- noma of the skin with cetuximab [Bauman] epithelioma (research letter) [Espan˜ a] 1209 tumor necrosis factor antibodies? [Corona] 889 (Jy) (Se) 405 (Mr) Charcoal Cicatrix Communication Consensus panel recommendations for chronic Staged hair transplantation in cicatricial alopecia Practice brochure: complement to, not supple- and acute wound dressings [Vaneau] 1291 after carbon dioxide laser–assisted scar tissue ment for, good physician-patient interaction (Oc) remodeling [Kwon] 457 (Ap) (research letter) [Fosse] 1447 (No) Chemokines Cinacalcet Compression Therapy Overexpression of matrix metalloproteinases, Cinacalcet for the treatment of calciphylaxis Physical activity and adherence to compres- chemokines, and chemokine receptors rel- [Robinson] 152 (Fe) sion therapy in patients with venous leg ulcers evant for metastasis in experimental models Sodium thiosulfate as first-line treatment for cal- [Heinen] 1283 (Oc) not an indication of lymph node metastases ciphylaxis (letter) [Ackermann] 1336 (re- Computer-Assisted Three-Dimensional Imaging in human melanoma (research letter) [Otto] ply) [Robinson] 1338 (Oc) see Imaging, Three-Dimensional 947 (Jy) Citrobacter freundii Confocal Microscopy see Microscopy, Confocal Chemotherapy, Adjuvant Spontaneous Citrobacter freundii infection in an CONSENSUS STATEMENTS Systemic adjuvant therapy for patients with high- immunocompetent patient (letter) [Whalen] Consensus panel recommendations for chronic risk melanoma [Tsai] 779 (Je) 124 (Ja) and acute wound dressings [Vaneau] 1291 Chemotherapy see Drug Therapy Clear Cell Papulosis (Oc) Chilblains Clear cell papulosis in Hispanic siblings Construction Workers Neurovascular instability syndrome: a unify- [Benouni] 358 (Mr) Skin disorders among construction workers fol- ing term to describe the coexistence of Clotrimazole lowing Hurricane Katrina and Hurricane Rita: temperature-related vascular disorders in Quality of dermatologic care delivered by phy- an outbreak investigation in New Orleans, affected patients (letter) [George] 274 (Fe) sician assistants: an analysis of prescribing Louisiana [Noe] 1393 (No) Child behavior for the combination antifungal agent Consultation, Remote see Remote Consultation Childhood atopic dermatitis impact scale: reli- clotrimazole-betamethasone (research let- Contact Dermatitis see Dermatitis, Contact ability, discriminative and concurrent valid- ter) [Satyaprakash] 1591 (De) CORRECTIONS ity, and responsiveness [Chamlin] 768 (Je) Cocaine Breaking strength of barbed polypropylene Childhood bullous pemphigoid: clinical and Acute generalized exanthematous pustulosis sutures: rater-blinded, controlled compari- immunological findings in a series of 4 cases caused by illicit street drugs? (letter) [Lu] 430 son with nonbarbed sutures of various cali- [Martinez-De Pablo] 215 (Fe) (Mr) bers [Rashid] 869 (Jy); correction, 1186 (Se)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E15 Effect of smoking on aging of photoprotected copy and immersion contact dermoscopy for Long-term follow-up of a child treated with efali- skin: evidence gathered using a new photo- the evaluation of skin lesions [Benvenuto- zumab for atopic dermatitis (letter) [Siegfried] numeric scale [Helfrich] 397 (Mr); correc- Andrade] 329 (Mr) 1077 (Au) tion, 633 (My) Fractional photothermolysis for the treatment Role of filaggrin mutations as an etiologic fac- Epidermal Langerhans cell movement in situ: a of adult colloid milium [Marra] 572 (My) tor in atopic dermatitis [Zirwas] 1437 (No) model for understanding immunologic func- Cytokines Suppression of the HPA axis in pediatric patients tion in the skin [Mohr] 1352 (Oc); correc- Functional dysregulation of dendritic cells in with atopic dermatitis (letter) [Ishay] 1449 tion, 1438 (No) patients with papular urticaria caused by flea- (No) Nephrogenic systemic fibrosis: relationship to bite [Cue´llar] 1415 (No) Dermatitis, Contact gadolinium and response to photopheresis Cytomegalovirus Infections Acute and recurrent vesicular hand dermatitis [Richmond] 1025 (Au); correction, 1565 (De) Tender erythema of the left lower extremity not pompholyx or dyshidrosis [Storrs] 1578 Outbreak of Vibrio vulnificus infection in [Szyfelbein] 535 (Ap) (De) Kumamoto, Japan, 2001 [Inoue] 140:888 (Jy); 3-year causative study of pompholyx in 120 correction, 143:391 (Mr) D patients [Guillet] 1504 (De) Randomized, double-blind, placebo- Dermatitis, Exfoliative controlled trial of pentoxifylline for the treat- Darier’s Disease see Keratosis Follicularis “Louse blouse” as a cause of erythroderma ment of recurrent aphthous stomatitis Daunorubicin [Irizarry] 682 (My) [Thornhill] 463 (Ap); correction, 716 (Je) Leukemia cutis: a presenting sign in acute pro- Dermatitis, Occupational Randomized double-blind trial of treatment of myelocytic leukemia (letter) [Markowski] Skin disorders among construction workers fol- vitiligo: efficacy of psoralen–UV-A therapy vs 1220 (Se) lowing Hurricane Katrina and Hurricane Rita: narrowband–UV-B therapy [Yones] 578 (My); Debridement an outbreak investigation in New Orleans, correction, 906 (Jy) Consensus panel recommendations for chronic Louisiana [Noe] 1393 (No) Store-and-forward teledermatology in skin can- and acute wound dressings [Vaneau] 1291 Dermatitis, Radiation-Induced see Radio- cer triage: experience and evaluation of 2009 (Oc) dermatitis teleconsultations [Moreno-Ramirez] 479 (Ap); Lichen spinulosus: excellent response to treti- correction, 886 (Jy) Dermatobia hominis noin gel and hydroactive adhesive applica- Dermoscopic diagnosis of furuncular myiasis Corticosteroids see Adrenal Cortex Hormones tions (letter) [Forman] 122 (Ja) (letter) [Bakos] 123 (Ja) Cosmetic Techniques Decision Making Dermatofibroma see Histiocytoma, Benign Cosmetic permanent fillers for soft tissue aug- Balancing the benefits and risks of drug treat- Fibrous mentation: a new contraindication for inter- ment: a stated-preference, discrete choice feron therapies [Fischer] 507 (Ap) Dermatofibrosarcoma experiment with patients with psoriasis Clinical, histologic, and molecular study of 9 Costello Syndrome [Seston] 1175 (Se) cases of congenital dermatofibrosarcoma pro- Verrucous papules and plaques in a pediatric Delivery of Health Care tuberans [Maire] 203 (Fe) patient [Gonzalez] 1201 (Se) Effect of health care delivery models on mela- Costs and Cost Analysis Dermatology noma thickness and stage in a university- Academic dermatology manpower: issues of Visual screening for malignant melanoma: a cost- based referral center: an observational pilot effectiveness analysis [Losina] 21 (Ja) recruitment and retention [Loo] 341 (Mr) study [Swetter] 30 (Ja) Academic workforce in dermatology [Olerud] County Government see Local Government Dendritic Cells 409 (Mr) Crohn Disease Dendritic cells in pigmented basal cell carci- Accessible evidence-based medicine: critically Infliximab-induced palmoplantar pustulosis in noma: a relevant finding by reflectance- appraised topics [Barzilai] 1189 (Se) a patient with Crohn disease (letter) [Sladden] mode confocal microscopy [Segura] 883 (Jy) Archives of Dermatology Web site: adding new 1449 (No) Epidermal Langerhans cell movement in situ: a dimensions to the literature [Bhatia] 1320 (Oc) CUTTING EDGE (Hruza GJ, Heffernan MP, model for understanding immunologic func- Awareness of generational differences is the first Ammirati C, eds) tion in the skin [Mohr] 1352 (Oc); correc- step (letter) [Garcia] 120 (Ja) Adalimumab treatment for pyoderma gangreno- tion, 1438 (No) Dermatology and the human genome: an epi- sum [Heffernan] 306 (Mr) Functional dysregulation of dendritic cells in demiologic approach [Gwinn] 1194 (Se) Cinacalcet for the treatment of calciphylaxis patients with papular urticaria caused by flea- Evidence-based dermatology section wel- [Robinson] 152 (Fe) bite [Cue´llar] 1415 (No) comes a new feature: critically appraised top- ␣ Cutting edge [Hruza] 1062 (Au) Yin and yang of TNF- inhibition [Fiorentino] ics [Bigby] 1185 (Se) Fractional photothermolysis for the treatment 233 (Fe) Ex vivo dermoscopy of melanocytic tumors: time of adult colloid milium [Marra] 572 (My) Dermatitis for dermatopathologists to learn dermos- Fractional resurfacing: a new therapeutic modal- Acute blue patch on the forearm [Heydendael] copy [Scope] 1548 (De) ity for Becker’s nevus [Glaich] 1488 (De) 937 (Jy) Leadership workforce in academic dermatol- Infliximab as a therapy for idiopathic hyper- Bleomycin-induced “flagellate dermatitis” (let- ogy (research letter) [Turner] 948 (Jy) eosinophilic syndrome [Taverna] 1110 (Se) ter) [Arseculeratne] 1461 (No) Melanoma outcomes for Medicare patients: asso- Intralesional bleomycin for angiolymphoid Brown and black scaly patches on the lower leg ciation of stage and survival with detection by hyperplasia [Akdeniz] 841 (Jy) [Soderberg] 1441 (No) a dermatologist vs a nondermatologist [Pennie] Negative pressure dressing in the management Intertriginous eruption associated with chemo- 488 (Ap) of pyoderma gangrenosum ulcer [Ghersi] 1249 therapy in pediatric patients [Webber] 67 (Ja) Next frontier of dermatologic research (Oc) Perioral dermatitis associated with an inhaled [Robinson] 1195 (Se) Progressive extragenital lichen sclerosus suc- corticosteroid (letter) [Poulos] 1460 (No) Practice brochure: complement to, not supple- cessfully treated with narrowband UV-B pho- Poor adherence to treatments: a fundamental ment for, good physician-patient interaction totherapy [Colbert] 19 (Ja) principle of dermatology [Ali] 912 (Jy) (research letter) [Fosse] 1447 (No) Pulsed-dye laser treatment of nonhealing chronic Prevalence of skin diseases and cutaneous mani- Quality of care from a patient’s perspective (re- ulcer with hypergranulation tissue [Wang] 700 festations among Iranian children: a survey of search letter) [Regula] 1592 (De) (Je) 1417 children (research letter) [Toossi] 115 Quality of dermatologic care delivered by phy- Staged hair transplantation in cicatricial alope- (Ja) sician assistants: an analysis of prescribing cia after carbon dioxide laser–assisted scar tis- Psoriasis and pustular dermatitis triggered by behavior for the combination antifungal agent ␣ sue remodeling [Kwon] 457 (Ap) TNF- inhibitors in patients with rheumato- clotrimazole-betamethasone (research let- Successful treatment of notalgia paresthetica with logic conditions [de Gannes] 223 (Fe) ter) [Satyaprakash] 1591 (De) botulinum toxin type A [Weinfeld] 980 (Au) Widespread granulomatous dermatitis of infancy: Sponsorship of graduate medical education: one Successful treatment of the erythema and flush- an early sign of Blau syndrome [Schaffer] 386 successful model (letter) [James] 1211 (Se) ing of rosacea using a topically applied selec- (Mr) Store-and-forward teledermatology in skin can- ␣ tive 1-adrenergic receptor agonist, oxy- Dermatitis, Allergic Contact cer triage: experience and evaluation of 2009 metazoline [Shanler] 1369 (No) Allergic contact dermatitis: another adverse effect teleconsultations [Moreno-Ramirez] 479 (Ap); Cylindroma see Carcinoma, Adenoid Cystic of over-the-counter topical hydrocortisone (let- correction, 886 (Jy) Cystoscopy ter) [Watsky] (reply) [Eaglstein] 1217 (Se) Teledermatology: extending specialty care Ortho-phthalaldehyde causing facial stains after Dermatitis, Atopic beyond borders [Burdick] 1581 (De) cystoscopy (letter) [Abdulla] 670 (My) Childhood atopic dermatitis impact scale: reli- Topical hydrocortisone from prescription to Cysts ability, discriminative and concurrent valid- over-the-counter sale: a past controversy: a cau- Differences between polarized light dermos- ity, and responsiveness [Chamlin] 768 (Je) tionary tale [Ravis] 413 (Mr)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E16 Wikis: the application of Web 2.0 [Johnson] Identification of incipient tumors by means of Equinology [Peterson] 438 (Mr) 1065 (Au) sequential dermoscopy imaging: a new way to Erythema and blistering of the left leg Wound complications following diagnostic skin inflate the “epidemic” of melanoma? (letter) [Shimanovich] 535 (Ap) biopsies in dermatology inpatients [Wahie] [Carli] (reply) [Kittler] 805 (Je) Erythematous atrophic macules and papules 1267 (Oc) Nevus type in dermoscopy is related to skin type following the lines of Blaschko [Quain] 109 Wound healing [Kirsner] 1318 (Oc) in white persons [Zalaudek] 351 (Mr) (Ja) Dermatomycoses Palmar basal cell carcinoma in a patient with Erythematous papules and plaques involving the Beefy red plaque in the popliteal fossa [Grekin] Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) groin and scrotum [Breedlove] 1067 (Au) 1323 (Oc) Pigmented mammary Paget disease: dermo- Ex vivo dermoscopy of melanocytic tumors: time Nodular lesions on the arm [Chrusciak-Talhari] scopic, in vivo reflectance-mode confocal for dermatopathologists to learn dermos- 1323 (Oc) microscopic, and immunohistochemical study copy [Scope] 1548 (De) Dermatomyositis of a case [Longo] 752 (Je) Exclusively benign dermoscopic pattern in a Pilot trial of rituximab in the treatment of patients Seborrheic keratosislike melanoma with follicu- patient with acral melanoma (letter) [Braun] with dermatomyositis [Chung] 763 (Je) lotropism [Carrera] 373 (Mr) 1213 (reply) [Saida] 1215 (Se) Dermatophytes see Arthrodermataceae Variations in the dermoscopic features of Firm papule on the lateral tongue [Suwattee] acquired acral melanocytic nevi [Ozdemir] 1583 (De) Dermatoses see Skin Diseases 1378 (No) Fulminant cutaneous eruption in a 51-year-old Dermoscopy Virologic safety of polyvinyl chloride film in der- man [Thakuria] 255 (Fe) Age- and site-specific variation in the dermo- moscopic analysis of mucosal areas (research Generalized papules in a patient with acute scopic patterns of congenital melanocytic nevi: letter) [Zampino] 945 (Jy) myeloid leukemia [Nakahigashi] 1583 (De) an aid to accurate classification and assess- Diabetes Complications Glistening brown nodule [Scheinfeld] 255 (Fe) ment of melanocytic nevi [Changchien] 1007 Goosefleshlike lesions and hypohidrosis (Au) Diabetic muscle infarction (letter) [MacGregor] 1456 (No) [Dimon] 1323 (Oc) Clinical and dermoscopic features of agmi- Head-tilt maneuver: a clinical aid in recogniz- nated blue nevus (letter) [Pizzichetta] 1225 Diabetes Mellitus Tuberous necrobiosis lipoidica (letter) ing head and neck angiosarcomas [Asgari] 75 (Se) (Ja) Correlation of dermoscopic structures of mela- [Michaels] 546 (Ap) Histologic cutaneous modifications after the use nocytic lesions to reflectance confocal micros- Diagnosis of EMLA cream, a diagnostic pitfall: review of copy [Scope] 176 (Fe) Acute blue patch on the forearm [Heydendael] 13 cases (research letter) [Cazes] 1074 (Au) Correlation of dermoscopy with in vivo reflec- 937 (Jy) Hyperpigmented keratotic nodules [Chua] 1201 tance confocal microscopy of streaks in mela- Ambiguous igneous rocks (letter) [Reynolds] (Se) nocytic lesions [Scope] 727 (Je) 118 (Ja) Identification of incipient tumors by means of Dermatoscopic changes in acquired melano- Antemortem diagnosis of rabies via nuchal skin sequential dermoscopy imaging: a new way to cytic nevi and seborrheic keratoses after the biopsy (letter) [Perez] 663 (My) inflate the “epidemic” of melanoma? (letter) application of a self-tanning airbrush (letter) Asymptomatic cutaneous lip plaque [Redd] 791 [Carli] (reply) [Kittler] 805 (Je) [Martin] 1453 (No) (Je) Increasing ratio of thin to thick melanoma Dermoscopic changes in acral melanocytic nevi Asymptomatic nodule of the tongue [Mataix] during digital follow-up [Altamura] 1372 (No) 653 (My) lesions: pathogenesis and early detection of this Dermoscopic diagnosis of furuncular myiasis Atrophic macules and soft papules in a 24-year- cancer (letter) [Bystryn] (reply) [Lipsker] 804 (letter) [Bakos] 123 (Ja) old woman [Pascual] 109 (Ja) (Je) Dermoscopic findings in Laugier-Hunziker syn- Auricular erythema with nodules and scale Keratotic papules on the right side of the neck drome [Gencoglan] 631 (My) [Hutchin] 1441 (No) and back [Bowe] 535 (Ap) Dermoscopic patterns of acral melanocytic nevi: Beefy red plaque in the popliteal fossa [Grekin] Lymphomatoid keratosis: an epidermotropic type their variations, changes, and significance 1323 (Oc) of cutaneous lymphoid hyperplasia: clinico- [Saida] 1423 (No) Bilateral symmetrical nodules on the feet [Fang] pathological, immunohistochemical, and Dermoscopic vascular patterns in nodular “pure” 417 (Mr) molecular biological study of 6 cases [Arai] 53 amelanotic melanoma [Cavicchini] 556 (Ap) Blue-black pigmentation of legs and arms in a 68- (Ja) Dermoscopy in vulvar basal cell carcinoma (let- year-old woman [Lo´pez-Pestan˜ a] 1441 (No) Melanoma outcomes for Medicare patients: asso- ter) [de Giorgi] 426 (Mr) Blue-gray subungual discoloration [Dalle] 937 (Jy) ciation of stage and survival with detection by Dermoscopy insights into nevogenesis: “abtrop- Brown and black scaly patches on the lower leg a dermatologist vs a nondermatologist [Pennie] fung” vs “hochsteigerung” [Zalaudek] 284 (Fe) [Soderberg] 1441 (No) 488 (Ap) Dermoscopy not yet shown to increase sensi- Burgeoning nodule on the scalp of a 65-year- Multiple painless papules on the wrists [Callaly] tivity of melanoma diagnosis in real practice old man [Farhi] 653 (My) 791 (Je) (letter) [Carli] 664 (replies) [Menzies, Clinicopathologic correlation of cutaneous Multiple plaques on the hands and feet [Lambert] Zalaudek] 665, 666 (My) metastases: experience from a cancer center 109 (Ja) Dermoscopy of active lichen planus [Sariya] 613 (My) Nodular lesions on the arm [Chrusciak-Talhari] [Va´zquez-Lo´pez] 1092 (Au) Confusing message will not improve the detec- 1323 (Oc) Dermoscopy of port-wine stains tion of melanoma (letter) [Bystryn] (reply) Nodule on a boy’s back [De Aloe] 417 (Mr) [Va´zquez-Lo´pez] 962 (Jy) [Kelly] 806 (Je) Nodule on the toe [Dapprich] 1067 (Au) Dermoscopy of pyogenic granulomas [Zaballos] Crusted violaceous plaques on an immunocom- Painful nodule on the knee [Heffernan] 937 (Jy) 824 (Je) promised host [Xu] 417 (Mr) Papular eruption in an HIV-infected man [Swick] Dermoscopy of solitary angiokeratomas: a mor- Dermal plaques of the face and scalp [Cohen] 255 (Fe) phological study [Zaballos] 318 (Mr) 109 (Ja) Papules and plaques on the nose [Evers] 535 Dermoscopy patterns of eczemalike melanoma Dermoscopic diagnosis of furuncular myiasis (Ap) (letter) [Giacomel] 1081 (Au) (letter) [Bakos] 123 (Ja) Persistent violaceous papules on the ears Dermoscopy subpattern of plaque-type psoria- Dermoscopic findings in Laugier-Hunziker syn- [Blumetti] 417 (Mr) sis: red globular rings [Va´zquez-Lo´pez] 1612 drome [Gencoglan] 631 (My) Petechial and red-brown papular lesions in a (De) Dermoscopic patterns of acral melanocytic nevi: 2-year-old girl [Williams] 1067 (Au) Differences between polarized light dermos- their variations, changes, and significance Pruritic patches on the back and papules on the copy and immersion contact dermoscopy for [Saida] 1423 (No) legs [Garg] 255 (Fe) the evaluation of skin lesions Dermoscopy not yet shown to increase sensi- Rapidly enlarging necrotic ulcer on the right calf [Benvenuto-Andrade] 329 (Mr) tivity of melanoma diagnosis in real practice [Chakrabarti] 791 (Je) Early melanomas dermoscopically character- (letter) [Carli] 664 (replies) [Menzies, Recurrent calcified cutaneous nodule of the peri- ized by reticular depigmentation (letter) Zalaudek] 665, 666 (My) anal region [Patrizi] 1441 (No) [Lozzi] 808 (Je) Dermoscopy patterns of eczemalike melanoma Recurrent, pruritic dermal plaques and bullae Ex vivo dermoscopy of melanocytic tumors: time (letter) [Giacomel] 1081 Au [Green] 791 (Je) for dermatopathologists to learn dermos- Diagnostic yield of histopathologic sampling Scaly plaque on the scalp [Borer] 1067 (Au) copy [Scope] 1548 (De) techniques in PAN-associated cutaneous ulcers Seborrheic keratosislike melanoma with follicu- Exclusively benign dermoscopic pattern in a (research letter) [Ricotti] 1334 (Oc) lotropism [Carrera] 373 (Mr) patient with acral melanoma (letter) [Braun] Diffuse cutaneous nodules [Abdelmalek] 937 Soft papules and nodules on the buttock 1213 (reply) [Saida] 1215 (Se) (Jy) [Pol-Rodriguez] 1583 (De) Fast-growing and slow-growing melanomas (let- Diffuse nodules in a woman with renal failure Solitary cutaneous nodule in an immunocom- ter) [Argenziano] 802 (reply) [Kelly] 803 (Je) [Lesesky] 1201 (Se) promised patient [Singh] 1583 (De)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E17 Store-and-forward teledermatology in skin can- Doxycycline Incidence and risk factors for psoriasis in the gen- cer triage: experience and evaluation of 2009 Adult disseminated primary papular xanthoma eral population [Huerta] 1559 (De) teleconsultations [Moreno-Ramirez] 479 (Ap); treated with doxycycline (letter) [Bastida] 667 Infliximab-induced palmoplantar pustulosis in correction, 886 (Jy) (My) a patient with Crohn disease (letter) [Sladden] Subcutaneous nodule and diffuse lymphade- Dressings see Bandages 1449 (No) nopathy in a 6-month-old boy from Africa Drug Abuse, Intravenous see Substance Abuse, Intertriginous eruption associated with chemo- [Friedman] 1323 (Oc) Intravenous therapy in pediatric patients [Webber] 67 (Ja) Tender erythema of the left lower extremity Drug Eruptions Lymphomatoid granulomatosis induced by ima- [Szyfelbein] 535 (Ap) Erythema and blistering of the left leg tinib treatment (letter) [Yazdi] 1222 (Se) Tender nodules on the palms and soles [Shimanovich] 535 (Ap) Multiple subcutaneous lipomas induced by [Esler-Brauer] 1201 (Se) Erythema nodosum–like eruption as a manifes- HAART in the absence of protease inhibitors Ulceronecrotic nasoparanasal lesion [Martı´n] 653 tation of azathioprine hypersensitivity in (letter) [Balestreire] 1596 (De) ␣ (My) patients with inflammatory bowel disease [de Onset of psoriasis during treatment with TNF- Verrucous nodules on the toes of a renal trans- Fonclare] 744 (Je) antagonists: a report of 3 cases (letter) plant recipient [Levy] 653 (My) High procalcitonin levels in patients with severe [Ubriani] 270 (Fe) Verrucous papules and plaques in a pediatric drug reactions (research letter) [Sfia] 1591 Ortho-phthalaldehyde causing facial stains after patient [Gonzalez] 1201 (Se) (De) cystoscopy (letter) [Abdulla] 670 (My) Virologic safety of polyvinyl chloride film in der- Intertriginous eruption associated with chemo- Pemphigus variant associated with penicillin use: moscopic analysis of mucosal areas (research therapy in pediatric patients [Webber] 67 (Ja) a case-cohort study of 363 patients from Israel letter) [Zampino] 945 (Jy) Psoriasiform eruptions during anti–TNF-␣ treat- [Heymann] 704 (Je) Wound complications following diagnostic skin ment: psoriasis or not? (letter) [Seneschal] Perioral dermatitis associated with an inhaled biopsies in dermatology inpatients [Wahie] 1593 (reply) [de Gannes] 1595 (De) corticosteroid (letter) [Poulos] 1460 (No) 1267 (Oc) Short-term thallium intoxication: dermatologi- Phenylephrine-induced microvascular occlu- Diagnosis, Differential cal findings correlated with thallium concen- sion syndrome in a patient with a heterozy- Acute and recurrent vesicular hand dermatitis tration [Lu] 93 (Ja) gous factor V Leiden mutation [Kalajian] 1314 not pompholyx or dyshidrosis [Storrs] 1578 Drug Hypersensitivity (Oc) (De) Acute generalized exanthematous pustulosis Pneumocystis carinii pneumonia in infant treated Clinical and dermoscopic features of agmi- caused by illicit street drugs? (letter) [Lu] 430 with oral steroids for hemangioma (letter) nated blue nevus (letter) [Pizzichetta] 1225 (Mr) [Maronn] 1224 (Se) (Se) Allergic contact dermatitis: another adverse effect Psoriasiform eruptions during anti–TNF-␣ treat- Dermoscopy of solitary angiokeratomas: a mor- of over-the-counter topical hydrocortisone (let- ment: psoriasis or not? (letter) [Seneschal] phological study [Zaballos] 318 (Mr) ter) [Watsky] (reply) [Eaglstein] 1217 (Se) 1593 (reply) [de Gannes] 1595 (De) Epidermolysis bullosa nevus: an exception to the Erythema nodosum–like eruption as a manifes- Rebound vasodilation from long-term topical clinical and dermoscopic criteria for mela- tation of azathioprine hypersensitivity in corticosteroid use (letter) [Rapaport] 268 (Fe) noma [Cash] 1164 (Se) patients with inflammatory bowel disease [de Reliability of the Roenigk classification of liver Leukemia cutis: a presenting sign in acute pro- Fonclare] 744 (Je) damage after methotrexate treatment for pso- myelocytic leukemia (letter) [Markowski] Drug Industry riasis: a clinicopathologic study of 160 liver 1220 (Se) Topical calcineurin inhibitors revisited (letter) biopsy specimens [Berends] 1515 (De) Pigmented mammary Paget disease: dermo- [Qureshi] 545 (Ap) Retinal toxic reactions following photopher- scopic, in vivo reflectance-mode confocal esis [Vagace] 622 (My) microscopic, and immunohistochemical study Drug Labeling National Eczema Association and topical calci- Subcutaneous nodule and diffuse lymphade- of a case [Longo] 752 (Je) nopathy in a 6-month-old boy from Africa ␣ neurin inhibitor labeling (letter) [Cooper] 546 Psoriasiform eruptions during anti–TNF- treat- [Friedman] 1323 (Oc) ment: psoriasis or not? (letter) [Seneschal] (Ap) Drug Reaction, Adverse Telithromycin-induced TEN: report of a case 1593 (reply) [de Gannes] 1595 (De) (letter) [Be´dard] 427 (Mr) Reflectance-mode confocal microscopy for the Allergic contact dermatitis: another adverse effect of over-the-counter topical hydrocortisone (let- Topical hydrocortisone from prescription to diagnosis of sebaceous hyperplasia in vivo over-the-counter sale: a past controversy: a cau- [Propperova] 134 (Ja) ter) [Watsky] (reply) [Eaglstein] 1217 (Se) ␤ tionary tale [Ravis] 413 (Mr) Diagnostic Errors Association between the use of -adrenergic receptor agents and the development of venous What are the risks of serious infections and Crusted Norwegian scabies in an adult with malignancies for patients treated with anti- Langerhans cell histiocytosis: mishaps lead- leg ulcers [Margolis] 1275 (Oc) Atrial tachycardia associated with isotretinoin tumor necrosis factor antibodies? [Corona] ing to systemic chemotherapy [Kartono] 626 405 (Mr) (My) use (letter) [Dresden] 1084 (Au) Balancing the benefits and risks of drug treat- What is the chance of a normal pregnancy in a Diagnostic Imaging ment: a stated-preference, discrete choice woman whose fetus has been exposed to Digital image analysis: a reliable tool in the experiment with patients with psoriasis isotretinoin? [Sladden] 1187 (Se) quantitative evaluation of cutaneous lesions ␣ [Seston] 1175 (Se) Yin and yang of TNF- inhibition [Fiorentino] and beyond (research letter) [Pressley] Bleomycin-induced “flagellate dermatitis” (let- 233 (Fe) 1331 (Oc) ter) [Arseculeratne] 1461 (No) Drug Resistance Digital Imaging Blue-black pigmentation of legs and arms in a Skin microecology: the old and the new Digital image analysis: a reliable tool in the quan- 68-year-old woman [Lo´pez-Pestan˜ a] 1441 [Webster] 105 (Ja) titative evaluation of cutaneous lesions and (No) Drug Therapy beyond (research letter) [Pressley] 1331 (Oc) Comparison of oral methylprednisolone plus aza- Angiogenesis in cutaneous lesions of leprosy: Dinitrofluorobenzene thioprine or mycophenolate mofetil for the implications for treatment [Bhandarkar] 1527 Epidermal Langerhans cell movement in situ: a treatment of bullous pemphigoid [Beissert] (De) model for understanding immunologic func- 1536 (De) Association between the use of ␤-adrenergic tion in the skin [Mohr] 1352 (Oc); correc- Comparison of treatment options for a Monsel receptor agents and the development of venous tion, 1438 (No) tattoo (letter) [Rao] 1452 (No) leg ulcers [Margolis] 1275 (Oc) Disease Models, Animal Cosmetic permanent fillers for soft tissue aug- Balancing the benefits and risks of drug treat- Topical oxygen emulsion: a novel wound therapy mentation: a new contraindication for inter- ment: a stated-preference, discrete choice [Davis] 1252 (Oc) feron therapies [Fischer] 507 (Ap) experiment with patients with psoriasis DNA Cutaneous adverse reactions to valdecoxib dis- [Seston] 1175 (Se) Direct identification of dermatophyte DNA from tinct from Stevens-Johnson syndrome and British guidelines on the use of biological thera- clinical specimens by a nested polymerase toxic epidermal necrolysis [Ziemer] 711 (Je) pies for psoriasis: a note of clarification on the chain reaction assay (research letter) [Yang] Erythema nodosum–like eruption as a manifes- role of etanercept (letter) [Smith] 1595 (De) 799 (Je) tation of azathioprine hypersensitivity in Comparison of oral methylprednisolone plus aza- Phenotypic variation in familial melanoma: con- patients with inflammatory bowel disease [de thioprine or mycophenolate mofetil for the sequences for predictive DNA testing Fonclare] 744 (Je) treatment of bullous pemphigoid [Beissert] [Bergman] 525 (Ap) Focal acne during topical tacrolimus therapy for 1536 (De) DNFB see Dinitrofluorobenzene vitiligo (letter) [Bakos] 1223 (Se) Crusted Norwegian scabies in an adult with Docetaxel High procalcitonin levels in patients with severe Langerhans cell histiocytosis: mishaps lead- Docetaxel monotherapy for angiosarcoma in an drug reactions (research letter) [Sfia] 1591 ing to systemic chemotherapy [Kartono] 626 elderly patient (letter) [Nagano] 1602 (De) (De) (My)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E18 Era of targeted therapies: increasing role for novel Prevalence of skin diseases and cutaneous mani- Teledermatology: extending specialty care oncologic drugs in dermatology [Montella] 788 festations among Iranian children: a survey of beyond borders [Burdick] 1581 (De) (Je) 1417 children (research letter) [Toossi] 115 Efalizumab Infliximab as a therapy for idiopathic hyper- (Ja) Efalizumab in the treatment of discoid lupus ery- eosinophilic syndrome [Taverna] 1110 (Se) Role of furry pets in eczema: a systematic review thematosus [Usmani] 873 (Jy) Intertriginous eruption associated with chemo- [Langan] 1570 (De) Efalizumab-associated papular psoriasis [Hassan] therapy in pediatric patients [Webber] 67 (Ja) Eczema, Dyshidrotic 900 (Jy) Level of agreement with the British guidelines Acute and recurrent vesicular hand dermatitis not Long-term follow-up of a child treated with efali- for the use of biological therapies for psoria- pompholyx or dyshidrosis [Storrs] 1578 (De) zumab for atopic dermatitis (letter) [Siegfried] sis [Nijsten] 1567 (De) 3-year causative study of pompholyx in 120 1077 (Au) New and old therapeutics for oral ulcerations patients [Guillet] 1504 (De) 8-Methoxypsoralen see Methoxsalen [Bruce] 519 (Ap) Eczema, Vesicular Palmoplantar see Eczema, Electromyography Poor adherence to treatments: a fundamental Dyshidrotic Randomized double-blind study of the effect of principle of dermatology [Ali] 912 (Jy) Botox and Dysport/Reloxin on forehead Primary cutaneous diffuse large B-cell lym- EDITORIALS wrinkles and electromyographic activity (re- phoma, leg type: clinicopathologic features and Academic workforce in dermatology [Olerud] search letter) [Karsai] 1447 (No) prognostic analysis in 60 cases [Grange] 1144 409 (Mr) ELISA see Enzyme-Linked Immunosorbent (Se) Acute and recurrent vesicular hand dermatitis not Assay pompholyx or dyshidrosis [Storrs] 1578 (De) Drug Therapy, Combination Embolism Combination immunosuppressive therapies: the Archives of Dermatology Web site: adding new Generalized papules in a patient with acute promise and the peril [Robinson] 1053 (Au) dimensions to the literature [Bhatia] 1320 (Oc) myeloid leukemia [Nakahigashi] 1583 (De) Balneophototherapy for psoriasis using saltwa- Resolution of chronic pain and fingertip ulcer- Embryopathies see Fetal Diseases ter baths and UV-B irradiation, revisited ation due to hand-arm vibration syndrome fol- Endemic Diseases [Gambichler] 647 (My) lowing combination pharmacotherapy (let- Endemic pemphigus vulgaris [Rocha-Alvarez] Call for papers for On the Horizon [Wood] 253 ter) [Buell] 1343 (Oc) 895 (Jy) (Fe) Drug Toxicity Endothelial Cells Current status of evaluation and treatment of Comparison of oral methylprednisolone plus aza- AKT1 overexpression in endothelial cells leads high-risk cutaneous melanoma: therapeutic thioprine or mycophenolate mofetil for the to the development of cutaneous vascular mal- breakthroughs remain elusive [Kanzler] 785 treatment of bullous pemphigoid [Beissert] formations in vivo [Perry] 504 (Ap) (Je) 1536 (De) Painful nodule on the knee [Heffernan] 937 (Jy) Cutaneous T-cell lymphoma epidemiology: Retinal toxic reactions following photopher- Endothelin Receptor Antagonists see Receptors, patients providing the power [Lessin] 916 (Jy) esis [Vagace] 622 (My) Endothelin Drugs, Nonprescription Cutting edge [Hruza] 1062 (Au) Enterobacter cloacae Allergic contact dermatitis: another adverse effect Dermatology and the human genome: an epi- Black tongue and Enterobacter cloacae (letter) [El of over-the-counter topical hydrocortisone (let- demiologic approach [Gwinn] 1194 (Se) Sayed] 815 (Je) ter) [Watsky] (reply) [Eaglstein] 1217 (Se) Dermoscopic patterns of acral melanocytic nevi: Environmental Exposure Topical hydrocortisone from prescription to their variations, changes, and significance Skin disorders among construction workers fol- over-the-counter sale: a past controversy: a cau- [Saida] 1423 (No) lowing Hurricane Katrina and Hurricane Rita: tionary tale [Ravis] 413 (Mr) Era of targeted therapies: increasing role for novel an outbreak investigation in New Orleans, Duct Tape oncologic drugs in dermatology [Montella] 788 Louisiana [Noe] 1393 (No) Duct tape for the treatment of common warts (Je) Enzyme-Linked Immunosorbent Assay in adults: a double-blind randomized con- Evidence-based dermatology section wel- Herpes gestationis in a mother and newborn: trolled trial [Wenner] 309 (Mr) comes a new feature: critically appraised top- immunoclinical perspectives based on a weekly Dysplastic Nevus Syndrome ics [Bigby] 1185 (Se) follow-up of the enzyme-linked immunosor- Correlation of dermoscopic structures of mela- Long-term treatment for severe psoriasis: we’re bent assay index of a bullous pemphigoid anti- nocytic lesions to reflectance confocal micros- halfway there, with a long way to go [Gelfand] gen noncollagenous domain [Aoyama] 1168 copy [Scope] 176 (Fe) 1191 (Se) (Se) Multiple melanomas after treatment for Hodg- Melanoma screening: focusing the public health Eosinophilia kin lymphoma in a non-Dutch p16-Leiden journey [Koh] 101 (Ja) Persistent eosinophilia as a presenting sign of mutation carrier with 2 MC1R high-risk vari- Monthly final page: skINsight [Grichnik] 1433 ants [Figl] 495 (Ap) scabies in patients with disorders of keratini- (No) zation (letter) [Sluzevish] 670 (My) Phenotypic variation in familial melanoma: con- New and old therapeutics for oral ulcerations Epidemiology sequences for predictive DNA testing [Bruce] 519 (Ap) [Bergman] 525 (Ap) Dermatology and the human genome: an epi- The Off-Center Fold [Ming] 935 (Jy) demiologic approach [Gwinn] 1194 (Se) Phenotypic variation in familial melanoma: con- E Next frontier of dermatologic research sequences for predictive DNA testing [Robinson] 1195 (Se) [Bergman] 525 (Ap) Ear Epidermal Necrolysis, Toxic Poor adherence to treatments: a fundamental Auricular erythema with nodules and scale Cutaneous adverse reactions to valdecoxib dis- principle of dermatology [Ali] 912 (Jy) [Hutchin] 1441 (No) tinct from Stevens-Johnson syndrome and Question the obvious [Nijsten] 1429 (No) Persistent violaceous papules on the ears toxic epidermal necrolysis [Ziemer] 711 (Je) Skin microecology: the old and the new [Blumetti] 417 (Mr) Telithromycin-induced TEN: report of a case [Webster] 105 (Ja) Early Diagnosis (letter) [Be´dard] 427 (Mr) Teens and tans: implementing behavioral change Dermoscopic patterns of acral melanocytic nevi: Epidermis [Haas] 1058 (Au) their variations, changes, and significance Epidermal Langerhans cell movement in situ: a Teledermatology: extending specialty care [Saida] 1423 (No) model for understanding immunologic func- beyond borders [Burdick] 1581 (De) Increasing ratio of thin to thick melanoma tion in the skin [Mohr] 1352 (Oc); correc- Vitiligo: to treat or not to treat [Lim] 643 (My) lesions: pathogenesis and early detection of this tion, 1438 (No) Wound healing [Kirsner] 1318 (Oc) cancer (letter) [Bystryn] (reply) [Lipsker] 804 ␣ Lymphomatoid keratosis: an epidermotropic type (Je) Yin and yang of TNF- inhibition [Fiorentino] of cutaneous lymphoid hyperplasia: clinico- Eccrine Glands 233 (Fe) pathological, immunohistochemical, and Tender nodules on the palms and soles Education, Medical, Continuing molecular biological study of 6 cases [Arai] 53 [Esler-Brauer] 1201 (Se) Wikis: the application of Web 2.0 [Johnson] (Ja) Eczema 1065 (Au) Epidermolysis Bullosa Dermoscopy patterns of eczemalike melanoma Education, Medical, Graduate Epidermolysis bullosa nevus: an exception to the (letter) [Giacomel] 1081 (Au) Academic dermatology manpower: issues of clinical and dermoscopic criteria for mela- Eczematoid graft-vs-host disease: a novel form recruitment and retention [Loo] 341 (Mr) noma [Cash] 1164 (Se) of chronic cutaneous graft-vs-host disease and Academic workforce in dermatology [Olerud] Epidermolysis Bullosa Acquisita its response to psoralen–UV-A therapy 409 (Mr) Clinical response of severe mechanobullous epi- [Creamer] 1157 (Se) Awareness of generational differences is the first dermolysis bullosa acquisita to combined treat- National Eczema Association and topical calci- step (letter) [Garcia] 120 (Ja) ment with immunoadsorption and ritux- neurin inhibitor labeling (letter) [Cooper] 546 Sponsorship of graduate medical education: one imab (anti-CD20 monoclonal antibodies) (Ap) successful model (letter) [James] 1211 (Se) [Niedermeier] 192 (Fe)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E19 Epithelium EVIDENCE-BASED DERMATOLOGY: Head-tilt maneuver: a clinical aid in recogniz- Consensus panel recommendations for chronic CRITICALLY APPRAISED TOPIC ing head and neck angiosarcomas [Asgari] 75 and acute wound dressings [Vaneau] 1291 Evidence-based dermatology section wel- (Ja) (Oc) comes a new feature: critically appraised top- Ortho-phthalaldehyde causing facial stains after Erdheim-Chester Disease ics [Bigby] 1185 (Se) cystoscopy (letter) [Abdulla] 670 (My) Verruca plana–like papules as a new manifes- What is the chance of a normal pregnancy in a Face Lift see Rhytidoplasty tation of Erdheim-Chester disease (letter) woman whose fetus has been exposed to Facial Dermatoses [Yanagi] 952 (Jy) isotretinoin? [Sladden] 1187 (Se) Successful treatment of Favre-Racouchot dis- Erythema EVIDENCE-BASED DERMATOLOGY: ease with 0.05% tazarotene gel (letter) [Rallis] Auricular erythema with nodules and scale RESEARCH COMMENTARY 810 (Je) [Hutchin] 1441 (No) Cloud over sentinel node biopsy: unlikely Factor V Erythema and blistering of the left leg survival benefit in melanoma [Gonza´lez] Phenylephrine-induced microvascular occlu- [Shimanovich] 535 (Ap) 775 (Je) sion syndrome in a patient with a heterozy- Erythematous atrophic macules and papules Level of agreement with the British guidelines gous factor V Leiden mutation [Kalajian] 1314 following the lines of Blaschko [Quain] 109 for the use of biological therapies for psoria- (Oc) (Ja) sis [Nijsten] 1567 (De) Faculty, Medical Erythematous papules and plaques involving the Systemic adjuvant therapy for patients with high- Academic dermatology manpower: issues of groin and scrotum [Breedlove] 1067 (Au) risk melanoma [Tsai] 779 (Je) recruitment and retention [Loo] 341 (Mr) Late-onset familial Mediterranean fever: an atypi- Use of antibiotic ointment after clean cutane- Academic workforce in dermatology [Olerud] cal presentation of dermatologic interest (let- ous surgery [Bigby] 1180 (Se) 409 (Mr) ter) [Satta] 1080 (Au) What are the risks of serious infections and Awareness of generational differences is the first Leukemia cutis: a presenting sign in acute pro- malignancies for patients treated with anti- step (letter) [Garcia] 120 (Ja) myelocytic leukemia (letter) [Markowski] tumor necrosis factor antibodies? [Corona] Leadership workforce in academic dermatol- 1220 (Se) 405 (Mr) ogy (research letter) [Turner] 948 (Jy) Rebound vasodilation from long-term topical EVIDENCE-BASED DERMATOLOGY: REVIEW Sponsorship of graduate medical education: one corticosteroid use (letter) [Rapaport] 268 (Fe) Role of furry pets in eczema: a systematic review successful model (letter) [James] 1211 (Se) Successful treatment of the erythema and flush- [Langan] 1570 (De) Familial Atypical Multiple Mole-Melanoma see ing of rosacea using a topically applied selec- EVIDENCE-BASED DERMATOLOGY: STUDY Dysplastic Nevus Syndrome tive ␣1-adrenergic receptor agonist, oxy- (Bigby M, Abeni D, Corona R, et al., eds) Familial Mediterranean Fever metazoline [Shanler] 1369 (No) Balancing the benefits and risks of drug treat- Late-onset familial Mediterranean fever: an atypi- Tender erythema of the left lower extremity ment: a stated-preference, discrete choice cal presentation of dermatologic interest (let- [Szyfelbein] 535 (Ap) experiment with patients with psoriasis ter) [Satta] 1080 (Au) Erythema, Necrolytic Migratory [Seston] 1175 (Se) Fatigue Necrolytic migratory erythema: the outermost Childhood atopic dermatitis impact scale: reli- Palliative care in patients with primary cutane- marker for glucagonoma syndrome (letter) ability, discriminative and concurrent valid- ous lymphoma: symptom burden and char- [Gantcheva] 1221 (Se) ity, and responsiveness [Chamlin] 768 (Je) acteristics of hospital palliative care team input Erythema Nodosum Effect of smoking on aging of photoprotected (research letter) [LeBon] 423 (Mr) Erythema nodosum–like eruption as a manifes- skin: evidence gathered using a new photo- Favre-Racouchot Syndrome see Facial tation of azathioprine hypersensitivity in numeric scale [Helfrich] 397 (Mr); correc- Dermatoses patients with inflammatory bowel disease [de tion, 633 (My) Ferrochelatase Fonclare] 744 (Je) Incidence and risk factors for psoriasis in the gen- Clinical, biochemical, and genetic study of 11 eral population [Huerta] 1559 (De) Erythroderma see Dermatitis, Exfoliative patients with erythropoietic protoporphyria Evidence-Based Medicine including one with homozygous disease Erythroderma, Bullous Congenital Ichthyosi- Accessible evidence-based medicine: critically [Herrero] 1125 (Se) form see Hyperkeratosis, Epidermolytic appraised topics [Barzilai] 1189 (Se) Fetal Diseases Erythromelalgia Evidence-based dermatology section wel- What is the chance of a normal pregnancy in a Neurovascular instability syndrome: a unify- comes a new feature: critically appraised top- woman whose fetus has been exposed to ing term to describe the coexistence of tem- ics [Bigby] 1185 (Se) isotretinoin? [Sladden] 1187 (Se) perature-related vascular disorders in affected Exanthema Fibroblast Growth Factor Receptor 3 see patients (letter) [George] 274 (Fe) Acute generalized exanthematous pustulosis Receptor, Fibroblast Growth Factor, Type 3 Erythropoietic Protoporphyria see caused by illicit street drugs? (letter) [Lu] 430 Fibroblasts Protoporphyria, Erythropoietic (Mr) Novel treatment for knuckle pads with intra- Escherichia coli Susceptibility to UV-A and UV-B provocation lesional fluorouracil (letter) [Weiss] 1458 (No) Clinical, biochemical, and genetic study of 11 does not correlate with disease severity of poly- Fibroma patients with erythropoietic protoporphyria morphic light eruption [Janssens] 599 (My) Firm papule on the lateral tongue [Suwattee] including one with homozygous disease Exercise 1583 (De) [Herrero] 1125 (Se) Physical activity and adherence to compres- Fibrosis Etanercept sion therapy in patients with venous leg ulcers Nephrogenic systemic fibrosis: relationship to British guidelines on the use of biological thera- [Heinen] 1283 (Oc) gadolinium and response to photopheresis pies for psoriasis: a note of clarification on the Exfoliatins [Richmond] 1025 (Au); correction, 1565 (De) role of etanercept (letter) [Smith] 1595 (De) Staphylococcus aureus virulence factors associ- Filaggrin Clinical improvement of pityriasis rubra pilaris ated with infected skin lesions: influence on Role of filaggrin mutations as an etiologic fac- with combination etanercept and acitretin the local immune response [Mertz] 1259 (Oc) tor in atopic dermatitis [Zirwas] 1437 (No) therapy (letter) [Davis] 1597 (De) Exfoliative Toxins see Exfoliatins Fingernails see Nails Level of agreement with the British guidelines Exostoses Fingers for the use of biological therapies for psoria- Subungual exostosis [Sa´nchez-Castellanos] 1234 Acute digital gangrene in a newborn (letter) sis [Nijsten] 1567 (De) (Se) [Wollina] 121 (Ja) Long-term safety and efficacy of 50 mg of etaner- Eye Protective Devices Bosentan as a rescue therapy in scleroderma cept twice weekly in patients with psoriasis Pupil damage after periorbital laser treatment of refractory digital ulcers (letter) [Chamaillard] [Tyring] 719 (Je) 125 (Ja) ␣ a port-wine stain [Hammes] 392 (Mr) Onset of psoriasis during treatment with TNF- Novel treatment for knuckle pads with intra- antagonists: a report of 3 cases (letter) F lesional fluorouracil (letter) [Weiss] 1458 (No) [Ubriani] 270 (Fe) Paraneoplastic Raynaud phenomenon with digi- Europe Face tal necrosis associated with hyperhomocys- Importance of serum bile acid level analysis and Cosmetic permanent fillers for soft tissue aug- teinemia and antiphospholipid antibodies (let- treatment with ursodeoxycholic acid in intra- mentation: a new contraindication for inter- ter) [Carducci] 1342 (Oc) hepatic cholestasis of pregnancy: a case series feron therapies [Fischer] 507 (Ap) Resolution of chronic pain and fingertip ulcer- from Central Europe [Ambros-Rudolph] 757 Dermal plaques of the face and scalp [Cohen] ation due to hand-arm vibration syndrome fol- (Je) 109 (Ja) lowing combination pharmacotherapy (let- European Continental Ancestry Group Evaluation of plasma skin regeneration tech- ter) [Buell] 1343 (Oc) Nevus type in dermoscopy is related to skin type nology in low-energy full-facial rejuvenation FISH Technique see In Situ Hybridization, in white persons [Zalaudek] 351 (Mr) [Bogle] 168 (Fe) Fluorescence

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E20 Fish-Odor Syndrome see Metabolic Diseases Dermoscopic diagnosis of furuncular myiasis Eczematoid graft-vs-host disease: a novel form Flavins (letter) [Bakos] 123 (Ja) of chronic cutaneous graft-vs-host disease and Trimethylaminuria (fish-odor syndrome): a case its response to psoralen–UV-A therapy report [Arseculeratne] 81 (Ja) G [Creamer] 1157 (Se) Fleas Grafting, Skin see Skin Transplantation Gadolinium Functional dysregulation of dendritic cells in Granulation Tissue Nephrogenic systemic fibrosis: relationship to patients with papular urticaria caused by flea- Consensus panel recommendations for chronic gadolinium and response to photopheresis bite [Cue´llar] 1415 (No) and acute wound dressings [Vaneau] 1291 [Richmond] 1025 (Au); correction, 1565 (De) Florida (Oc) Gangrene Pulsed-dye laser treatment of nonhealing chronic Skin cancer awareness and sun protection behav- Acute digital gangrene in a newborn (letter) iors in white Hispanic and white non- ulcer with hypergranulation tissue [Wang] 700 [Wollina] 121 (Ja) (Je) Hispanic high school students in Miami, Gastrointestinal Stromal Tumors Florida [Ma] 983 (Au) Granuloma Lymphomatoid granulomatosis induced by ima- Widespread granulomatous dermatitis of infancy: Fluocinonide tinib treatment (letter) [Yazdi] 1222 (Se) an early sign of Blau syndrome [Schaffer] 386 Suppression of the HPA axis in pediatric patients Gatekeeping (Mr) with atopic dermatitis (letter) [Ishay] 1449 Effect of health care delivery models on mela- Granuloma Annulare (No) noma thickness and stage in a university- Granuloma annulare: long-term follow-up (re- Fluorescent Antibody Technique based referral center: an observational pilot search letter) [Dahl] 946 (Jy) Epidermal Langerhans cell movement in situ: a study [Swetter] 30 (Ja) Granuloma, Pyogenic model for understanding immunologic func- Gels Dermoscopy of pyogenic granulomas [Zaballos] tion in the skin [Mohr] 1352 (Oc); correc- Successful treatment of Favre-Racouchot dis- 824 (Je) tion, 1438 (No) ease with 0.05% tazarotene gel (letter) [Rallis] Granulomatosis, Lymphomatoid see Lympho- Fluorescent Protein Tracing see Fluorescent 810 (Je) matoid Granulomatosis Antibody Technique Generation Gap see Intergenerational Rela- Great Britain Fluoroscopy tions British guidelines on the use of biological thera- Fluoroscopy-induced chronic radiation skin Genes, CDKN2 see Genes, p16 pies for psoriasis: a note of clarification on the injury: a disease perhaps often overlooked Genes, p16 role of etanercept (letter) [Smith] 1595 (De) [Frazier] 637 (My) Multiple melanomas after treatment for Hodg- Incidence and risk factors for psoriasis in the gen- Fluorouracil kin lymphoma in a non-Dutch p16-Leiden eral population [Huerta] 1559 (De) Novel treatment for knuckle pads with intrale- mutation carrier with 2 MC1R high-risk vari- Level of agreement with the British guidelines sional fluorouracil (letter) [Weiss] 1458 (No) ants [Figl] 495 (Ap) for the use of biological therapies for psoria- Fluticasone Multiple primary melanomas in a CDKN2A sis [Nijsten] 1567 (De) Perioral dermatitis associated with an inhaled mutation carrier exposed to ionizing radia- Groin corticosteroid (letter) [Poulos] 1460 (No) tion [Eliason] 1409 (No) Erythematous papules and plaques involving the Focal Dermal Hypoplasia Genetic Predisposition Testing see Genetic groin and scrotum [Breedlove] 1067 (Au) Erythematous atrophic macules and papules fol- Screening Gross, Paul lowing the lines of Blaschko [Quain] 109 (Ja) Genetic Predisposition to Disease Sponsorship of graduate medical education: one Clinical, biochemical, and genetic study of 11 Folliculitis successful model (letter) [James] 1211 (Se) patients with erythropoietic protoporphyria Skin disorders among construction workers fol- including one with homozygous disease lowing Hurricane Katrina and Hurricane Rita: H [Herrero] 1125 (Se) an outbreak investigation in New Orleans, Dermatology and the human genome: an epi- HAART see Antiretroviral Therapy, Highly Louisiana [Noe] 1393 (No) demiologic approach [Gwinn] 1194 (Se) Active Foot Familial acanthosis nigricans due to K650T Hair Bilateral symmetrical nodules on the feet [Fang] FGFR3 mutation [Berk] 1153 (Se) Scalp biopsy specimens: transverse vs vertical 417 (Mr) Next frontier of dermatologic research sections (research letter) [Garcia] 268 (Fe) Melanoma of the foot and ankle: a case series [Robinson] 1195 (Se) Hair Color of an underrecognized entity (research let- Palmar basal cell carcinoma in a patient with Hair graying in substance addiction (research letter) [Greenway] 543 (Ap) Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) ter) [Reece] 116 (Ja) Multiple plaques on the hands and feet [Lambert] Retinal toxic reactions following photopher- Hair Follicle 109 (Ja) esis [Vagace] 622 (My) Seborrheic keratosislike melanoma with follicu- Tender nodules on the palms and soles Role of filaggrin mutations as an etiologic fac- lotropism [Carrera] 373 (Mr) [Esler-Brauer] 1201 (Se) tor in atopic dermatitis [Zirwas] 1437 (No) Hair Transplantion Unusual presentation of cutaneous larva migrans Trimethylaminuria (fish-odor syndrome): a case Staged hair transplantation in cicatricial alope- (letter) [Sarasombath] 955 (Jy) report [Arseculeratne] 81 (Ja) cia after carbon dioxide laser–assisted scar tis- Forehead Genetic Screening sue remodeling [Kwon] 457 (Ap) Randomized double-blind study of the effect of Phenotypic variation in familial melanoma: con- Hamartoma Botox and Dysport/Reloxin on forehead sequences for predictive DNA testing Soft papules and nodules on the buttock wrinkles and electromyographic activity (re- [Bergman] 525 (Ap) [Pol-Rodriguez] 1583 (De) search letter) [Karsai] 1447 (No) Genome, Human Hand Fungal Infections Dermatology and the human genome: an epi- Acute and recurrent vesicular hand dermatitis Auricular erythema with nodules and scale demiologic approach [Gwinn] 1194 (Se) not pompholyx or dyshidrosis [Storrs] 1578 [Hutchin] 1441 (No) Next frontier of dermatologic research (De) Beefy red plaque in the popliteal fossa [Grekin] [Robinson] 1195 (Se) Multiple painless papules on the wrists [Callaly] 1323 (Oc) Geography 791 (Je) Crusted violaceous plaques on an immunocom- Distance to diagnosing provider as a measure of Multiple plaques on the hands and feet [Lambert] promised host [Xu] 417 (Mr) access for patients with melanoma 109 (Ja) Direct identification of dermatophyte DNA from [Stitzenberg] 991 (Au) Tender nodules on the palms and soles clinical specimens by a nested polymerase Giant Cells [Esler-Brauer] 1201 (Se) chain reaction assay (research letter) [Yang] Firm papule on the lateral tongue [Suwattee] Hand-Arm Vibration Syndrome 799 (Je) 1583 (De) Resolution of chronic pain and fingertip ulcer- Generalized papules in a patient with acute Glucagonoma ation due to hand-arm vibration syndrome fol- myeloid leukemia [Nakahigashi] 1583 (De) Necrolytic migratory erythema: the outermost lowing combination pharmacotherapy (let- Growth inhibition of Trichophyton species by marker for glucagonoma syndrome (letter) ter) [Buell] 1343 (Oc) Pseudomonas aeruginosa [Treat] 61 (Ja) [Gantcheva] 1221 (Se) Head and Neck Neoplasms Histopathologic findings of disseminated coc- Gluteal Region see Buttocks Head-tilt maneuver: a clinical aid in recogniz- cidioidomycosis with hyphae (letter) [Kappel] Goltz Syndrome see Focal Dermal Hypoplasia ing head and neck angiosarcomas [Asgari] 75 548 (Ap) Gorlin Syndrome see Basal Cell Nevus Syndrome (Ja) Nodular lesions on the arm [Chrusciak-Talhari] Gout Health Care Team see Patient Care Team 1323 (Oc) Diffuse nodules in a woman with renal failure Health Education Fungus Diseases see Mycoses [Lesesky] 1201 (Se) Teens and tans: implementing behavioral change Furunculosis Graft vs Host Disease [Haas] 1058 (Au)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E21 Health Knowledge, Attitudes, Practice Histiocytosis Hyaluronic Acid Teens and tans: implementing behavioral change Verruca plana–like papules as a new manifes- In vivo stimulation of de novo collagen produc- [Haas] 1058 (Au) tation of Erdheim-Chester disease (letter) tion caused by cross-linked hyaluronic acid Health Services Accessibility [Yanagi] 952 (Jy) dermal filler injections in photodamaged Distance to diagnosing provider as a measure of Histiocytosis, Langerhans-Cell human skin [Wang] 155 (Fe) access for patients with melanoma Crusted Norwegian scabies in an adult with Hydrocolloid Dressings see Bandages, [Stitzenberg] 991 (Au) Langerhans cell histiocytosis: mishaps leading Hydrocolloid Heart to systemic chemotherapy [Kartono] 626 (My) Hydrocortisone Signsofa“brokenheart”:suspectedMuehrckelines Era of targeted therapies: increasing role for novel Allergic contact dermatitis: another adverse effect after cardiac surgery (letter) [Weiser] 815 (Je) oncologic drugs in dermatology [Montella] 788 of over-the-counter topical hydrocortisone (let- Heart Atria (Je) ter) [Watsky] (reply) [Eaglstein] 1217 (Se) Atrial tachycardia associated with isotretinoin Petechial and red-brown papular lesions in a Topical hydrocortisone from prescription to use (letter) [Dresden] 1084 (Au) 2-year-old girl [Williams] 1067 (Au) over-the-counter sale: a past controversy: a cau- Heart Atrium see Heart Atria When a bump can be a hole (letter) [Fiala] 1083 tionary tale [Ravis] 413 (Mr) Hemangioendothelioma, Epithelioid (Au) Hydrogels Painful nodule on the knee [Heffernan] 937 (Jy) Histiocytosis, Non-Langerhans-Cell Consensus panel recommendations for chronic Hemangioma Adult disseminated primary papular xanthoma and acute wound dressings [Vaneau] 1291 AKT1 overexpression in endothelial cells leads treated with doxycycline (letter) [Bastida] 667 (Oc) to the development of cutaneous vascular mal- (My) Dressings for acute and chronic wounds: a sys- formations in vivo [Perry] 504 (Ap) Imatinib as a treatment option for systemic non- tematic review [Chaby] 1297 (Oc) Pneumocystis carinii pneumonia in infant treated Langerhans cell histiocytoses [Utikal] 736 (Je) Hydroxyurea with oral steroids for hemangioma (letter) Histiocytosis, Sinus Hydroxyurea-induced leg ulcers treated with a [Maronn] 1224 (Se) Imatinib as a treatment option for systemic non- protease-modulating matrix [Romanelli] 1310 Three-dimensional images and vessel render- Langerhans cell histiocytoses [Utikal] 736 (Je) (Oc) ing using optical coherence tomography Histocytological Preparation Techniques Hyperbaric Oxygenation [Thomas] 1468 (No) Diagnostic yield of histopathologic sampling Topical oxygen emulsion: a novel wound therapy Hemangioma, Capillary techniques in PAN-associated cutaneous ulcers [Davis] 1252 (Oc) Dermoscopy of pyogenic granulomas [Zaballos] (research letter) [Ricotti] 1334 (Oc) Hypereosinophilic Syndrome 824 (Je) Histological Techniques Hypereosinophilic syndrome with peripheral cir- Hemangiosarcoma Clinicopathologic correlation of cutaneous culatory insufficiency and cutaneous micro- Docetaxel monotherapy for angiosarcoma in an metastases: experience from a cancer center thrombi (letter) [Hamada] 812 (Je) elderly patient (letter) [Nagano] 1602 (De) [Sariya] 613 (My) Infliximab as a therapy for idiopathic hyper- Head-tilt maneuver: a clinical aid in recogniz- Exclusively benign dermoscopic pattern in a eosinophilic syndrome [Taverna] 1110 (Se) ing head and neck angiosarcomas [Asgari] 75 patient with acral melanoma (letter) [Braun] Hyperhidrosis (Ja) 1213 (reply) [Saida] 1215 (Se) Treatment of hyperhidrosis with oxybutynin (let- Hematopoietic Stem Cell Transplantation Histologic cutaneous modifications after the use ter) [Schollhammer] 544 (Ap) Eczematoid graft-vs-host disease: a novel form of EMLA cream, a diagnostic pitfall: review of Hyperhomocysteinemia of chronic cutaneous graft-vs-host disease and 13 cases (research letter) [Cazes] 1074 (Au) Paraneoplastic Raynaud phenomenon with digi- its response to psoralen–UV-A therapy Histoplasmosis tal necrosis associated with hyperhomocys- [Creamer] 1157 (Se) Papular eruption in an HIV-infected man [Swick] teinemia and antiphospholipid antibodies (let- Hemochromatosis 255 (Fe) ter) [Carducci] 1342 (Oc) Brown and black scaly patches on the lower leg History of Medicine Hyper-IgE Syndrome see Job’s Syndrome [Soderberg] 1441 (No) Topical hydrocortisone from prescription to Hyperkeratosis, Epidermolytic Hemorrhage over-the-counter sale: a past controversy: a cau- Persistent eosinophilia as a presenting sign of Consensus panel recommendations for chronic tionary tale [Ravis] 413 (Mr) scabies in patients with disorders of keratini- and acute wound dressings [Vaneau] 1291 (Oc) HIV Infections zation (letter) [Sluzevish] 670 (My) Hemostatic Techniques Multiple subcutaneous lipomas induced by Hyperparathyroidism Comparison of treatment options for a Monsel HAART in the absence of protease inhibitors Sodium thiosulfate as first-line treatment for cal- tattoo (letter) [Rao] 1452 (No) (letter) [Balestreire] 1596 (De) ciphylaxis (letter) [Ackermann] 1336 (re- Herpes Genitalis Papular eruption in an HIV-infected man [Swick] ply) [Robinson] 1338 (Oc) Virologic safety of polyvinyl chloride film in der- 255 (Fe) Hyperparathyroidism, Secondary moscopic analysis of mucosal areas (research Virologic safety of polyvinyl chloride film in der- Cinacalcet for the treatment of calciphylaxis letter) [Zampino] 945 (Jy) moscopic analysis of mucosal areas (research [Robinson] 152 (Fe) Herpes Gestationis see Pemphigoid Gestationis letter) [Zampino] 945 (Jy) Hyperpigmentation Herpes Simplex Hodgkin Disease Blue-black pigmentation of legs and arms in a 68- Intractable wounds from a herpes simplex infec- Multiple melanomas after treatment for Hodg- year-old woman [Lo´pez-Pestan˜ a] 1441 (No) tion in an immunosuppressed patient with kin lymphoma in a non-Dutch p16-Leiden Dermoscopic findings in Laugier-Hunziker syn- rheumatoid arthritis (letter) [Hanafusa] 1340 mutation carrier with 2 MC1R high-risk vari- drome [Gencoglan] 631 (My) (Oc) ants [Figl] 495 (Ap) Effect of cold air cooling on the incidence of Herpes Simplex, Genital see Herpes Genitalis Relapsing polychondritis and malignant lym- postinflammatory hyperpigmentation after Herpes Zoster phoma: is polychondritis paraneoplastic? Q-switched Nd:YAG laser treatment of Case of zosteriform pigmented purpuric derma- [Yanagi] 89 (Ja) acquired bilateral nevus of Ota–like macules tosis (letter) [Hamada] 1599 (De) Home Monitoring [Manuskiatti] 1139 (Se) Hidradenitis Teledermatological monitoring of leg ulcers in Hyperpigmented keratotic nodules [Chua] 1201 Tender nodules on the palms and soles cooperation with home care nurses [Binder] (Se) [Esler-Brauer] 1201 (Se) 1511 (De) Sock-line hyperpigmentation: case series and lit- Hispanic Americans Teledermatology: extending specialty care erature review (letter) [Berk] 428 (Mr) Clear cell papulosis in Hispanic siblings beyond borders [Burdick] 1581 (De) Hyperplasia [Benouni] 358 (Mr) Homocysteine Reflectance-mode confocal microscopy for the Prevalence of self-diagnosed melasma among Methotrexate and risk for lymphoma (letter) diagnosis of sebaceous hyperplasia in vivo premenopausal Latino women in Dallas and [Whitmore] 663 (My) [Propperova] 134 (Ja) Fort Worth, Tex (research letter) [Werlinger] Horses Hypertension, Pulmonary 424 (Mr) Equinology [Peterson] 438 (Mr) Bosentan as a rescue therapy in scleroderma Skin cancer awareness and sun protection behav- Hospitalization refractory digital ulcers (letter) [Chamaillard] iors in white Hispanic and white non- Wound complications following diagnostic skin 125 (Ja) Hispanic high school students in Miami, biopsies in dermatology inpatients [Wahie] Hyperuricemia Florida [Ma] 983 (Au) 1267 (Oc) Diffuse nodules in a woman with renal failure Histiocytoma, Benign Fibrous Hospitals, Teaching [Lesesky] 1201 (Se) Differences between polarized light dermos- Sponsorship of graduate medical education: one Hyphae copy and immersion contact dermoscopy for successful model (letter) [James] 1211 (Se) Histopathologic findings of disseminated coc- the evaluation of skin lesions [Benvenuto- Human Genome see Genome, Human cidioidomycosis with hyphae (letter) [Kappel] Andrade] 329 (Mr) Hurricanes see Natural Disasters 548 (Ap)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E22 Hypohidrosis Clinicopathologic correlation of cutaneous Inflammatory Bowel Diseases Goosefleshlike lesions and hypohidrosis metastases: experience from a cancer center Erythema nodosum–like eruption as a manifes- [Dimon] 1323 (Oc) [Sariya] 613 (My) tation of azathioprine hypersensitivity in Hypothalamo-Hypophyseal System Pigmented mammary Paget disease: dermo- patients with inflammatory bowel disease [de Suppression of the HPA axis in pediatric patients scopic, in vivo reflectance-mode confocal Fonclare] 744 (Je) with atopic dermatitis (letter) [Ishay] 1449 (No) microscopic, and immunohistochemical study Infliximab of a case [Longo] 752 (Je) Infliximab as a therapy for idiopathic hyper- I Immunologic Factors eosinophilic syndrome [Taverna] 1110 (Se) Epidermal Langerhans cell movement in situ: a Infliximab-induced palmoplantar pustulosis in Ichthyosiform Erythroderma, Bullous model for understanding immunologic func- a patient with Crohn disease (letter) [Sladden] Congenital see Hyperkeratosis, Epidermolytic tion in the skin [Mohr] 1352 (Oc); correc- 1449 (No) Idiopathic Hypereosinophilic Syndrome see tion, 1438 (No) Onset of psoriasis during treatment with TNF-␣ Hypereosinophilic Syndrome Immunosorbent Techniques antagonists: a report of 3 cases (letter) IgE see Immunoglobulin E Clinical response of severe mechanobullous epi- [Ubriani] 270 (Fe) Igneous Rock Sign see Lichen Planus dermolysis bullosa acquisita to combined treat- What are the risks of serious infections and Ileostomy ment with immunoadsorption and ritux- malignancies for patients treated with anti- Peristomal pyoderma gangrenosum associated imab (anti-CD20 monoclonal antibodies) tumor necrosis factor antibodies? [Corona] with collagenous colitis (letter) [Davis] 669 [Niedermeier] 192 (Fe) 405 (Mr) (My) Imaging, Three-Dimensional Immunosuppression Information Systems Three-dimensional images and vessel render- Intractable wounds from a herpes simplex infec- Wikis: the application of Web 2.0 [Johnson] ing using optical coherence tomography tion in an immunosuppressed patient with 1065 (Au) [Thomas] 1468 (No) rheumatoid arthritis (letter) [Hanafusa] 1340 Interferon Alfa Wound assessment by 3-dimensional laser scan- (Oc) Current status of evaluation and treatment of ning (research letter) [Romanelli] 1333 (Oc) Immunosuppressive Agents high-risk cutaneous melanoma: therapeutic Imatinib Combination immunosuppressive therapies: the breakthroughs remain elusive [Kanzler] 785 Era of targeted therapies: increasing role for novel promise and the peril [Robinson] 1053 (Au) (Je) oncologic drugs in dermatology [Montella] 788 In Situ Hybridization, Fluorescence Psoriasis and pustular dermatitis triggered by ␣ (Je) Clinical, histologic, and molecular study of 9 TNF- inhibitors in patients with rheumato- Imatinib as a treatment option for systemic non- cases of congenital dermatofibrosarcoma pro- logic conditions [de Gannes] 223 (Fe) Langerhans cell histiocytoses [Utikal] 736 (Je) tuberans [Maire] 203 (Fe) Systemic adjuvant therapy for patients with high- Lymphomatoid granulomatosis induced by ima- risk melanoma [Tsai] 779 (Je) Incidence ␣ tinib treatment (letter) [Yazdi] 1222 (Se) Incidence and risk factors for psoriasis in the gen- Yin and yang of TNF- inhibition [Fiorentino] Imiquimod eral population [Huerta] 1559 (De) 233 (Fe) Fifty-five basal cell carcinomas treated with topi- Infant Interferon Alfa-2a cal imiquimod: outcome at 5-year follow-up Childhood bullous pemphigoid: clinical and Cosmetic permanent fillers for soft tissue aug- (research letter) [Vidal] 266 (Fe) immunological findings in a series of 4 cases mentation: a new contraindication for inter- Treatment of atypical nevi with imiquimod 5% [Martinez-De Pablo] 215 (Fe) feron therapies [Fischer] 507 (Ap) cream [Somani] 379 (Mr) Clinical, histologic, and molecular study of 9 Interferon Alfa-2b Immune System cases of congenital dermatofibrosarcoma pro- Delayed wound healing following treatment with Functional dysregulation of dendritic cells in tuberans [Maire] 203 (Fe) low-dose interferon alfa-2b for cutaneous mela- patients with papular urticaria caused by flea- Pneumocystis carinii pneumonia in infant treated noma (letter) [Ammoury] 1339 (Oc) bite [Cue´llar] 1415 (No) with oral steroids for hemangioma (letter) Interferon Type I Staphylococcus aureus virulence factors associ- [Maronn] 1224 (Se) Psoriasiform eruptions during anti–TNF-␣ treat- ated with infected skin lesions: influence on Sock-line hyperpigmentation: case series and lit- ment: psoriasis or not? (letter) [Seneschal] the local immune response [Mertz] 1259 (Oc) erature review (letter) [Berk] 428 (Mr) 1593 (reply) [de Gannes] 1595 (De) Immunization Subcutaneous nodule and diffuse lymphade- Psoriasis and pustular dermatitis triggered by Subcutaneous nodule and diffuse lymphadenopathy in a 6-month-old boy from Africa TNF-␣ inhibitors in patients with rheumato- nopathy in a 6-month-old boy from Africa [Friedman] 1323 (Oc) logic conditions [de Gannes] 223 (Fe) [Friedman] 1323 (Oc) What is the chance of a normal pregnancy in a Yin and yang of TNF-␣ inhibition [Fiorentino] Immunoadsorbent Techniques see Immuno- woman whose fetus has been exposed to 233 (Fe) sorbent Techniques isotretinoin? [Sladden] 1187 (Se) Intergenerational Relations Immunocompromised Host When a bump can be a hole (letter) [Fiala] 1083 Awareness of generational differences is the first Intractable wounds from a herpes simplex infec- (Au) step (letter) [Garcia] 120 (Ja) tion in an immunosuppressed patient with rheu- Widespread granulomatous dermatitis of infancy: Internet matoid arthritis (letter) [Hanafusa] 1340 (Oc) an early sign of Blau syndrome [Schaffer] 386 Solitary cutaneous nodule in an immunocom- Accessible evidence-based medicine: critically (Mr) appraised topics [Barzilai] 1189 (Se) promised patient [Singh] 1583 (De) Infant, Newborn Immunoglobulin A Archives of Dermatology Web site: adding new Acute digital gangrene in a newborn (letter) dimensions to the literature [Bhatia] 1320 (Oc) Childhood bullous pemphigoid: clinical and [Wollina] 121 (Ja) immunological findings in a series of 4 cases Wikis: the application of Web 2.0 [Johnson] Erythematous atrophic macules and papules fol- 1065 (Au) [Martinez-De Pablo] 215 (Fe) lowing the lines of Blaschko [Quain] 109 (Ja) Internship and Residency Immunoglobulin E Herpes gestationis in a mother and newborn: Awareness of generational differences is the first Rituximab in a patient with hyper-IgE syn- immunoclinical perspectives based on a weekly step (letter) [Garcia] 120 (Ja) drome (letter) [Trendelenburg] 807 (Je) follow-up of the enzyme-linked immunosor- Role of IgE anti–basement membrane zone auto- bent assay index of a bullous pemphigoid anti- Interobserver Variation see Observer Variation antibodies in bullous pemphigoid [Woodley] gen noncollagenous domain [Aoyama] 1168 Intertrigo 249 (Fe) (Se) Intertriginous eruption associated with chemo- Immunoglobulin G Infarction therapy in pediatric patients [Webber] 67 (Ja) Childhood bullous pemphigoid: clinical and Diabetic muscle infarction (letter) [MacGregor] 3-year causative study of pompholyx in 120 immunological findings in a series of 4 cases 1456 (No) patients [Guillet] 1504 (De) [Martinez-De Pablo] 215 (Fe) Intoxication see Poisoning Role of IgE anti–basement membrane zone auto- Infection antibodies in bullous pemphigoid [Woodley] What are the risks of serious infections and Intrahepatic Cholestasis see Cholestasis, 249 (Fe) malignancies for patients treated with anti- Intrahepatic Immunoglobulin M tumor necrosis factor antibodies? [Corona] Iran Chronic urticaria and monoclonal IgM gam- 405 (Mr) Prevalence of skin diseases and cutaneous mani- mopathy (Schnitzler syndrome): report of 11 Infectious Diseases see Communicable Diseases festations among Iranian children: a survey of cases treated with pefloxacin [Asli] 1046 (Au) Inflammation 1417 children (research letter) [Toossi] 115 Immunohistochemistry Recurrent calcified cutaneous nodule of the peri- (Ja) Clinical, histologic, and molecular study of 9 anal region [Patrizi] 1441 (No) Isotretinoin cases of congenital dermatofibrosarcoma pro- Treatment of atypical nevi with imiquimod 5% Atrial tachycardia associated with isotretinoin tuberans [Maire] 203 (Fe) cream [Somani] 379 (Mr) use (letter) [Dresden] 1084 (Au)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E23 What is the chance of a normal pregnancy in a Kidney Transplantation Digital image analysis: a reliable tool in the quan- woman whose fetus has been exposed to Verrucous nodules on the toes of a renal trans- titative evaluation of cutaneous lesions and isotretinoin? [Sladden] 1187 (Se) plant recipient [Levy] 653 (My) beyond (research letter) [Pressley] 1331 (Oc) Israel Korea Hydroxyurea-induced leg ulcers treated with a Pemphigus variant associated with penicillin use: Association of androgenetic alopecia with smok- protease-modulating matrix [Romanelli] 1310 a case-cohort study of 363 patients from Israel ing and its prevalence among Asian men: a (Oc) [Heymann] 704 (Je) community-based survey [Su] 1401 (No) Physical activity and adherence to compres- Ivermectin sion therapy in patients with venous leg ulcers Crusted Norwegian scabies in an adult with L [Heinen] 1283 (Oc) Langerhans cell histiocytosis: mishaps lead- Skin cancer presenting as a nonhealing wound: Lacazia loboi ing to systemic chemotherapy [Kartono] 626 the association of polio and skin cancer (let- Nodular lesions on the arm [Chrusciak-Talhari] (My) ter) [Vu] 1338 (Oc) 1323 (Oc) Persistent eosinophilia as a presenting sign of Sodium thiosulfate as first-line treatment for cal- Langerhans Cells scabies in patients with disorders of keratini- ciphylaxis (letter) [Ackermann] 1336 (re- Epidermal Langerhans cell movement in situ: a zation (letter) [Sluzevish] 670 (My) ply) [Robinson] 1338 (Oc) model for understanding immunologic func- Teledermatological monitoring of leg ulcers in J tion in the skin [Mohr] 1352 (Oc); correc- cooperation with home care nurses [Binder] tion, 1438 (No) 1511 (De) Japan Larva Migrans Teledermatology: extending specialty care Exclusively benign dermoscopic pattern in a Unusual presentation of cutaneous larva migrans beyond borders [Burdick] 1581 (De) patient with acral melanoma (letter) [Braun] (letter) [Sarasombath] 955 (Jy) Wound assessment by 3-dimensional laser scan- 1213 (reply) [Saida] 1215 (Se) Lasers ning (research letter) [Romanelli] 1333 (Oc) Effect of cold air cooling on the incidence of Jaundice, Neonatal Legislation postinflammatory hyperpigmentation after Evidence insufficient to recommend mela- Indoor UV tanning youth access laws: update Q-switched Nd:YAG laser treatment of noma surveillance following phototherapy for 2007 [McLaughlin] 529 (Ap) acquired bilateral nevus of Ota–like macules jaundice (letter) [Newman] (reply) [Manuskiatti] 1139 (Se) LEOPARD Syndrome [Descamps] 1216 (Se) Fractional photothermolysis for the treatment Novel PTPN11 gene mutation in a patient with Job’s Syndrome of adult colloid milium [Marra] 572 (My) LEOPARD syndrome (research letter) Rituximab in a patient with hyper-IgE syn- Fractional resurfacing: a new therapeutic modal- [Du-Thanh] 1210 (Se) drome (letter) [Trendelenburg] 807 (Je) ity for Becker’s nevus [Glaich] 1488 (De) Leprosy Pupil damage after periorbital laser treatment of Angiogenesis in cutaneous lesions of leprosy: K a port-wine stain [Hammes] 392 (Mr) implications for treatment [Bhandarkar] 1527 Pulsed-dye laser treatment of nonhealing chronic (De) Kaposi Sarcoma see Sarcoma, Kaposi ulcer with hypergranulation tissue [Wang] 700 Letterer-Siwe Syndrome see Histiocytosis, Katrina, Hurricane see Natural Disasters (Je) Langerhans-Cell Keratins Staged hair transplantation in cicatricial alope- Leukemia, Myeloid Persistent eosinophilia as a presenting sign of cia after carbon dioxide laser–assisted scar tis- Generalized papules in a patient with acute scabies in patients with disorders of keratini- sue remodeling [Kwon] 457 (Ap) myeloid leukemia [Nakahigashi] 1583 (De) zation (letter) [Sluzevish] 670 (My) Wound assessment by 3-dimensional laser scan- Leukemia, Promyelocytic, Acute Keratoacanthoma ning (research letter) [Romanelli] 1333 (Oc) Leukemia cutis: a presenting sign in acute pro- Eruptive keratoacanthomas in a new tattoo (let- Laugier-Hunziker Syndrome see Hyper- myelocytic leukemia (letter) [Markowski] ter) [Chorny] 1457 (No) pigmentation 1220 (Se) Learning Keratosis Leukocidins Accessible evidence-based medicine: critically Crusted Norwegian scabies in an adult with Staphylococcus aureus virulence factors associ- appraised topics [Barzilai] 1189 (Se) Langerhans cell histiocytosis: mishaps lead- ated with infected skin lesions: influence on Efficacy of a partner assistance intervention ing to systemic chemotherapy [Kartono] 626 the local immune response [Mertz] 1259 (Oc) (My) designed to increase skin self-examination per- Leukocyte Count Hyperpigmented keratotic nodules [Chua] 1201 formance [Robinson] 37 (Ja) Staphylococcus aureus virulence factors associ- (Se) Leflunomide ated with infected skin lesions: influence on Prevalence of skin diseases and cutaneous mani- Onset of psoriasis during treatment with TNF-␣ the local immune response [Mertz] 1259 (Oc) festations among Iranian children: a survey of antagonists: a report of 3 cases (letter) 1417 children (research letter) [Toossi] 115 [Ubriani] 270 (Fe) Leukoencephalopathy, Progressive Multifocal (Ja) Leg Disseminated cutaneous Kaposi sarcoma and Beefy red plaque in the popliteal fossa [Grekin] progressive multifocal leukoencephalopathy Keratosis, Actinic ϩ Sun-related factors, Betapapillomavirus, and ac- 1323 (Oc) in a patient with idiopathic CD4 T lympho- tinic keratoses: a prospective study [McBride] Dermoscopy subpattern of plaque-type psoriasis: cytopenia (letter) [Inhoff] 673 (My) 862 (Jy) red globular rings [Va´zquez-Lo´pez] 1612 (De) Levofloxacin see Ofloxacin Keratosis Follicularis Diabetic muscle infarction (letter) [MacGregor] Lice Infestations Keratotic papules on the right side of the neck 1456 (No) “Louse blouse” as a cause of erythroderma and back [Bowe] 535 (Ap) Erythema and blistering of the left leg [Irizarry] 682 (My) [Shimanovich] 535 (Ap) Lichen Amyloidosis Keratosis, Lymphomatoid see Pseudolymphoma Glistening brown nodule [Scheinfeld] 255 (Fe) Keratosis, Seborrheic Pruritic patches on the back and papules on the Injection drug use: an understudied cause of legs [Garg] 255 (Fe) Dermatoscopic changes in acquired melano- venous disease [Pieper] 1305 (Oc) cytic nevi and seborrheic keratoses after the Nocardia otitidiscaviarum: cause of long-term Lichen Myxedematosus see Scleromyxedema application of a self-tanning airbrush (letter) cutaneous abscesses on the leg of an immu- Lichen Planus [Martin] 1453 (No) nocompetent man (letter) [Thoms] 1086 (Au) Ambiguous igneous rocks (letter) [Reynolds] Differences between polarized light dermos- Primary cutaneous diffuse large B-cell lymphoma, 118 (Ja) copy and immersion contact dermoscopy for leg type: clinicopathologic features and prognos- Dermoscopy of active lichen planus the evaluation of skin lesions tic analysis in 60 cases [Grange] 1144 (Se) [Va´zquez-Lo´pez] 1092 (Au) [Benvenuto-Andrade] 329 (Mr) Rapidly enlarging necrotic ulcer on the right calf New and old therapeutics for oral ulcerations Seborrheic keratosislike melanoma with follicu- [Chakrabarti] 791 (Je) [Bruce] 519 (Ap) lotropism [Carrera] 373 (Mr) Results of radiotherapy in 153 primary cutane- Oral lichen planus: a case series with emphasis Kidney Failure ous B-cell lymphomas classified according to on therapy [Torti] 511 (Ap) Diffuse nodules in a woman with renal failure the WHO-EORTC classification [Senff] 1520 Treatment of oral erosive lichen planus with 1% [Lesesky] 1201 (Se) (De) pimecrolimus cream: a double-blind, random- Kidney Failure, Chronic Tender erythema of the left lower extremity ized, prospective trial with measurement of Rapidly enlarging necrotic ulcer on the right calf [Szyfelbein] 535 (Ap) pimecrolimus levels in the blood [Passeron] [Chakrabarti] 791 (Je) Leg Ulcer 472 (Ap) Sodium thiosulfate as first-line treatment for cal- Association between the use of ␤-adrenergic Lichen Sclerosus et Atrophicus ciphylaxis (letter) [Ackermann] 1336 (re- receptor agents and the development of venous Narrowband UV-B phototherapy for extrageni- ply) [Robinson] 1338 (Oc) leg ulcers [Margolis] 1275 (Oc) tal lichen sclerosus (letter) [Kreuter] 1213 (Se)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E24 Progressive extragenital lichen sclerosus suc- Relapsing polychondritis and malignant lym- Mediterranean Fever, Familial see Familial cessfully treated with narrowband UV-B pho- phoma: is polychondritis paraneoplastic? Mediterranean Fever totherapy [Colbert] 19 (Ja) [Yanagi] 89 (Ja) Melanocytes Lichenoid Eruptions Second lymphomas and other malignant neo- Ex vivo dermoscopy of melanocytic tumors: time Lichen spinulosus: excellent response to treti- plasms in patients with mycosis fungoides and for dermatopathologists to learn dermos- noin gel and hydroactive adhesive applica- Se´zary syndrome: evidence from population- copy [Scope] 1548 (De) tions (letter) [Forman] 122 (Ja) based and clinical cohorts [Huang] 45 (Ja) Koebner phenomenon in vitiligo: not always an Lidocaine Lymphoma, B-Cell indication of surgical failure (research letter) Histologic cutaneous modifications after the use Persistent violaceous papules on the ears [Mulekar] 801 (Je) of EMLA cream, a diagnostic pitfall: review of [Blumetti] 417 (Mr) Melanoma 13 cases (research letter) [Cazes] 1074 (Au) Primary cutaneous diffuse large B-cell lym- Cloud over sentinel node biopsy: unlikely sur- phoma, leg type: clinicopathologic features and Light vival benefit in melanoma [Gonza´lez] 775 (Je) prognostic analysis in 60 cases [Grange] 1144 In vivo stimulation of de novo collagen produc- Confusing message will not improve the detection caused by cross-linked hyaluronic acid (Se) tion of melanoma (letter) [Bystryn] (reply) dermal filler injections in photodamaged Results of radiotherapy in 153 primary cutane- [Kelly] 806 (Je) human skin [Wang] 155 (Fe) ous B-cell lymphomas classified according to Correlation of dermoscopy with in vivo reflec- Light Sensitivity see Photophobia the WHO-EORTC classification [Senff] 1520 tance confocal microscopy of streaks in mela- (De) Light Therapy see Phototherapy nocytic lesions [Scope] 727 (Je) Lymphoma, Large-Cell, Ki-1 Lip Neoplasms Current status of evaluation and treatment of Fulminant cutaneous eruption in a 51-year-old Asymptomatic cutaneous lip plaque [Redd] 791 high-risk cutaneous melanoma: therapeutic man [Thakuria] 255 (Fe) (Je) breakthroughs remain elusive [Kanzler] 785 Nodule on a boy’s back [De Aloe] 417 (Mr) Lipid Peroxides (Je) Lymphoma, Large-Cell, Diffuse Effect of intense pulsed-light exposure on lipid Delayed wound healing following treatment with Persistent violaceous papules on the ears peroxides and thymine dimers in human skin low-dose interferon alfa-2b for cutaneous mela- in vivo [Sorg] 363 (Mr) [Blumetti] 417 (Mr) noma (letter) [Ammoury] 1339 (Oc) Primary cutaneous diffuse large B-cell lym- Lipodystrophy Dermoscopy not yet shown to increase sensi- phoma, leg type: clinicopathologic features and Multiple subcutaneous lipomas induced by tivity of melanoma diagnosis in real practice HAART in the absence of protease inhibitors prognostic analysis in 60 cases [Grange] 1144 (letter) [Carli] 664 (replies) [Menzies, (letter) [Balestreire] 1596 (De) (Se) Zalaudek] 665, 666 (My) Lymphoma, Malignant see Lymphoma Lipoma Distance to diagnosing provider as a measure of Multiple subcutaneous lipomas induced by Lymphoma, Non-Hodgkin access for patients with melanoma HAART in the absence of protease inhibitors Relapsing polychondritis and malignant lym- [Stitzenberg] 991 (Au) (letter) [Balestreire] 1596 (De) phoma: is polychondritis paraneoplastic? Early melanomas dermoscopically character- Liver [Yanagi] 89 (Ja) ized by reticular depigmentation (letter) Comparison of oral methylprednisolone plus aza- Lymphoma, T-Cell, Cutaneous [Lozzi] 808 (Je) thioprine or mycophenolate mofetil for the Apoptotic responses to all-trans retinoic acid of Effect of health care delivery models on mela- treatment of bullous pemphigoid [Beissert] ϩ targretin-resistant, malignant, CD4 periph- noma thickness and stage in a university- 1536 (De) eral blood T cells from patients with Se´zary based referral center: an observational pilot Liver Cirrhosis syndrome (research letter) [Newton] 661 (My) study [Swetter] 30 (Ja) Reliability of the Roenigk classification of liver Cutaneous T-cell lymphoid dyscrasia: a unify- Efficacy of a partner assistance intervention damage after methotrexate treatment for pso- ing term for idiopathic chronic dermatoses designed to increase skin self-examination per- riasis: a clinicopathologic study of 160 liver with persistent T-cell clones [Guitart] 921 (Jy) formance [Robinson] 37 (Ja) biopsy specimens [Berends] 1515 (De) Cutaneous T-cell lymphoma epidemiology: Epidermolysis bullosa nevus: an exception to the Liver Fibrosis see Liver Cirrhosis patients providing the power [Lessin] 916 (Jy) clinical and dermoscopic criteria for mela- Liver Neoplasms Incidence of cutaneous T-cell lymphoma in the noma [Cash] 1164 (Se) Lymphomatoid granulomatosis induced by ima- United States, 1973-2002 [Criscione] 854 (Jy) Evidence insufficient to recommend mela- tinib treatment (letter) [Yazdi] 1222 (Se) Measuring HRQOL in patients with cutaneous noma surveillance following phototherapy for Lobomycosis T-cell lymphoma undergoing therapy with oral jaundice (letter) [Newman] (reply) Nodular lesions on the arm [Chrusciak-Talhari] bexarotene and extracorporeal photopher- [Descamps] 1216 (Se) 1323 (Oc) esis (research letter) [Demierre] 659 (My) Ex vivo dermoscopy of melanocytic tumors: time Local Government Palliative care in patients with primary cutane- for dermatopathologists to learn dermos- Indoor UV tanning youth access laws: update ous lymphoma: symptom burden and char- copy [Scope] 1548 (De) 2007 [McLaughlin] 529 (Ap) acteristics of hospital palliative care team input Exclusively benign dermoscopic pattern in a Lupus Erythematosus, Discoid (research letter) [LeBon] 423 (Mr) patient with acral melanoma (letter) [Braun] Discoid and subacute lupus erythematosus Retinal toxic reactions following photopher- 1213 (reply) [Saida] 1215 (Se) treated with 0.5% r-salbutamol cream (re- esis [Vagace] 622 (My) Fast-growing and slow-growing melanomas (let- search letter) [Wulf] 1589 (De) Lymphomatoid Granulomatosis ter) [Argenziano] 802 (reply) [Kelly] 803 (Je) Efalizumab in the treatment of discoid lupus ery- Lymphomatoid granulomatosis induced by ima- Identification of incipient tumors by means of thematosus [Usmani] 873 (Jy) tinib treatment (letter) [Yazdi] 1222 (Se) sequential dermoscopy imaging: a new way to Lymph Node Excision Lymphomatoid Keratosis see Pseudolymphoma inflate the “epidemic” of melanoma? (letter) Cloud over sentinel node biopsy: unlikely sur- [Carli] (reply) [Kittler] 805 (Je) vival benefit in melanoma [Gonza´lez] 775 (Je) M Immunohistochemical expression of platelet Current status of evaluation and treatment of growth factor and vascular endothelial growth high-risk cutaneous melanoma: therapeutic Malignant Melanoma see Melanoma factor in patients with melanoma with and breakthroughs remain elusive [Kanzler] 785 Marghoob, Ashfaq A without redness (Brenner sign) [Mashiah] (Je) Monthly final page: skINsight [Grichnik] 1433 1001 (Au) Lymphadenectomy see Lymph Node Excision (No) Increasing ratio of thin to thick melanoma Lymphadenopathy see Lymphatic Diseases Marijuana see Cannabis lesions: pathogenesis and early detection of this Lymphatic Diseases Mass Screening cancer (letter) [Bystryn] (reply) [Lipsker] 804 Subcutaneous nodule and diffuse lymphade- Melanoma screening: focusing the public health (Je) nopathy in a 6-month-old boy from Africa journey [Koh] 101 (Ja) Indoor UV tanning youth access laws: update [Friedman] 1323 (Oc) Visual screening for malignant melanoma: a cost- 2007 [McLaughlin] 529 (Ap) T-Lymphocytopenia, Idiopathic CD4-Positive effectiveness analysis [Losina] 21 (Ja) Long-term follow-up of a patient with eruptive Disseminated cutaneous Kaposi sarcoma and Matrix Metalloproteinases melanocytic nevi after Stevens-Johnson syn- progressive multifocal leukoencephalopathy Hydroxyurea-induced leg ulcers treated with a drome [Gelfer] 1555 (De) ϩ in a patient with idiopathic CD4 T lympho- protease-modulating matrix [Romanelli] 1310 Melanoma of the foot and ankle: a case series cytopenia (letter) [Inhoff] 673 (My) (Oc) of an underrecognized entity (research let- Lymphoid Hyperplasia, Reactive see Medicare ter) [Greenway] 543 (Ap) Pseudolymphoma Melanoma outcomes for Medicare patients: asso- Melanoma outcomes for Medicare patients: asso- Lymphoma ciation of stage and survival with detection by ciation of stage and survival with detection by Methotrexate and risk for lymphoma (letter) a dermatologist vs a nondermatologist [Pennie] a dermatologist vs a nondermatologist [Pennie] [Whitmore] 663 (reply) [Stern] 664 (My) 488 (Ap) 488 (Ap)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E25 Melanoma screening: focusing the public health not an indication of lymph node metastases Mothers journey [Koh] 101 (Ja) in human melanoma (research letter) [Otto] Herpes gestationis in a mother and newborn: Multiple melanomas after treatment for Hodg- 947 (Jy) immunoclinical perspectives based on a weekly kin lymphoma in a non-Dutch p16-Leiden Metalloproteinases see Metalloproteases follow-up of the enzyme-linked immunosorbent mutation carrier with 2 MC1R high-risk vari- Methotrexate assayindexofabullouspemphigoidantigennon- ants [Figl] 495 (Ap) Methotrexate and risk for lymphoma (letter) collagenous domain [Aoyama] 1168 (Se) Multiple primary melanomas in a CDKN2A [Whitmore] 663 (reply) [Stern] 664 (My) Motor Activity mutation carrier exposed to ionizing radia- New and old therapeutics for oral ulcerations Physical activity and adherence to compres- tion [Eliason] 1409 (No) [Bruce] 519 (Ap) sion therapy in patients with venous leg ulcers Osteopontin expression in Spitz nevi (research Onset of psoriasis during treatment with TNF-␣ [Heinen] 1283 (Oc) letter) [Winfield] 1076 (Au) antagonists: a report of 3 cases (letter) Mouth Overexpression of matrix metalloproteinases, [Ubriani] 270 (Fe) New and old therapeutics for oral ulcerations chemokines, and chemokine receptors rel- Oral lichen planus: a case series with emphasis [Bruce] 519 (Ap) evant for metastasis in experimental models on therapy [Torti] 511 (Ap) Oral lichen planus: a case series with emphasis not an indication of lymph node metastases Reliability of the Roenigk classification of liver on therapy [Torti] 511 (Ap) in human melanoma (research letter) [Otto] damage after methotrexate treatment for pso- Perioral dermatitis associated with an inhaled 947 (Jy) riasis: a clinicopathologic study of 160 liver corticosteroid (letter) [Poulos] 1460 (No) Patterns of indoor tanning use: implications for biopsy specimens [Berends] 1515 (De) Randomized, double-blind, placebo-controlled clinical interventions [Hillhouse] 1530 (De) Methoxsalen trial of pentoxifylline for the treatment of re- Phenotypic variation in familial melanoma: con- Retinal toxic reactions following photopher- current aphthous stomatitis [Thornhill] 463 sequences for predictive DNA testing esis [Vagace] 622 (My) (Ap); correction, 716 (Je) [Bergman] 525 (Ap) Methyl Aminolevulinate Treatment of oral erosive lichen planus with 1% Pigmented mammary Paget disease: dermo- Five-year follow-up of a randomized, prospec- pimecrolimus cream: a double-blind, random- scopic, in vivo reflectance-mode confocal tive trial of topical methyl aminolevulinate ized, prospective trial with measurement of microscopic, and immunohistochemical study photodynamic therapy vs surgery for nodu- pimecrolimus levels in the blood [Passeron] of a case [Longo] 752 (Je) lar basal cell carcinoma [Rhodes] 1131 (Se) 472 (Ap) Seborrheic keratosislike melanoma with follicu- Methylprednisolone Mucinoses lotropism [Carrera] 373 (Mr) Comparison of oral methylprednisolone plus aza- Blaschko linear nodular morphea with dermal Subungual melanoma in situ in a Hispanic girl thioprine or mycophenolate mofetil for the mucinosis (letter) [Jain] 953 (Jy) treated with functional resection and recon- treatment of bullous pemphigoid [Beissert] Multiple painless papules on the wrists [Callaly] struction with onychocutaneous toe free flap 1536 (De) 791 (Je) (letter) [Motta] 1600 (De) Mice Mupirocin Systemic adjuvant therapy for patients with high- AKT1 overexpression in endothelial cells leads Use of antibiotic ointment after clean cutane- risk melanoma [Tsai] 779 (Je) to the development of cutaneous vascular mal- ous surgery [Bigby] 1180 (Se) Visual screening for malignant melanoma: a cost- formations in vivo [Perry] 504 (Ap) Muscles effectiveness analysis [Losina] 21 (Ja) Microscopy, Confocal Diabetic muscle infarction (letter) [MacGregor] Melanoma, Amelanotic Correlation of dermoscopic structures of mela- 1456 (No) Dermoscopic vascular patterns in nodular “pure” nocytic lesions to reflectance confocal micros- Music amelanotic melanoma [Cavicchini] 556 (Ap) copy [Scope] 176 (Fe) Resolution of chronic pain and fingertip ulcer- Dermoscopy patterns of eczemalike melanoma Correlation of dermoscopy with in vivo reflec- ation due to hand-arm vibration syndrome fol- (letter) [Giacomel] 1081 (Au) tance confocal microscopy of streaks in mela- lowing combination pharmacotherapy (let- Differences between polarized light dermos- nocytic lesions [Scope] 727 (Je) ter) [Buell] 1343 (Oc) copy and immersion contact dermoscopy for Dendritic cells in pigmented basal cell carci- Mutation the evaluation of skin lesions noma: a relevant finding by reflectance- Clinical, biochemical, and genetic study of 11 [Benvenuto-Andrade] 329 (Mr) mode confocal microscopy [Segura] 883 (Jy) patients with erythropoietic protoporphyria Melanosis Pigmented mammary Paget disease: dermo- including one with homozygous disease Fractional resurfacing: a new therapeutic modal- scopic, in vivo reflectance-mode confocal [Herrero] 1125 (Se) ity for Becker’s nevus [Glaich] 1488 (De) microscopic, and immunohistochemical study Dermatology and the human genome: an epi- Prevalence of self-diagnosed melasma among of a case [Longo] 752 (Je) demiologic approach [Gwinn] 1194 (Se) premenopausal Latino women in Dallas and Reflectance-mode confocal microscopy for the Familial acanthosis nigricans due to K650T Fort Worth, Tex (research letter) [Werlinger] diagnosis of sebaceous hyperplasia in vivo FGFR3 mutation [Berk] 1153 (Se) 424 (Mr) [Propperova] 134 (Ja) Multiple melanomas after treatment for Hodg- Melanotic Macule Miliaria kin lymphoma in a non-Dutch p16-Leiden Effect of cold air cooling on the incidence of Goosefleshlike lesions and hypohidrosis mutation carrier with 2 MC1R high-risk vari- postinflammatory hyperpigmentation after [Dimon] 1323 (Oc) ants [Figl] 495 (Ap) Q-switched Nd:YAG laser treatment of Mixed Function Oxygenases Multiple primary melanomas in a CDKN2A acquired bilateral nevus of Ota–like macules Trimethylaminuria (fish-odor syndrome): a case mutation carrier exposed to ionizing radia- [Manuskiatti] 1139 (Se) report [Arseculeratne] 81 (Ja) tion [Eliason] 1409 (No) Melasma see Melanosis Mohs Surgery Novel PTPN11 gene mutation in a patient with Men’s Health Pulsed-dye laser treatment of nonhealing chronic LEOPARD syndrome (research letter) Association of androgenetic alopecia with smok- ulcer with hypergranulation tissue [Wang] 700 [Du-Thanh] 1210 (Se) ing and its prevalence among Asian men: a (Je) Phenylephrine-induced microvascular occlu- community-based survey [Su] 1401 (No) Molecular Diagnostic Techniques sion syndrome in a patient with a heterozy- Mental Health Clinical, histologic, and molecular study of 9 gous factor V Leiden mutation [Kalajian] 1314 Predictors of skin-related quality of life after treat- cases of congenital dermatofibrosarcoma pro- (Oc) ment of cutaneous basal cell carcinoma and tuberans [Maire] 203 (Fe) Role of filaggrin mutations as an etiologic fac- squamous cell carcinoma [Chen] 1386 (No) Mongolian Spot tor in atopic dermatitis [Zirwas] 1437 (No) Mentors Prevalence of skin diseases and cutaneous mani- Trimethylaminuria (fish-odor syndrome): a case Sponsorship of graduate medical education: one festations among Iranian children: a survey of report [Arseculeratne] 81 (Ja) successful model (letter) [James] 1211 (Se) 1417 children (research letter) [Toossi] 115 (Ja) Mutation, Missense Meta-Analysis Monitoring, Physiologic Novel missense mutation in the CYLD gene in a What are the risks of serious infections and Wound assessment by 3-dimensional laser scan- Spanish family with multiple familial trichoepi- malignancies for patients treated with anti- ning (research letter) [Romanelli] 1333 (Oc) thelioma (research letter) [Espan˜ a] 1209 (Se) tumor necrosis factor antibodies? [Corona] Monoclonal Gammopathies see Mycobacterium bovis 405 (Mr) Paraproteinemias Subcutaneous nodule and diffuse lymphade- Metabolic Diseases Monooxygenases see Mixed Function nopathy in a 6-month-old boy from Africa Trimethylaminuria (fish-odor syndrome): a case Oxygenases [Friedman] 1323 (Oc) report [Arseculeratne] 81 (Ja) Morphea see Scleroderma, Localized Mycobacterium chelonae Metalloproteases Mortality Dissemination of a localized cutaneous infec- Overexpression of matrix metalloproteinases, Risk of mortality in patients with psoriasis: results tion with Mycobacterium chelonae under immu- chemokines, and chemokine receptors rel- from a population-based study [Gelfand] 1493 nosuppressive treatment (letter) evant for metastasis in experimental models (De) [Hoetzenecker] 951 (Jy)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E26 Mycobacterium leprae Leukemia cutis: a presenting sign in acute pro- Nevus, Blue Angiogenesis in cutaneous lesions of leprosy: myelocytic leukemia (letter) [Markowski] Blue-gray subungual discoloration [Dalle] 937 implications for treatment [Bhandarkar] 1527 1220 (Se) (Jy) (De) Lymphomatoid granulomatosis induced by ima- Clinical and dermoscopic features of agmi- Mycophenolate Mofetil tinib treatment (letter) [Yazdi] 1222 (Se) nated blue nevus (letter) [Pizzichetta] 1225 Comparison of oral methylprednisolone plus aza- Nodule on the toe [Dapprich] 1067 (Au) (Se) thioprine or mycophenolate mofetil for the Overexpression of matrix metalloproteinases, Dermoscopy insights into nevogenesis: “abtrop- treatment of bullous pemphigoid [Beissert] chemokines, and chemokine receptors rel- fung” vs “hochsteigerung” [Zalaudek] 284 (Fe) 1536 (De) evant for metastasis in experimental models Differences between polarized light dermos- Mycoses not an indication of lymph node metastases copy and immersion contact dermoscopy for Generalized papules in a patient with acute in human melanoma (research letter) [Otto] the evaluation of skin lesions myeloid leukemia [Nakahigashi] 1583 (De) 947 (Jy) [Benvenuto-Andrade] 329 (Mr) Solitary cutaneous nodule in an immunocom- Second lymphomas and other malignant neo- Nevus, Dysplastic promised patient [Singh] 1583 (De) plasms in patients with mycosis fungoides and Ex vivo dermoscopy of melanocytic tumors: time Mycosis Fungoides Se´zary syndrome: evidence from population- for dermatopathologists to learn dermos- Cutaneous T-cell lymphoid dyscrasia: a unify- based and clinical cohorts [Huang] 45 (Ja) copy [Scope] 1548 (De) ing term for idiopathic chronic dermatoses Neoplasm Recurrence, Local Nevus, Epithelioid and Spindle Cell with persistent T-cell clones [Guitart] 921 (Jy) Systemic adjuvant therapy for patients with high- Involution: the natural evolution of pigmented Measuring HRQOL in patients with cutaneous risk melanoma [Tsai] 779 (Je) Spitz and Reed nevi? (letter) [Argenziano] 549 T-cell lymphoma undergoing therapy with oral Treatment of recurrent squamous cell carci- (Ap) bexarotene and extracorporeal photopher- noma of the skin with cetuximab [Bauman] Osteopontin expression in Spitz nevi (research esis (research letter) [Demierre] 659 (My) 889 (Jy) letter) [Winfield] 1076 (Au) Multiple plaques on the hands and feet [Lambert] Neoplasm Staging 109 (Ja) Effect of health care delivery models on mela- Nevus, Melanocytic see Nevus, Pigmented Second lymphomas and other malignant neo- noma thickness and stage in a university- Nevus of Ota plasms in patients with mycosis fungoides and based referral center: an observational pilot Effect of cold air cooling on the incidence of Se´zary syndrome: evidence from population- study [Swetter] 30 (Ja) postinflammatory hyperpigmentation after based and clinical cohorts [Huang] 45 (Ja) Melanoma outcomes for Medicare patients: asso- Q-switched Nd:YAG laser treatment of Myelodysplastic Syndromes ciation of stage and survival with detection by acquired bilateral nevus of Ota–like macules Relapsing polychondritis and malignant lym- a dermatologist vs a nondermatologist [Pennie] [Manuskiatti] 1139 (Se) phoma: is polychondritis paraneoplastic? 488 (Ap) Nevus, Pigmented [Yanagi] 89 (Ja) Neoplasms Age- and site-specific variation in the dermo- Myiasis What are the risks of serious infections and scopic patterns of congenital melanocytic nevi: Dermoscopic diagnosis of furuncular myiasis malignancies for patients treated with anti- an aid to accurate classification and assess- (letter) [Bakos] 123 (Ja) tumor necrosis factor antibodies? [Corona] ment of melanocytic nevi [Changchien] 1007 405 (Mr) N (Au) Neoplasms, Adnexal and Skin Appendage Correlation of dermoscopic structures of mela- Clinicopathologic correlation of cutaneous Nails nocytic lesions to reflectance confocal micros- metastases: experience from a cancer center Blue-gray subungual discoloration [Dalle] 937 copy [Scope] 176 (Fe) [Sariya] 613 (My) (Jy) Dermatoscopic changes in acquired melano- Neoplasms, Basal Cell Signs of a “broken heart”: suspected Muehrcke cytic nevi and seborrheic keratoses after the Five-year follow-up of a randomized, prospec- lines after cardiac surgery (letter) [Weiser] 815 application of a self-tanning airbrush (letter) tive trial of topical methyl aminolevulinate (Je) [Martin] 1453 (No) photodynamic therapy vs surgery for nodu- Subungual exostosis [Sa´nchez-Castellanos] 1234 Dermoscopic changes in acral melanocytic nevi lar basal cell carcinoma [Rhodes] 1131 (Se) (Se) during digital follow-up [Altamura] 1372 (No) Subungual melanoma in situ in a Hispanic girl Neovascularization, Pathologic Dermoscopic patterns of acral melanocytic nevi: treated with functional resection and recon- Active angiogenesis in an extensive arteriove- their variations, changes, and significance struction with onychocutaneous toe free flap nous vascular malformation: a possible thera- [Saida] 1423 (No) (letter) [Motta] 1600 (De) peutic target? [Redondo] 1043 (Au) Dermoscopy insights into nevogenesis: “abtrop- National Eczema Association for Science and Angiogenesis in cutaneous lesions of leprosy: fung” vs “hochsteigerung” [Zalaudek] 284 (Fe) Education implications for treatment [Bhandarkar] 1527 Differences between polarized light dermoscopy National Eczema Association and topical calci- (De) and immersion contact dermoscopy for the neurin inhibitor labeling (letter) [Cooper] 546 Nephrogenic Fibrosing Dermopathy evaluation of skin lesions [Benvenuto-Andrade] (Ap) Nephrogenic systemic fibrosis: relationship to 329 (Mr) Natural Disasters gadolinium and response to photopheresis Epidermolysis bullosa nevus: an exception to the Skin disorders among construction workers fol- [Richmond] 1025 (Au); correction, 1565 (De) clinical and dermoscopic criteria for mela- lowing Hurricane Katrina and Hurricane Rita: Nephrogenic Systemic Fibrosis noma [Cash] 1164 (Se) an outbreak investigation in New Orleans, Nephrogenic systemic fibrosis: relationship to Evidence insufficient to recommend melanoma Louisiana [Noe] 1393 (No) gadolinium and response to photopheresis surveillance following phototherapy for jaun- Neck [Richmond] 1025 (Au); correction, 1565 (De) dice(letter)[Newman](reply)[Descamps]1216 Antemortem diagnosis of rabies via nuchal skin Neutrophilic Dermatosis of the Dorsal Hands (Se) biopsy (letter) [Perez] 663 (My) Overlapping neutrophilic dermatosis in a patient Ex vivo dermoscopy of melanocytic tumors: time Keratotic papules on the right side of the neck with SAPHO syndrome (letter) [Bachmeyer] for dermatopathologists to learn dermos- and back [Bowe] 535 (Ap) 275 (Fe) copy [Scope] 1548 (De) Necrobiosis Lipoidica Nevi and Melanomas Exclusively benign dermoscopic pattern in a Tuberous necrobiosis lipoidica (letter) Identification of incipient tumors by means of patient with acral melanoma (letter) [Braun] [Michaels] 546 (Ap) sequential dermoscopy imaging: a new way to 1213 (reply) [Saida] 1215 (Se) Necrosis inflate the “epidemic” of melanoma? (letter) Involution: the natural evolution of pigmented Paraneoplastic Raynaud phenomenon with digi- [Carli] (reply) [Kittler] 805 (Je) Spitz and Reed nevi? (letter) [Argenziano] 549 tal necrosis associated with hyperhomocys- Nevus (Ap) teinemia and antiphospholipid antibodies (let- Bilateral symmetrical nodules on the feet [Fang] Long-term follow-up of a patient with eruptive ter) [Carducci] 1342 (Oc) 417 (Mr) melanocytic nevi after Stevens-Johnson syn- Ulceronecrotic nasoparanasal lesion [Martı´n] 653 Differences between polarized light dermos- drome [Gelfer] 1555 (De) (My) copy and immersion contact dermoscopy for Nevus type in dermoscopy is related to skin type Neoplasm Metastasis the evaluation of skin lesions in white persons [Zalaudek] 351 (Mr) Clinicopathologic correlation of cutaneous [Benvenuto-Andrade] 329 (Mr) Prevalence of skin diseases and cutaneous mani- metastases: experience from a cancer center Fractional resurfacing: a new therapeutic modal- festations among Iranian children: a survey of [Sariya] 613 (My) ity for Becker’s nevus [Glaich] 1488 (De) 1417 children (research letter) [Toossi] 115 Diffuse cutaneous nodules [Abdelmalek] 937 Soft papules and nodules on the buttock (Ja) (Jy) [Pol-Rodriguez] 1583 (De) Variations in the dermoscopic features of Erythematous papules and plaques involving the Treatment of atypical nevi with imiquimod 5% acquired acral melanocytic nevi [Ozdemir] groin and scrotum [Breedlove] 1067 (Au) cream [Somani] 379 (Mr) 1378 (No)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E27 New Orleans Diffuse cutaneous nodules [Abdelmalek] 937 Role of filaggrin mutations as an etiologic fac- Skin disorders among construction workers fol- (Jy) tor in atopic dermatitis [Zirwas] 1437 (No) lowing Hurricane Katrina and Hurricane Rita: Diffuse nodules in a woman with renal failure Role of IgE anti–basement membrane zone auto- an outbreak investigation in New Orleans, [Lesesky] 1201 (Se) antibodies in bullous pemphigoid [Woodley] Louisiana [Noe] 1393 (No) Erythema and blistering of the left leg 249 (Fe) Nifedipine [Shimanovich] 535 (Ap) Wikis: the application of Web 2.0 [Johnson] Resolution of chronic pain and fingertip ulcer- Erythematous atrophic macules and papules fol- 1065 (Au) ation due to hand-arm vibration syndrome following the lines of Blaschko [Quain] 109 (Ja) Oncogene Protein v-akt lowing combination pharmacotherapy (let- Erythematous papules and plaques involving the AKT1 overexpression in endothelial cells leads ter) [Buell] 1343 (Oc) groin and scrotum [Breedlove] 1067 (Au) to the development of cutaneous vascular mal- Nocardia Infections Firm papule on the lateral tongue [Suwattee] formations in vivo [Perry] 504 (Ap) Nocardia otitidiscaviarum: cause of long-term 1583 (De) Oral Ulcer cutaneous abscesses on the leg of an immu- Fulminant cutaneous eruption in a 51-year-old New and old therapeutics for oral ulcerations nocompetent man (letter) [Thoms] 1086 (Au) man [Thakuria] 255 (Fe) [Bruce] 519 (Ap) Nose Generalized papules in a patient with acute Oral lichen planus: a case series with emphasis Papules and plaques on the nose [Evers] 535 myeloid leukemia [Nakahigashi] 1583 (De) on therapy [Torti] 511 (Ap) (Ap) Glistening brown nodule [Scheinfeld] 255 (Fe) Randomized, double-blind, placebo- Ulceronecrotic nasoparanasal lesion [Martıń] 653 Goosefleshlike lesions and hypohidrosis controlled trial of pentoxifylline for the treat- (My) [Dimon] 1323 (Oc) ment of recurrent aphthous stomatitis Hyperpigmented keratotic nodules [Chua] 1201 [Thornhill] 463 (Ap); correction, 716 (Je) O (Se) Treatment of oral erosive lichen planus with 1% Keratotic papules on the right side of the neck pimecrolimus cream: a double-blind, random- Observer Variation and back [Bowe] 535 (Ap) ized, prospective trial with measurement of Effect of smoking on aging of photoprotected Multiple painless papules on the wrists [Callaly] pimecrolimus levels in the blood [Passeron] skin: evidence gathered using a new photo- 791 (Je) 472 (Ap) numeric scale [Helfrich] 397 (Mr); correc- Multiple plaques on the hands and feet [Lambert] Orbit tion, 633 (My) 109 (Ja) Pupil damage after periorbital laser treatment of Reliability of the Roenigk classification of liver Nodular lesions on the arm [Chrusciak-Talhari] a port-wine stain [Hammes] 392 (Mr) damage after methotrexate treatment for pso- 1323 (Oc) ortho-Phthalaldehyde see o-Phthalaldehyde riasis: a clinicopathologic study of 160 liver Nodule on a boy’s back [De Aloe] 417 (Mr) Osteochondroma biopsy specimens [Berends] 1515 (De) Nodule on the toe [Dapprich] 1067 (Au) Subungual exostosis [Sańchez-Castellanos] 1234 Occlusive Dressings The Off-Center Fold [Ming] 935 (Jy) (Se) Negative pressure dressing in the management Painful nodule on the knee [Heffernan] 937 (Jy) of pyoderma gangrenosum ulcer [Ghersi] 1249 Osteodystrophy, Renal see Renal Osteo- Papular eruption in an HIV-infected man [Swick] (Oc) dystrophy 255 (Fe) Occupational Exposure Osteoma Papules and plaques on the nose [Evers] 535 Dermal plaques of the face and scalp [Cohen] Skin disorders among construction workers fol- (Ap) lowing Hurricane Katrina and Hurricane Rita: 109 (Ja) Persistent violaceous papules on the ears Osteopontin an outbreak investigation in New Orleans, [Blumetti] 417 (Mr) Louisiana [Noe] 1393 (No) Osteopontin expression in Spitz nevi (research Petechial and red-brown papular lesions in a letter) [Winfield] 1076 (Au) Occupational Health 2-year-old girl [Williams] 1067 (Au) Resolution of chronic pain and fingertip ulcer- Ota’s Nevus see Nevus of Ota Pruritic patches on the back and papules on the Outcome Assessment (Health Care) ation due to hand-arm vibration syndrome fol- legs [Garg] 255 (Fe) lowing combination pharmacotherapy (let- Bath PUVA and saltwater baths followed by UV-B Rapidly enlarging necrotic ulcer on the right calf phototherapy as treatments for psoriasis: a ran- ter) [Buell] 1343 (Oc) [Chakrabarti] 791 (Je) Odds Ratio domized controlled trial [Schiener] 586 (My) Recurrent calcified cutaneous nodule of the peri- Clinical severity of psoriasis in last 20 years of Risk of mortality in patients with psoriasis: results anal region [Patrizi] 1441 (No) from a population-based study [Gelfand] 1493 PUVA study [Nijsten] 1113 (Se) Recurrent, pruritic dermal plaques and bullae Comparison of oral methylprednisolone plus aza- (De) [Green] 791 (Je) Odors thioprine or mycophenolate mofetil for the Scaly plaque on the scalp [Borer] 1067 (Au) treatment of bullous pemphigoid [Beissert] Consensus panel recommendations for chronic Soft papules and nodules on the buttock and acute wound dressings [Vaneau] 1291 1536 (De) [Pol-Rodriguez] 1583 (De) Effect of health care delivery models on mela- (Oc) Solitary cutaneous nodule in an immunocom- Trimethylaminuria (fish-odor syndrome): a case noma thickness and stage in a university- promised patient [Singh] 1583 (De) based referral center: an observational pilot report [Arseculeratne] 81 (Ja) Subcutaneous nodule and diffuse lymphade- OFF-CENTER FOLD (Ming M, ed) study [Swetter] 30 (Ja) nopathy in a 6-month-old boy from Africa Efficacy of a partner assistance intervention Acute blue patch on the forearm [Heydendael] [Friedman] 1323 (Oc) 937 (Jy) designed to increase skin self-examination per- Tender erythema of the left lower extremity formance [Robinson] 37 (Ja) Asymptomatic cutaneous lip plaque [Redd] 791 [Szyfelbein] 535 (Ap) (Je) Fifty-five basal cell carcinomas treated with topi- Tender nodules on the palms and soles cal imiquimod: outcome at 5-year follow-up Asymptomatic nodule of the tongue [Mataix] [Esler-Brauer] 1201 (Se) 653 (My) (research letter) [Vidal] 266 (Fe) Ulceronecrotic nasoparanasal lesion [Martıń] 653 Five-year follow-up of a randomized, prospec- Atrophic macules and soft papules in a 24-year- (My) old woman [Pascual] 109 (Ja) tive trial of topical methyl aminolevulinate Verrucous nodules on the toes of a renal trans- photodynamic therapy vs surgery for nodu- Auricular erythema with nodules and scale plant recipient [Levy] 653 (My) [Hutchin] 1441 (No) lar basal cell carcinoma [Rhodes] 1131 (Se) Verrucous papules and plaques in a pediatric Melanoma outcomes for Medicare patients: asso- Beefy red plaque in the popliteal fossa [Grekin] patient [Gonzalez] 1201 (Se) 1323 (Oc) ciation of stage and survival with detection by Bilateral symmetrical nodules on the feet [Fang] Ofloxacin a dermatologist vs a nondermatologist [Pennie] 417 (Mr) Blue-black pigmentation of legs and arms in a 488 (Ap) Blue-black pigmentation of legs and arms in a 68-year-old woman [Lo´pez-Pestan˜ a] 1441 Question the obvious [Nijsten] 1429 (No) 68-year-old woman [Lo´pez-Pestan˜ a] 1441 (No) Results of radiotherapy in 153 primary cutane- (No) Ointments ous B-cell lymphomas classified according to Blue-gray subungual discoloration [Dalle] 937 Histologic cutaneous modifications after the use the WHO-EORTC classification [Senff] 1520 (Jy) of EMLA cream, a diagnostic pitfall: review of (De) Brown and black scaly patches on the lower leg 13 cases (research letter) [Cazes] 1074 (Au) Visual screening for malignant melanoma: a cost- [Soderberg] 1441 (No) Use of antibiotic ointment after clean cutane- effectiveness analysis [Losina] 21 (Ja) Burgeoning nodule on the scalp of a 65-year- ous surgery [Bigby] 1180 (Se) Overweight old man [Farhi] 653 (My) ON THE HORIZON (Wood GS, ed) Incidence and risk factors for psoriasis in the gen- Crusted violaceous plaques on an immunocom- Accessible evidence-based medicine: critically eral population [Huerta] 1559 (De) promised host [Xu] 417 (Mr) appraised topics [Barzilai] 1189 (Se) Oxybutynin Dermal plaques of the face and scalp [Cohen] Call for papers for On the Horizon [Wood] 253 Treatment of hyperhidrosis with oxybutynin (let- 109 (Ja) (Fe) ter) [Schollhammer] 544 (Ap)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E28 Oxygen Poor adherence to treatments: a fundamental Pentoxifylline Topical oxygen emulsion: a novel wound therapy principle of dermatology [Ali] 912 (Jy) New and old therapeutics for oral ulcerations [Davis] 1252 (Oc) Patient Care Team [Bruce] 519 (Ap) Oxygenation, Hyperbaric see Hyperbaric Palliative care in patients with primary cutane- Randomized, double-blind, placebo- Oxygenation ous lymphoma: symptom burden and char- controlled trial of pentoxifylline for the treat- Oxymetazoline acteristics of hospital palliative care team input ment of recurrent aphthous stomatitis Successful treatment of the erythema and flush- (research letter) [LeBon] 423 (Mr) [Thornhill] 463 (Ap); correction, 716 (Je) ing of rosacea using a topically applied selec- Patient Education Resolution of chronic pain and fingertip ulcer- tive ␣1-adrenergic receptor agonist, oxy- Efficacy of a partner assistance intervention ation due to hand-arm vibration syndrome fol- metazoline [Shanler] 1369 (No) designed to increase skin self-examination per- lowing combination pharmacotherapy (let- formance [Robinson] 37 (Ja) ter) [Buell] 1343 (Oc) P Patient-Physician Relationship Peptide Hydrolases Practice brochure: complement to, not supple- Hydroxyurea-induced leg ulcers treated with a Paget’s Disease, Mammary ment for, good physician-patient interaction protease-modulating matrix [Romanelli] 1310 Pigmented mammary Paget disease: dermo- (research letter) [Fosse] 1447 (No) (Oc) scopic, in vivo reflectance-mode confocal Quality of care from a patient’s perspective (re- Peptides microscopic, and immunohistochemical study search letter) [Regula] 1592 (De) Skin microecology: the old and the new of a case [Longo] 752 (Je) Patient Preference see Patient Satisfaction [Webster] 105 (Ja) Pain Patient Satisfaction Perniosis see Chilblains Diabetic muscle infarction (letter) [MacGregor] Balancing the benefits and risks of drug treat- Personnel Selection 1456 (No) ment: a stated-preference, discrete choice Academic dermatology manpower: issues of Injection drug use: an understudied cause of experiment with patients with psoriasis recruitment and retention [Loo] 341 (Mr) venous disease [Pieper] 1305 (Oc) [Seston] 1175 (Se) Petechiae see Purpura Palliative care in patients with primary cutane- Practice brochure: complement to, not supple- ous lymphoma: symptom burden and char- Petrolatum ment for, good physician-patient interaction Persistent eosinophilia as a presenting sign of acteristics of hospital palliative care team input (research letter) [Fosse] 1447 (No) (research letter) [LeBon] 423 (Mr) scabies in patients with disorders of keratini- Patients zation (letter) [Sluzevish] 670 (My) Pain, Intractable Quality of care from a patient’s perspective (re- Pets see Animals, Domestic Resolution of chronic pain and fingertip ulcer- search letter) [Regula] 1592 (De) Phenotype ation due to hand-arm vibration syndrome fol- Question the obvious [Nijsten] 1429 (No) lowing combination pharmacotherapy (let- Phenotypic variation in familial melanoma: con- Pediculosis see Lice Infestations sequences for predictive DNA testing ter) [Buell] 1343 (Oc) Pefloxacin Palliative Care [Bergman] 525 (Ap) Chronic urticaria and monoclonal IgM gam- Phenylephrine Palliative care in patients with primary cutane- mopathy (Schnitzler syndrome): report of 11 ous lymphoma: symptom burden and char- Phenylephrine-induced microvascular occlu- cases treated with pefloxacin [Asli] 1046 (Au) sion syndrome in a patient with a heterozy- acteristics of hospital palliative care team input Pemphigoid, Bullous (research letter) [LeBon] 423 (Mr) gous factor V Leiden mutation [Kalajian] 1314 Childhood bullous pemphigoid: clinical and (Oc) Palmar Plate see Volar Plate immunological findings in a series of 4 cases Photoaging of Skin see Skin Aging Pancreatic Neoplasms [Martinez-De Pablo] 215 (Fe) Multiple melanomas after treatment for Hodg- Clinical evidence of an intermolecular epitope Photochemotherapy kin lymphoma in a non-Dutch p16-Leiden spreading in a patient with pemphigus folia- Five-year follow-up of a randomized, prospec- mutation carrier with 2 MC1R high-risk vari- ceus converting into bullous pemphigoid (let- tive trial of topical methyl aminolevulinate ants [Figl] 495 (Ap) ter) [Peterson] 272 (Fe) photodynamic therapy vs surgery for nodu- Necrolytic migratory erythema: the outermost Comparison of oral methylprednisolone plus aza- lar basal cell carcinoma [Rhodes] 1131 (Se) marker for glucagonoma syndrome (letter) thioprine or mycophenolate mofetil for the National Psoriasis Foundation clinical consen- [Gantcheva] 1221 (Se) treatment of bullous pemphigoid [Beissert] sus on disease severity [Pariser] 239 (Fe) Papilloma 1536 (De) Response of Bowen disease to ALA-PDT using Verrucous papules and plaques in a pediatric Herpes gestationis in a mother and newborn: im- a single and a 2-fold illumination scheme (re- patient [Gonzalez] 1201 (Se) munoclinical perspectives based on a weekly search letter) [de Haas] 264 (Fe) Papulosis, Clear Cell see Clear Cell Papulosis follow-up of the enzyme-linked immunosorbent Successful treatment of pityriasis versicolor with Paraffin assayindexofabullouspemphigoidantigennon- 5-aminolevulinic acid photodynamic therapy Dressings for acute and chronic wounds: a sys- collagenous domain [Aoyama] 1168 (Se) (letter) [Kim] 1218 (Se) tematic review [Chaby] 1297 (Oc) Role of IgE anti–basement membrane zone auto- Vitiligo: to treat or not to treat [Lim] 643 (My) Paraneoplastic Syndromes antibodies in bullous pemphigoid [Woodley] Photodermatitis see Photosensitivity Disorders Paraneoplastic Raynaud phenomenon with digi- 249 (Fe) Photodynamic Therapy see Photochemotherapy tal necrosis associated with hyperhomocys- Pemphigoid Gestationis Photography teinemia and antiphospholipid antibodies (let- Herpes gestationis in a mother and newborn: im- Effect of smoking on aging of photoprotected ter) [Carducci] 1342 (Oc) munoclinical perspectives based on a weekly skin: evidence gathered using a new photonu- Paraneoplastic relapsing polychondritis (let- follow-up of the enzyme-linked immunosorbent meric scale [Helfrich] 397 (Mr); correction, ter) [Cohen] 949 (Jy) assayindexofabullouspemphigoidantigennon- 633 (My) Relapsing polychondritis and malignant lym- collagenous domain [Aoyama] 1168 (Se) Photopheresis phoma: is polychondritis paraneoplastic? Pemphigus Measuring HRQOL in patients with cutaneous [Yanagi] 89 (Ja) Clinical evidence of an intermolecular epitope T-cell lymphoma undergoing therapy with oral Paraproteinemias spreading in a patient with pemphigus folia- bexarotene and extracorporeal photopher- Chronic urticaria and monoclonal IgM gam- ceus converting into bullous pemphigoid (let- esis (research letter) [Demierre] 659 (My) mopathy (Schnitzler syndrome): report of 11 ter) [Peterson] 272 (Fe) Nephrogenic systemic fibrosis: relationship to cases treated with pefloxacin [Asli] 1046 (Au) Endemic pemphigus vulgaris [Rocha-Alvarez] gadolinium and response to photopheresis Parathyroid Hormone 895 (Jy) [Richmond] 1025 (Au); correction, 1565 (De) Sodium thiosulfate as first-line treatment for cal- Frequency of shifts over time in the profile of Retinal toxic reactions following photopher- ciphylaxis (letter) [Ackermann] 1336 (re- antidesmoglein antibodies in pemphigus vul- esis [Vagace] 622 (My) ply) [Robinson] 1338 (Oc) garis (research letter) [Weitz] 1073 (Au) Photophobia Paresthesia Pemphigus variant associated with penicillin use: Susceptibility to UV-A and UV-B provocation Successful treatment of notalgia paresthetica with a case-cohort study of 363 patients from Israel does not correlate with disease severity of poly- botulinum toxin type A [Weinfeld] 980 (Au) [Heymann] 704 (Je) morphic light eruption [Janssens] 599 (My) Pathology, Clinical Treatment of severe pemphigus with ritux- Photosensitivity Disorders Ex vivo dermoscopy of melanocytic tumors: time imab: report of 12 cases and a review of the Skin disorders among construction workers fol- for dermatopathologists to learn dermos- literature [Cianchini] 1033 (Au) lowing Hurricane Katrina and Hurricane Rita: copy [Scope] 1548 (De) Pemphigus Vulgaris see Pemphigus an outbreak investigation in New Orleans, Patient Adherence Penicillins Louisiana [Noe] 1393 (No) Physical activity and adherence to compres- Pemphigus variant associated with penicillin use: Susceptibility to UV-A and UV-B provocation sion therapy in patients with venous leg ulcers a case-cohort study of 363 patients from Israel does not correlate with disease severity of poly- [Heinen] 1283 (Oc) [Heymann] 704 (Je) morphic light eruption [Janssens] 599 (My)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E29 Phototherapy Treatment of oral erosive lichen planus with 1% Persistent eosinophilia as a presenting sign of Balneophototherapy for psoriasis using saltwa- pimecrolimus cream: a double-blind, random- scabies in patients with disorders of keratini- ter baths and UV-B irradiation, revisited ized, prospective trial with measurement of zation (letter) [Sluzevish] 670 (My) [Gambichler] 647 (My) pimecrolimus levels in the blood [Passeron] Porokeratosis, Disseminated Superficial Actinic Bath PUVA and saltwater baths followed by UV-B 472 (Ap) see Porokeratosis phototherapy as treatments for psoriasis: a ran- Pituitary-Adrenal System Port-Wine Stain domized controlled trial [Schiener] 586 (My) Suppression of the HPA axis in pediatric patients Dermoscopy of port-wine stains [Va´zquez-Lo´pez] Effect of intense pulsed-light exposure on lipid with atopic dermatitis (letter) [Ishay] 1449 962 (Jy) peroxides and thymine dimers in human skin (No) Pupil damage after periorbital laser treatment of in vivo [Sorg] 363 (Mr) Pityriasis Rubra Pilaris a port-wine stain [Hammes] 392 (Mr) Evidence insufficient to recommend melanoma Clinical improvement of pityriasis rubra pilaris Postoperative Care surveillance following phototherapy for jaun- with combination etanercept and acitretin Use of antibiotic ointment after clean cutane- dice(letter)[Newman](reply)[Descamps]1216 therapy (letter) [Davis] 1597 (De) ous surgery [Bigby] 1180 (Se) (Se) Pityriasis Versicolor see Tinea Versicolor Postoperative Complications Fractional photothermolysis: a novel treat- Plasma Koebner phenomenon in vitiligo: not always an ment for disseminated superficial actinic poro- Evaluation of plasma skin regeneration tech- indication of surgical failure (research letter) keratosis (letter) [Chrastil] 1450 (No) nology in low-energy full-facial rejuvenation [Mulekar] 801 (Je) Fractional photothermolysis for the treatment [Bogle] 168 (Fe) Peristomal pyoderma gangrenosum associated of adult colloid milium [Marra] 572 (My) Platelet-Derived Endothelial Cell Growth Factor with collagenous colitis (letter) [Davis] 669 Narrowband UV-B phototherapy, alefacept, and see Thymidine Phosphorylase (My) clearance of psoriasis [Legat] 1016 (Au) Platelet-Derived Growth Factor Signs of a “broken heart”: suspected Muehrcke Narrowband UV-B phototherapy for extrageni- Era of targeted therapies: increasing role for novel lines after cardiac surgery (letter) [Weiser] 815 tal lichen sclerosus (letter) [Kreuter] 1213 (Se) oncologic drugs in dermatology [Montella] 788 (Je) National Psoriasis Foundation clinical consen- (Je) Spontaneous Citrobacter freundii infection in an sus on disease severity [Pariser] 239 (Fe) Immunohistochemical expression of platelet immunocompetent patient (letter) [Whalen] Progressive extragenital lichen sclerosus suc- growth factor and vascular endothelial growth 124 (Ja) cessfully treated with narrowband UV-B pho- factor in patients with melanoma with and Practice Guidelines totherapy [Colbert] 19 (Ja) without redness (Brenner sign) [Mashiah] Level of agreement with the British guidelines Randomized double-blind trial of treatment of 1001 (Au) for the use of biological therapies for psoria- vitiligo: efficacy of psoralen–UV-A therapy vs Pneumonia, Pneumocystis carinii sis [Nijsten] 1567 (De) narrowband–UV-B therapy [Yones] 578 (My); Pneumocystis carinii pneumonia in infant treated Practice Management correction, 906 (Jy) with oral steroids for hemangioma (letter) Practice brochure: complement to, not supple- Vitiligo: to treat or not to treat [Lim] 643 (My) [Maronn] 1224 (Se) ment for, good physician-patient interaction o-Phthalaldehyde Poisoning (research letter) [Fosse] 1447 (No) Ortho-phthalaldehyde causing facial stains after Short-term thallium intoxication: dermatologi- Prednisolone cystoscopy (letter) [Abdulla] 670 (My) cal findings correlated with thallium concen- Pneumocystis carinii pneumonia in infant treated Physical Examination tration [Lu] 93 (Ja) with oral steroids for hemangioma (letter) Head-tilt maneuver: a clinical aid in recogniz- Poliomyelitis [Maronn] 1224 (Se) ing head and neck angiosarcomas [Asgari] 75 Skin cancer presenting as a nonhealing wound: Pregnancy (Ja) the association of polio and skin cancer (let- Herpes gestationis in a mother and newborn: ter) [Vu] 1338 (Oc) Physician Assistants immunoclinical perspectives based on a weekly Polyarteritis Nodosa Quality of dermatologic care delivered by phy- follow-up of the enzyme-linked immunosor- Diagnostic yield of histopathologic sampling sician assistants: an analysis of prescribing bent assay index of a bullous pemphigoid anti- techniques in PAN-associated cutaneous ulcers behavior for the combination antifungal agent gen noncollagenous domain [Aoyama] 1168 (research letter) [Ricotti] 1334 (Oc) clotrimazole-betamethasone (research let- (Se) ter) [Satyaprakash] 1591 (De) Polychondritis, Relapsing Importance of serum bile acid level analysis and Paraneoplastic relapsing polychondritis (let- treatment with ursodeoxycholic acid in intra- Physicians ter) [Cohen] 949 (Jy) hepatic cholestasis of pregnancy: a case series Academic dermatology manpower: issues of Relapsing polychondritis and malignant lym- from Central Europe [Ambros-Rudolph] 757 recruitment and retention [Loo] 341 (Mr) phoma: is polychondritis paraneoplastic? (Je) Academic workforce in dermatology [Olerud] [Yanagi] 89 (Ja) Pregnancy Complications 409 (Mr) Polymerase Chain Reaction What is the chance of a normal pregnancy in a Leadership workforce in academic dermatol- Direct identification of dermatophyte DNA from woman whose fetus has been exposed to ogy (research letter) [Turner] 948 (Jy) clinical specimens by a nested polymerase isotretinoin? [Sladden] 1187 (Se) Melanoma outcomes for Medicare patients: asso- chain reaction assay (research letter) [Yang] Prescriptions, Drug ciation of stage and survival with detection by 799 (Je) Quality of dermatologic care delivered by phy- a dermatologist vs a nondermatologist [Pennie] Virologic safety of polyvinyl chloride film in der- sician assistants: an analysis of prescribing 488 (Ap) moscopic analysis of mucosal areas (research behavior for the combination antifungal agent Practice brochure: complement to, not supple- letter) [Zampino] 945 (Jy) clotrimazole-betamethasone (research let- ment for, good physician-patient interaction Polymethyl Methacrylate ter) [Satyaprakash] 1591 (De) (research letter) [Fosse] 1447 (No) Cosmetic permanent fillers for soft tissue aug- Prilocaine Pigmentation mentation: a new contraindication for inter- Histologic cutaneous modifications after the use Early melanomas dermoscopically character- feron therapies [Fischer] 507 (Ap) of EMLA cream, a diagnostic pitfall: review of ized by reticular depigmentation (letter) Polyneuropathies 13 cases (research letter) [Cazes] 1074 (Au) [Lozzi] 808 (Je) Short-term thallium intoxication: dermatologi- Procalcitonin Nevus type in dermoscopy is related to skin type cal findings correlated with thallium concen- High procalcitonin levels in patients with severe in white persons [Zalaudek] 351 (Mr) tration [Lu] 93 (Ja) drug reactions (research letter) [Sfia] 1591 (De) Vitiligo: to treat or not to treat [Lim] 643 (My) Polyneuropathy, Acquired see Polyneuropa- Professional Practice Location Pigmentation Disorders thies Distance to diagnosing provider as a measure of Case of zosteriform pigmented purpuric derma- Polyurethanes access for patients with melanoma tosis (letter) [Hamada] 1599 (De) Negative pressure dressing in the management [Stitzenberg] 991 (Au) Pigmented Purpuric Dermatoses of pyoderma gangrenosum ulcer [Ghersi] 1249 Prognosis Case of zosteriform pigmented purpuric derma- (Oc) Dermoscopic patterns of acral melanocytic nevi: tosis (letter) [Hamada] 1599 (De) Polyvinyl Chloride their variations, changes, and significance Pimecrolimus Virologic safety of polyvinyl chloride film in der- [Saida] 1423 (No) National Eczema Association and topical calci- moscopic analysis of mucosal areas (research Predictors of skin-related quality of life after treat- neurin inhibitor labeling (letter) [Cooper] 546 letter) [Zampino] 945 (Jy) ment of cutaneous basal cell carcinoma and (Ap) Pompholyx see Eczema, Dyshidrotic squamous cell carcinoma [Chen] 1386 (No) New and old therapeutics for oral ulcerations Porokeratosis Primary cutaneous diffuse large B-cell lym- [Bruce] 519 (Ap) Fractional photothermolysis: a novel treat- phoma, leg type: clinicopathologic features and Topical calcineurin inhibitors revisited (letter) ment for disseminated superficial actinic poro- prognostic analysis in 60 cases [Grange] 1144 [Qureshi] 545 (Ap) keratosis (letter) [Chrastil] 1450 (No) (Se)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E30 Propionibacterium acnes Long-term safety and efficacy of 50 mg of etaner- Poor adherence to treatments: a fundamental Skin microecology: the old and the new cept twice weekly in patients with psoriasis principle of dermatology [Ali] 912 (Jy) [Webster] 105 (Ja) [Tyring] 719 (Je) Randomized double-blind trial of treatment of Prostatic Neoplasms Long-term treatment for severe psoriasis: we’re vitiligo: efficacy of psoralen–UV-A therapy vs Diffuse cutaneous nodules [Abdelmalek] 937 halfway there, with a long way to go [Gelfand] narrowband–UV-B therapy [Yones] 578 (My); (Jy) 1191 (Se) correction, 906 (Jy) Protease Inhibitors Methotrexate and risk for lymphoma (letter) Use of biological agents in patients with mod- Multiple subcutaneous lipomas induced by [Whitmore] 663 (My) erate to severe psoriasis: a cohort-based per- HAART in the absence of protease inhibitors Narrowband UV-B phototherapy, alefacept, and spective [Jones-Caballero] 846 (Jy) (letter) [Balestreire] 1596 (De) clearance of psoriasis [Legat] 1016 (Au) Pyoderma Gangrenosum Proteases see Peptide Hydrolases National Psoriasis Foundation clinical consen- Adalimumab treatment for pyoderma gangreno- Protein-Tyrosine-Phosphatase sus on disease severity [Pariser] 239 (Fe) sum [Heffernan] 306 (Mr) ␣ Novel PTPN11 gene mutation in a patient with Onset of psoriasis during treatment with TNF- Negative pressure dressing in the management LEOPARD syndrome (research letter) antagonists: a report of 3 cases (letter) of pyoderma gangrenosum ulcer [Ghersi] 1249 [Du-Thanh] 1210 (Se) [Ubriani] 270 (Fe) (Oc) Protoporphyria, Erythropoietic Poor adherence to treatments: a fundamental Peristomal pyoderma gangrenosum associated principle of dermatology [Ali] 912 (Jy) withcollagenouscolitis(letter)[Davis]669(My) Clinical, biochemical, and genetic study of 11 ␣ patients with erythropoietic protoporphyria Psoriasiform eruptions during anti–TNF- treat- Pyrimidine Dimers including one with homozygous disease ment: psoriasis or not? (letter) [Seneschal] Effect of intense pulsed-light exposure on lipid [Herrero] 1125 (Se) 1593 (reply) [de Gannes] 1595 (De) peroxides and thymine dimers in human skin Psoriasis and pustular dermatitis triggered by Pruritus in vivo [Sorg] 363 (Mr) TNF-␣ inhibitors in patients with rheumato- Importance of serum bile acid level analysis and logic conditions [de Gannes] 223 (Fe) Q treatment with ursodeoxycholic acid in intra- Reliability of the Roenigk classification of liver hepatic cholestasis of pregnancy: a case series damage after methotrexate treatment for pso- Quality of Health Care from Central Europe [Ambros-Rudolph] 757 riasis: a clinicopathologic study of 160 liver Quality of care from a patient’s perspective (re- (Je) biopsy specimens [Berends] 1515 (De) search letter) [Regula] 1592 (De) Infliximab as a therapy for idiopathic hyper- Risk of mortality in patients with psoriasis: results Quality of dermatologic care delivered by phy- eosinophilic syndrome [Taverna] 1110 (Se) from a population-based study [Gelfand] 1493 sician assistants: an analysis of prescribing Pruritic patches on the back and papules on the (De) behavior for the combination antifungal agent legs [Garg] 255 (Fe) Role of the quantiFERON-TB gold test as screen- clotrimazole-betamethasone (research let- Recurrent, pruritic dermal plaques and bullae ing prior to administration of tumor necrosis ter) [Satyaprakash] 1591 (De) [Green] 791 (Je) factor inhibitors (letter) [Martinez] 809 (Je) Quality of Life Successful treatment of notalgia paresthetica with Success of Goeckerman treatment in 2 patients Childhood atopic dermatitis impact scale: reli- botulinum toxin type A [Weinfeld] 980 (Au) with psoriasis not responding to biological ability, discriminative and concurrent valid- Pseudolymphoma drugs (letter) [Soares] 950 (Jy) ity, and responsiveness [Chamlin] 768 (Je) Lymphomatoid keratosis: an epidermotropic type Three-dimensional images and vessel render- Current status of evaluation and treatment of of cutaneous lymphoid hyperplasia: clinico- ing using optical coherence tomography high-risk cutaneous melanoma: therapeutic pathological, immunohistochemical, and [Thomas] 1468 (No) breakthroughs remain elusive [Kanzler] 785 molecular biological study of 6 cases [Arai] 53 Use of biological agents in patients with mod- (Je) (Ja) erate to severe psoriasis: a cohort-based per- Measuring HRQOL in patients with cutaneous Pseudomonas aeruginosa spective [Jones-Caballero] 846 (Jy) T-cell lymphoma undergoing therapy with oral Growth inhibition of Trichophyton species by Yin and yang of TNF-␣ inhibition [Fiorentino] bexarotene and extracorporeal photopher- Pseudomonas aeruginosa [Treat] 61 (Ja) 233 (Fe) esis (research letter) [Demierre] 659 (My) Psoralen Ultraviolet A Therapy see PUVA Psychometrics Predictors of skin-related quality of life after treat- Therapy Childhood atopic dermatitis impact scale: reli- ment of cutaneous basal cell carcinoma and Psoralens ability, discriminative and concurrent valid- squamous cell carcinoma [Chen] 1386 (No) Bath PUVA and saltwater baths followed by UV-B ity, and responsiveness [Chamlin] 768 (Je) Question the obvious [Nijsten] 1429 (No) phototherapy as treatments for psoriasis: a ran- Public Health Questionnaires domized controlled trial [Schiener] 586 (My) Confusing message will not improve the detec- Measuring HRQOL in patients with cutaneous Randomized double-blind trial of treatment of tion of melanoma (letter) [Bystryn] (reply) T-cell lymphoma undergoing therapy with oral vitiligo: efficacy of psoralen–UV-A therapy vs [Kelly] 806 (Je) bexarotene and extracorporeal photopher- narrowband–UV-B therapy [Yones] 578 (My); Melanoma screening: focusing the public health esis (research letter) [Demierre] 659 (My) correction, 906 (Jy) journey [Koh] 101 (Ja) Psoriasis R Pulmonary Hypertension see Hypertension, Balancing the benefits and risks of drug treat- Pulmonary ment: a stated-preference, discrete choice Rabies experiment with patients with psoriasis Pupil Antemortem diagnosis of rabies via nuchal skin [Seston] 1175 (Se) Pupil damage after periorbital laser treatment of biopsy (letter) [Perez] 663 (My) Balneophototherapy for psoriasis using saltwa- a port-wine stain [Hammes] 392 (Mr) Radiation ter baths and UV-B irradiation, revisited Purpura Susceptibility to UV-A and UV-B provocation [Gambichler] 647 (My) Petechial and red-brown papular lesions in a does not correlate with disease severity of poly- Bath PUVA and saltwater baths followed by UV-B 2-year-old girl [Williams] 1067 (Au) morphic light eruption [Janssens] 599 (My) phototherapy as treatments for psoriasis: a ran- Phenylephrine-induced microvascular occlu- Radiation Effects domized controlled trial [Schiener] 586 (My) sion syndrome in a patient with a heterozy- Effect of tacrolimus on vitiligo in absence of UV British guidelines on the use of biological thera- gous factor V Leiden mutation [Kalajian] 1314 radiation exposure (letter) [Sardana] 119 (re- pies for psoriasis: a note of clarification on the (Oc) ply) [Passeron] 120 (Ja) role of etanercept (letter) [Smith] 1595 (De) Pustulosis Palmaris et Plantaris see Psoriasis Multiple primary melanomas in a CDKN2A Clinical severity of psoriasis in last 20 years of PUVA Therapy mutation carrier exposed to ionizing radia- PUVA study [Nijsten] 1113 (Se) Bath PUVA and saltwater baths followed by UV-B tion [Eliason] 1409 (No) Dermoscopy subpattern of plaque-type psoria- phototherapy as treatments for psoriasis: a ran- Radiation Injuries sis: red globular rings [Va´zquez-Lo´pez] 1612 domized controlled trial [Schiener] 586 (My) Fluoroscopy-induced chronic radiation skin (De) Clinical severity of psoriasis in last 20 years of injury: a disease perhaps often overlooked Efalizumab-associated papular psoriasis [Hassan] PUVA study [Nijsten] 1113 (Se) [Frazier] 637 (My) 900 (Jy) Eczematoid graft-vs-host disease: a novel form Radiodermatitis Incidence and risk factors for psoriasis in the gen- of chronic cutaneous graft-vs-host disease and Fluoroscopy-induced chronic radiation skin eral population [Huerta] 1559 (De) its response to psoralen–UV-A therapy injury: a disease perhaps often overlooked Infliximab-induced palmoplantar pustulosis in [Creamer] 1157 (Se) [Frazier] 637 (My) a patient with Crohn disease (letter) [Sladden] Long-term treatment for severe psoriasis: we’re Radiotherapy 1449 (No) halfway there, with a long way to go [Gelfand] Results of radiotherapy in 153 primary cutane- Level of agreement with the British guidelines 1191 (Se) ous B-cell lymphomas classified according to for the use of biological therapies for psoria- Methotrexate and risk for lymphoma (letter) the WHO-EORTC classification [Senff] 1520 sis [Nijsten] 1567 (De) [Whitmore] 663 (My) (De)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E31 Randomized Trials Rejuvenation tive ␣1-adrenergic receptor agonist, oxy- Bath PUVA and saltwater baths followed by Evaluation of plasma skin regeneration tech- metazoline [Shanler] 1369 (No) UV-B phototherapy as treatments for pso- nology in low-energy full-facial rejuvenation Rosai-Dorfman Disease see Histiocytosis, Sinus riasis: a randomized controlled trial [Bogle] 168 (Fe) [Schiener] 586 (My) Remote Consultation S Duct tape for the treatment of common warts Store-and-forward teledermatology in skin can- in adults: a double-blind randomized con- cer triage: experience and evaluation of 2009 Salbutamol see Albuterol trolled trial [Wenner] 309 (Mr) teleconsultations [Moreno-Ramirez] 479 (Ap); Saline see Sodium Chloride Efficacy of a partner assistance intervention correction, 886 (Jy) Saltwater see Water designed to increase skin self-examination per- Renal Disease, End-Stage see Kidney Failure, SAPHO Syndrome see Acquired Hyperostosis formance [Robinson] 37 (Ja) Chronic Syndrome Sarcoidosis Five-year follow-up of a randomized, pro- Renal Osteodystrophy Widespread granulomatous dermatitis of infancy: spective trial of topical methyl aminolevuli- Sodium thiosulfate as first-line treatment for cal- an early sign of Blau syndrome [Schaffer] 386 nate photodynamic therapy vs surgery for ciphylaxis (letter) [Ackermann] 1336 (re- (Mr) nodular basal cell carcinoma [Rhodes] 1131 ply) [Robinson] 1338 (Oc) Sarcoma, Kaposi (Se) Research Randomized, double-blind, placebo- Disseminated cutaneous Kaposi sarcoma and Next frontier of dermatologic research progressive multifocal leukoencephalopathy controlled trial of pentoxifylline for the treat- [Robinson] 1195 (Se) in a patient with idiopathic CD4ϩ T lympho- ment of recurrent aphthous stomatitis Resource Allocation cytopenia (letter) [Inhoff] 673 (My) [Thornhill] 463 (Ap); correction, 716 (Je) Question the obvious [Nijsten] 1429 (No) Scabies Randomized double-blind study of the effect of Retina Crusted Norwegian scabies in an adult with Botox and Dysport/Reloxin on forehead Retinal toxic reactions following photopher- Langerhans cell histiocytosis: mishaps lead- wrinkles and electromyographic activity (re- esis [Vagace] 622 (My) ing to systemic chemotherapy [Kartono] 626 search letter) [Karsai] 1447 (No) Retinoic Acid see Tretinoin (My) Randomized double-blind trial of treatment of Persistent eosinophilia as a presenting sign of vitiligo: efficacy of psoralen–UV-A therapy vs Retinol see Vitamin A scabies in patients with disorders of keratini- narrowband–UV-B therapy [Yones] 578 (My); Reverse Transcriptase Polymerase Chain zation (letter) [Sluzevish] 670 (My) correction, 906 (Jy) Reaction Scalp Treatment of oral erosive lichen planus with 1% Clinical, histologic, and molecular study of 9 Burgeoning nodule on the scalp of a 65-year- pimecrolimus cream: a double-blind, random- cases of congenital dermatofibrosarcoma pro- old man [Farhi] 653 (My) ized, prospective trial with measurement of tuberans [Maire] 203 (Fe) Dermal plaques of the face and scalp [Cohen] pimecrolimus levels in the blood [Passeron] REVIEWS 109 (Ja) 472 (Ap) Combination immunosuppressive therapies: the Docetaxel monotherapy for angiosarcoma in an Use of antibiotic ointment after clean cutane- promise and the peril [Robinson] 1053 (Au) elderly patient (letter) [Nagano] 1602 (De) ous surgery [Bigby] 1180 (Se) Dressings for acute and chronic wounds: a sys- Rare manifestation of scalp necrosis in tempo- What are the risks of serious infections and tematic review [Chaby] 1297 (Oc) ral arteritis (letter) [Adams] 1079 (Au) malignancies for patients treated with anti- Role of furry pets in eczema: a systematic review Scalp biopsy specimens: transverse vs vertical tumor necrosis factor antibodies? [Corona] [Langan] 1570 (De) sections (research letter) [Garcia] 268 (Fe) 405 (Mr) Rhizopus Scaly plaque on the scalp [Borer] 1067 (Au) Rash see Exanthema Crusted violaceous plaques on an immunocompromised host [Xu] 417 (Mr) Schamberg’s Disease see Pigmentation Disorders Raynaud Disease Schnitzler Syndrome Rhytidoplasty Paraneoplastic Raynaud phenomenon with digi- Chronic urticaria and monoclonal IgM gam- Breaking strength of barbed polypropylene tal necrosis associated with hyperhomocys- mopathy (Schnitzler syndrome): report of 11 sutures: rater-blinded, controlled compari- teinemia and antiphospholipid antibodies (let- cases treated with pefloxacin [Asli] 1046 (Au) son with nonbarbed sutures of various cali- ter) [Carducci] 1342 (Oc) Scleroderma, Localized bers [Rashid] 869 (Jy); correction, 1186 (Se) Resolution of chronic pain and fingertip ulcer- Blaschko linear nodular morphea with dermal ation due to hand-arm vibration syndrome fol- Risk Assessment mucinosis (letter) [Jain] 953 (Jy) lowing combination pharmacotherapy (let- Balancing the benefits and risks of drug treat- Scleroderma, Systemic ter) [Buell] 1343 (Oc) ment: a stated-preference, discrete choice Bosentan as a rescue therapy in scleroderma experiment with patients with psoriasis Receptor, Fibroblast Growth Factor, Type 3 refractory digital ulcers (letter) [Chamaillard] [Seston] 1175 (Se) Familial acanthosis nigricans due to K650T 125 (Ja) FGFR3 mutation [Berk] 1153 (Se) Risk Factors Scleromyxedema ␤ Incidence and risk factors for psoriasis in the gen- Multiple painless papules on the wrists [Callaly] Receptors, Adrenergic, eral population [Huerta] 1559 (De) Association between the use of ␤-adrenergic 791 (Je) Risk of mortality in patients with psoriasis: results Sclerosis, Systemic see Scleroderma, Systemic receptor agents and the development of venous from a population-based study [Gelfand] 1493 leg ulcers [Margolis] 1275 (Oc) Scope, Alon (De) Monthly final page: skINsight [Grichnik] 1433 Receptors, Endothelin Second lymphomas and other malignant neo- (No) Bosentan as a rescue therapy in scleroderma plasms in patients with mycosis fungoides and Scrotum refractory digital ulcers (letter) [Chamaillard] Se´zary syndrome: evidence from population- Erythematous papules and plaques involving the 125 (Ja) based and clinical cohorts [Huang] 45 (Ja) groin and scrotum [Breedlove] 1067 (Au) Recurrence Risk Ratio see Odds Ratio Sebaceous Glands Randomized, double-blind, placebo- Rituximab Reflectance-mode confocal microscopy for the controlled trial of pentoxifylline for the treat- Clinical response of severe mechanobullous epi- diagnosis of sebaceous hyperplasia in vivo ment of recurrent aphthous stomatitis dermolysis bullosa acquisita to combined treat- [Propperova] 134 (Ja) [Thornhill] 463 (Ap); correction, 716 (Je) ment with immunoadsorption and ritux- Seborrheic Keratosis see Keratosis, Seborrheic Treatment of recurrent squamous cell carci- imab (anti-CD20 monoclonal antibodies) Self-Examination noma of the skin with cetuximab [Bauman] [Niedermeier] 192 (Fe) Efficacy of a partner assistance intervention 889 (Jy) Pilot trial of rituximab in the treatment of patients designed to increase skin self-examination per- Referral and Consultation with dermatomyositis [Chung] 763 (Je) formance [Robinson] 37 (Ja) Effect of health care delivery models on mela- Primary cutaneous diffuse large B-cell lym- Sensitivity and Specificity noma thickness and stage in a university- phoma, leg type: clinicopathologic features and Dermoscopy not yet shown to increase sensi- based referral center: an observational pilot prognostic analysis in 60 cases [Grange] 1144 tivity of melanoma diagnosis in real practice study [Swetter] 30 (Ja) (Se) (letter) [Carli] 664 (replies) [Menzies, Store-and-forward teledermatology in skin can- Rituximab in a patient with hyper-IgE syn- Zalaudek] 665, 666 (My) cer triage: experience and evaluation of 2009 drome (letter) [Trendelenburg] 807 (Je) Sentinel Lymph Node Biopsy teleconsultations [Moreno-Ramirez] 479 (Ap); Treatment of severe pemphigus with ritux- Cloud over sentinel node biopsy: unlikely sur- correction, 886 (Jy) imab: report of 12 cases and a review of the vival benefit in melanoma [Gonza´lez] 775 (Je) Regeneration literature [Cianchini] 1033 (Au) Current status of evaluation and treatment of Evaluation of plasma skin regeneration tech- Rosacea high-risk cutaneous melanoma: therapeutic nology in low-energy full-facial rejuvenation Successful treatment of the erythema and flush- breakthroughs remain elusive [Kanzler] 785 [Bogle] 168 (Fe) ing of rosacea using a topically applied selec- (Je)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E32 Severity of Illness Index Digital image analysis: a reliable tool in the quan- Differences between polarized light dermos- Childhood atopic dermatitis impact scale: reli- titative evaluation of cutaneous lesions and copy and immersion contact dermoscopy for ability, discriminative and concurrent valid- beyond (research letter) [Pressley] 1331 (Oc) the evaluation of skin lesions [Benvenuto- ity, and responsiveness [Chamlin] 768 (Je) Equinology [Peterson] 438 (Mr) Andrade] 329 (Mr) National Psoriasis Foundation clinical consen- Hyperpigmented keratotic nodules [Chua] 1201 Diffuse cutaneous nodules [Abdelmalek] 937 sus on disease severity [Pariser] 239 (Fe) (Se) (Jy) Risk of mortality in patients with psoriasis: results Incidence and risk factors for psoriasis in the gen- Disseminated cutaneous Kaposi sarcoma and from a population-based study [Gelfand] 1493 eral population [Huerta] 1559 (De) progressive multifocal leukoencephalopathy (De) Novel treatment for knuckle pads with intra- in a patient with idiopathic CD4ϩ T lympho- Sezary Syndrome lesional fluorouracil (letter) [Weiss] 1458 (No) cytopenia (letter) [Inhoff] 673 (My) Apoptotic responses to all-trans retinoic acid of Prevalence of skin diseases and cutaneous mani- Effect of health care delivery models on mela- targretin-resistant, malignant, CD4ϩ periph- festations among Iranian children: a survey of noma thickness and stage in a university- eral blood T cells from patients with Se´zary 1417 children (research letter) [Toossi] 115 based referral center: an observational pilot syndrome (research letter) [Newton] 661 (My) (Ja) study [Swetter] 30 (Ja) Measuring HRQOL in patients with cutaneous Recurrent calcified cutaneous nodule of the peri- Efficacy of a partner assistance intervention T-cell lymphoma undergoing therapy with oral anal region [Patrizi] 1441 (No) designed to increase skin self-examination per- bexarotene and extracorporeal photopher- Skin disorders among construction workers fol- formance [Robinson] 37 (Ja) esis (research letter) [Demierre] 659 (My) lowing Hurricane Katrina and Hurricane Rita: Era of targeted therapies: increasing role for novel Retinal toxic reactions following photopher- an outbreak investigation in New Orleans, oncologic drugs in dermatology [Montella] 788 esis [Vagace] 622 (My) Louisiana [Noe] 1393 (No) (Je) Second lymphomas and other malignant neo- Skin Diseases, Bacterial Erythematous papules and plaques involving the plasms in patients with mycosis fungoides and Dissemination of a localized cutaneous infec- groin and scrotum [Breedlove] 1067 (Au) Se´zary syndrome: evidence from population- tion with Mycobacterium chelonae under immu- Ex vivo dermoscopy of melanocytic tumors: time based and clinical cohorts [Huang] 45 (Ja) nosuppressive treatment (letter) for dermatopathologists to learn dermos- Shoulder [Hoetzenecker] 951 (Jy) copy [Scope] 1548 (De) Subcutaneous nodule and diffuse lymphade- Spontaneous Citrobacter freundii infection in an Fast-growing and slow-growing melanomas (let- nopathy in a 6-month-old boy from Africa immunocompetent patient (letter) [Whalen] ter) [Argenziano] 802 (reply) [Kelly] 803 (Je) [Friedman] 1323 (Oc) 124 (Ja) Five-year follow-up of a randomized, prospec- Skin Staphylococcus aureus virulence factors associ- tive trial of topical methyl aminolevulinate Effect of intense pulsed-light exposure on lipid ated with infected skin lesions: influence on photodynamic therapy vs surgery for nodu- peroxides and thymine dimers in human skin the local immune response [Mertz] 1259 (Oc) lar basal cell carcinoma [Rhodes] 1131 (Se) in vivo [Sorg] 363 (Mr) Skin Diseases, Eczematous Identification of incipient tumors by means of Epidermal Langerhans cell movement in situ: a Eczematoid graft-vs-host disease: a novel form sequential dermoscopy imaging: a new way to model for understanding immunologic func- of chronic cutaneous graft-vs-host disease and inflate the “epidemic” of melanoma? (letter) tion in the skin [Mohr] 1352 (Oc); correc- its response to psoralen–UV-A therapy [Carli] (reply) [Kittler] 805 (Je) tion, 1438 (No) [Creamer] 1157 (Se) Indoor UV tanning youth access laws: update Fluoroscopy-induced chronic radiation skin Skin Diseases, Fungal see Dermatomycoses 2007 [McLaughlin] 529 (Ap) injury: a disease perhaps often overlooked Skin Diseases, Genetic Leukemia cutis: a presenting sign in acute pro- [Frazier] 637 (My) Persistent eosinophilia as a presenting sign of myelocytic leukemia (letter) [Markowski] Improvement of naturally aged skin with vita- scabies in patients with disorders of keratini- 1220 (Se) min A (retinol) [Kafi] 606 (My) zation (letter) [Sluzevish] 670 (My) Melanoma screening: focusing the public health Intertriginous eruption associated with chemo- Skin Diseases, Infectious journey [Koh] 101 (Ja) therapy in pediatric patients [Webber] 67 (Ja) Combination immunosuppressive therapies: the Overexpressionofmatrixmetalloproteinases,che- Skin microecology: the old and the new promise and the peril [Robinson] 1053 (Au) mokines, and chemokine receptors relevant for [Webster] 105 (Ja) Nocardia otitidiscaviarum: cause of long-term metastasis in experimental models not an in- Wound complications following diagnostic skin cutaneous abscesses on the leg of an immu- dication of lymph node metastases in human biopsies in dermatology inpatients [Wahie] nocompetent man (letter) [Thoms] 1086 (Au) melanoma (research letter) [Otto] 947 (Jy) 1267 (Oc) Skin Diseases, Vascular Paraneoplastic Raynaud phenomenon with digi- Skin Abnormalities Neurovascular instability syndrome: a unify- tal necrosis associated with hyperhomocys- Clinical, histologic, and molecular study of 9 ing term to describe the coexistence of tem- teinemia and antiphospholipid antibodies (let- cases of congenital dermatofibrosarcoma pro- perature-related vascular disorders in affected ter) [Carducci] 1342 (Oc) tuberans [Maire] 203 (Fe) patients (letter) [George] 274 (Fe) Patterns of indoor tanning use: implications for Skin Aging Skin Diseases, Vesicular see Skin Diseases, clinical interventions [Hillhouse] 1530 (De) Effect of smoking on aging of photoprotected Vesiculobullous Predictors of skin-related quality of life after treat- skin: evidence gathered using a new photo- Skin Diseases, Vesiculobullous ment of cutaneous basal cell carcinoma and numeric scale [Helfrich] 397 (Mr); correc- Acute and recurrent vesicular hand dermatitis squamous cell carcinoma [Chen] 1386 (No) tion, 633 (My) not pompholyx or dyshidrosis [Storrs] 1578 Primary cutaneous diffuse large B-cell lym- Evaluation of plasma skin regeneration tech- (De) phoma, leg type: clinicopathologic features and nology in low-energy full-facial rejuvenation Childhood bullous pemphigoid: clinical and prognostic analysis in 60 cases [Grange] 1144 [Bogle] 168 (Fe) immunological findings in a series of 4 cases (Se) Improvement of naturally aged skin with vita- [Martinez-De Pablo] 215 (Fe) Question the obvious [Nijsten] 1429 (No) min A (retinol) [Kafi] 606 (My) Skin Diseases, Viral Results of radiotherapy in 153 primary cutane- Randomized double-blind study of the effect of Intractable wounds from a herpes simplex infec- ous B-cell lymphomas classified according to Botox and Dysport/Reloxin on forehead tion in an immunosuppressed patient with the WHO-EORTC classification [Senff] 1520 wrinkles and electromyographic activity (re- rheumatoid arthritis (letter) [Hanafusa] 1340 (De) search letter) [Karsai] 1447 (No) (Oc) Second lymphomas and other malignant neo- Smoking and skin aging in identical twins Skin Neoplasms plasms in patients with mycosis fungoides and [Doshi] 1543 (De) Clinicopathologic correlation of cutaneous Se´zary syndrome: evidence from population- Skin Care metastases: experience from a cancer center based and clinical cohorts [Huang] 45 (Ja) In vivo stimulation of de novo collagen produc- [Sariya] 613 (My) Skin cancer awareness and sun protection behav- tion caused by cross-linked hyaluronic acid Combination immunosuppressive therapies: the iors in white Hispanic and white non- dermal filler injections in photodamaged promise and the peril [Robinson] 1053 (Au) Hispanic high school students in Miami, human skin [Wang] 155 (Fe) Correlation of dermoscopic structures of mela- Florida [Ma] 983 (Au) Skin Diseases nocytic lesions to reflectance confocal micros- Skin cancer presenting as a nonhealing wound: Archives of Dermatology Web site: adding new copy [Scope] 176 (Fe) the association of polio and skin cancer (let- dimensions to the literature [Bhatia] 1320 (Oc) Current status of evaluation and treatment of ter) [Vu] 1338 (Oc) Case of zosteriform pigmented purpuric derma- high-risk cutaneous melanoma: therapeutic Store-and-forward teledermatology in skin can- tosis (letter) [Hamada] 1599 (De) breakthroughs remain elusive [Kanzler] 785 cer triage: experience and evaluation of 2009 Clear cell papulosis in Hispanic siblings (Je) teleconsultations [Moreno-Ramirez] 479 (Ap); [Benouni] 358 (Mr) Delayed wound healing following treatment with correction, 886 (Jy) Dermatology and the human genome: an epi- low-dose interferon alfa-2b for cutaneous mela- Teens and tans: implementing behavioral change demiologic approach [Gwinn] 1194 (Se) noma (letter) [Ammoury] 1339 (Oc) [Haas] 1058 (Au)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E33 Treatment of recurrent squamous cell carci- Dermoscopy of port-wine stains [Va´zquez- Substance-Related Disorders noma of the skin with cetuximab [Bauman] Lo´pez] 962 (Jy) Acute generalized exanthematous pustulosis 889 (Jy) Dermoscopy of pyogenic granulomas [Zaballos] caused by illicit street drugs? (letter) [Lu] 430 Visual screening for malignant melanoma: a cost- 824 (Je) (Mr) effectiveness analysis [Losina] 21 (Ja) Dermoscopy subpattern of plaque-type psoria- Hair graying in substance addiction (research let- Skin Pigmentation see Pigmentation sis: red globular rings [Va´zquez-Lo´pez] 1612 ter) [Reece] 116 (Ja) Skin Resurfacing (De) Sulfur Fractional photothermolysis: a novel treat- Epidermal Langerhans cell movement in situ: a Persistent eosinophilia as a presenting sign of ment for disseminated superficial actinic poro- model for understanding immunologic func- scabies in patients with disorders of keratini- keratosis (letter) [Chrastil] 1450 (No) tion in the skin [Mohr] 1352 (Oc); correc- zation (letter) [Sluzevish] 670 (My) Fractional photothermolysis for the treatment tion, 1438 (No) Sunscreening Agents of adult colloid milium [Marra] 572 (My) Equinology [Peterson] 438 (Mr) Skin cancer awareness and sun protection behav- Fractional resurfacing: a new therapeutic modal- “Louse blouse” as a cause of erythroderma iors in white Hispanic and white non- ity for Becker’s nevus [Glaich] 1488 (De) [Irizarry] 682 (My) Hispanic high school students in Miami, Monthlyfinalpage:skINsight[Grichnik]1433(No) Florida [Ma] 983 (Au) Skin Transplantation Reflectance-mode confocal microscopy for the Teens and tans: implementing behavioral change Koebner phenomenon in vitiligo: not always an diagnosis of sebaceous hyperplasia in vivo [Haas] 1058 (Au) indication of surgical failure (research letter) [Propperova] 134 (Ja) Surgical Flaps [Mulekar] 801 (Je) Subungual exostosis [Sa´nchez-Castellanos] 1234 Subungual melanoma in situ in a Hispanic girl Vitiligo: to treat or not to treat [Lim] 643 (My) (Se) treated with functional resection and recon- Skin Ulcer ␤ Three-dimensional images and vessel render- struction with onychocutaneous toe free flap Association between the use of -adrenergic ing using optical coherence tomography (letter) [Motta] 1600 (De) receptor agents and the development of venous [Thomas] 1468 (No) Surgical Procedures, Operative leg ulcers [Margolis] 1275 (Oc) Smoking Five-year follow-up of a randomized, prospec- Bosentan as a rescue therapy in scleroderma Association of androgenetic alopecia with smok- tive trial of topical methyl aminolevulinate refractory digital ulcers (letter) [Chamaillard] ing and its prevalence among Asian men: a photodynamic therapy vs surgery for nodu- 125 (Ja) community-based survey [Su] 1401 (No) lar basal cell carcinoma [Rhodes] 1131 (Se) Diagnostic yield of histopathologic sampling Effect of smoking on aging of photoprotected Survival techniques in PAN-associated cutaneous ulcers skin: evidence gathered using a new photo- Cloud over sentinel node biopsy: unlikely (research letter) [Ricotti] 1334 (Oc) numeric scale [Helfrich] 397 (Mr); correc- survival benefit in melanoma [Gonza´lez] Digital image analysis: a reliable tool in the quan- tion, 633 (My) 775 (Je) titative evaluation of cutaneous lesions and Incidence and risk factors for psoriasis in the gen- Current status of evaluation and treatment of beyond (research letter) [Pressley] 1331 (Oc) eral population [Huerta] 1559 (De) high-risk cutaneous melanoma: therapeutic Fluoroscopy-induced chronic radiation skin Smoking and skin aging in identical twins breakthroughs remain elusive [Kanzler] 785 injury: a disease perhaps often overlooked [Doshi] 1543 (De) (Je) [Frazier] 637 (My) Sodium Chloride Melanoma outcomes for Medicare patients: asso- Hydroxyurea-induced leg ulcers treated with a Dressings for acute and chronic wounds: a sys- ciation of stage and survival with detection by protease-modulating matrix [Romanelli] 1310 tematic review [Chaby] 1297 (Oc) a dermatologist vs a nondermatologist [Pennie] (Oc) Sodium Thiosulfate 488 (Ap) Intractable wounds from a herpes simplex infec- Systemic adjuvant therapy for patients with high- tion in an immunosuppressed patient with Calciphylaxis responding to sodium thiosulfate therapy (letter) [Baker] 269 (Fe) risk melanoma [Tsai] 779 (Je) rheumatoid arthritis (letter) [Hanafusa] 1340 Survivors (Oc) Sodium thiosulfate as first-line treatment for calciphylaxis (letter) [Ackermann] 1336 (re- Skin cancer presenting as a nonhealing wound: Negative pressure dressing in the management the association of polio and skin cancer (let- of pyoderma gangrenosum ulcer [Ghersi] 1249 ply) [Robinson] 1338 (Oc) Spitz Nevus see Nevus, Epithelioid and Spindle ter) [Vu] 1338 (Oc) (Oc) Sutures Physical activity and adherence to compres- Cell Sporotrichosis Breaking strength of barbed polypropylene sion therapy in patients with venous leg ulcers sutures: rater-blinded, controlled compari- [Heinen] 1283 (Oc) Auricular erythema with nodules and scale [Hutchin] 1441 (No) son with nonbarbed sutures of various cali- Pulsed-dye laser treatment of nonhealing chronic bers [Rashid] 869 (Jy); correction, 1186 (Se) ulcer with hypergranulation tissue [Wang] 700 Staphylococcus aureus Staphylococcus aureus virulence factors associ- Sweat Glands (Je) Treatment of hyperhidrosis with oxybutynin (let- Rapidly enlarging necrotic ulcer on the right calf ated with infected skin lesions: influence on the local immune response [Mertz] 1259 (Oc) ter) [Schollhammer] 544 (Ap) [Chakrabarti] 791 (Je) Swine Resolution of chronic pain and fingertip ulcer- State Government Indoor UV tanning youth access laws: update Topical oxygen emulsion: a novel wound therapy ation due to hand-arm vibration syndrome fol- [Davis] 1252 (Oc) lowing combination pharmacotherapy (let- 2007 [McLaughlin] 529 (Ap) ter) [Buell] 1343 (Oc) Stevens-Johnson Syndrome T Skin cancer presenting as a nonhealing wound: Cutaneous adverse reactions to valdecoxib dis- the association of polio and skin cancer (let- tinct from Stevens-Johnson syndrome and Tachycardia ter) [Vu] 1338 (Oc) toxic epidermal necrolysis [Ziemer] 711 (Je) Atrial tachycardia associated with isotretinoin Sodium thiosulfate as first-line treatment for cal- Long-term follow-up of a patient with eruptive use (letter) [Dresden] 1084 (Au) ciphylaxis (letter) [Ackermann] 1336 (re- melanocytic nevi after Stevens-Johnson syn- Tachyphylaxis ply) [Robinson] 1338 (Oc) drome [Gelfer] 1555 (De) Poor adherence to treatments: a fundamental Spontaneous Citrobacter freundii infection in an Stomatitis, Aphthous principle of dermatology [Ali] 912 (Jy) immunocompetent patient (letter) [Whalen] New and old therapeutics for oral ulcerations Tacrolimus 124 (Ja) [Bruce] 519 (Ap) Effect of tacrolimus on vitiligo in absence of UV Teledermatological monitoring of leg ulcers in Randomized, double-blind, placebo- radiation exposure (letter) [Sardana] 119 (re- cooperation with home care nurses [Binder] controlled trial of pentoxifylline for the treat- ply) [Passeron] 120 (Ja) 1511 (De) ment of recurrent aphthous stomatitis Focal acne during topical tacrolimus therapy for Ulceronecrotic nasoparanasal lesion [Martı´n] 653 [Thornhill] 463 (Ap); correction, 716 (Je) vitiligo (letter) [Bakos] 1223 (Se) (My) Street Drugs National Eczema Association and topical calci- Wound assessment by 3-dimensional laser scan- Acutegeneralizedexanthematouspustulosiscaused neurin inhibitor labeling (letter) [Cooper] 546 ning (research letter) [Romanelli] 1333 (Oc) by illicit street drugs? (letter) [Lu] 430 (Mr) (Ap) Wound healing [Kirsner] 1318 (Oc) Streptococcus Topical calcineurin inhibitors revisited (letter) Skin Wrinkling see Skin Aging Skin microecology: the old and the new [Qureshi] 545 (Ap) skINsight (Grichnik JM, ed) [Webster] 105 (Ja) Taiwan Dermoscopic vascular patterns in nodular “pure” Students Association of androgenetic alopecia with smok- amelanotic melanoma [Cavicchini] 556 (Ap) Patterns of indoor tanning use: implications for ing and its prevalence among Asian men: a Dermoscopy insights into nevogenesis: “abtrop- clinical interventions [Hillhouse] 1530 (De) community-based survey [Su] 1401 (No) fung” vs “hochsteigerung” [Zalaudek] 284 (Fe) Substance Abuse, Intravenous Tanning Dermoscopy of active lichen planus [Va´zquez- Injection drug use: an understudied cause of Indoor UV tanning youth access laws: update Lo´pez] 1092 (Au) venous disease [Pieper] 1305 (Oc) 2007 [McLaughlin] 529 (Ap)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E34 Targretin Tinea Versicolor Psoriasiform eruptions during anti–TNF-␣ treat- Apoptotic responses to all-trans retinoic acid of Successful treatment of pityriasis versicolor with ment: psoriasis or not? (letter) [Seneschal] targretin-resistant, malignant, CD4ϩ periph- 5-aminolevulinic acid photodynamic therapy 1593 (reply) [de Gannes] 1595 (De) eral blood T cells from patients with Se´zary (letter) [Kim] 1218 (Se) Psoriasis and pustular dermatitis triggered by syndrome (research letter) [Newton] 661 (My) Toes TNF-␣ inhibitors in patients with rheumato- Tattooing Growth inhibition of Trichophyton species by logic conditions [de Gannes] 223 (Fe) Comparison of treatment options for a Monsel Pseudomonas aeruginosa [Treat] 61 (Ja) Role of the quantiFERON-TB gold test as screen- tattoo (letter) [Rao] 1452 (No) Nodule on the toe [Dapprich] 1067 (Au) ing prior to administration of tumor necrosis Eruptive keratoacanthomas in a new tattoo (let- Verrucous nodules on the toes of a renal trans- factor inhibitors (letter) [Martinez] 809 (Je) ter) [Chorny] 1457 (No) plant recipient [Levy] 653 (My) Yin and yang of TNF-␣ inhibition [Fiorentino] Tazarotene Tomography, Optical Coherence 233 (Fe) Successful treatment of Favre-Racouchot dis- Three-dimensional images and vessel render- Tumor Necrosis Factors ease with 0.05% tazarotene gel (letter) [Rallis] ing using optical coherence tomography What are the risks of serious infections and 810 (Je) [Thomas] 1468 (No) malignancies for patients treated with anti- Telangiectasis Tongue tumor necrosis factor antibodies? [Corona] Three-dimensional images and vessel render- Black tongue and Enterobacter cloacae (letter) [El 405 (Mr) ing using optical coherence tomography Sayed] 815 (Je) Turkey [Thomas] 1468 (No) Firm papule on the lateral tongue [Suwattee] Variations in the dermoscopic features of Teleconsultation see Remote Consultation 1583 (De) acquired acral melanocytic nevi [Ozdemir] Telemedicine Tongue Neoplasms 1378 (No) Teledermatological monitoring of leg ulcers in Asymptomatic nodule of the tongue [Mataix] Twins cooperation with home care nurses [Binder] 653 (My) Smoking and skin aging in identical twins 1511 (De) Toxic Epidermal Necrolysis see Epidermal [Doshi] 1543 (De) Teledermatology: extending specialty care Necrolysis, Toxic beyond borders [Burdick] 1581 (De) Tretinoin U Telithromycin Apoptotic responses to all-trans retinoic acid of Telithromycin-induced TEN: report of a case targretin-resistant, malignant, CD4ϩ periph- Ulcer see Skin Ulcer (letter) [Be´dard] 427 (Mr) eral blood T cells from patients with Se´zary Ultraviolet Rays Temperature syndrome (research letter) [Newton] 661 (My) Effect of intense pulsed-light exposure on lipid Neurovascular instability syndrome: a unify- Lichen spinulosus: excellent response to treti- peroxides and thymine dimers in human skin ing term to describe the coexistence of tem- noin gel and hydroactive adhesive applica- in vivo [Sorg] 363 (Mr) perature-related vascular disorders in affected tions (letter) [Forman] 122 (Ja) Effect of tacrolimus on vitiligo in absence of UV patients (letter) [George] 274 (Fe) Triage radiation exposure (letter) [Sardana] 119 (re- Temporal Arteritis Store-and-forward teledermatology in skin can- ply) [Passeron] 120 (Ja) Rare manifestation of scalp necrosis in tempo- cer triage: experience and evaluation of 2009 Indoor UV tanning youth access laws: update ral arteritis (letter) [Adams] 1079 (Au) teleconsultations [Moreno-Ramirez] 479 (Ap); 2007 [McLaughlin] 529 (Ap) Terminology correction, 886 (Jy) Narrowband UV-B phototherapy, alefacept, and Acute and recurrent vesicular hand dermatitis not Trichoepithelioma clearance of psoriasis [Legat] 1016 (Au) pompholyx or dyshidrosis [Storrs] 1578 (De) Novel missense mutation in the CYLD gene in a Narrowband UV-B phototherapy for extra- Tetracycline Resistance Spanish family with multiple familial trichoepi- genital lichen sclerosus (letter) [Kreuter] Skin microecology: the old and the new thelioma (research letter) [Espan˜ a] 1209 (Se) 1213 (Se) [Webster] 105 (Ja) Trichophyton Nevus type in dermoscopy is related to skin type Texas Growth inhibition of Trichophyton species by in white persons [Zalaudek] 351 (Mr) Prevalence of self-diagnosed melasma among Pseudomonas aeruginosa [Treat] 61 (Ja) Patterns of indoor tanning use: implications for premenopausal Latino women in Dallas and Trimethoprim clinical interventions [Hillhouse] 1530 (De) Fort Worth, Tex (research letter) [Werlinger] Erythema and blistering of the left leg Susceptibility to UV-A and UV-B provocation 424 (Mr) [Shimanovich] 535 (Ap) does not correlate with disease severity of poly- Thailand Trimethoprim-Sulfamethoxazole Combination morphic light eruption [Janssens] 599 (My) Effect of cold air cooling on the incidence of Pneumocystis carinii pneumonia in infant treated Ultraviolet Therapy postinflammatory hyperpigmentation after with oral steroids for hemangioma (letter) Balneophototherapy for psoriasis using saltwa- Q-switched Nd:YAG laser treatment of [Maronn] 1224 (Se) ter baths and UV-B irradiation, revisited acquired bilateral nevus of Ota–like macules Trimethylaminuria see Metabolic Diseases [Gambichler] 647 (My) [Manuskiatti] 1139 (Se) Tropical Climate Bath PUVA and saltwater baths followed by Thallium Dermoscopic diagnosis of furuncular myiasis UV-B phototherapy as treatments for pso- Short-term thallium intoxication: dermatologi- (letter) [Bakos] 123 (Ja) riasis: a randomized controlled trial cal findings correlated with thallium concen- Tuberculosis [Schiener] 586 (My) tration [Lu] 93 (Ja) Role of the quantiFERON-TB gold test as screen- Progressive extragenital lichen sclerosus suc- Thigh ing prior to administration of tumor necrosis cessfully treated with narrowband UV-B pho- Late-onset familial Mediterranean fever: an atypi- factor inhibitors (letter) [Martinez] 809 (Je) totherapy [Colbert] 19 (Ja) cal presentation of dermatologic interest (let- Tuberculosis Vaccines Randomized double-blind trial of treatment of ter) [Satta] 1080 (Au) Subcutaneous nodule and diffuse lymphade- vitiligo: efficacy of psoralen–UV-A therapy vs Thrombosis nopathy in a 6-month-old boy from Africa narrowband–UV-B therapy [Yones] 578 (My); Hypereosinophilic syndrome with peripheral cir- [Friedman] 1323 (Oc) correction, 906 (Jy) culatory insufficiency and cutaneous micro- Tumor Necrosis Factor-␣ Success of Goeckerman treatment in 2 patients thrombi (letter) [Hamada] 812 (Je) Clinical improvement of pityriasis rubra pilaris with psoriasis not responding to biological Thymidine Phosphorylase with combination etanercept and acitretin drugs (letter) [Soares] 950 (Jy) Immunohistochemical expression of platelet therapy (letter) [Davis] 1597 (De) Vitiligo: to treat or not to treat [Lim] 643 (My) growth factor and vascular endothelial growth Onset of psoriasis during treatment with TNF-␣ United States factor in patients with melanoma with and antagonists: a report of 3 cases (letter) Incidence of cutaneous T-cell lymphoma in the without redness (Brenner sign) [Mashiah] [Ubriani] 270 (Fe) United States, 1973-2002 [Criscione] 854 (Jy) 1001 (Au) Psoriasiform eruptions during anti–TNF-␣ treat- United States Food and Drug Administration Thymine Dimers see Pyrimidine Dimers ment: psoriasis or not? (letter) [Seneschal] National Eczema Association and topical calci- Time Factors 1593 (reply) [de Gannes] 1595 (De) neurin inhibitor labeling (letter) [Cooper] 546 Balancing the benefits and risks of drug treat- Psoriasis and pustular dermatitis triggered by (Ap) ment: a stated-preference, discrete choice TNF-␣ inhibitors in patients with rheumato- Topical calcineurin inhibitors revisited (letter) experiment with patients with psoriasis logic conditions [de Gannes] 223 (Fe) [Qureshi] 545 (Ap) [Seston] 1175 (Se) Yin and yang of TNF-␣ inhibition [Fiorentino] University of Pennsylvania Tinea 233 (Fe) Sponsorship of graduate medical education: one Direct identification of dermatophyte DNA from Tumor Necrosis Factor Antagonists successful model (letter) [James] 1211 (Se) clinical specimens by a nested polymerase Onset of psoriasis during treatment with TNF-␣ Urinalysis chain reaction assay (research letter) [Yang] antagonists: a report of 3 cases (letter) Trimethylaminuria (fish-odor syndrome): a case 799 (Je) [Ubriani] 270 (Fe) report [Arseculeratne] 81 (Ja)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E35 Ursodeoxycholic Acid Vasopressor Agents see Vasoconstrictor Agents and acute wound dressings [Vaneau] 1291 Importance of serum bile acid level analysis and Venous Ulcer see Varicose Ulcer (Oc) treatment with ursodeoxycholic acid in intrahe- Verruca see Warts Delayed wound healing following treatment with patic cholestasis of pregnancy: a case series from Vesicular Palmoplantar Eczema see Eczema, low-dose interferon alfa-2b for cutaneous mela- Central Europe [Ambros-Rudolph] 757 (Je) Dyshidrotic noma (letter) [Ammoury] 1339 (Oc) Urticaria Veterinary Medicine Dressings for acute and chronic wounds: a sys- Chronic urticaria and monoclonal IgM gam- Accessible evidence-based medicine: critically tematic review [Chaby] 1297 (Oc) mopathy (Schnitzler syndrome): report of 11 appraised topics [Barzilai] 1189 (Se) Hydroxyurea-induced leg ulcers treated with a cases treated with pefloxacin [Asli] 1046 (Au) Video Recording protease-modulating matrix [Romanelli] 1310 Functional dysregulation of dendritic cells in Archives of Dermatology Web site: adding new (Oc) patients with papular urticaria caused by flea- dimensions to the literature [Bhatia] 1320 (Oc) Injection drug use: an understudied cause of bite [Cue´llar] 1415 (No) Virulence Factors venous disease [Pieper] 1305 (Oc) Skin disorders among construction workers fol- Staphylococcus aureus virulence factors associ- Koebner phenomenon in vitiligo: not always an lowing Hurricane Katrina and Hurricane Rita: ated with infected skin lesions: influence on indication of surgical failure (research letter) an outbreak investigation in New Orleans, the local immune response [Mertz] 1259 (Oc) [Mulekar] 801 (Je) Louisiana [Noe] 1393 (No) Vitamin A Negative pressure dressing in the management Improvement of naturally aged skin with vita- of pyoderma gangrenosum ulcer [Ghersi] 1249 V min A (retinol) [Kafi] 606 (My) (Oc) Vitiligo Physical activity and adherence to compres- Vaccines Effect of tacrolimus on vitiligo in absence of UV sion therapy in patients with venous leg ulcers Subcutaneous nodule and diffuse lymphade- radiation exposure (letter) [Sardana] 119 (re- [Heinen] 1283 (Oc) nopathy in a 6-month-old boy from Africa ply) [Passeron] 120 (Ja) Skin cancer presenting as a nonhealing wound: [Friedman] 1323 (Oc) Focal acne during topical tacrolimus therapy for the association of polio and skin cancer (let- Valdecoxib vitiligo (letter) [Bakos] 1223 (Se) ter) [Vu] 1338 (Oc) Cutaneous adverse reactions to valdecoxib dis- Koebner phenomenon in vitiligo: not always an Teledermatological monitoring of leg ulcers in tinct from Stevens-Johnson syndrome and indication of surgical failure (research letter) cooperation with home care nurses [Binder] toxic epidermal necrolysis [Ziemer] 711 (Je) [Mulekar] 801 (Je) 1511 (De) Varicose Ulcer Randomized double-blind trial of treatment of Topical oxygen emulsion: a novel wound therapy ␤ Association between the use of -adrenergic vitiligo: efficacy of psoralen–UV-A therapy vs [Davis] 1252 (Oc) receptor agents and the development of venous narrowband–UV-B therapy [Yones] 578 (My); Use of antibiotic ointment after clean cutane- leg ulcers [Margolis] 1275 (Oc) correction, 906 (Jy) ous surgery [Bigby] 1180 (Se) Injection drug use: an understudied cause of Vitiligo: to treat or not to treat [Lim] 643 (My) Wound healing [Kirsner] 1318 (Oc) venous disease [Pieper] 1305 (Oc) Volar Plate Wound Infection Physical activity and adherence to compres- Palmar basal cell carcinoma in a patient with Intractable wounds from a herpes simplex infec- sion therapy in patients with venous leg ulcers Gorlin-Goltz syndrome (letter) [Cabo] 813 (Je) tion in an immunosuppressed patient with [Heinen] 1283 (Oc) Vulvar Neoplasms rheumatoid arthritis (letter) [Hanafusa] 1340 Wound assessment by 3-dimensional laser scan- Dermoscopy in vulvar basal cell carcinoma (let- (Oc) ning (research letter) [Romanelli] 1333 (Oc) ter) [de Giorgi] 426 (Mr) Wound complications following diagnostic skin Wound healing [Kirsner] 1318 (Oc) biopsies in dermatology inpatients [Wahie] Vascular Diseases W 1267 (Oc) Injection drug use: an understudied cause of venous disease [Pieper] 1305 (Oc) Warts Wounds and Injuries Neurovascular instability syndrome: a unify- Duct tape for the treatment of common warts In vivo stimulation of de novo collagen producing term to describe the coexistence of tem- in adults: a double-blind randomized con- tion caused by cross-linked hyaluronic acid perature-related vascular disorders in affected trolled trial [Wenner] 309 (Mr) dermal filler injections in photodamaged patients (letter) [George] 274 (Fe) Scaly plaque on the scalp [Borer] 1067 (Au) human skin [Wang] 155 (Fe) Vascular Endothelial Growth Factors Verruca plana–like papules as a new manifes- Wound assessment by 3-dimensional laser scan- Immunohistochemicalexpressionofplateletgrowth tation of Erdheim-Chester disease (letter) ning (research letter) [Romanelli] 1333 (Oc) factor and vascular endothelial growth factor in [Yanagi] 952 (Jy) patients with melanoma with and without red- Verrucous nodules on the toes of a renal trans- X ness (Brenner sign) [Mashiah] 1001 (Au) plant recipient [Levy] 653 (My) Vasculitis Verrucous papules and plaques in a pediatric Xanthoma see Xanthomatosis Diagnostic yield of histopathologic sampling patient [Gonzalez] 1201 (Se) Xanthoma Disseminatum see Histiocytosis, techniques in PAN-associated cutaneous ulcers Water Non-Langerhans-Cell (research letter) [Ricotti] 1334 (Oc) Balneophototherapy for psoriasis using saltwa- Xanthomatosis Paraneoplastic Raynaud phenomenon with digi- ter baths and UV-B irradiation, revisited Burgeoning nodule on the scalp of a 65-year- tal necrosis associated with hyperhomocys- [Gambichler] 647 (My) old man [Farhi] 653 (My) teinemia and antiphospholipid antibodies (let- Bath PUVA and saltwater baths followed by UV-B Scaly plaque on the scalp [Borer] 1067 (Au) ter) [Carducci] 1342 (Oc) phototherapy as treatments for psoriasis: a ran- Tuberous necrobiosis lipoidica (letter) Vasoconstriction domized controlled trial [Schiener] 586 (My) [Michaels] 546 (Ap) Phenylephrine-induced microvascular occlu- Web Sites see Internet sion syndrome in a patient with a heterozy- Wells Syndrome Y gous factor V Leiden mutation [Kalajian] 1314 Recurrent, pruritic dermal plaques and bullae (Oc) [Green] 791 (Je) Yeasts Vasoconstrictor Agents Women’s Health Solitary cutaneous nodule in an immunocom- Phenylephrine-induced microvascular occlu- Prevalence of self-diagnosed melasma among promised patient [Singh] 1583 (De) sion syndrome in a patient with a heterozy- premenopausal Latino women in Dallas and gous factor V Leiden mutation [Kalajian] 1314 Fort Worth, Tex (research letter) [Werlinger] Z (Oc) 424 (Mr) Vasodilation World Wide Web see Internet Zinc Compounds Rebound vasodilation from long-term topical Wound Healing Poor adherence to treatments: a fundamental corticosteroid use (letter) [Rapaport] 268 (Fe) Consensus panel recommendations for chronic principle of dermatology [Ali] 912 (Jy)

ARCH DERMATOL / VOL 142, DEC 2007 WWW.ARCHDERMATOL.COM E36