Journal of the American Osteopathic College of Dermatology
Volume 14, Number 1 SPONSORS: ',/"!, 0!4(/,/'9 ,!"/2!4/29 s -%$)#)3 July 2009 '!,$%2-! s 2!."!89 www.aocd.org Journal of the American Osteopathic College of Dermatology Journal of the American Osteopathic College of Dermatology
2008-2009 Officers President: Donald K. Tillman, Jr., D.O., FAOCD President Elect: Marc I. Epstein, D.O., FAOCD First Vice President: Leslie Kramer, D.O., FAOCD Second Vice President: Bradley P. Glick, D.O., FAOCD Third Vice President: James B. Towry, D.O., FAOCD Secretary-Treasurer: Jere J. Mammino, D.O., FAOCD Immediate Past President: Jay S. Gottlieb, D.O., FAOCD Trustees: David L. Grice, D.O., FAOCD Mark A. Kuriata, D.O., FAOCD Karen E. Neubauer, D.O., FAOCD Editors Rick Lin, D.O., FAOCD Jay S. Gottlieb, DO Suzanne Rozenberg, D.O., FAOCD Jon Keeling, DO David Geiss, D.O., FAOCD Andrew Racette, DO Executive Director: Rebecca (Becky) Mansfield
Editorial Review Board Kevin Belasco, DO Sponsors: Iqbal Bukhari, MD Global Pathology Laboratory Daniel Buscaglia, DO Medicis Igor Chaplik, DO Tejas Desai, DO Galderma Brad Glick, DO Ranbaxy Melinda Greenfield, DO Andrew Hanley, MD David Horowitz, DO
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CONTENTS
Letter from the JAOCD Editors ...... 4 Letter from the President ...... 5 PDT in the Treatment of Comedonal Acne: A Case Presentation ...... 6 Kristy P. Gilbert DO, Lloyd J. Cleaver DO, FAOCD Axillary Granular Parakeratosis: A Case Presentation and Discussion ...... 9 Nicole Bright, DO, Sharon Zellis, DO, Tanya Ermolovich, DO Off-label uses of Topical Pimecrolimus ...... 11 Iqbal A. Bukhari, King Faisal University, Dammam, Saudi Arabia Eczema Herpeticum in Chronic Hand and Foot Eczema: A Case Presentation ...... 14 Lisa Zaleski, DO, LT, MC, USN; Michael Yablonsky, MD, FAAD, LCDR, MC, USN Unusual Presentation of Localized Urticaria Pigmentosa in a Five-year-old ...... 16 Joseph Del Priore, DO, David C. Horowitz, DO Overview of the Diagnosis and Treatment of Hair Loss ...... 21 Edward Galiczynski, DO, Leonid Trost, MD, Shannon Harrison, Wilma Bergfeld, MD Leukemic Vasculitis and Cutaneous Manifestations of Acute Myelogenous Leukemia ...... 27 David Cleaver DO, Jenny Cotton MD, PHD, Brian Shapiro MD, Daniel Stewart DO Piebaldism ...... 31 Maryam Shahsavari, DO, Gloria Stevens, MD, Ronald Liskanich, DO, David Horowitz, DO Work-up of Suspected Cobb Syndrome Reveals a Tethered Spinal Cord ...... 32 Jack Griffith, DO, Mark Horowitz, DO, David Horowitz, DO, FAOCD, FAAD Allergic Contact Dermatitis to Black Henna Tattoo in Siblings ...... 34 Peter Saitta, DO, Karthik Krishnamurthy, DO, Lisa Gruson, M.D, Ronald Brancaccio, MD Cindy Hoffman, DO Retroauricular ulcer in a patient with a history of multiple skin cancers ...... 36 Tony Nakhla, DO, Helia Eragi, OMS IV, Mark K. Horowitz, DO, David C. Horowitz, DO, FAAD, FAOCD Erythema Ab Igne ...... 38 Robert A. Norman, DO, Mindy Ly, OMS III Diffuse Macular Amyloidosis: Case Report ...... 40 Todd Kreitzer, DO, RPh, Jonathan Bass, MD, Joan Tamburro, DO Multicentric Castleman’s disease and AIDS-associated Kaposi’s sarcoma occurring together: A case report and discussion ...... 42 Lyubov Avshalumova, DO, Richard Miller, DO, FAOCD Linear Papular Erythema in a One-Year-Old Male ...... 47 Reagan Anderson, DO, MPH, MCS, Leela Athalye, MS III, Steven Grekin, DO, FAOCD Dermatological Manifestations of HIV/AIDS: Relevance in a Post-HAART Era...... 49 Kevin T. Belasco, DO, MS Metastatic Renal Cell Carcinoma ...... 59 Joseph Machuzak, DO, Megan Goff Machuzak, DO Widespread Creeping Eruption Secondary to Diffuse Contact with Tropical Hookworm ...... 60 Aaron J. Peterson, DO, Kendal J. Jensen, BS, S. Ray Peterson, MD, FAOCD, Brian Bradshaw, MD, C. Riley Nelson, PhD Familial Multiple Lipomatosis with Concurrent Angiolipomas: A Case Report and Review of the Literature ...... 62 Melissa Voutsalath DO, Michelle Bruner DO, Michael Whitworth DO Infectious Mononucleosis Presentig as Acute Urticaria ...... 65 Kristy P. Gilbert DO, Lloyd J. Cleaver DO, FAOCD Lymphomatoid Papulosis: A Case Presentation and Discussion ...... 69 David B. Roy, DO, Kyle M. McWhirter, DO, Don A. Anderson, DO, FAOCD, FASMS Pemphigus Erythematosus: A Case Report and Overview of Pemphigus Variants ...... 71 Risa Ross, DO, David Esguerra, DO, FAOCD, Richard Miller, DO, FAOCD Loxosceles Reclusa Bite: Case Presentation and Literature Review ...... 74 Boris Ioffe, DO, PharmD, Alyn Hatter, DO, Bill V. Way, DO, FAOCD LETTER FROM THE EDITORS
JAY GOTTLIEB, DO, JON KEELING, DO, ANDREW RACETTE, DO, FAOCD Senior Editor FAOCD Editor FAOCD Editor
We would like to extend our thanks to all of the submitting authors, including medical students, interns, residents, program directors, and private-practice dermatologists, for all of your hard work and excellent papers. We hope that you will continue to think of the JAOCD first when you are submit- ting your journal papers. The JAOCD will continue to have an emphasis on residents and supporting the future of dermatology. Besides case reports, the journal has several other sections in which we encourage authors to submit papers, including therapy, current opinions, basic science, dermatologic surgery, dermatopathology, cosmetic dermatology, pearls, and pharmaceutical dermatology.
The JAOCD has now transitioned to a completely online submission process through Editorial Manager at www.editorialmanager.com/jaocd. The process has taken some getting used to for everyone involved, but most of the issues have been worked out. The process is getting easier for authors, reviewers, and the editors, and this will only make our journal stronger in the long run.
In addition, we would like to thank the reviewers of the JAOCD for your endless efforts to help improve the quality of each and every article we publish. Without you, we would not be able to take the next step of trying to become an indexed journal on Pubmed. Your efforts have not gone unnoticed, and the JAOCD cannot thank you enough for your hard work. We also want to thank Julia Layton, our editorial proofreader, for her dedication to excellence in helping prepare each issue of the JAOCD in a timely and efficient fashion.
Last but definitely not least, we thank our sponsors, who continue to help make our journal a reality by contributing even in these difficult times. Without your unwavering support, we would not be able to continue to publish a high-quality journal for osteopathic residents and dermatologists.
Sincerely,
Jay Gottlieb, DO, FAOCD - Senior Editor
Jon Keeling, DO, FAOCD - Editor
Andrew Racette, DO, FAOCD - Editor
4 LETTER FROM THE EDITORS LETTER FROM THE PRESIDENT OF THE AOCD
DONALD TILLMAN, DO, FAOCD
PRESIDENT
May is a beautiful month to visit western Kansas. Usually hot and arid, this month we have had rain and the wheat looks great. There are many beautiful wildflowers lining the roads and fields. But you better come fast, because it won’t last long!
Increasing communication has been one of the goals of my presidency. This month, I want to highlight the AOCD website. For those of you who have not visited the site, please take some time go to www.aocd.org. Dr. Jere Mammino has worked tirelessly in perfecting this site. It will pop up on many Google searches for dermatologic terms, directing visitors to the AOCD website. For example, last night I was Googling actinic keratosis, and the first site on the list was the AOCD. We are currently averaging over 3 million visitors per year, who view about 4.5 million pages. Ninety- five percent of the visitors are viewing the dermatologic disease database, which was a collaboration between many members of our college. This database has a tremendous amount of useful information, which can be shared with your patients to help explain diseases and treatment. Our website is in the top 1% of all sites visited on the web. I encourage members to check out their profiles under the “Find a D.O. Dermatologist” tab. Feel free to send us updates, corrections or things you want to add to your profile. This is a very cost-effective means of advertisement.
I again want to congratulate Jere, Roger Watson, and all those who have helped organize and contribute to this site. I continually respond to e-mails from the membership, and I encourage you to e-mail either me, at [email protected], or Becky at [email protected], regarding any questions or concerns with the college.
Donald Tillman, DO, FAOCD
AOCD President, 2008-2009
LETTER FROM THE PRESIDENT 5 PDT IN THE TREATMENT OF COMEDONAL ACNE: A CASE PRESENTATION
Kristy P. Gilbert DO*, Lloyd J. Cleaver DO, FAOCD** *Dermatology Resident, 2nd Year, Northeast Regional Medical Center **Program Chairman, Northeast Regional Medical Center, Clinical Professor Department of Internal Medicine, Dermatology Chair, A.T. Still University- Kirksville College of Osteopathic Medicine
ABSTRACT
Acne affects approximately 80% of individuals between the ages of 11 and 30 and almost 100% of the population at some point in their lives.1,2,3 There are numerous studies now available demonstrating the efficacy of PDT in the treatment of moderate to severe acne. We present here a case of moderate comedonal acne that responded extremely well to PDT after a series of treatments with a 20% 5-aminolevulinic acid photosensitizer followed by exposure to blue light as an adjuvant to topical acne therapy.
Background reported, its effect on comedonal acne has also been demonstrated.8,9 Acne is responsible for an estimated 30% or more of all visits to dermatologists, Case Report making it the most frequently diagnosed condition seen in dermatology offices.2,4 An 18-year-old female college student Treatments have historically consisted of presented with a two-year history of benzoyl peroxides, topical antibiotic agents comedonal acne. Previous treatments and retinoids, various cleansers, corticoster- as prescribed by another dermatologist oids, hormonal therapies, oral antibiotics, included minocycline (Minocin®), 1% and oral isotretinoin. Physical modalities clindamycin and 5% benzoyl peroxide Figure 1 such as microdermabrasion and chemical gel (Duac®), tazarotene cream 0.05% peels have also been utilized.1,4 Concerns (Tazorac®), adapalene 0.1% gel (Differin®), are ever prevalent regarding antibiotic Minocin® plus amoxicillin pulse therapy, resistance, side effects and risks of oral azithromycin, and finally minocyline antibiotics and oral isotretinoin, as well as hydrochloride (Solodyne®). Along with the sometimes irritant potential of topical medical therapy, the patient had undergone preparations. The desire for other effective, several microdermabrasion procedures. long-lasting therapies that offer minimal The patient reported minimal improve- side effects has lead researchers and clini- ment with any of the above combined cians alike to pursue alternative treatment treatment regimens, and insisted that she 5 modalities. Over the past several years, was compliant with each of the varying Figure 2 there has been increasing interest in the use treatment plans. On physical exam, there of lasers, light sources, and radiofrequency were numerous open and closed come- devices in the treatment of acne vulgaris. dones, increased over the upper three- Photodynamic therapy (PDT) has in quarters of the face, as well as moderate recent years proved itself to be an effective mandibular angle, submental, and neck new treatment in the management of many involvement with similar lesions noted. dermatologic diseases including acne. In Inferolateral cheeks were spared, with photodynamic therapy, photosensitizers only a few comedonal lesions appreciated. are used, which selectively accumulate Scattered inflammatory papules were also in abnormal tissues. These photosensi- noted, though comedonal lesions predomi- nated (Fig.1-3). tizers are then activated by light of various Figure 3 wavelengths in the presence of oxygen to An extensive discussion was under- initiate chemical reactions that destroy or taken regarding compliance and treat- allowed to incubate for 30 minutes. It was modify these selected cells.4,6 Reported ment options, including both topical and then removed with Cetaphil® cleanser, uses of PDT in dermatology include treat- oral therapies, as well as photodynamic followed by another alcohol wipe. The ment of actinic keratoses, non-melanotic therapy (PDT). We elected to start the patient on azeleic acid (Finacea®) twice patient was then exposed to BLU-U® light skin cancers, psoriasis, cutaneous T-cell for 16 minutes, 40 seconds. There were lymphoma, localized scleroderma, lichen daily, to continue Differin® each night and Solodyne® 90mg once daily. A PDT treat- no in-office or post-procedure complaints planus, lichen sclerosis, HPV, MRSA, tinea, or complications. One week after the ment was scheduled for the following week. molluscum contagiosum, hidradenitis procedure, the patient and mother felt that suppurativa, alopecia areata, Darier’s The PDT was performed using 20% her acne had improved significantly after disease, photorejuvenation, sebaceous 5-aminolevulinic acid (ALA) solu- one treatment. A second treatment was hyperplasias, nevus sebaceous and acne tion (Levulan Kerastick®, DUSA 5,7 performed four weeks after the first treat- vulgaris. There are numerous studies Pharmaceuticals, Inc.) and blue light ment. The patient was exposed to BLU-U® now available demonstrating the efficacy (BLU-U®, DUSA). Treatment protocol light therapy for the same amount of time, of PDT in the treatment of moderate to for the first treatment was as follows. The but without pre-treatment with ALA. The severe acne. Most of these reports show skin was prepped with Cetaphil® cleanser patient reported dissatisfaction with the this modality to be more effective on followed by alcohol wipe. The ALA was results of this therapy and no change in inflammatory acne. Although infrequently applied to the entire face and neck and 6 PDT IN THE TREATMENT OF COMEDONAL ACNE: A CASE PRESENTATION treatments on a four-to-six month basis. for weeks, but topical application of this One year after starting therapy using PDT photosensitizer was impossible due to as an adjunct, the patient’s comedonal acne this large molecule’s inability to penetrate continued to show significant improvement the skin. The introduction of porphyrin with use of a topical retinoid only three to precursors 5-aminolevulinic acid (5-ALA) four times per week (Fig. 4-6). and methyl aminolevulinate (MAL) provided low-molecular-weight molecules Discussion with the ability to penetrate skin. In 1990, topical aminolevulinic acid In ALA-PDT, the topical agent penetrates for photosensitization was introduced for Figure 4 the stratum corneum and accumulates in the treatment of cutaneous disease.10,11,12 the epidermis and dermis of abnormal Currently, 5-ALA hydrochloride (Levulan target cells. The photosensitizers are not Kerastick,® DUSA Pharmaceuticals, Inc.) photoactive by themselves, but prefer- and blue light treatment are approved in entially accumulate in diseased cells and the United States for treatment of non- are metabolized into photosensitizing hyperkeratotic actinic keratoses on the face porphyrins inside these cells. Specifically, and scalp, and blue light (BLU-U,® DUSA this photosensitizer is protoporphyrin IX Pharmaceuticals) was approved in 2003 for 6,10 (PpIX). When light of a certain wave- the treatment of acne.6,11 length is absorbed, the energy is trans- The success of photodynamic therapy in ferred to oxygen and highly reactive oxygen the treatment of acne is based on several species (ROS). This leads directly to cell factors. Propionibacterium acnes contain Figure 5 and tissue damage and indirectly stimulates 11,12 the endogenous porphyrins coproporphyrin inflammatory cell mediators. III and uroporphyrin III, and exposure Again, photodynamic therapy relies on to even visible light has shown to activate two primary components: light and photo- these porphyrins, driving a photodynamic sensitizers. An ideal light source should reaction leading to destruction of some of have rapid administration and adequate these bacteria. With light, the porphyrin absorption by a photosensitizer, be able production within the bacteria markedly to reach target cells by adequate depth of increases, the photodynamic reaction is penetration, have sufficient photon energy initiated, and highly reactive oxygen species to initiate the needed photochemical lead to the destruction of the bacteria by process, and have a low side effect profile oxidizing the lipids in the cell wall of the both during treatment and after the proce- bacteria.1,9,11,14 It has also been found that Figure 6 10,11 dure. Potential wavelengths for PDT ALA preferentially accumulates in seba- must be above the UV spectrum (400nm), ceous glands.2,9,10,11,15 Topical ALA added to appearance of lesions. A third treat- with the limited tissue penetration of PDT therefore increases its efficacy due to ment was performed six weeks after the shorter-wavelength UV light and there- its apparent effect of decreasing numbers 2,13 second treatment, again using the Levulan fore less risk of cancer induction. Light of sebaceous glands and sebum produc- Kerastick®, with the incubation time of sources should be chosen based on the tion. Hongcharu et al. demonstrated this the ALA extended to one hour prior to absorption spectrum of the photosensi- histologic damage to sebaceous glands after exposure to the blue light. Though there tizer. Porphyrins absorb light maximally ALA-PDT treatment of acne.4,10,11,15 were no in-office complaints, the day in the Soret range (400-410nm) with Several light sources have been used following the procedure the patient called additional peaks, called Q bands, between 2,10,11 for photodynamic therapy in the treat- and complained of significant burning, 500nm and 635nm. Most studies have ment of acne, including IPL, blue-light erythema and peeling. These side effects focused on light sources that emit wave- emitters, red-light emitters, and numerous were treated with hydrocortisone butyrate lengths in the blue and red range. Blue lasers with varying degrees of efficacy 0.1% with resolution within two days. light corresponds to maximal absorption and side effects.2,4,5,8 Light with longer Upon questioning, the patient admitted to by porphyrins, while red light has less wavelengths and deeper penetration have inadequate sun avoidance and protection optimal absorption but deeper penetration. more significant side effect profiles, but in the 24 hours following the procedure. 5-ALA is converted within target cells with may have increased efficacy secondary to Again, upon phone consult with both the a maximum blue peak at 417nm and small 6,11,12 possible anti-inflammatory properties due patient and her parents, it was felt that red peak at 630-650nm. to its influence on macrophage release of her acne had significantly improved. Of Photosensitizers used in photodynamic cytokines.16 A consensus conference on note, the patient admitted that due to the therapy can be traced back to ancient PDT was convened in June of 2005 with marked improvement she experienced with cultures of Egypt, Greece, and India. The a conclusion that ALA-PDT in regard to the first PDT treatment, she never used use of natural plant psoralens applied to acne provides the best results when treating the Finacea® on a consistent basis, with the skin followed by exposure to sunlight cystic and inflammatory acne, and more reported application of only two to three to treat pigmentary disorders during these modest results with comedonal acne. This times weekly. She also reported similar times can be considered the first forms of same panel concluded that ALA combined 6,11 sporadic use of Differin® gel, and she had photodynamic therapy. Initial studies with long-pulsed PDL has provided the decreased her use of Solodyne® to every in Germany at the turn of the 20th century most beneficial and longstanding effects in other day. focused on topically applied dyes like eosin the treatment of all types of acne.4,10 At four-month follow-up, the patient’s and erythrosine. Studies soon began on We presented a case in which a simple acne remained markedly improved. We the tumor-localizing properties of porphy- series of ALA topical plus BLU-U light continued use of topical retinoids, and after rins. In the late 1970s, systemic hemato- therapy proved to be an extremely effective a short trial of minocycline 100mg daily, porphyrin derivative (HpD) was initially therapy for a patient’s previously treat- the patient was content to continue only used for the treatment of skin cancer. The ment-resistant acne, supporting a previous topical retinoid therapy with repeat PDT photosensitization of systemic HpD lasted study conducted by Goldman and Boyce GILBERT, CLEAVER 7 that demonstrated the beneficial effects ment of acne vulgaris, both as an alterna- 9. Pollock B. Topical aminolevulinic acid-photodynamic therapy for the treatment of acne vulgaris: a study of of blue light alone and blue light plus tive and adjunct to traditional therapies. clinical efficacy and mechanism of action. Br J Dermatol ALA therapy. In that study, improvement Limitations lie in drug and light-source 2004; 152(3): 616-22. 10. Alexiades-Armenakas M. Aminolevulinic Acid Photo- was seen in all types of acne, including costs and availability, as well as pharmaceu- dynamic Therapy for Actinic Keratoses/Actinic Chelitis/ comedonal lesions.17 Numerous other tical and third-party payer support. With Acne: Vascular Lasers. Dermatol Clinics 2007; 25(1): 25-33. studies have also reported modest benefits continued studies, new technologies, and 11. MacCormack MA. Photodynamic Therapy. Advances in of ALA-PDT on non-inflammatory acne possible future insurance coverage, PDT Dermatology 2006; 22: 219-258. 12. Babilas P. Photodynamic Therapy in dermatology- an 5,9,15,16,18 lesions. In addition to its effects may become a mainstay in the treatment of update. Photodermatol Photoimmunol Photomed 2005; on sebaceous glands and P. acnes, there is acne vulgaris. 21(3): 142-9. 13. Gold MH. The use of a novel intense pulsed light and supportive evidence that PDT also facili- heat source and ALA-PDT in the treatment of moderate tates keratinocyte turnover and therefore to severe inflammatory acne vulgaris. J Drugs Dermatol References 2004; 3(6 Suppl): S15-9. reduces follicular obstruction that leads 1. Ortiz A, Van Vliet M, Lask GP, Yamauchi PS. A review of 14. Ramstad S. The temperature dependence of porphyrin to not only inflammatory acne lesions, lasers and light sources in the treatment of acne vulgaris. production in Propionibacterium acnes after incubation J Cosmet Laser Ther 2005; 7(2): 69-75. with 5-aminolevulinic acid (ALA) and its methyl ester but also non-inflammatory lesions such 2. Bhardwaj SS, Rohrer TE, Arndt K. Lasers and Light (m-ALA). Photochem Photobiol Sci 2006; 5(1): 66-72. as comedones.9,10,17 We feel our case is Therapy for Acne Vulgaris. Semin Cutan Med Surg 2005; 15. Hongcharu W, Taylor CR, Chang Y, et al. Topical ALA- 24: 107-112. photodynamic therapy for the treatment of acne vulgaris. evidence that ALA-PDT can be of signifi- 3. Harper JC. An update on the pathogenesis and manage- J Invest Dermatol 2000; 115(2): 183-192. cant benefit in treating comedonal acne. ment of acne vulgaris. J Am Acad Dermatol 2004; 51(1 16. Hong SB. Topical Aminolevulinic acid-photodynamic Suppl): S36-8. therapy for treatment of acne vulgaris. Photodermatol With the advent of novel lasers and light 4. Nestor MS. The Use of Photodynamic Therapy for Treat- Photoimmunol Photomed 2005; 21(6): 322-5. sources ongoing, the field of photodynamic ment of Acne Vulgaris. Dermatol Clinics 2007; 25(1): 17. Goldman MP, Boyce SM. A single center study of amin- 47-57. olevulinic acid and 417 NM photodynamic therapy in the therapy is ever-changing. “Off-label” uses 5. Taub AF. Photodynamic Therapy in Dermatology: History treatment of moderate to severe acne vulgaris. J Drugs of PDT in the treatment of cutaneous and Horizons. J Drugs Dermatol 2004; 3:S8-S25. Dermatol 2003; 2: 393-6. 6. Nootheti PK, Goldman MP. Aminolevulinic Acid- Photo- 18. Taub AF. Photodynamic therapy for the treatment of disease abound, and there is considerable dynamic Therapy for Photorejuvenation. Dermatol Clinics acne: a pilot study. J Drugs Dermatol 2004; 3(Suppl): promising research ongoing in the treat- 2007; 25(1): 35-45. S10-4. 7. Taub AF. Photodynamic Therapy: Other Uses. Dermatol ment of AKs, non-melanotic skin cancer, Clinics 2007; 25(1): 101-9. . photodamage and photorejuvenation, and 8. Gold MH. Treatment of moderate to severe inflammatory acne vulgaris: photodynamic therapy with 5- aminolevu- inflammatory dermatoses such as acne. linic acid and a novel advanced fluorescence technology PDT is proving to be a highly effective, pulsed light source. J Drugs Dermatol 2007; 6(3): 319- minimally invasive modality for the treat- 22.
8 PDT IN THE TREATMENT OF COMEDONAL ACNE: A CASE PRESENTATION AXILLARY GRANULAR PARAKERATOSIS A CASE PRESENTATION AND DISCUSSION
Nicole Bright, D.O.,* Sharon Zellis, D.O.,** Tanya Ermolovich, D.O.*** *First-year resident, Dermatology, Philadelphia College of Osteopathic Medicine/Frankford Hospitals **Clinical faculty, Philadelphia College of Osteopathic Medicine/Frankford Hospitals ***Program Director, Philadelphia College of Osteopathic Medicine /Frankford Hospitals
ABSTRACT
Axillary granular parakeratosis is a condition of unknown etiology, but it may be triggered by a number of different factors. These triggers include mechanical irritation, humidity, soaps and antiperspirant use. Fungal infections may also play a role. There is no widely accepted effective treatment regimen for this condition. We present a case of axillary granular parakeratosis and discuss the potential etiology, clinical manifestations and proposed treatments for this condition.
Case Report A 70-year-old female presented with a several-month history of hyperpigmented pruritic lesions in bilateral axillae. She denied any odor, tenderness or drainage from the area. She had not attempted any pharmacologic or non-pharmacologic therapies. Her past medical history was significant for arthritis, thyroid disease, diabetes, and hypertension. Her medications included pioglitazone, calcium, valsartan and Figure 1a - Left axilla Figure 2 a thyroid medication. She denied any changes in her soap or laundry detergent. The patient’s lesions persisted despite switching brand of deodorant. She denied dryer-sheet usage but admitted to using a scented fabric softener. She had no known medication allergies. She was retired, denied alcohol use and admitted to tobacco use more than 13 years prior. Cutaneous examination revealed a well- appearing, darkly pigmented female with dark brown, flat-topped papules coalescing into plaques in bilateral axillae. Moderate scale was present, and the lesions were Figure 1b - Right axilla Figure 3 more prominent in the left axilla than the right (Fig. 1a, 1b). No fissures or erosions eral brown plaques or papules. It typically granules interspersed in the stratum were apparent. There were no lesions on affects intertriginous areas such as the corneum and a superficial perivascular the neck or groin region. axillae, groin, and abdominal, intermam- infiltrate.5 Histopathologic examination of a mary and perianal regions.3 Differential There has not been a consistently effec- shave biopsy from the left axilla revealed a diagnosis of granular parakeratosis includes tive therapeutic regimen established. compact stratum corneum with extensive pemphigus vegetans, acanthosis nigricans, Treatment of this condition includes the parakeratosis and numerous fine keratohy- contact dermatitis, tinea corporis, inverse following topical medications: antifungals, alin granules interspersed in the stratum 8 psoriasis and Hailey-Hailey. The disorder antibiotics, steroids, retinoids, and vitamin corneum. Perivascular lymphocytic infil- may be caused by a number of different D analogs. Contreras et al. reported a case trate was present in the superficial dermis factors. Physiologically, a defect of profil- of a 70 y/o male treated with calcipotriene (Fig. 2, 3). PAS staining was negative for aggrin to filaggrin during the process of and ammonium lactate 12% BID. His hyphae. Based on these findings and her cornification has been suggested. Filaggrin clinical presentation, a diagnosis of gran- lesions completely resolved at two months acts as an adhesion matrix for keratohyalin ular axillary parakeratosis was rendered. and had not recurred in either axilla at a granules during normal cornification.9 nine-month follow-up.5 Vitamin D analogs Discussion Fungal infections may play a role in the induce terminal differentiation in kerati- etiology due to location. Other more estab- nocytes and inhibit proliferation. This may Granular parakeratosis is a unique lished triggers include mechanical irrita- support the theory that the etiology is a disorder of keratinization. It has been tion, humidity, soaps and antiperspirant defect of profilaggrin to filaggrin during reported in children but primarily occurs use.3 the process of cornification. Chamberlain in women over 50 years of age. Lesions The typical histologic presentation is et al. also reported a series of three cases are characterized by unilateral or bilat- extensive parakeratosis with keratohyalin of patients who rapidly responded to BRIGHT, ZELLIS, ERMOLOVICH 9 potent topical steroids.8 In vitro studies have shown glucocorticoid involvement in profilaggrin expression and conversion to filaggrin, which may also support the theory of etiology stated above. Behavioral modi- fications, such as discontinuing or altering deodorants, along with cryotherapy have also shown improvement in the condition.2 Spontaneous resolution of lesions has also been reported. Conclusion Axillary granular parakeratosis is a rela- tively rare disorder of keratinization. The proposed pathophysiologic mechanism is a defect of profilaggrin to filaggrin during the process of cornification. Many thera- pies have been implemented, but there is no definitive treatment recommendation. Our patient was treated with naftifine hydro- chloride gel daily and Arm and Hammer deodorant initially. There was moderate improvement with this therapy. One month later, Zeasorb-AF powder was added to the regimen, and there was no improvement.
References: 1. Srivastava M, Cohen D. Axillary Granular Parakeratosis. Dermatology Online Journal 2004; 10(3):20 2. Wallace CA, Pichardo RO, Yosipovitch G, Hancox J, Sangueza OP. Granular parakeratosis: a case report and literature review. Journal of Cutaneous Pathology 2003; 30:332-335 3. Metze D, Rutten A. Granular parakeratosis: a unique acquired disorder of keratinization. Journal of Cutaneous Pathology 1999; 26:339-352 4. Scheinfeld NS, Mones J. Granular parakeratosis: Patho- logic and clinical correlation of 18 cases of granular parak- eratosis. JAAD 2005; 52(5) 5. Contreras M, et al. Axillary intertriginous granular parak- eratosis responsive to topical calcipotriene and ammonium lactate 2003; 42:382-383 6. Weedon D, Strutton G. (2002) Skin Pathology. China: Elsevier 7. Ming M. Scaling lesions on the Axillary skin of a 52 year old man. Archives of Dermatology 2004;140(9)1161-1166 8. Chamberlain AJ, et al. Intertriginous granular parakeratosis responsive to potent topical steroids. Clinical and experi- mental Dermatology 2003;28:50-52 9. Presland RB, et al. Regulation of human profilaggrin pro- moter activity in cultured epithelial cells by retinoic acid and glucocorticoids. Journal of Dermatological Science 2001;27:192-205
10 AXILLARY GRANULAR PARAKERATOSIS A CASE PRESENTATION AND DISCUSSION OFF-LABEL USES OF TOPICAL PIMECROLIMUS
Iqbal A. Bukhari* *Associate Professor and consultant dermatologist, Dermatology Department, College of Medicine, King Faisal University, Dammam, Saudi Arabia
ABSTRACT
Pimecrolimus is an immunomodulator that targets T-cells. It is mainly used in atopic dermatitis, but recently many reports have proved its effectiveness in other cutaneous conditions. In this report, we are suggesting new off-label uses of topical pimecrolimus. Key words: pimecrolimus, calcineurin inhibitor, pustular psoriasis, oral lichen planus
Introduction: negative. The patient refused skin biopsy. So we diagnosed the case clinically as Pimecrolimus is a macrolactam immu- palmoplantar pustulosis. Since the patient nomodulator with calcineurin inhibition did not respond to the topical steroids and mode of action which selectively targets was not in favor of taking any systemic T cells and mast cells. It inhibits T-cell therapy, we thought pimecrolimus could proliferation, production and release of be an option since it proved its effective- (interleukin) IL-2, IL-4, interferon-gamma, ness in psoriasis vulgaris. The patient was tumour necrosis factor-alpha and mast started on pimecrolimus 1% cream and a cell degranulation.1,2 Pimecrolimus does topical steroid of moderate potency applied not easily permeate through the skin, so it twice daily for one week; then the steroid has a very low risk of systemic side effects. was discontinued. After four weeks, the Figure 1: 40-year-old female with pal- It has been shown to be effective in both eruption cleared almost 90%, with postin- moplantar pustulosis adults and children with mild to moderate flammatory hyperpigmentation and no atopic dermatitis,3 intertriginous psori- new eruption. By the end of the twelfth a. before treatment with topical pime- crolimus 1% cream asis,4 seborrheic dermatitis,5 chronic hand week, the condition cleared completely. The dermatitis,6 oral lichen planus7,8 and cuta- patient was followed up every 16 weeks for neous lupus erythematosus.9 Case reports three years, with recurrence of few lesions of clinical success have been reported for that disappeared after the immediate use of cutaneous lichen planus,10 vitiligo11 and topical pimecrolimus. chronic graft-vs.-host disease.12 Compared to corticosteroids, pimecrolimus and Discussion: tacrolimus do not affect endothelial cells and fibroblasts, therefore telangiectasia and Palmoplantar pustulosis is a chronic, skin atrophy do not occur.13 In this article , persistent, localized form of pustular psori- we are reporting additional off-label uses of asis which usually occurs on the palms topical pimecrolimus in dermatology. and soles of middle-aged women. It is usually treated by topical steroids, topical Case 1: calcipotriol, Psoralen and ultraviolet radia- b. after 12 weeks of treatment, showing A 48-year-old Arabic female presented tion (PUVA), acitretin, methotrexate or complete resolution to our dermatology clinic with a two-year cyclosporine.14-17 Combination treatments history of non itchy pustular eruption of PUVA and acitretin, topical calcitriol and affecting the palms and soles. According to tacrolimus, calcipotriol and betamethasone used to wax and wane with no complete the patient, the eruption takes two weeks to dipropionate, or topical betamethasone resolution. She was treated with topical and resolve and become topped with a brown valerate and oral tetracycline are reported oral steroids prescribed by other derma- scale, which peels later. At a private clinic, to be effective.18-21 The efficacy of pime- tologists, with no improvement. These the patient was treated with topical steroids crolimus in the therapy of inverse psoriasis lesions interfered with eating and drinking, of different potencies, tar-containing has been documented in a randomised, which led to gradual weight loss. There creams, local psoralen and ultraviolet double-blind, placebo-controlled clinical were no other lesions on the skin. Baseline radiation with no response. There was no trial involving 57 adult patients, which investigations including complete blood history of arthralgia. The patient medical showed clearance in almost 71% of the count, liver function and renal function history, family history, allergy history and patients after therapy with pimecrolimus tests were normal. Hepatitis profile was drug history were negative. She was a non- for eight weeks.22 In our case, topical pime- negative. Biopsy from the affected buccal smoker. On examination of the hands and crolimus 1% was additionally shown to mucosa revealed the diagnosis of erosive feet, there were pustules, less than 5 mm in be effective in localized pustular psoriasis, oral lichen planus. The patient requested diameter, studded over erythematous-based which had not been reported previously. not to be started on topical or oral steroids lesions (Figures 1a, 1b). The rest of the Case 2: due her past experience, so we started her body was free of similar lesions. No axillary on pimecrolimus 1% cream twice daily. or inguinal lymphadenopathy was noted. A 50-year-old Arabic female presented to Clinical evaluation with photograph was Baseline investigations revealed borderline our dermatology clinic with painful, eroded performed weekly, and all adverse events hypercholesterolemia only. Gram stain and surface of the buccal mucosa of 10 years were documented. After two weeks, the culture of the newly opened pustule was duration (Figures 2a, 2b). The condition patient reported gradual improvement BUKHARI 11 Case 3: mented with no evidence of side effects such as redness or atrophy. Follow-up of A 6-year-old Arabic female child the patient for five years after discontinua- presented to our dermatology clinic with tion of topical pimecrolimus did not reveal two months history of hypopigmented any recurrence of vitiligo in the treated patches affecting the face, chest, arms and area. legs. She was prescribed hydrocortisone cream applied twice daily for two months Discussion with no response. The patient was asth- matic, and family history was negative for Vitiligo is a chronic, depigmenting similar skin conditions. On examination of cutaneous disorder which has an autoim- the skin, there were hypopigmented patches mune basis. Many treatment modalities Figure 2: 40-year-old female with with indistinct borders and fine, whitish are available, but results are inconsistent erosive oral lichen planus scaling in some of the lesions. Woods light and variable. Several clinical studies have a. before treatment with topical and KOH scrapings were negative. Systemic been conducted involving the use of topical pimecrolimus 1% cream examination was normal. So the patient tacrolimus in the treatment of vitiligo, was diagnosed as a case of extensive pityri- and all proved its effectiveness in this asis alba. Topical pimecrolimus 1% cream disorder.26-30 In this report, we used topical applied twice daily was initiated. After 12 pimecrolimus, which has similar action to weeks, the condition resolved completely tacrolimus, in a patient with persistent viti- with no recurrence. ligo. Initially our patient responded with diffuse and perifollicular repigmentation Discussion: pattern, which by the end of the 12-week period became complete repigmentation Pityriasis alba is a type of endogenous with no reported side effects. This diffuse eczema which usually affects children pattern of pigmentation was reported below the age of 12 years. It is characterized previously by Lepe and his colleagues in by hypopigmented patches with indistinct their study of tacrolimus in childhood viti- borders affecting the face, the neck, upper ligo.26 Adding to this favorable effect, pime- b. after 8 weeks of treatment, showing chest, and arms. Sometimes, fine scales can crolimus lacks the atrophogenic potential complete healing of the buccal mucosa be seen in these patches. The cause of pityr- seen with prolonged use of topical steroids, iasis alba is unknown, but it is more notice- making it safer for the patient. Our findings able in summertime. The condition should suggest that pimecrolimus is an option in be differentiated from tinea versicolor and the treatment of chronic persistent vitiligo. of her symptoms, with transient burning vitiligo. Usually it is self resolving, but sensations. Complete resolution of the moisturizers or hydrocortisone cream can Conclusion: condition occurred after eight weeks, which be used. In our patient, pimecrolimus was made the patient resume her normal diet. used since it has proven its success in other In this report, topical pimecrolimus Later, the patient reported bouts of a few types of endogenous eczema such as atopic 1% cream has shown a good therapeutic lesions which immediately subsided with dermatitis and seborrheic dermatitis.3,5 benefit in various dermatoses, including the application of pimecrolimus cream for Interestingly, in our patient, the condition localized pustular psoriasis, erosive oral one week. Now the patient is free of any resolved almost completely by the tenth lichen planus, pityriasis alba and vitiligo, active lesions after one year of follow-up. week of treatment, which lends further which should be supported by future support to topical pimecrolimus cream. double-blind controlled studies. Discussion: Case 4: References: Erosive oral lichen planus is a severe, A 19-year-old male of skin type IV 1 Marsland AM, Griffiths CE. The macrolide immunosup- intensely painful form of mucosal lichen presented to our clinic. He was a known pressants in dermatology: mechanisms of action. Eur J Dermatol 2002; 12: 618–22. planus with periods of remission and case of vitiligo since the age of 10 years, 2 Grassberger M, Steinhoff M, Schneider D, et al. Pime- relapse. It is usually treated by topical with regular follow-up in our dermatology crolimus – an anti-inflammatory drug targeting the skin. Exp Dermatol 2004; 13: 721–30. steroids, antimalarial agents, oral retin- clinic. The patient used to have bilateral, 3 Gisondi P, Ellis CN, Girolomoni G. Pimecrolimus in der- oids, systemic steroids, immunosuppressive symmetrical disease affecting the knees matology: atopic dermatitis and beyond. Int J Clin Pract. 2005 Aug;59(8):969-74. drugs, and extracorporeal photochemo- and the periorbital areas. He was treated 4 Gribetz C, Ling M, Lebwohl M, et al. Pimecrolimus cream therapy. The effectiveness of pimecrolimus intermittently over four years using topical 1% in the treatment of intertriginous psoriasis: a double- psoralen with sun exposure and medium- blind, randomized study. J Am Acad Dermatol 2004; 51: 1% cream in EOLP has been suggested in 731–8. a few case reports23,24 and in one recent potency topical steroids, which gradually 5 Rigopoulos D, Ioannides D, Kalogeromitros D, et al. resolved his lesions except over the left Pimecrolimus cream 1% vs. betamethasone 17-valerate comparative study in France that proved 0.1% cream in the treatment of seborrhoeic dermatitis. A knee, which was resistant to treatment and randomized open-label clinical trial. Br J Dermatol 2004; its effectiveness with few mild side effects.25 remained stationary until the age of 17 151: 1071–5. However, topical steroids are much less 6 Belsito DV, Fowler JF Jr, Marks JG Jr, et al. Pimecrolimus years [should this be “19 years” – when cream 1%: a potential new treatment for chronic hand expensive and more available than topical he presented in the following case?]. The dermatitis. Cutis 2004; 73: 31–8. calcineurin inhibitors, which makes topical 7 Esquivel-Pedraza L, Fernandez-Cuevas L, Ortiz-Pedroza patient had positive family history of viti- G, et al. Treatment of oral lichen planus with topical pime- calcineurin inhibitors a good second-line ligo as his uncle and niece were affected. crolimus 1% cream. Br J Dermatol 2004; 150: 771–3. therapy. 8 Dissemond J, Schroter S, Franckson T, et al. Pimecroli- His autoantibodies profile for thyroid and mus in an adhesive ointment as a new treatment option Further studies on a larger population for oral lichen planus. Br J Dermatol 2004; 150: 782–4. adrenal glands were negative. We started 9 Kreuter A, Gambichler T, Breuckmann F, et al. Pimecroli- with long-term follow-up and monitoring him on topical pimecrolimus 1% cream mus 1% cream for cutaneous lupus erythematosus. J Am of the blood level of pimecrolimus are Acad Dermatol 2004; 51: 407–10. twice daily for 12 weeks. Initially, the lesion 10 Lim SJ, Love EW. Steroid-free pimecrolimus (Elidel) for required to better evaluate its usefulness repigmented with diffuse and perifollicular mono-therapy of lichen planus. J Drugs Dermatol 2004; and safety compared with other therapeutic 3: 563–4. pattern, and by the end of the treatment 11 Mayoral FA, Gonzalez C, Shah NS, et al. Repigmentation modalities. period the area was completely repig- of vitiligo with pimecrolimus cream: a case report. Derma- 12 OFF-LABEL USES OF TOPICAL PIMECROLIMUS tology 2003; 207: 322–3. 12 Ziemer M, Gruhn B, Thiele JJ, et al. Treatment of extensive chronic cutaneous graft-versus-host disease in an infant with topical pimecrolimus. J Am Acad Dermatol 2004; 50: 946–8. 13 Queille-Roussel C, Paul C, Duteil L, et al. The new topi- cal ascomycin derivative SDZ ASM 981 does not induce skin atrophy when applied to normal skin for 4 weeks: a randomized, double-blind controlled study. Br J Dermatol 2001; 144: 507–13. 14 Behrens S, von Kobyletzki G, Hoffmann K, et al. PUVA- bath photochemotherapy in Hallopeau’s acrodermatitis continua suppurativa. Hautarzt. 1997 Nov;48(11):824-7.. 15 Chowdhury MM, Motley RJ. Treatment of acrodermatitis continua of Hallopeau with oral propylthiouracil and metho- trexate. Clin Exp Dermatol. 2001 Nov;26(8):657-60. 16 Reitamo S, Erkko P, Remitz A, et al. Cyclosporine in the treatment of palmoplantar pustulosis. A randomized, dou- ble-blind, placebo-controlled study. Arch Dermatol. 1993 Oct;129(10):1273-9. 17. Emtestam L, Wedén U. Successful treatment for acroder- matitis continua of Hallopeau using topical calcipotriol. Br J Dermatol. 1996 Oct;135(4):644-6. 18 Kuijpers AL, van Dooren-Greebe RJ, van de Kerkhof PC. Acrodermatitis continua of Hallopeau: response to com- bined treatment with acitretin and calcipotriol ointment. Dermatology 1996;192(4):357-9. 19. Brunasso AM, Lo Scocco G, Massone C. Recalcitrant acrodermatitis continua of hallopeau treated with calcitriol and tacrolimus 0.1% topical treatment. J Eur Acad Derma- tol Venereol. 2008 Apr 14. 20. Sotiriadis D, Patsatsi A, Sotiriou E, et al. Acrodermatitis continua of Hallopeau on toes successfully treated with a two-compound product containing calcipotriol and betame- thasone dipropionate. J Dermatolog Treat. 2007;18(5):315- 8. 21 Piquero-Casals J, Fonseca de Mello AP, Dal Coleto C, et al. Using oral tetracycline and topical betamethasone val- erate to treat acrodermatitis continua of hallopeau. Cutis. 2002 Aug;70(2):106-8. 22 Gribetz C, Ling M, Lebwohl M, et al. Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a dou- ble-blind, randomized study. J Am Acad Dermatol. 2004 Nov;51(5):731-8. 23 Dissemond J, Schroter S, Franckson T, et al. Pimecrolimus in an adhesive ointment as a new treatment option for oral lichen planus. Br J Dermatol. 2004;150:782-784. 24. Esquivel-Pedraza L, Fernandez-Cuevas L, Ortiz-Pedroza G, et al. Treatment of oral lichen planus with topical pime- crolimus 1% cream. Br J Dermatol. 2004;150:771-773. 25. Passeron T, Lacour JP, Fontas E, et al. Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double-blind, randomized, prospective trial with measure- ment of pimecrolimus levels in the blood. Arch Dermatol. 2007 Apr;143(4):472-6. 26. Lepe V, Moncada B, Castanedo-Cazares JP, et al. A double-blind randomized trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment of childhood vitiligo. Arch Der- matol 2003; 139: 581-5. 27. Travis LB, Weinberg JM, Silverberg NB. Successful treat- ment of vitiligo with 0.1% tacrolimus ointment. Arch Derma- tol 2003; 139: 571-4. 28. Grimes PE, Soriano T, Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol 2002; 47: 789-91. 29. Smith DA, Tofte SJ, Hanifin JM. Repigmentation of vitiligo with topical tacrolimus. Dermatology 2002; 205: 301-3. 30. Tanghetti EA. Tacrolimus ointment 0.1% produces repig- mentation in patients with vitiligo: results of a prospective patient series. Cutis 2003; 71: 158-62.
BUKHARI 13 ECZEMA HERPETICUM IN CHRONIC HAND AND FOOT ECZEMA: A CASE PRESENTATION
Lisa Zaleski, D.O., LT, MC, USN;* Michael Yablonsky, M.D., FAAD, LCDR, MC, USN** *General Medical Officer, Expeditionary Health Services for the Atlantic Fleet, Norfolk, VA **Dermatology Department of the Naval Medical Center, Portsmouth, VA
The views expressed in this article are those of the author and do not reflect the official policy of the Department of the Navy, Department of Defense, or U.S. Government. The author military service member. This work was prepared as part of the author’s official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person’s official duties.
ABSTRACT
Eczema herpeticum (EH) or Kaposi’s varicelliform eruption is an uncommon cutaneous condition where a viral infection disseminates over a region of underlying skin disease. EH typically presents in children as a herpes simplex virus outbreak in an area of current or resolved atopic dermatitis. We present a case of eczema herpeticum in an adult in the distribution of chronic hand and foot eczema.
Introduction: patient had no significant medical history other than his eczema and denied any Eczema herpeticum (EH) or Kaposi’s malaise or fever. varicelliform eruption is an uncommon, Physical examination revealed a healthy- potentially life-threatening complication appearing male with erythematous, demar- of a pre-existing skin disorder due to impe- cated scaling plaques, numerous purpuric tiginization of abnormal and normal skin crusts, and several punched-out erosions with a viral infection. Herpes simplex virus on the bilateral hands and feet (Figures 2, is the most common virus associated with 3, and 4). The vermillion border of the EH, but infection with coxsackievirus virus lower lip had a crusted, violaceous papule. A16 and vaccinia have also been implicated. There was no lymphadenopathy, malodor, Figure 2: Punched-out erosions and EH was originally considered a disease of or purulent drainage. The differential purpuric crusts in the region of the infants, but it is more common in children diagnosis included eczema herpeticum, a patient’s chronic hand dermatitis and can occur at any age.1 We report a dyshidrotic flare, and impetiginization with bilaterally. case of eczema herpeticum in an adult in bacterial overgrowth. the distribution of chronic hand and foot Laboratory examination revealed a viral eczema. culture positive for herpes simplex virus. A diagnosis of eczema herpeticum was Case Report: made based on the history, clinical appear- ance, and laboratory data. While awaiting A 35-year-old Caucasian male presented culture results, the patient was treated with a one-day unusual flare of his chronic empirically with valacyclovir 1000mg orally hand and foot eczema with erythematous twice daily for 10 days with a complete spots and “dipping-in” wounds. Prior to resolution (Figure 5). the onset of the flare, the patient had been Figure 3: A closer view of the right using mid-potency topical steroids for his Discussion: hand with numerous purpuric eczema with good control. Notably, a cold Eczema herpeticum (EH) or Kaposi’s erosions and thin crusts on an sore had erupted on his lower lip two to erythematous base. three days prior to the flare (Figure 1). The varicelliform eruption was first described by Mortiz Kaposi in 1887 as a fungal infec- tion. Later, histologic examination with skin barrier, dysfunction of cell-mediated the finding of inclusion bodies suggested immunity, decreased levels of antimicrobial a viral etiology. EH is now described as peptides in the skin, and contamination 3 a disseminated herpes simplex, coxsacki- secondary to scratching. Other primary evirus, or vaccinia in the regions of an skin disorders can include irritant contact active or recently resolved underlying skin dermatitis, psoriasis, seborrheic dermatitis, condition.2 pemphigus foliaceus, pemphigus vulgaris, Classically, EH is associated with a Darier disease, pemphigus vulgaris, T-cell herpes simplex virus (HSV) type-1 or 2 lymphoma, Sezary syndrome, Wiskott- infection and atopic dermatitis. The viral Aldrich syndrome, and congenital icthyosi- 4,5 infection is believed to be contracted from form erythroderma. an infected contact or auto-inoculation EH presents with erythema of the Figure 1: An eroded, crusted, in a host with a latent infection. Patients regions of atopic dermatitis or eczema violaceous papule of the left lower with atopic dermatitis are at an increased with crops of grouped umbilicated vesi- vermillion border representing an 1 HSV-1 outbreak. risk for developing viral infections such as cles. The vesiculopustules can progress HSV-1 or 2 due to the disruption of the to painful, punched-out, hemorrhagic, 14 ECZEMA HERPETICUM IN CHRONIC HAND AND FOOT ECZEMA: A CASE PRESENTATION as valacyclovir, acyclovir, and famci- administration: intestinal absorption and liver metabolism. J Pharmacol Exp Ther. 2004;311(2):659-667. clovir. Valacyclovir has a bioavailability 11. Muelleman PJ, Doyle JA, House RF Jr. Eczema Herpe- that is three to five times greater than ticum treated with oral acyclovir. J Am Acad Dermatol. 1986;15:716-717. oral acyclovir; it can result in blood levels 12. Jawitz JC, Hines HC, Moshell AN. Treatment of eczema similar to those attained with parenteral herpeticum with systemic acyclovir. Arch Dermatol. 1985;121:274-275. 10 acyclovir. Valacyclovir dosed twice daily 13. Brook I, Frazier EH, Yeager JK. Microbiology of and oral acyclovir dosed 25-30mg/kg/day infected eczema herpeticum. J Am Acad Dermatol. 1998;38(4):627-629. has been shown to be effective along with 14. Fivenson DP, Breneman DL, Wander AH. Kaposi’s vari- cool wet compresses.11 For more serious celliform eruption. Absence of ocular involvement. Arch Dermatol. 1990;126:1037-1039. cases, adults respond well to IV acyclovir at 250mg three times daily. Infants should Figure 4: The right plantar foot be treated with IV acyclovir at 1500mg/ demonstrating some typical punched- m2/day administered over a 1-hour period out erosions and ulcers. The patient 12 had self-treated with gentian violet three times daily. previously prescribed for a macerated Staphylococcal and streptococcal super- toe-web infection. infections are also common, presenting with yellow crusting, and are treated with antibiotic therapy tailored to the organism found in the culture. Topical silver sulfa- diazine is commonly used as a preventative therapy when a secondary bacterial infec- tion is not present.4 Patients who have chronic skin disease and recurrent HSV infections should be offered either acyclovir or valacyclovir prophylaxis.13 Although herpetic keratitis is a rare complication, it has been recommended to treat with topical ophthalmic antiviral medication Figure 5: The patient’s one-month in addition to systemic antiviral therapy.14 follow-up demonstrates a complete resolution of active lesions with The use of topical calcineurin inhibitors residual erythema but no scarring. for atopic dermatitis treatment have been associated with the onset of EH and are contraindicated during an EH outbreak.1 crusted erosions that are prone to bacterial colonization. A high fever and lymphade- nopathy typically occur two to three days Conclusion: after the onset of vesicles, lasting four to The presenting lesions and laboratory five days. The severity of symptoms can evidence support the diagnosis of HSV-1 vary greatly. Complications with EH can in an adult with chronic hand and foot include viremia with infection of internal eczema. This patient presentation differs organs, secondary bacterial infections from the classic presentation of EH in that leading to bacterial sepsis, herpes keratitis, he is an adult and the distribution is on and death. However, recurrent disease is the hands and feet instead of the classic typically milder, without constitutional atopic dissemination. Early recognition symptoms.6 and treatment with antiviral medications is Risk factors for eczema herpeticum key to improving the mortality associated include an early onset of atopic derma- with this disease. titis, elevated serum total IgE levels, and a reduced production of cytokines such References: 5,7 as INF-B or CXCL-10/IP-10. Mortality 1. Segura S, Romero D, Carrera C, Iranzo P, Estrach T. rates range from 1% to 9% but have been Eczema herpeticum during treatment of atopic derma- titis with 1% pimecrolimus cream. Acta Derm Venereol. as high as 75% prior to the use of effective 2005;85:524-525. antiviral medications. The incidence of EH 2. Kramer SC, Thomas CJ, Tyler WB, Elston DM. Kaposi’s varicelliform eruption: a case report and review of the is unknown due to a lack of large studies literature. Cutis. 2004;73:115-122. 5,8 and the rare nature of the disease. 3. Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C, Pavicic T, Boguniewicz M, Leung DY. Cathe- The differential diagnosis includes vari- licidin deficiency predisposes to eczema herpeticum. J cella-zoster virus, eczema vaccinatum, and Allergy Clin Immunol. 2006;117:836-41. 4. Mackley CL, Adams ER, Anderson B, Miller JJ. Eczema impetigo. The diagnosis is mainly clinical, herpeticum: a dermatologic emergency. Dermatol Nurs. but laboratory testing can be helpful. 2002;14(5):307-310, 323; quiz313. 5. Wollenberg A, Wetzel S, Burgdorf W, Haas J. Viral infec- Direct fluorescent antibody staining will tions in atopic dermatitis: pathogenic aspects and clinical give results in a few hours with an accurate management. J Allergy Clin Immunol. 2003;112:667-673. 6. Olson J, Robles DT, Kirby P, Colven R. Kaposi varicel- diagnosis. A viral culture takes at least 48 liform eruption (eczema herpeticum). Dermatol Online J. hours to obtain results but is both specific 2008;28;14(2):18. 2,9 7. Peng WM, Jenneck C, Bussmann C, Bogdanow M, Hart and sensitive for HSV. The finding of J, Leung DY, Bieber T, Eis-Hubinger AM, Novak N. Risk multinucleated giant cells on a Tzank smear factors of atopic dermatitis patients for eczema herpeti- cum. J Invest Dermatol. 2007;127:1261-1263. is a quick test to complete but is nonspe- 8. Atherton DJ, Marshall WC. Eczema herpeticum. Practitio- cific for HSV. ner. 1982;226:971-973. 9. Treadwell PA. Eczema and Infection. Pediatr Infect Dis J. EH is generally treated with oral nucleo- 2008;27:551-552. side analogue antiviral medications such 10. Anand BS, Katragadda S, Mitra AK. Pharmacokinetics of novel dipeptide ester prodrugs of acyclovir after oral
ZALESKI, YABLONSKY 15 UNUSUAL PRESENTATION OF LOCALIZED URTICARIA PIGMENTOSA IN A FIVE-YEAR-OLD
Joseph Del Priore, DO,* David C. Horowitz, DO** *1st-year dermatology resident, Western University of Health Sciences / Pacific Hospital, Long Beach, CA **Dermatology Program Director, Western University of Health Sciences / Pacific Hospital, Long Beach, CA
ABSTRACT
Mastocytosis is an abnormal accumulation of mast cells in the skin and at times in other systems in the body. Childhood-onset mastocytosis always involves skin lesions, which may be symptomatic with pruritus, redness, and urtication of the skin. Urticaria pigmentosa is the most common type, which presents with red, brown, and yellow papules, macules, or nodules sparing the face, palms, soles and scalp. We present a five-year-old male with several 1-2mm yellow/tan waxy papules located solely on the cheeks bilaterally. The diagnosis of mastocytosis was confirmed histopathologically. This case represents an unusual presentation of urticaria pigmentosa.
Case Report A five-year-old male presented with a six-month history of several “spots” on his face. The spots had previously been diagnosed by another dermatologist as benign moles. However, when more spots continued to form, the mother became concerned. The lesions were asymptom- atic, but the mother was concerned with their appearance as well as their origin. When questioned further, the mother stated that at times the lesions become red and irritated, especially when the child was at play. There was no history of flushing, headache, nausea, vomiting, or any other systemic complaints. The mother related that the child had exercise-induced asthma, particularly in cold weather. The only other Figure 2: Numerous mast cells were present within the dermis and this was significant medical history was diabetes clarified with Leder Stain which confirmed our clinical suspicion for urticaria mellitus type I, which had been diagnosed pigmentosa two years prior and was being managed with insulin. were present within the dermis, and this indolent course. The aggressive type can The physical exam revealed several was clarified with a Leder stain, which present with organ infiltration of mast cells 1-2mm yellow/tan waxy papules located confirmed our clinical suspicion for urti- demonstrating symptoms of bone pain due solely on the cheeks bilaterally. After caria pigmentosa (see figure 2). to lytic bone lesions, hepatosplenomegaly, the lesions were stroked firmly with a The patient’s mother was then reassured lymphadenopathy, and cytopenias. This wooden tongue blade, slight urticaria with of the benign nature of the condition and type usually does not have skin involve- a surrounding erythematous flare was that the lesions would resolve over a period ment. Adults with extensive, long-standing noted. No other lesions were found after a of time. lesions tend to have a more virulent course complete skin examination (see figure 1). than children.5 In order to diagnosis A 2mm punch biopsy of a lesion was Discussion systemic mastocytosis there must be either done on the patient’s left cheek and was one major and one minor or three minor sent for H&E stain. Numerous mast cells Mastocytosis is an abnormal accumula- criteria through examination of the bone tion of mast cells in the skin and at times marrow, shown in Table 1.6 Systemic symp- in other systems in the body. Mast cells toms due to mediator release previously contain preformed mediators such as hista- mentioned above are commonly seen due mine, cytokines, heparin, and prostaglan- to mast-cell degranulation, which can be dins. When activated, these mediators can precipitated spontaneously or by ingestion cause a broad range of local and systemic of known degranulators such as morphine, vasoactive effects, including flushing, codeine, alcohol, or by extended rubbing urticaria, pruritus, headache, dyspnea, of the skin. Non-mast-cell hematologic diarrhea, abdominal pain, syncope and conditions such as chronic myelogenous palpitaions.1-4 Mast cells also contain other leukemia, lymphocytic leukemia, myelofi- substances such as tryptase and chymase, brosis, polycythemia vera, and Hodgkin’s along with other natural proteases that are disease may also cause an increase of homologous with pancreatic proteases.3,5 systemic amounts of mast cells.4,7 Figure 1 Systemic mastocytosis is most common Cutaneous mastocytosis is most common in adults and runs either an aggressive or in childhood, with accumulated mast-cell 16 UNUSUAL PRESENTATION OF LOCALIZED URTICARIA PIGMENTOSA IN A FIVE-YEAR-OLD Table 1: World Health Organization Table 2: Drugs that can stimulate Mast cells criteria for systemic mastocytosis Aspirin Codeine MAJOR: - Multifocal dense infiltrates of mast cells (>15 in aggre- Amphotericin B NSAIDs gate) in typtase-stained biopsy sections of the bone mar- d-Tubocurarine Polymyxin B row or of another extracutaeous organ Dextromethorphan Quinine MINOR: Ethanol Radiographic contrast - More than 25% of mast cells in bone marrow or other extracutaneous organ show abnormal morphology in multi- Gallium Reserpine focal lesions in histological examination Morphine Scopolomine - KIT mutation at codon 816 in extracutaneous organ Meperidine - Kit + mast cells in bone marrow show aberrant expres- sion of CD2 and/or CD25 - Serum total tryptase >20 ng/mL proliferation limited to the skin. The most the skin. This is termed homme orange. necessary and reassurance should be common symptoms in cutaneous mastocy- The central region and scalp are mostly provided.2,13 The vast majority of cuta- tosis are pruritus, redness, and urtication affected.2,3 Widespread spontaneous blis- neous lesions present during childhood of the skin.2,6 Uncommonly, more severe tering, various degrees of erythroderma, completely resolve by the age of 10.2 systemic symptoms can be produced, which strong dermatographism, and itching can Pruritus, urtication, and flushing often provides a difficult diagnostic challenge to be present at birth or early infancy.2,3 require an H1-receptor antagonist with dermatologists, often requiring extended Diagnosis of childhood onset masto- an addition of H2-antagonist if there are workups. cytosis is confirmed histologically by an GI symptoms. Disodium cromoglycate Childhood-onset mastocytosis must be increase of mast cells in the skin. A positive has also been shown to be effective for histologically proven before the age of 15. Darier’s sign helps confirm clinical suspi- symptoms of diarrhea as well as flushing Most cases (60-80%) present during the cion. Darier’s sign involves rubbing the and pruritus.2,13,14 Topical steroids are of first year of life.1,2,4 Children with masto- lesion with a blunt object and observing a limited value due to the risk of striae cytosis always have skin lesions, but only the lesion for five minutes. If there is along with other side effects. Surgical 60% experience mast-cell mediator-related swelling and redness of the stroked lesion removal of solitary mastocytomas may be symptoms.8 In most children, skin lesions it is then considered positive. It may not necessary if there are severe and persistent regress during or shortly before puberty.6 be positive in diffuse disease.2 Histologic symptoms. Symptomatic patients with The most common type of childhood analysis employs dyes such as Giemsa, mastocytosis should identify triggering onset mastocytosis is urticaria pigmen- toluidine blue or naphthol AS-D chloro- factors such as extremes of temperature, tosa, which represents 60-80% of cases.1-2 acetate esterase (Leder stain) in order to alcohol and certain drugs (Table 2). PUVA Often seen within the first weeks of life, visualize mast cells. Immunohistochemical therapy is known to provide improvement it presents with pruritic, urticarial, lightly staining with anti-tryptase antibodies is in skin lesions with temporary relief of 7 pigmented macules, papules or nodules. strongly recommended if these dyes are symptoms. They can be red, brown and yellow and inconclusive.9,10 This case demonstrates a rare presenta- can vary in size from several millimeters to Once the diagnosis is made, it may be tion of urticaria pigmentosa presenting over a centimeter in diameter. Erythema, useful to assess whether bone marrow with multiple lesions localized only to the swelling, and blister formation as well as biopsy is necessary. This information is cheeks. itching of the lesions may occur spontane- useful to determine prognosis and to rule ously or after stroking or rubbing. There out other non-mast-cell hematologic disor- References 11 1. Azana JM, Torrelo A, Mediero IG, Zambrano A. Urticaria is usually sparing of the face, palms, soles ders. In a child with early onset disease pigmentosa: a review of 67 pediatric cases. Pediatric and scalp.2 and without any systemic symptoms, the Dermatology. 11(2):102-6, 1994 Jun 7 2. Heide R, Tank B, Oranje AP. Mastocytosis in childhood. In 10-35% of the childhood type, there child may be simply observed. Children Pediatric Dermatology. 19(5):375-81, 2002 Sep-Oct. is only one lesion, called solitary mastocy- older than five years of age at the onset of 3. Janniger CK. Childhood Mastocytosis. Cutis. 50: 187- 88, 98, 1992 Sept. toma. This form carries the best prognosis, disease or with symptoms of persistent 4. Stein DH. Mastocytosis: a review. Pediatric Dermatology. with a mild course and generally a complete localized pain, severe gastrointestinal symp- 3(5):365-75, 1986 Nov. 5. Brockow K, Akin C, Huber M, Metcalfe DD. Assessment resolution before adulthood. There is some toms, hepatomegaly, splenomegaly, lymph- of the extent of cutaneous involvement in children and confusion within the literature, charac- adenopathy or other systemic complaints adults with mastocytosis: relationship to symptomatology, tryptase levels, and bone marrow pathology. J Am Acad terizing the solitary form by five or fewer should receive a CBC with differential and Dermatology. 49(4): 508-516, 2003 Apr. lesions that may be macules, papules, a trypase level and, if abnormal, a bone 6. Valent P. Diagnostic evaluation and classification of mas- 2-4,7 2,9,13 tocytosis. Immunology & Allergy Clinics of North America. raised round or oval plaques, or tumors. marrow biopsy. Adults with asymp- 26(3):515-34, 2006 Aug. Perhaps this type should be redefined as tomatic cutaneous lesions should at least 7. Alto WA, Clarcq L. Cutaneous and systemic manifes- tations of mastocytosis. American Family Physician. pauci-solitary mastocytoma, as the existing get an annual CBC, serum tryptase and 59(11):3047-54, 3059-60, 1999 Jun. nomenclature seems misleading. complete H&P. Most authorities recom- 8. Middelkamp Hup MA, Heide R, Tank B, Mulder PG, Oranje AP. Comparison of mastocytosis with onset in Diffuse cutaneous mastocytosis is an mend a bone marrow biopsy in these children and adults. Journal of the European Academy of uncommon form which at times can be patients. A tryptase level greater than 20 Dermatology & Venereology. 16(2):115-20, 2002 Mar. 9. Horny HP, Valent P. Histopathological and immuno- seen in childhood. It consists of a wide- suggests that a bone marrow biopsy should histochemical aspects of mastocytosis. International 5,11 spread involvement of the skin, with thick- be performed. Archives of Allergy & Immunology. 127(2):115-7, 2002 Feb. ening due to infiltration with mast cells. Treatment of asymptomatic cutaneous 10. Wolff K, Komar M, Petzelbauer P. Clinical and histopatho- There is a characteristic orange color to mastocytosis in children is generally not logical aspects of cutaneous mastocytosis. Leukemia DEL PRIORE, HOROWITZ 17 Research. 25(7):519-28, 2001 Jul. 11. Fearfield LA, Francis N, Henry K, Costello C, Bunker CB. Bone marrow involvement in cutaneous mastocytosis. British Journal of Dermatology. 144(3):561-6, 2001 Mar. 12 Wolff K. Treatment of cutaneous mastocytosis. Interna- tional Archives of Allergy & Immunology. 127(2):156-9, 2002 Feb. 13. Hungness SI, Akin C. Mastocytosis: advances in diag- nosis and treatment. Current Allergy & Asthma Reports. 7(4):248-54, 2007 Jul. 14. Kissling S, Kernland K, Gerbig AW, Hunziker T. Strate- gies in childhood and adult mastocytosis. Dermatology. 198(4):426-30, 1999.
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MICROBIOLOGY The plasma concentrations of doxycycline achieved with ORACEA during administration (see DOSAGE AND ¥ ADMINISTRATION) are less than the concentration required to treat bacterial diseases. In vivo microbiological studies utilizing a similar drug exposure for up to 18 months demonstrated no detectable long-term effects on bacterial flora of the oral cavity, skin, intestinal tract, and vagina. Carcinogenesis, Mutagenesis, Impairment of Fertility: Doxycycline was assessed for potential to induce carcinogenesis in a study in which the compound was administered to Sprague-Dawley rats by gavage at Brief Summary of Full Prescribing Information dosages of 20, 75, and 200 mg/kg/day for two years. An increased incidence of uterine polyps was observed INDICATIONS AND USAGE in female rats that received 200 mg/kg/day, a dosage that resulted in a systemic exposure to doxycycline ORACEA is indicated for the treatment of only inflammatory lesions (papules and pustules) of rosacea in approximately 12.2 times that observed in female humans who use ORACEA (exposure comparison based upon adult patients. area under the curve (AUC) values). No impact upon tumor incidence was observed in male rats at 200 mg/kg/ The dosage of ORACEA differs from that of doxycycline used to treat infections. To reduce the development day, or in either gender at the other dosages studied. Evidence of oncogenic activity was obtained in studies with of resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, ORACEA should be related compounds, i.e., oxytetracycline (adrenal and pituitary tumors) and minocycline (thyroid tumors). used only as indicated. Doxycycline demonstrated no potential to cause genetic toxicity in an in vitro point mutation study with CLINICAL PHARMACOLOGY mammalian cells (CHO/HGPRT forward mutation assay) or in an in vivo micronucleus assay conducted in CD-1 mice. However, data from an in vitro assay with CHO cells for potential to cause chromosomal aberrations Pharmacokinetics suggest that doxycycline is a weak clastogen. ORACEA capsules are not bioequivalent to other doxycycline products. Oral administration of doxycycline to male and female Sprague-Dawley rats adversely affected fertility and CONTRAINDICATIONS reproductive performance, as evidenced by increased time for mating to occur, reduced sperm motility, velocity, This drug is contraindicated in persons who have shown hypersensitivity to doxycycline or any of the other and concentration, abnormal sperm morphology, and increased pre-and post-implantation losses. Doxycycline tetracyclines. induced reproductive toxicity at all dosages that were examined in this study, as even the lowest dosage WARNINGS tested (50 mg/kg/day) induced a statistically significant reduction in sperm velocity. Note that 50 mg/kg/day is Teratogenic effects: 1) Doxycycline, like other tetracycline-class antibiotics, can cause fetal harm approximately 3.6 times the amount of doxycycline contained in the recommended daily dose of ORACEA for a when administered to a pregnant woman. If any tetracycline is used during pregnancy or if the 60-kg human when compared on the basis of AUC estimates. Although doxycycline impairs the fertility of rats patient becomes pregnant while taking these drugs, the patient should be informed of the potential when administered at sufficient dosage, the effect of ORACEA on human fertility is unknown. hazard to the fetus and treatment stopped immediately. Pregnancy: Teratogenic Effects: Pregnancy Category D. (see WARNINGS section). Results from animal ORACEA should not be used during pregnancy (see PRECAUTIONS: Pregnancy). studies indicate that doxycycline crosses the placenta and is found in fetal tissues. 2) The use of drugs of the tetracycline class during tooth development (last half of pregnancy, Nonteratogenic effects: (see WARNINGS section). infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth Labor and Delivery: The effect of tetracyclines on labor and delivery is unknown. (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been Nursing Mothers: Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions observed following repeated short-term courses. Enamel hypoplasia has also been reported. Tetracycline drugs, therefore, should not be used during tooth development unless other drugs are not likely to in infants from doxycycline, ORACEA should not be used in mothers who breastfeed. (see WARNINGS section). be effective or are contraindicated. Pediatric Use: ORACEA should not be used in infants and children less than 8 years of age (see WARNINGS 3) All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate section). ORACEA has not been studied in children of any age with regard to safety or efficacy, therefore use has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. in children is not recommended. This reaction was shown to be reversible when the drug was discontinued. ADVERSE REACTIONS Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can Adverse Reactions in Clinical Trials of ORACEA: In controlled clinical trials of adult patients with mild to cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted moderate rosacea, 537 patients received ORACEA or placebo over a 16-week period. The most frequent in animals treated early in pregnancy (see PRECAUTIONS: Pregnancy section). adverse reactions occurring in these studies are listed in the table below. Gastrointestinal effects: Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis Incidence (%) of Selected Adverse Reactions in Clinical Trials of ORACEA (n=269) vs. Placebo (n=268) in patients who present with diarrhea subsequent to the administration of antibacterial agents. ORACEA Placebo Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Nasopharyngitis 13 (4.8) 9 (3.4) Studies indicate that a toxin produced by Clostridium difficile is a primary cause of “antibiotic-associated colitis”. Pharyngolaryngeal Pain 3 (1.1) 2 (0.7) If a diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild Sinusitis 7 (2.6) 2 (0.7) cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and Nasal Congestion 4 (1.5) 2 (0.7) treatment with an antibacterial drug clinically effective against Clostridium difficile colitis. Fungal Infection 5 (1.9) 1 (0.4) Metabolic effects: The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this Influenza 5 (1.9) 3 (1.1) is not a problem in those with normal renal function, in patients with significantly impaired function, higher Diarrhea 12 (4.5) 7 (2.6) serum levels of tetracycline-class antibiotics may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulations of the Abdominal Pain Upper 5 (1.9) 1 (0.4) drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy Abdominal Distention 3 (1.1) 1 (0.4) is prolonged, serum level determinations of the drug may be advisable. Abdominal Pain 3 (1.1) 1 (0.4) Photosensitivity: Photosensitivity manifested by an exaggerated sunburn reaction has been observed in Stomach Discomfort 3 (1.1) 2 (0.7) some individuals taking tetracyclines. Although this was not observed during the duration of the clinical studies with ORACEA, patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or Note: Percentages based on total number of study participants in each treatment group. UVA/B treatment) while using ORACEA. If patients need to be outdoors while using ORACEA, they should Adverse Reactions for Tetracyclines: The following adverse reactions have been observed in patients wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures receiving tetracyclines at higher, antimicrobial doses: with their physician. Gastrointestinal: anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory PRECAUTIONS lesions (with vaginal candidiasis) in the anogenital region. Hepatotoxicity has been reported rarely. Rare instances General: Safety of ORACEA beyond 9 months has not been established. of esophagitis and esophageal ulcerations have been reported in patients receiving the capsule forms of the As with other antibiotic preparations, use of ORACEA may result in overgrowth of non-susceptible micro- drugs in the tetracycline class. Most of the patients experiencing esophagitis and/or esophageal ulceration took organisms, including fungi. If superinfection occurs, ORACEA should be discontinued and appropriate therapy their medication immediately before lying down. (see DOSAGE AND ADMINISTRATION section). instituted. Although not observed in clinical trials with ORACEA, the use of tetracyclines may increase the Skin: maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. incidence of vaginal candidiasis. Photosensitivity is discussed above. (see WARNINGS section). ORACEA should be used with caution in patients with a history of or predisposition to candidiasis overgrowth. Renal toxicity: Rise in BUN has been reported and is apparently dose-related.(see WARNINGS section). Bacterial resistance to tetracyclines may develop in patients using ORACEA. Because of the potential for drug- Hypersensitivity reactions: urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, resistant bacteria to develop during the use of ORACEA, it should be used only as indicated. pericarditis, and exacerbation of systemic lupus erythematosus. Autoimmune Syndromes: Tetracyclines have been associated with the development of autoimmune Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported. syndromes. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use OVERDOSAGE of all tetracycline-class drugs should be discontinued immediately. In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdose. Tissue Hyperpigmentation: Tetracycline class antibiotics are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral DOSAGE AND ADMINISTRATION tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves. Skin and oral pigmentation has THE DOSAGE OF ORACEA DIFFERS FROM THAT OF DOXYCYCLINE USED TO TREAT INFECTIONS. been reported to occur independently of time or amount of drug administration, whereas other pigmentation EXCEEDING THE RECOMMENDED DOSAGE MAY RESULT IN AN INCREASED INCIDENCE OF SIDE has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation EFFECTS INCLUDING THE DEVELOPMENT OF RESISTANT MICROORGANISMS. as well as over sites of scars or injury. One ORACEA Capsule (40 mg) should be taken once daily in the morning on an empty stomach, preferably at Pseudotumor cerebri: Bulging fontanels in infants and benign intracranial hypertension in adults have least one hour prior to or two hours after meals. been reported in individuals receiving tetracyclines. These conditions disappeared when the drug was Efficacy beyond 16 weeks and safety beyond 9 months have not been established. discontinued. Administration of adequate amounts of fluid along with the capsules is recommended to wash down the Laboratory Tests: Periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic capsule to reduce the risk of esophageal irritation and ulceration. (see ADVERSE REACTIONS section). studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated. Drug Interactions: 1. Because tetracyclines have been shown to depress plasma prothrombin activity, HOW SUPPLIED patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. ORACEA (beige opaque capsule printed with CGPI 40) containing doxycycline, USP in an amount equivalent to 2. Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid 40 mg of anhydrous doxycycline. Bottle of 30 (NDC 64682-009-01). giving tetracycline-class drugs in conjunction with penicillin. 3. The concurrent use of tetracycline and Storage: All products are to be stored at controlled room temperatures of 15°C-30°C (59°F-86°F) and methoxyflurane has been reported to result in fatal renal toxicity. 4. Absorption of tetracyclines is impaired by dispensed in tight, light-resistant containers (USP). Keep out of reach of children. bismuth subsalicylate, proton pump inhibitors, antacids containing aluminum, calcium or magnesium and iron- Patent Information: U.S. Patents 5,789,395; 5,919,775; 7,232,572; 7,211,267 and patents pending. containing preparations. 5. Doxycycline may interfere with the effectiveness of low dose oral contraceptives. To ORACEA is a registered trademark of CollaGenex Pharmaceuticals, Inc. avoid contraceptive failure, females are advised to use a second form of contraceptive during treatment with doxycycline. 6. There have been reports of pseudotumor cerebri (benign intracranial hypertension) associated Manufactured by: Marketed by: with the concomitant use of isotretinoin and tetracyclines. Since both oral retinoids, including isotretinoin CardinalHealth Galderma Laboratories, L.P. and acitretin, and the tetracyclines, primarily minocycline, can cause increased intracranial pressure, the Winchester, KY 40391 Fort Worth, TX 76177 concurrent use of an oral retinoid and a tetracycline should be avoided. 7961-01 BPI 06/08 OVERVIEW OF THE DIAGNOSIS AND TREATMENT OF HAIR LOSS
Edward Galiczynski, DO,* Leonid Trost, MD,** Shannon Harrison,*** Wilma Bergfeld, MD**** *R1-Cleveland Clinic Foundation **Private Practice- Palm Beach Dermatology ***FACD Research Fellow-Cleveland Clinic Foundation ****Staff-Cleveland Clinic Foundation Acknowledgement: Dr. S. Harrison is funded by the Australasian College of Dermatologists and the F. C. Florance Bequest.
Introduction be replaced every three to five years, with about 150 hairs being lost per day in a Hair loss is a prominent condition seen random distribution.5 The hair life cycle in many dermatology practices. The causes is divided into the anagen, catagen, and of hair loss are numerous and are typi- telogen phases. In the anagen phase, hair cally divided into cicatricial (scarring) and grows at a rate of roughly 0.35 mm/day for non-cicatricial (nonscarring) alopecia. an average of two to five years.1 The final Non-cicatricial alopecia may be reversible, hair length is proportional to the duration whereas cicatricial alopecia is rarely revers- of this stage. This accounts for differences ible. Some of the more common types of in length such as that between scalp and hair loss will be discussed in this article. eyebrow hair. During the catagen phase, the hair follicle goes through a process Normal hair of involution that involves apoptosis of Figure 1 follicular keratinocytes.1 This phase lasts three to six weeks. Finally, in the telogen health foods and fad dieting should be Type, distribution, and or rest phase, the hair shaft miniaturizes evaluated.11 structure of hair into a club hair and is shed after about three months.1,6 A club hair, also known as Humans are born with all of their hair a telogen hair, has no outer root sheath or Physical Examination follicles already formed, with roughly 5 pigment and is distinguished from other Every hair-bearing site of the body million covering the body.1 Although no 7 hairs by its swollen, clubbed end. The should be examined for abnormalities. The additional follicles are formed after birth, distribution of scalp hair follicles in anagen, scalp should be examined specifically for their size and type can change under the catagen, and telogen is 90% to 95%, <1%, inflammation, scaling, erythema and folli- influence of various mediators.1 Individual 8 and 5% to 10%, respectively. cular hyperkeratosis or plugging. Follicles, hairs can be classified as lanugo, vellus, although difficult to see clinically when and terminal. Lanugo hair, extremely Diagnosis of Hair miniaturized, are preserved in nonscar- fine hair present on the body of the fetus, ring alopecia. The pattern and distribu- is subsequently replaced by vellus and Disorders tion of hair as well as the hair shaft quality terminal hairs. Vellus hairs are fine and light colored, and are often seen on the face History and integrity should be noted. Specific and arms of young children as well as the patterns of hair loss include diffuse thin- A thorough history is essential in the ning, bitemporal recession, vertex thinning, face, chest, and abdomen of most women. 10 Terminal hairs are coarse and thick and are approach to diagnosis of hair conditions. and one or more patchy areas. Additional characteristically found on the face, chest, Age of onset, duration, and pattern of both light sources such as a Wood’s light are and abdomen of men.1 Hair grows on all scalp and body hair loss or gain should often needed to better discern scaling and surfaces of the skin except the palms, soles, be ascertained.9 It is also important to the presence of Malassezia (previously glans, and prepuce. Approximately 100,000 assess whether the hair is coming out by Pityrosporum) organisms (which fluoresce hairs cover the scalp.2 the roots or if it is breaking. All cosmetic orange due to porphyrins). Dermoscopy is helpful in accessing surface changes such as The entire proliferating region from and hair care practices such as bleaching, 10 scaling, perifollicular scales and follicular which the hair shaft develops is called the back-combing, and permanent waving pustules. hair follicle. The lower proliferative region, must be reviewed and evaluated. known as the hair bulb, contains matrix In the medical history, special attention The hair-pull test is a useful way to assess cells that multiply to form hair.3 Located should be paid to endocrine dysfunction scalp hair. When 20 to 40 hairs are firmly at the insertion of the arrector pili muscle, (especially thyroid disease), recent illness, (but not vigorously) pulled, less than one the bulge area contains epithelial stem cells hospitalization, and surgery. Both current in 10 hairs should be extracted. These which, at the end of a hair-growth cycle, and past medication history may be signifi- extracted hairs should be telogen or club migrate and differentiate into the different cant. In women, a history should include hairs. Greater than 10% of hairs being layers of the hair follicle.4 If the bulge menstrual patterns, pregnancy, use of oral extracted is considered a positive hair-pull region is injured, no hair can regrow, and a contraceptives, infertility, galactorrhea, test and is suggestive of telogen effluvium.9 scarring alopecia results.1 hirsutism, signs and symptoms of viriliza- If there are numerous dystrophic anagen tion, obesity and acne. A family history hairs, the diagnosis is anagen effluvium. Hair life cycle of hair loss should also be ascertained. Extracted hairs that are broken are consid- Lifestyle, stress, and diet are extremely ered an abnormal finding.12 Dystrophic The progression of each hair though its important. Adequacy of protein, calorie, (tapered proximal end plus lack of root life cycle causes the entire scalp hair to iron, and vitamin intake as well as use of sheaths) anagen hairs can be seen in hair GALICZYNSKI, TROST, HARRISON, BERGFELD 21 pulls in alopecia areata, LPP and DLE. and serum laboratory examinations. In Typically, dystrophic anagen hairs are seen equivocal cases, a 4-mm punch biopsy of with cytotoxic agents. the scalp is necessary, especially if scarring A hair pluck, which consists of using a alopecia is suspected.13 rubber-tipped hemostat to dislodge about 50 hairs, can give the physician additional Types of Alopecia information such as hair diameters and anagen/telogen ratio. If trichodystrophy is Alopecia can be classified into three suspected, a hair pull or clipping is more categories (see Error: Reference source not beneficial. found): A two-week hair collection represents s .ONCICATRICIAL NONSCARRING AND POTEN- a snapshot picture of daily shedding tially reversible) numbers. Hair is collected daily and s #ICATRICIAL SCARRING AND USUALLY Figure 2 placed into envelopes with a notation of irreversible) the shampoo day. The collection should be s (AIR SHAFT ABNORMALITIES done in the morning during hair grooming. Daily hair collections of greater than 100 hairs per day represent an effluvium. If Noncicatricial alopecia the hair has an adherent envelope, it is a telogen hair. In tinea capitis, spores and hyphae can be observed with the use of Androgenetic alopecia PAS or methylene blue stain. Androgenetic alopecia (also called Scalp biopsy can also be very helpful. 14 Biopsy technique differs depending on the “common baldness,” “male pattern hair race of the patient. African Americans loss [MPHL],” “female pattern alopecia,” 15 have helical hair and a diagonal follicle. and “female pattern hair loss [FPHL])” is Therefore, the punch biopsy should be an androgen-dependent process that results Figure 3 slightly angled in the direction of the hair. in miniaturization of scalp hair follicles. It In Caucasians with no helical-curly hair, is the most common form of hair loss in 16 the biopsy would be a routine vertical both men and women, affecting about punch. 40% to 50% of men and women by age 50.10,17 Androgenetic alopecia has a poly- Laboratory Studies genic pattern of inheritance.19 Follicular type 2 5A-reductase converts testosterone Routine laboratory studies should to dihydrotestosterone (DHT),14 causing include complete blood count (CBC), shortening of the anagen phase and complete metabolic profile (CMP), miniaturization (reduced follicle diam- thyroid-stimulating hormone, free T4, eter), resulting in smaller terminal follicles and zinc and serum ferritin levels. More and an increased number of vellus hairs.18 in-depth studies may be done based on Interestingly, this same intrafollicular the findings of the history and physical reaction causes vellus hairs of the beard, Figure 4 examination. If a hormonal imbalance is chest, axillary, and pubic hairs to convert suspected, an androgen screening should into terminal hairs during puberty when 19 be performed. Often, the diagnosis can be there is a natural elevation of the adrenal sulfate (DHEAS) and other androgens. made based on the history, physical exam, androgen, dihydroepiandrostenedione The patient often initially complains of gradual hair thinning10 or increased frequency of sunburns on the scalp. Table 1. 4YPES OF ALOPECIA Affected areas contain short, low-density s .ONCICATRICIAL NONSCARRING AND POTENTIALLY REVERSIBLE hair.15 Women most commonly have s !NDROGENETIC ALOPECIA widening of the central part and reduced Alopecia areata hair density in the frontal scalp and crown Telogen effluvium (see Figure 1). The frontal hairline is Tinea capitis* usually maintained,20 although many other Traction alopecia** Trichotillomania forms of pattern hair loss can occur. These Drug-induced alopecia patterns of hair loss have been classified by Ludwig.21 Rarely do women go completely s #ICATRICIAL SCARRING AND USUALLY IRREVERSIBLE bald.11 s 4RAUMA Men, on the other hand, often begin with s )NFECTIOUS bitemporal recession of the frontal hair line Herpes zoster, folliculitis decalvans***, dissecting cellulitis of the scalp***, folliculitis keloidalis*** and subsequent thinning on the vertex (see s .ONINFECTIOUS INFLAMMATORY Figure 2). Classically, these areas grow and Discoid lupus erythematosus, lichen planopilaris, pseudopelade merge until eventually only some parietal s .ONINFECTIOUS NONINFLAMMATORY hair and the occipital hair remain.17 Male Central centrifugal cicatricial alopecia, developmental abnormalities, genetic disorders, neoplastic infiltrates pattern androgenetic hair loss has been s (AIR SHAFT ABNORMALITIES classified by Hamilton,22 Norwood,23 and Trichorrhexis nodosa Savin.24 *Potential to become cicatricial alopecia with kerion formation if left untreated Androgens play less of a role in female **Prolonged traction can result in scarring *** These etiologies may have infectious etiologies and abnormal host response. Infection may also contribute to pathogenesis. pattern hair loss than in male pattern hair loss. However, around one-third of women 22 OVERVIEW OF THE DIAGNOSIS AND TREATMENT OF HAIR LOSS Table 2: )NITIAL ,ABORATORY be used in women who are, may become proximally, giving them the look of an 7ORK UP FOR !NDROGENETIC or wish to become pregnant because of its exclamation mark.29 Nail changes, occur- !LOPECIA ability to feminize male fetuses. Side effects ring in 3% to 30% of cases, involve pitting, include menstrual irregularities, post- longitudinal ridging, and trachyonychia s #OMPLETE "LOOD #OUNT #"# menopausal bleeding, breast tenderness or (roughening of the surface).34 Serum TSH, s #OMPLETE -ETABOLIC 0ANEL #-0 s 4HYROID 3CREEN 43( 4 enlargement, and fatigue. Effective contra- T4 and either microsomal antibodies or s &ERRITIN ception must be used in pre-menopausal anti-thyroid peroxidase antibody should s :INC females on spironolactone. be drawn due to the association of alopecia s 4ESTOSTERONE FREE AND TOTAL Flutamide inhibits androgen uptake as areata with thyroid disease (frequently s $EHYDROEPIANDROSTERONE 3ULFATE $(%!3 well as nuclear androgen binding within Hashimoto’s thyroiditis).15 s !NDROSTENEDIONE target tissue, but its potential for hepatotox- Intralesional corticosteroid injections s 3EX (ORMONE "INDING 'LOBULIN 3("' icity makes it an unfavorable alternative.19 are the first-line therapy for adult patients with less than 50% of scalp involvement.34 with FPML have clinical signs of increased Oral contraceptive pills (OCP) have also been used with some success, particu- Injections of triamcinolone, 2 to 10 mg/mL, androgen levels including: seborrhea, acne, are into the subcutaneous tissue of affected hirsutism and alopecia (SAHA). Excess larly estrogens combined with drosperi- done [personal communication with WF areas. Regrowth is often seen within androgen conditions include adrenal four to eight weeks. Treatments may be hyperplasia, polycystic ovarian syndrome Bergfeld]. If an OCP is used, the progestin should have as little androgenetic activity repeated every four to six weeks. The main (PCOS) and postmenopausal androgen side effect is local skin atrophy, which can excess. as possible (e.g., norgestimate or ethyno- diol diacetate).13 be prevented by avoiding injections that are Initial laboratory tests include CBC, Oral finasteride (Propecia®), a too great in volume per injected site, too CMP, thyroid screen (TSH, T4), ferritin, 29 competitive inhibitor of peripheral type frequent, or too superficial. Minoxidil has zinc, testosterone free and total, DHEAS 2 5 -reductase, blocks the conversion of an immunomodulatory effect in patients (dehydroepiandrosterone sulfate), sex A testosterone to DHT and can increase with AA and may be used alone or in hormone binding globulin, and andros- 35 scalp hair coverage in men, although its combination with other treatments. Hair tenedione. Additional tests will depend effect in men over the age of 60 years is regrowth in patients with AA using topical on clinical history and results of the less pronounced.8 Adverse effects have minoxidil solution has been shown to be screening tests (see Table 2).25 The pres- been minimal but include decreased approximately 20% to 45% in patients with ence of acne, hirsutism, menstrual irregu- 36,37 libido, erectile dysfunction and ejacula- 20% to 99% scalp involvement. Topical larities, or virilization in women suggests tion disorder, but they often diminish in anthralin, an irritant, and the contact sensi- androgen excess. Referral to an endocri- men who stop the drug and even in most tizer diphenylcyclopropenone (DPCP) have nologist may be necessary. A scalp biopsy 38 men who continue finasteride therapy.26 been used in refractory cases of AA. is generally unnecessary and shows hair 6 Clinical studies suggest that the incidence miniaturization. of prostate cancer is lessened with the use Telogen effluvium of finasteride, but when present it is more Telogen effluvium (TE), commonly Treatment 8 aggressive. Finasteride should be avoided known as shedding, is the most common in premenopausal females, as it is preg- Minoxidil (Rogaine®), originally an 8 cause of diffuse hair loss and is usually antihypertensive, promotes hair growth by nancy category X. Finasteride is ineffec- associated with a trigger factor. Most tive in postmenopausal women under the increasing the duration of the anagen phase 27 commonly, anagen hairs are stimulated and enlarging miniaturized hair follicles. age of 60 years. prematurely to enter the telogen phase, The exact mechanism of action is unknown causing an increase in the number of but is considered to be a potassium channel Alopecia areata telogen hairs.40 Other variations of this opener, vasodilator and inhibitor of apop- mechanism exist, such as immediate 2 Alopecia areata is an erratic, non-scarring, tosis. Treatment with 2% or 5% solution and recurring autoimmune inflammatory twice per day is effective, with the 5% being 28 disorder of the hair and nails. It primarily Table 3. $RUGS THAT CAUSE ALOPECIA clinically superior (60% vs. 41% regrowth at presents as hair loss on the scalp but can 2 one year). However, in females, distal and involve total scalp hair loss (alopecia totalis) !NAGEN EFFLUVIUM 4ELOGEN EFFLUVIUM facial hirsutism is noted, especially with the or total body hair loss (alopecia univer- 2 Bleomycin Beta blockers 5%. Rogaine foam 5% was approved by salis).29 It occurs in approximately 1.7% Carmustine the FDA in 2006 for men as an OTC. The of the population30 and affects men and Bromocriptine initial growth of miniaturized hairs with women equally.30 It is associated with a high Colchicine Captopril decreased life cycles actually causes an initial frequency of positive family history (ranging Cyclophosphamide Cimetidine increase in shedding in the first 10 to 12 from 10% to 20%)31 and has a multifactorial Cytarabine Coumadin weeks of therapy. Adverse effects include pattern of inheritance related to the HLA scalp irritation and dryness, allergic contact complex on chromosome 6.32 It is an auto- Daunorubicin Enalapril dermatitis, photoallergic contact derma- immune T lymphocyte-mediated response Doxorubicin Fluoxetine titis, and hypertrichosis. Blood pressure is to an unknown antigen29 and is associated Etoposide Interferons not significantly altered.8 If treatment with with other autoimmune diseases such as minoxidil is halted, scalp hairs will return thyroid disease, diabetes, pernicious anemia, 5-Fluorouracil Isotretinoin 19 rapidly to their pretreatment state. lupus erythematosus, Crohn’s and vitiligo.6 Hydroxyurea Lithium Topical minoxidil 2% or 5% is effec- Onset of hair loss is usually abrupt and Methotrexate Oral contraceptives tive in women and may be used alone or can involve any hair-bearing site. On the in combination with other therapies.19 scalp, it presents as one or more patches of Thiopental Retinoids However, only the 2% is FDA-approved in hair loss without scarring (see Figure 3).33 Vinblastine Thiouracil women. Patches are often round and smooth with Vincristine Sulfasalazine Systemic treatments such as antiandro- exclamation mark hairs at their margins. gens like spironolactone are effective for Exclamation mark hairs are short and Valproic acid female pattern hair loss.12 They should not broken hairs which progressively narrow Adapted from Pillians and Woods 1995 and Tosti et al. 1994. GALICZYNSKI, TROST, HARRISON, BERGFELD 23 anagen release, delayed anagen release, occur in adults. It has an overall incidence overall griseofulvin is generally safe and short anagen phase, immediate telogen of 4% but is most prevalent in African well tolerated.45 An anti-fungal shampoo release, and delayed telogen release.41 No American children. Trichophyton tonsurans should also be used. genetic cause has been identified thus far.15 is the most common causative organism Clinically, TE can present as acute (<6 in African Americans, while Microsporum Traction Alopecia months), chronic (>6 months) and chronic audouinii is the most common in repetitive. Caucasians.43 The fungi are keratinophilic Traction alopecia is a form of traumatic In acute telogen effluvium, diffuse shed- and either invade the hair shaft (endo- hair loss due to the application of forces ding occurs less than four months after an thrix infection) or remain outside the hair to the hair and scalp. It is more common identifiable trigger such as childbirth, high shaft (ectothrix infection). Sometimes, in women, African Americans,47 and fever, surgical trauma, sudden starvation, they invade subcutaneously, forming a children.48 Styles such as backcombing, hemorrhage, emotional stress, or crash kerion.44 Transmission occurs by infected braiding, brushing, cornrowing, ponytails, dieting. This form of shedding resolves persons, individual infected hairs, animals, rollers, weaving, and hair extensions can spontaneously within three to six months, and fomites such as towels, clothing, hats, cause traction on the hair and alopecia, provided the trigger has been removed.5 brushes, combs, and barbershop instru- with the location of hair loss directly Occasionally, shedding can persist longer ments. Large family size, crowded living related to where the offending forces are 49 than six months. This is called chronic conditions, and low socioeconomic status greatest. diffuse telogen hair loss and should not be are factors associated with a high prevalence Marginal alopecia, most commonly confused with chronic telogen effluvium. of tinea capitis in urban populations.45 occurring in African Americans who use Chronic diffuse telogen hair loss, like Patients usually complain of a pruritic tight curlers, rollers, or straighteners, acute telogen effluvium, is associated with and scaling scalp, often with hair loss. Hair involves hair loss in the temporal scalp a trigger. Accepted triggers for chronic shafts are broken, leaving fragments of (see Figure 4). Chignon alopecia, seen in diffuse telogen hair loss include thyroid proximal hair in the classic “black dot” women who frequently wear chignons, disorders, profound iron deficiency anemia, pattern, although the dots actually will be involves patchy hair loss at the lamb- acrodermatitis enteropathica, acquired zinc the color of the patient’s original hair (e.g., doid suture.42 Regular use of a hot comb deficiency, and malnutrition.5 a patient with red hair will have “red dots”). may lead to central centrifugal cicatricial Chronic telogen effluvium, on the other Hair loss, if present, is patchy and irregular, alopecia (CCCA) in predisposed indi- hand, is an idiopathic disorder of hair and the scalp has diffuse scaling. Cervical viduals and to permanent alopecia. In its shedding and is a diagnosis of exclusion. and occipital lymphadenopathy is a consis- early stages, hair loss can be reversed by It can last for years and commonly occurs tent finding.40 Inflammation may occur, substitution of socially acceptable but less in females between 30 and 50 years of age. with kerion forming in extreme cases. A traumatic hair styles; but left untreated, Women have increased shedding all over kerion is an inflamed, boggy, and tender traction alopecia can lead to permanent the scalp and often have bitemporal reces- plaque with pustule formation. Systemic hair loss.42 sion, causing this disorder to be confused manifestations include fever and malaise.39 with AGA.42 If untreated, serious complications such as Trichotillomania The hair-pull test (see above) is usually tinea corporis, lymphadenitis, secondary bacterial infection, and scarring alopecia Trichotillomania (TTM) is defined by positive in acute telogen effluvium at the 38 vertex and scalp margins, but a negative may occur. the American Psychiatric Association as hair pull test does not rule out the diag- Small spore ectothrix infections (M. noticeable hair loss caused by the recurrent 5 audouinii and M. canis) fluoresce green compulsion to deliberately pull out one’s nosis. Basic tests include CBC, CMP,TSH, 50 T4, zinc and serum ferritin.35 If chronic under Wood’s light examination, while hair. The compulsion is characterized by telogen effluvium is suspected, a scalp endothrix infections (T. tonsurans) do increasing tension that is finally relieved not fluoresce.46 To evaluate for fungal when the hair is pulled. Its lifetime inci- biopsy may be necessary to distinguish it 50 from AGA. In chronic telogen effluvium, hyphae and spores microscopically in the dence is estimated at 0.6%. TTM occurs the ratio of terminal to vellus hairs is much office, remove several hairs with forceps equally among males and females in chil- higher than in AGA.37 and scrape the scalp for scales. Place them dren but is much more common in adult women.50 Although there are similarities to Therapy for TE is directed by clinical onto a glass slide and heat them in 10% to obsessive-compulsive disorder, TTM is not evaluation and identification of triggering 15% KOH solution. Fungal cultures can associated with obsessions. There is signif- events. The primary focus of the physi- be helpful and are obtained by rubbing icant evidence of high rates of psychiatric cian is to remove and treat or inhibit the a small brush over the scalp about 10 comorbidity as well as physical, emotional, triggers of TE. Adequate nutrition is essen- times. Alternatively, cotton swabs or gauze and psychosocial sequelae.51 Sibling rivalry, tial and should include a multivitamin. pads soaked in saline can be rubbed over 40 Expectations for hair growth are as follows: infected areas. The hair fragments and lack of attention, divorced parents, learning scales are then placed on fungal culture disabilities, and unhappiness or teasing at at two months, diminished TE; four to 44 six months, evidence of regrowth; and 12 medium such as Sabouraud’s dextrose school are all associated with TTM. months, recovery or plateau of the thera- agar. Positive cultures can be expected in Hair pulling episodes may be brief or peutic benefit of the treatment regimen. seven to 10 days, but 30 days are neces- may last for hours. Patients can examine It is often beneficial for patients to keep a sary in order for a culture to be declared the hair root, twirl it off, pull the strands 40 health calendar to record levels of shed- negative. between their teeth, and may even eat it ding, medical events, drugs and emotional Although numerous clinical trials (trichophagia). Trichophagia can result stress levels during treatment.37 Topical demonstrate the effectiveness of flucon- in bezoars which eventually may cause minoxidil can be used in some cases to aid azole, itraconazole and terbinafine, griseof- anemia, abdominal pain, nausea, vomiting, in regrowth. ulvin is the mainstay for treatment of and bowel obstruction.45 Some patients tinea capitis in children. Griseofulvin has report scalp pruritus that is relieved by Tinea capitis exhibited an exceptional safety profile and hair pulling, but this symptom is believed has been widely used for the treatment of to be psychogenic.52 Often, patients will Tinea capitis, a fungal infection of dermatophyte infections in both adults and conceal their actions and will not describe the scalp and hair follicle, is primarily a children. Known side effects include head- it explicitly to the physician.44 On physical disease of children, although it can also aches and gastrointestinal disturbances, but examination, there are areas of partial hair 24 OVERVIEW OF THE DIAGNOSIS AND TREATMENT OF HAIR LOSS loss which can occur on any area of the body, including Table 4: 4REATMENT OF .ON #ICATRICIAL !LOPECIA eyebrows, eyelashes, and pubic hairs. The patches are .ONCICATRICIAL NONSCARRING AND POTENTIALLY REVERSIBLE 4REATMENT frequently contralateral to the !NDROGENETIC ALOPECIA Males: dominant hand.47 Topical Minoxidil (Rogaine ®) solution The Diagnostic and Oral finasteride Statistical Manual of Mental Surgery (e.g., hair transplantation Disorders (DSM-IV-TR) lists Females: the essential criteria for the Topical minoxidil solution diagnosis of TTM. These Spironolactone, include noticeable hair loss Maintain serum ferritin > 70 g/L from recurrent pulling out !LOPECIA AREATA Intralesional corticosteroids of one’s hair, an increasing Potent topical steroid tension before pulling out Topical anthralin the hair, and pleasure or relief Minoxidil lotion when pulling out the hair. Contact immunotherapy Other causes such as mental 4ELOGEN EFFLUVIUM Identify and remove trigger disorders and general medical Multivitamin conditions must be excluded, Topical Minoxidil and the disturbance must Adequate Nutrition cause clinically significant 4INEA CAPITIS Systemic treatment required. distress or impairment in 45 First line: griseofulvin, functioning. Occasionally, a Second line: terbinafine biopsy is necessary. The major itraconazole, criteria for the diagnosis by fluconazole biopsy are trichomalacia (the complete distortion of a 4RACTION ALOPECIA Reversible in its early stages fully developed terminal hair Avoid styling forces in the bulb) and pigmented 4RICHOTILLOMANIA Cognitive behavioral therapy casts.53 Treatment of tricho- Psychotropic drugs tillomania includes behavior Referral to a psychiatrist or clinical psychologist modification, supportive $RUG INDUCED ALOPECIA Discontinue drug psychotherapy and appro- priate psychopharmacologic Cicatricial or scarring alopecia is an irre- involvement. Treatment depends on the medications.54 Referral to a psychiatrist is versible form of hair loss most commonly type of cicatricial alopecia. The North usually needed. due to hair follicle stem-cell failure. American Hair Society can be referenced Clinically, cicatricial alopecia appears as for the classification of cicatricial alopecia. Drug-induced alopecia areas of hair loss with absence of follicular Intralesional, topical and oral corticos- ostia. Lesions may also demonstrate peri- teroids, as well as oral retinoids, tetracycline Medications are a common cause of hair follicular papules, erythematous plaques, and topical macrolactams have all been used loss. Any evaluation of alopecia should or pustules. Permanent hair loss occurs to treat different types of cicatricial alopecia include a detailed drug history that includes from the replacement of follicles by without much success. Therapy is aimed past and current medications, doses and fibrosis and hyalinized collagen. Therefore, at halting progression rather than complete dosage changes. There are two main mech- prompt identification and diagnosis of this resolution. Specific therapy for cicatricial anisms for drug-induced alopecia. The condition is essential. The main disease alopecia is beyond the scope of this article. first, termed anagen effluvium, involves categories include trauma (such as burns), the termination mitotic activity in hair infectious, noninfectious inflammatory, Hair-shaft abnormalities matrix cells and occurs days to weeks and noninfectious noninflammatory.57 after drug administration. The second, Infectious causes include kerion and Hair-shaft abnormalities result in fragile termed telogen effluvium (discussed possibly folliculitis decalvans, dissecting hair and broken hair fibers. The most above), involves the premature conversion cellulitis of the scalp and folliculitis kelo- common type of hair shaft abnormality is of follicles from anagen to telogen phase. idalis.10 Noninfectious inflammatory trichorrhexis nodosa. In this condition, Anagen effluvium is a frequent complica- diseases include autoimmune (e.g., discoid hair shafts fracture at the sites of nodes, tion of antineoplastic drugs, while telogen lupus erythematosus) (see Figure 5), lichen frequently due to trauma. Patients present effluvium can be associated with a wide planopilaris, and pseudopelade,58 while with hair breakage at various lengths.10 range of medications. Hair loss by either noninfectious noninflammatory diseases Generally, trichorrhexis nodosa is a result mechanism is usually reversible by cessa- include CCCA, developmental abnor- of weathering from environmental and tion of drug intake.55 malities, genetic disorders, and neoplastic cosmetic factors. Individual hairs will According to the World Health infiltrates.4 progressively degenerate from the root to Organization, the most common drugs Unlike nonscarring alopecias, a scalp the tip.60 In proximal trichorrhexis nodosa, associated with alopecia are valproic acid, biopsy is always necessary both to diagnose most commonly seen in African American isotretinoin, fluoxetine, and enalapril.56 cicatricial alopecia and to determine its female adolescents who repeatedly chemi- For a list of other common drugs associ- underlying cause. Initial evaluation also cally or thermally straighten or relax their ated with hair loss, see Table 3. entails cultures for bacteria and fungal hair, cuticular cells are lost locally.43 infection as well as a 4-mm punch Light microscopic examination of the Cicatricial (scarring) biopsy.4,59 Although cicatricial alopecia hairs is required. Two samples of about 50 alopecia is irreversible, early diagnosis and treat- hairs each should be cut or plucked from ment is paramount in attempting to limit the affected and normal sites.7 During light
GALICZYNSKI, TROST, HARRISON, BERGFELD 25 microscopy, cortical cells appear to frag- New England Journal of Medicine, 1999: p. 341: 491-7. review. Arch Dermatol, 1993. 129(3): p. 356-63. 2. Odom, R., James, WD and T.G. Berger. Andrew’s Dis- 42. Whiting, D.A. Chronic telogen effluvium: increased scalp ment out, and the hair looks like the bris- eases of the Skin. Philadelphia. 2000: W.B. Saunders hair shedding in middle-aged women. J Am Acad Derma- tles of two paint brushes pushed into each Company. 943-52. tol, 1996. 35(6): p. 899-906. 3. Ebling, F. The biology of hair. 1987. Dermatologic Clinics: 61 43. Frieden, I.J. and R. Howard. Tinea capitis: epidemiology, other. Treatment of hair shaft disorders p. 5:467-81. diagnosis, treatment, and control. J Am Acad Dermatol, is directed at removing the cause, especially 4. Wiseman, M.C. and J. Shapiro. Scarring alopecia. J 1994. 31(3 Pt 2): p. S42-6. Cutan Med Surg, 1999. 3 Suppl 3: p. S45-8. 44. Gupta, A.K., et al. Tinea capitis: an overview with empha- if the abnormality is secondary to trauma. 5. Harrison, S. and R. Sinclair. Telogen effluvium. Clin Exp sis on management. Pediatr Dermatol, 1999. 16(3): p. Leave-on conditioners may enhance hair Dermatol, 2002. 27(5): p. 389-5. 171-89. 6. Mulinari-Brenner, F. and W.F. Bergfeld. Hair loss: an over- 55 45. Elewski, B.E.. Tinea capitis: a current perspective. J Am strength and prevent breakage. view. Dermatol Nurs, 2001. 13(4): p. 269-72, 277-8. Acad Dermatol, 2000. 42(1 Pt 1): p. 1-20; quiz 21-4. 7. de Berker, D. and R.D. Sinclair. The hair shaft: normality, 46. Ceburkovas, O., R.A. Schwartz, and C.K. Janniger, Tinea abnormality, and genetics. Clin Dermatol, 2001. 19(2): p. capitis: current concepts. J Dermatol, 2000. 27(3): p. 144- Psychological aspects of 129-34. 8. 8. Wood, A. Treatment of hair loss. New England Journal of 47. Hantash, B.M. and R.A. Schwartz. Traction alopecia in hair loss Medicine, 1999. 341: p. 964-73. children. Cutis, 2003. 71(1): p. 18-20. 9. Rietschel, R.L. A simplified approach to the diagnosis of 48. Laude, T.A. Approach to dermatologic disorders in black alopecia. Dermatol Clin, 1996. 14(4): p. 691-5. children. Semin Dermatol, 1995. 14(1): p. 15-20. The psychological aspects of hair loss 10. Shapiro, J., Wiseman, M and H. Lui. Practical manage- 49. Whiting, D.A. Traumatic alopecia. Int J Dermatol, 1999. should not be underestimated, and any ment of hair loss. Canadian Family Physician, 2000. 46: 38 Suppl 1: p. 34-44. p. 1469-77. 50. DSM-IV-TR, D.a.s.m.o.m.d., ed. A.P. Association. 2000, treatment of hair loss in women or men 11. Drake, L.A., et al. Guidelines of care for androgenetic alo- Washington, DC. 674-7. must address the frequently profound asso- pecia. J Am Acad Dermatol, 1996. 35(3 Pt 1): p. 465-9. 51. Keuthen, N.J., R.L. O’Sullivan, and S. Sprich-Buckmin- 12. Hoffmann, R. and R. Happle. Current understanding of ster. Trichotillomania: current issues in conceptualization ciated psychosocial implications. In our androgenetic alopecia. Part II: clinical aspects and treat- and treatment. Psychother Psychosom, 1998. 67(4-5): p. society, hair is vital to a woman’s sense of ment. Eur J Dermatol, 2000. 10(5): p. 410-7. 202-13. 13. Mulinari-Brenner, F., and W.F. Bergfeld. Hair disorders. 52. Schneider, D. and C.K. Janniger. Trichotillomania. Cutis, attractiveness, gender identity, and sexu- In: Rakel, RE and Bope, ET, eds. Conn’s current therapy, 1994. 53(6): p. 289-90, 294. ality. At any age, hair loss for women is ed. Saunders. 2003, Philadelphia. 843-7. 53. Bergfeld, W., et al. The combined utilization of clinical and 62 14. Hoffmann, R., Male androgenetic alopecia. Clin Exp Der- histological findings in the diagnosis of trichotillomania. J much more distressing than for men. matol, 2002. 27(5): p. 373-82. Cutan Pathol, 2002. 29(4): p. 207-14. Women who experience hair loss may have 15. Chartier, M.B., D.M. Hoss, and J.M. Grant-Kels. Approach 54. Siddappa, K. Trichotillomania. Indian J Dermatol Venereol to the adult female patient with diffuse nonscarring alope- Leprol, 2003. 69(2): p. 63-8. feelings of anxiety, helplessness, and unat- cia. J Am Acad Dermatol, 2002. 47(6): p. 809-18; quiz 55. Tosti, A., Misciali, C, Piraccini, BM, Peluso, AM and tractiveness. Quality of life is often severely 818-20. Bardazzi, F.. Drug-induced hair loss and hair growth: inci- 63 16. Hoffmann, R. and R. Happle. Current understanding of dence, management, and avoidance. Drug Safety, 1994. impacted. In addition, some women may androgenetic alopecia. Part I: etiopathogenesis. Eur J 10: p. 310-7. actually decrease their social interactions Dermatol, 2000. 10(4): p. 319-27. 56. Pillans, P.I. and D.J. Woods. Drug-associated alopecia. 17. Sinclair, R. Male pattern androgenetic alopecia. Bmj, Int J Dermatol, 1995. 34(3): p. 149-58. with other people in response to severe hair 1998. 317(7162): p. 865-9. 57. Headington, J.T. Cicatricial alopecia. Dermatol Clin, 1996. loss.64 18. Bergfeld, W.F. Androgenetic alopecia: an autosomal 14(4): p. 773-82. dominant disorder. Am J Med, 1995. 98(1A): p. 95S-98S. 58. Bergfeld, W.F. Alopecia: histologic changes. Adv Derma- Even though hair loss is considered 19. Sinclair, R.D. and R.P. Dawber. Androgenetic alopecia in tol, 1989. 4: p. 301-20; discussion 321. normal in men,19 most men still view it as men and women. Clin Dermatol, 2001. 19(2): p. 167-78. 59. Mulinari-Brenner, F. and W.F. Bergfeld. Hair loss: diagno- 20. Birch, M., Lalla, SC and Messenger, AG. Female pattern sis and management. Cleve Clin J Med, 2003. 70(8): p. moderately stressful, although a majority hair loss. Clinical Dermatology, 2002. 27: p. 383-8. 705-6, 709-10, 712. adapt without functional impairment. 21. Ludwig, E. Classification of the types of androgenetic 60. Dawber, R.P. An update of hair shaft disorders. Dermatol alopecia (common baldness) occurring in the female sex. Clin, 1996. 14(4): p. 753-72. Balding may make some men feel less Br J Dermatol, 1977. 97(3): p. 247-54. 61. Hordinsky, M.K., Alopecias. J. Bolognia, Jorizzo, JL and attractive overall and may decrease their 22. Hamilton, J.B. Patterned loss of hair in man; types and Rapini, RP, eds. Vol. 1. 2003, London: Mosby. 1033- 62 incidence. Ann N Y Acad Sci, 1951. 53(3): p. 708-28. 1050. quality of life. 23. Norwood, O.T. Male pattern baldness: classification and 62. Cash, T.F. The psychological effects of androgenetic incidence. South Med J, 1975. 68(11): p. 1359-65. alopecia in men. J Am Acad Dermatol, 1992. 26(6): p. The physician must actively seek to 24. Savin, R.C. Use of topical minoxidil in the treatment of 926-31. understand the psychosocial effects that male pattern baldness. J Am Acad Dermatol, 1987. 16(3 63. Cash, T.F., V.H. Price, and R.C. Savin. Psychological Pt 2): p. 696-704. effects of androgenetic alopecia on women: comparisons hair loss is having on the patient, as well 25. Barth, J.H. Rational investigations in the diagnosis and with balding men and with female control subjects. J Am as the patient’s expectations of treat- management of women with hirsutism or androgenetic Acad Dermatol, 1993. 29(4): p. 568-75. alopecia. Clin Dermatol, 2001. 19(2): p. 155-60. 64. Van Neste, D.J. and DH Rushton. Hair problems in ment results. The patient’s feelings must 26. Whiting, D.A. Advances in the treatment of male androge- women. Clin Dermatol, 1997. 15: p. 113-25. be normalized. This involves explaining netic alopecia: a brief review of finasteride studies. Eur J 65. Cash, T.F. The psychology of hair loss and its implications Dermatol, 2001. 11(4): p. 332-4. for patient care. Clin Dermatol, 2001. 19(2): p. 161-6. to the patient that his or her feelings and 27. Whiting, D.A., et al. Measuring reversal of hair minia- concerns about body image are normal and turization in androgenetic alopecia by follicular counts in horizontal sections of serial scalp biopsies: results of expected. In addition, the physician must finasteride 1 mg treatment of men and postmenopausal ensure that the patient’s ideas of treatment women. J Investig Dermatol Symp Proc, 1999. 4(3): p. 65 282-4. efficacy are realistic. Often, reversal or 28. Shapiro, J. and S. Madani. Alopecia areata: diagnosis stabilization of hair loss will alleviate much and management. Int J Dermatol, 1999. 38 Suppl 1: p. 19-24. of the distress. In severe cases, cognitive- 29. Madani, S. and J. Shapiro. Alopecia areata update. J Am behavioral therapy is the treatment of Acad Dermatol, 2000. 42(4): p. 549-66; quiz 567-70. 55 30. McDonagh, A.J. and R. Tazi-Ahnini. Epidemiology and choice. genetics of alopecia areata. Clin Exp Dermatol, 2002. 27(5): p. 405-9. 31. McDonagh, A.J. and A.G. Messenger. Alopecia areata. Conclusion Clin Dermatol, 2001. 19(2): p. 141-7. 32. Duvic, M., A. Nelson, and M. de Andrade. The genetics of Alopecia is a common disorder and can alopecia areata. Clin Dermatol, 2001. 19(2): p. 135-9. 33. Papadopoulos, A.J., R.A. Schwartz, and C.K. Janniger. be a manifestation of systemic disease. It Alopecia areata. Pathogenesis, diagnosis, and therapy. can also have profound psychosocial effects. Am J Clin Dermatol, 2000. 1(2): p. 101-5. 34. Shapiro, J. Alopecia areata. Update on therapy. Dermatol Accurate diagnosis through history, phys- Clin, 1993. 11(1): p. 35-46. ical examination and laboratory testing is 35. Khoury, E.L., et al. Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration. J Invest essential. Nutritional support and avoid- Dermatol, 1992. 99(1): p. 40-7. ance of damaging hair-care procedures is 36. Shapiro, J. and V.H. Price. Hair regrowth. Therapeutic agents. Dermatol Clin, 1998. 16(2): p. 341-56. essential. Care should be taken to under- 37. Buhl, A.E. Minoxidil’s action in hair follicles. J Invest Der- stand and address the patient’s psychoso- matol, 1991. 96(5): p. 73S-74S. 38. Dall’oglio, F., et al. Topical immunomodulator therapy with cial needs as well as to establish realistic squaric acid dibutylester (SADBE) is effective treatment expectations in order to achieve optimal for severe alopecia areata (AA): results of an open-label, paired-comparison, clinical trial. J Dermatolog Treat, results. 2005. 16(1): p. 10-4. 39. Whitmont, K.J. and A.J. Cooper. PUVA treatment of alo- pecia areata totalis and universalis: a retrospective study. Australas J Dermatol, 2003. 44(2): p. 106-9. References 40. Sinclair, R. Diffuse hair loss. Int J Dermatol, 1999. 38 Suppl 1: p. 8-18. 1. Paus, R. and G. Cotsarelis. The biology of the hair follicle. 41. Headington, J.T. Telogen effluvium. New concepts and
26 OVERVIEW OF THE DIAGNOSIS AND TREATMENT OF HAIR LOSS LEUKEMIC VASCULITIS AND CUTANEOUS MANIFESTATIONS OF ACUTE MYELOGENOUS LEUKEMIA
David Cleaver DO,* Jenny Cotton MD, PHD,** Brian Shapiro MD,** Daniel Stewart DO** *1st-year resident, St. Joseph Mercy Health System, Ann Arbor, MI **Dermatology Residency Director, St. Joseph Mercy Health System, Ann Arbor, MI
ABSTRACT
Leukemia cutis and leukemic vasculitis are specific cutaneous manifestations of leukemia. Clinically, leukemia cutis presents with a variety of morphologies from erythematous or violaceous papules to large ulcerative plaques. Leukemic vasculitis results from leukemic cells infiltrating blood vessels, causing a vasculitis. Both entities represent a poor prognosis for the patient. We present a case of a previously healthy female who presented with leukemia cutis and leukemic vasculitis secondary to acute myelogenous leukemia and had a rapidly downhill course.
Case Report dyspnea on exertion, as well as tender “sores” in her mouth that began at the same A 60-year-old Caucasian female was time as the other cutaneous lesions. The admitted to the hospital with a two-week patient’s past medical history was signifi- history of a rash. The patient first noticed cant for hypothyroidism. The patient’s a slightly pruritic red nodule on her left medications included levothyroxine and, forearm that she believed was from a spider taken recently, one over-the-counter diet bite. The lesion progressively enlarged and pill. became dusky red. It was evaluated by her On exam, there were multiple erythema- primary care physician (PCP) one week tous-to-violaceous papules, coalescing prior to admission. The lesion was treated into plaques involving the bilateral lower as a cellulitis, with trimethoprim/sulfame- extremities, buttocks, and proximal arms Low Power thoxazole. The patient had no improve- (see pictures). The buttocks had larger ment, and developed additional lesions plaques with a diameter up to 8 cm, and involving the bilateral lower extremities and three erythematous, edematous papules the right buttock. The lesions were mini- were noted on the central face. Exam of mally tender and minimally pruritic. The the oral mucosa revealed three shallow patient returned to the PCP three days later erythematous erosions on the hard palate. with worsening rash and had an episode The palms, soles, and other mucous of spontaneous epistaxis. Laboratory membranes were spared, and no lymph- blood tests were drawn, and the patient’s adenopathy was present. On exam the antibiotic was changed to cephalexin. The next day, the lesions had enlarged and new laboratory tests revealed pancytopenia with lesions had evolved. The abdomen, back, hemoglobin of 6.6 gm/dL, platelet count and chest were now involved. of 30,000/mcL, and white blood cell count Two punch biopsies were performed on Medium Power of 1,900/mcL with absolute neutropenia. the arm and the leg. The biopsies had a The patient was admitted, and a derma- superficial and mid-dermal perivascular tology consult and bone marrow biopsy lymphoid infiltrate with foci of fibrinoid were ordered. necrosis in the vessel walls (see low-power and medium-power pictures). In addi- A detailed history revealed that the tion to the lymphocytes, there were large, patient had progressive generalized weak- atypical mononuclear cells with irregular ness during the two weeks prior to admis- nuclear contours and fine purple chro- sion. This was accompanied by decreased matin. Some of these large, atypical mono- appetite, as well as persistent headache. nuclear cells infiltrated the vessel wall (see She complained of occasional chills and high-power pictures). Focal cytoclasis was also noted. Immunohistochemical stains revealed the lymphocytes to be predomi- nantly T cells with only a few B cells. The High Power atypical mononuclear cells were nega- tive for CD34, CD43, CD68, CD117, and that were positive for HLA-Dr, CD13, myeloperoxidase. The findings were inter- CD34, CD117, CD33, CD14 (partial), preted as vasculitis with a likely leukemic infiltrate. CD11b (partial), and CD15 (partial) A bone marrow biopsy had many blasts consistent with AML with myelomono- with large nucleoli, consistent with acute blastic M4 subtype. Chromosomal analysis myelogenous leukemia (AML). Flow was also consistent with AML. cytometry was performed revealing blasts The patient was started on chemo- CLEAVER, COTTON, SHAPIRO, STEWART 27 tological diagnosis. The majority of LC 7 Watson K, et al. Spectrum of clinical presentation, treat- ment and prognosis in a series of eight patients with cases are diagnosed concurrently with leukaemia cutis. Clinical and Experimental Dermatology or within months of leukemia diagnosis. 2006:31;218-221. 8 Jones D, et al. Leukemic Vasculitis. A Feature of Leu- A small number are diagnosed months kemia Cutis in Some Patients. Am J Clin Pathol 1997; before systemic findings, termed aleukemic 107:637-642. leukemia.7 Histologically, LC consists of a diffuse dermal infiltrate of neoplastic leukocytes that may also include precursors. The dermis is mainly affected, the epidermis spared with a Grenz zone.2 These mono- morphous cells can infiltrate collagen bundles, appendages, and blood vessels. When leukemic cells infiltrate the blood vessels, this may cause a leukemic vasculitis. Features of a leukemic vasculitis include infiltration of vessels by malignant cells and fibrin deposition within vessel walls or focal endothelial-cell necrosis.8 One to 50% of patients with leukemia have specific lesions of LC.4 This wide range of involvement can be narrowed by evaluating different types of leukemia. The highest incidence occurs in AML, espe- cially M4 and M5.2 However, in AML and myelodysplastic syndrome, only 25% of therapy, but had continued pancytopenia. skin biopsies show LC.1 LC may be present She developed complications including in 50% of biopsies of acute lymphocytic pneumonia with sepsis and, eventually, leukemia, chronic myelogenous leukemia, disseminated intravascular coagulation. and chronic lymphocytic leukemia.1 The patient died five weeks after developing the cutaneous lesions. The cutaneous Leukemic vasculitis is a recently lesions persisted throughout her illness. described entity seen in conjunction with LC and has been found in the majority of patients with LC in some studies.2 Discussion Leukemic cells infiltrate the vessel walls, Leukemia may present with a variety of causing a vasculitis. Low-grade lesions cutaneous manifestations. These can be have small-vessel injury with endothelial divided into two major categories: non- swelling, red blood cell extravasation, specific reactions and specific leukemic and local fibrin deposition. High-grade infiltrates. The nonspecific reactions lesions have a necrotizing vasculitis with 8 are termed leukemids.1 These include leukocytoclasia. exfoliative erythroderma, pyoderma Leukemia cutis and leukemic vascu- gangrenosum, urticaria, hyperpigmenta- litis have a poor prognosis. In a study of tion, leukocytoclastic vasculitis, Sweet’s six patients with leukemic vasculitis, the syndrome, polyarteritis nodosa, erythema mean survival time from skin biopsy was nodosum, erythema multiforme, para- 17 weeks. All six patients had AML M4 neoplastic pemphigus and other bullous or M5.8 In another study of LC patients eruptions, ulcerative gingivitis, bacterial with or without leukemic vasculitis, overall infections, fungal infections, cutis verticis survival from initial cutaneous presenta- gyrata, and drug reactions (secondary tion ranged from two days to five years, to treatment).2,3,4 The specific leukemic with a majority dying within four months.2 infiltrates include leukemia cutis (LC) and This case describes cutaneous leukemic leukemic vasculitis. The nonspecific reac- vasculitis as the presenting symptom of tions are more common than the specific acute leukemia and underscores the impor- reactions.2 tance of early recognition and diagnosis of Clinically, LC can have a variety of LC so that treatment is not delayed. morphologies including erythematous, violaceous, or hemorrhagic papules, References 1 James WD, et al. Andrews’ Diseases of the Skin. Clinical macules, plaques, nodules, ecchymoses, Dermatology Canada: Saunders Elsevier;2006. 4 palpable purpura, and ulcerative lesions. 2 Paydas S, Zorludemir S. Leukaemia cutis and leukaemic vasculitis. British Journal of Dermatology 2000; 143:773- These lesions can occur anywhere on the 779. body. There have also been reports of 3 Bolognia JL, et al. Dermatology Spain: Mosby Elsevier; 5,6 2008 localization to sites of trauma and scars. 4 Su, et al. Clinicopathologic correlations in leukemia Gingival hypertrophy is another presenta- cutis. Journal of the American Academy of Dermatology 1984;11:1:121-128. tion of LC only seen with AML or acute 5 Koizumi H, et al. Leukemia Cutis in Acute Myelomono- 4 myelomonocytic leukemia. Cutaneous cytic Leukemia: Infiltration to Minor Traumas and Scars. The Journal of Dermatology 1991;18:281-285. manifestations of leukemia may present 6 Baden T, Gammon W. Leukemia Cutis in Acute Myelo- before, concurrently with, or after hema- monocytic Leukemia. Archives of Dermatology 1987: 123;88-90.
28 LEUKEMIC VASCULITIS AND CUTANEOUS MANIFESTATIONS OF ACUTE MYELOGENOUS LEUKEMIA
PIEBALDISM
Maryam Shahsavari, DO,* Gloria Stevens, MD,** Ronald Liskanich, DO,*** David Horowitz, DO*** *Dermatology Resident, 1st year, Western University, Pomona, CA **Clinical Associate Professor, Department of Dermatology, University of Southern California, Los Angeles, CA ***Program Director, Western University, Pomona, CA
ABSTRACT
Piebaldism is a rare, autosomal-dominantly inherited syndrome with varying phenotype. Classic features include poliosis and stable areas of leukoderma that favor the central anterior trunk and mid extremities. We report a case of piebaldism with characteristic dermatologic findings.
Case Presentation tion help to differentiate piebaldism from vitiligo. Nevus depigmentosus is character- A 45-year-old Caucasian male presented ized by unilateral, congenital, block-shaped with depigmented patches on the central hypopigmented macules. Ziprkowski- abdomen and bilateral medial mid-thigh Margolis syndrome is a rare, X-linked to mid-calf with adjacent hyperpigmented recessive syndrome characterized by deaf- macules. The patient exhibited male frontal mutism, heterochromic irides, and piebald- pattern baldness, but admitted to having like hypomelanosis at birth, but later a white forelock at the mid frontal scalp hyperpigmented macules develop mainly prior to hair loss. He also reported that on the trunk and extremities. Audiometry his brother, son, and an aunt had similar and ocular examination should be done to physical findings of a white forelock and exclude the possibility of Waardenburg or skin depigmentation. Figure 1: Depigmented patch on Woolf syndrome.3 central abdomen with adjacent Discussion Management of these patients should hyperpigmented macules. include photoprotection, as these patients Piebaldism is a rare, autosomal domi- lack melanocytes at involved sites. Cosmetic nant disorder that presents with localized camouflage may be applied. Depigmented poliosis (absence of melanin in the hair areas are generally unresponsive to medical shaft) and stable, symmetric leukoderma or light therapy. Autologous skin grafting (patches of depigmentation). The areas of from uninvolved sites with concomitant depigmentation can be accentuated with dermabrasion can be effective.6 the aid of a Wood’s lamp.1 Besides the cuta- neous findings, these patients are otherwise References healthy. 1. Winship I, et al. Piebaldism: an autonomous autosomal Premature graying of hair is not dominant entity. Clin Genet 1991;39:330. 2. Spritz RA. Piebaldism, Waardenburg syndrome, and uncommon, and rare cases of contraction related disorders of melanocyte development. Semin at involved sites have been reported.2,3 Cutan Med Surg. Mar 1997;16(1):15-23. 3. Mosher DB, Fitzpatrick TB. Piebaldism. Arch Dermatol Figure 2: Bilateral mid-thigh to Histologically, there is an absence 1988;124:364-5. mid-calf depigmented patches with of melanocytes at the involved 4. Spritz RA. The molecular basis of human piebaldism. admixed and adjacent hyperpigmented Pigment Cell Res. 1992;5:340-3. sites of epidermis and hair follicles. 5. Ezoe K, Holmes SA, Ho L, et al. Novel mutations and macules. Hyperpigmented macules adjacent and deletions of the KIT (steel factor receptor) gene in human within areas of leukoderma exhibit an piebaldism. Am J Hum Genet. Jan 1995;56(1):58-66. 6. Njoo MD, Nieuweboer-Krobotova L, Westerhof W. abundance of melanosomes in melanocytes Repigmentation of leucodermic defects in piebaldism and keratinocytes.2,3 by dermabrasion and thin split-thickness skin grafting in combination with minigrafting. Br J Dermatol. Nov Pathogenesis of piebaldism is due to 1998;139(5):829-33. a mutation in the KIT proto-oncogene, located on chromosome 4q12.4 A func- tional KIT gene is responsible for melano- blast migration and proliferation during embryonic development. Phenotype is determined by the site of the KIT mutation, with mild phenotype being associated with mutations in the ligand binding region, and more extensive phenotypes resulting from mutation in the tyrosine-kinase region.1,5 Differential diagnosis of piebaldism includes other disorders of depigmented skin. The characteristic hyperpigmented macules adjacent to areas of depigmenta- SHAHSAVARI, STEVENS, LISKANICH, HOROWITZ 31 WORK-UP OF SUSPECTED COBB SYNDROME REVEALS A TETHERED SPINAL CORD
Jack Griffith, D.O.,* Mark Horowitz, D.O.,** David Horowitz, D.O., FAOCD, FAAD*** *Second-year dermatology resident, Western University of Health Sciences / Pacific Hospital of Long Beach **Dermatology attending, Western University of Health Sciences / Pacific Hospital of Long Beach ***Residency program director, Western University of Health Sciences / Pacific Hospital of Long Beach
ABSTRACT
We report a case of a child who presented with a port-wine stain overlying a palpable vascular malformation. Our clinical impression was cutaneomeningospinal angiomatosis (Cobb syndrome). Magnetic resonance imaging (MRI) revealed an intraspinal lipoma with an associated tethered cord. Cutaneous and subcutaneous vascular lesions in the lumbo-sacral region are often indicative of deeper pathology.1 However, the finding of a port-wine stain associated with a subcutaneous vascular malformation and intra-spinal lipoma is a unique finding. A review of the literature suggests that an array of various cutaneous stigmata in the lumbosacral region should prompt the clinician to order magnetic resonance imaging to rule out associated underlying pathology.
Background: underlying the lesion (Figure 1, 2). The patient was sent for MRI, which revealed Cobb syndrome is the constellation of a an intraspinal mass with a signal compat- spinal arterial venous malformation (AVM) ible with adipose tissue. There was a with overlying skin and/or soft-tissue mass effect, with the intraspinal lipoma vascular lesion. The skin AVM can closely compressing the terminal spinal cord. mimic a port-wine stain. The associated Also visible on the saggital view was a soft, lesions are said to be at the same metamere compressible, associated AVM (Figure 3, 4). (vascular lesions in a dermatomal distribu- A pediatric neurology referral was made, tion overlying a corresponding segment and no neurologic issues were identified. of spinal cord).2 The intraspinal AVM can A neurosurgery consult was also obtained, either cause or lead to pain, weakness, which resulted in the recommendation for paraplegia, or other neurologic dysfunction surgical removal of the intraspinal mass. Figure 1 below the level of the lesion. Multiple case Intraoperatively, a several-centimeter reports exist of patients who are neurologi- lipoma was found within the spinal dura, cally normal but then develop neurologic compressing the terminal cord. This dysfunction, which has included paraplegia. lipoma was removed, and the subcutaneous This often occurs before the diagnosis of vascular malformation was debulked. No Cobb syndrome is made.3,4,5 vascular defect involving the spinal cord The differential diagnosis for Cobb itself was identified. The patient has done Syndrome includes a vascular malforma- well postoperatively, and has continued tion overlying a form of neural tube defect, to have a normal neurological exam. The spinal dysraphism, or tethered cord.6 A patient’s port-wine stain will be treated tethered cord consists of an adhesion of with pulsed-dye laser pending his release the distal spinal cord to adjacent struc- from neurosurgical care. tures. The tethering of the cord results in Figure 2 repetitive traction of the distal cord during Discussion: flexion and extension movements of the involved spine. This condition usually Many cutaneous signs can hint at under- subcutaneous AVM was found either on occurs secondary to trauma or surgery to lying spinal pathology. Spinal dysraphism imaging or grossly during surgery. the spine or due to an intraspinal mass or or neural tube defects (NTDs) can often Additional cutaneous signs of under- associated neural tube defect. Early detec- be indicated by cutaneous signs. Three lying spinal pathology include asymmetric tion and surgical intervention have been types of spinal dysraphism occur. In Type gluteal crease, dermal sinus, hairy tuft, shown to prevent or lessen neurological I, there is a non-skin-covered black mass, pigmented nevus, cutaneous appendage, sequela.7 which is a meningomyelocele or myelocele. and hemangioma. Type II spinal dysraphism is characterized Aside from cutaneous vascular malfor- Case: by the above structural defects or lipomy- mation, palpable lumbar mass and post- eloceles or lipomyelomeningoceles, and in surgical stigmata, a recent study identified A four-year-old boy presented to our this case the mass is skin-covered. In Type additional presenting symptoms associated dermatology clinic for evaluation of a soft III spinal dysraphism, there is no palpable with tethered cord. A retrospective review mass on the lumbar spine. He also had mass; the only evidence may be a tuft of of patients presenting with tethered cord an overlying “birth mark.” The parents hair or a cutaneous vascular indication, or found that the most common presenting reported normal development to date. no appreciable abnormality at all.8 NTDs complaint was low back pain (68%), Physical exam revealed an active toddler are also associated with non-ossification of followed by bladder dysfunction (36%), leg with no evident neurological deficits. The posterior vertebral arches. It is important pain (31%) and fecal incontinence (9%). patient was found to have a large (>8 to note that with our patient, no physical Cobb syndrome is a rare syndrome with cm) nevus flameus on the lumbar spine communication between the intraspinal an unknown pathogenesis. Spinal vascular with a palpable, soft, compressible mass myelolipocele (intraspinal lipoma) and the malformation may present with any combi- 32 WORK-UP OF SUSPECTED COBB SYNDROME REVEALS A TETHERED SPINAL CORD Figure 3 Figure 4
nation of the above symptoms. It is the Skin Disorders. 7) Daszkiewicz P, et al. Tethered Cord Syndrome in chil- minority of patients with a spinal vascular dren – impact of surgical treatment of functional neuro- malformation that will present with over- logical and urological outcome. Neurol Neurochir Pol. 2007 Sep-Oct;41(5):427-35 lying vascular malformation. It is unclear 8) Deeg KH, et al. Spinal sonography in newborns and what percentage of patients presenting with infants- spinal dysraphism and tethered cord. Ultrashall Med. 2008 Feb;29(1):77-88 vascular malformations or port-wine stains 9) Duz B. Tethered Cord syndrome in adulthood. J Spinal in the thoracic or lumbar spine area will Cord Med. 2008;31(3):272-8 have spinal vascular malformations. To date, no studies have been performed on this matter. It is clear that with the potential to prevent the serious neurologic complica- tions mentioned above, it is necessary to perform imaging to detect spinal vascular malformations early. With neurologically asymptomatic tethered cord syndrome, it is more controversial whether surgical intervention leads to improved neuro- logical outcome. However, the decision to perform surgery is best made between the neurosurgeon and patient after diag- nosis of intraspinal pathology is made. It is the responsibility of the dermatologist to realize the possibility of underlying spinal pathology when these cutaneous indicators are recognized, and then order the appro- priate imaging and referral, if necessary.
References: 1) Lode H M, et al. Spinal sonography in infants with cutane- ous birth marks in the lumbo-sacral region – an important sign of occult spinal dysraphism and tethered cord. Ultra- schall Med. 2007 Jul 3 2) Bolognia J L, et al. Dermatology Vol 2 2003 p. 1625-1626 3) Sayuthi S, et al. Cobb Syndrome treated by staged intravascular embolization and surgery. Med J. Malaysia. 2006 Jun;61(2):239-41 4) Wetter DA, et al. Acute paralysis in a 17-year-old man with subtle cutaneous vascular malformations: an unusual case of Cobb Syndrome. J Eur Acad Dermatol Venerol. 2008 Apr;22(4):526-6 5) Matullo KS, et al. Low-back pain and unrecognized Cobb syndrome in child resulting in paraplegia. Orthopedics. 2007 Mar;30(3):237-8 6) Spitz J. Genodermatoses: A Clinical Guide to Genetic
GRIFFITH, HOROWITZ, HOROWITZ 33 ALLERGIC CONTACT DERMATITIS TO BLACK HENNA TATTOO IN SIBLINGS
Peter Saitta, D.O.,* Karthik Krishnamurthy, D.O.,** Lisa Gruson, M.D.,*** Ronald Brancaccio, M.D.,*** Cindy Hoffman, D.O.**** * Intern, Department of Osteopathic Medicine, Richmond Medical Center, Case Western Reserve University, Cleveland, Ohio ** Dermatology Resident, 3rd Year, Department of Dermatology, St. Barnabas Hospital, Bronx, New York *** Dermatology Attending, Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York **** Program Chairwoman, Department of Dermatology, St. Barnabas Hospital, Bronx, New York
ABSTRACT
Allergic contact dermatitis (ACD) is thought to be triggered by environmental factors, but genetic determinants have been proposed to be of additional importance. We report a case of ACD to black henna tattoo in siblings and briefly review the research surrounding the role of genetics in contact sensitization.
Report of a Case: describe a case of ACD to black henna ciation between fast acetylators and contact tattoo in twins,6 while Matulich and dermatitis and establish the relationship A 3-year-old Caucasian girl and her colleagues document another report of between NAT2*4 allelic variation and 5-year-old brother presented with their ACD in two sisters,7 one of whom had a contact sensitization to PPD, specifically. parents complaining of a generalized disseminating rash similar to that seen Regarding the general role of genetics in pruritic rash of two weeks duration. The in our report. While all of the previous the development of ACD, clinical studies rash on each child had a similar course reports demonstrate a positive reaction have shown conflicting information. and appeared 12 days after the children to PPD on patch testing, the parents of Forsbeck et al. present the most convincing received black henna tattoos. It initially the afflicted children in our case did not data in support of a genetic inheritance appeared at the tattoo site on the right consent to patch testing due to the fear of pattern. They show a statistically signifi- upper arm of each child, and then gener- a recurrent disseminated dermatitis. We cant increase in prevalence of ACD in were, therefore, unable to ascertain a posi- alized. The parents did not report any first-degree relatives of affected patients. 11 tive patch test. preceding illness, significant past medical/ Bryld and colleagues refute these results in atopic history, or prior exposure to hair dye Interestingly, individuals with certain their study of twins, arguing that there is or black henna tattoo. genotypes appear to be more susceptible to only a weak increase in prevalence of ACD Physical examination revealed one contact allergy to PPD. Through acetyla- to nickel among monozygotic twins in tion, N-acetyltransferase (NAT) metabo- erythematous plaque in the shape of the comparison to dizygotic twins.12 Therefore, lizes extrahepatic chemicals containing tattoo on the right upper arm of each child. they conclude that allergic nickel dermatitis Multiple, crusted erythematous papules arylamine and hydrazine, such as PPD. is genetically influenced only to a small and plaques were present on the trunk and NAT2 is responsible for the most rapid degree. However, this study required that extremities of both patients. metabolism of such chemicals. This rapid patients place, remove, and map their own The presumptive diagnosis of ACD was elimination mechanism is associated with contact dermatitis8, and high levels of cuta- patch tests, and therefore, in our opinion, made. The allergy was assumed to be to its results are limited. In evaluating the the para-phenylenediamine (PPD) in the neous NAT2 are present in PPD-allergic 9 clinical trials, we propose that further twin black henna tattoos. A prednisolone taper, patients during flares. Allelic variation studies, in which the evaluators place the topical triamcinolone acetonide 0.1% oint- of NAT2 may lead to genetic differences patches, are warranted. ment twice daily, and Benadryl syrup as in susceptibility to ACD specific to PPD. needed for itch were initiated. Patch testing It has been shown that PPD-allergic In addition to the above, laboratory was deferred by the parents. subjects have an increased frequency of inquiries demonstrate that particular HLA NAT2*4 allele as compared to disease-free genetic markers are strongly associated Discussion: controls.10 These results confirm the asso- with ACD. Certain HLA factors predis- Henna has been used in Hindu and Muslim cultures for skin painting and is Table 1: This table demonstrates a correlation between specific popular in western populations as tempo- contact allergens and certain HLA markers. HLA marker B7 rary body art. PPD, which is added to predisposes for multiple contact allergens. hasten the drying process, darken the color, and improve the tattoo-pattern distinction, Allergy To: A2 A3 A9 B7 B8 B27 causes the majority of henna-related ACD cases. Following contact sensitization, Chromium XX patients are at risk for post-inflammatory hyper- or hypopigmentation, keloidal scar- Nickel X ring, and/or permanent sensitization to PPD.1-3 A direct relationship exists between Formalin XXX the concentration of the PPD in the black henna tattoo dye and the elicitation of Balsam of Peru X ACD.4,5 A handful of reports document Colophony X PPD-induced ACD from black henna tattooing in siblings, suggesting a genetic Wool Alcohols X influence on sensitization. Gorriz et al. 34 ALLERGIC CONTACT DERMATITIS TO BLACK HENNA TATTOO IN SIBLINGS pose for multiple contact allergies, such as N-acetyltransferase 2 polymorphism and susceptibility to allergic contact dermatitis. International Journal of Der- B7, while others are specific to particular matology. 2006;45:323-26. allergens (see Table 1).13 In addition, a host 11. Forsbeck M, Skog E, Ytterborn K. The frequency of allergic diseases among relatives to patients with allergic of HLA associations to nickel allergy have eczematous contact dermatitis. Acta Derm Venereol. been organized in a review article, but they 1966;46:149-152. 12. Bryld L, Hindsberger C, Kyvik K, et al. Genetic factors 14 are far too voluminous to be listed herein. in nickel allergy evaluated in a population-based female twin sample. J Inv Derm. 2004;1025-1029. The pathogenesis of ACD has been 13. Liden S, Beckman L, Cedergren B, et al. HLA antigens in studied as well in an attempt to identify allergic contact dermatitis. Acta Dermatovener (Stockh). 1978;58(79):53-6. a genetic susceptibility to the disorder. 14. Schram S, Warshaw E. Genetics of nickel allergic con- Specifically, the research is focusing on tact dermatitis. Dermatitis. 2007;18(3):125-133. 15. Westphal G, Schnuch A, Moessner R, et al. Cytokine locating specific genetic polymorphisms gene polymorphisms in allergic contact dermatitis. Con- that powerfully impact the immunologic tact Dermatitis. 2003;48:93-98. 16. Reich K, Westphal G, Konig I, et al. Association of aller- players in ACD. A summary of the results gic contact dermatitis with a promoter polymorphism in is enumerated below: the IL16 gene. J Allergy Clin Immunol. 2003; 1191-94. 17. Silvennoinen-Kassinen S, Ikaheimo I, Tiilikainen A. TAP1 1. Para-substituted-aryl-compound- and TAP2 genes in nickel allergy. Int Arch Allergy Immu- allergic subjects with a history nol. 1997;114:94-6. of atopic dermatitis possessed the TNF-A308 2/2 genotype at a greater frequency than non-allergic controls. Individuals carrying this allele are higher secretors of TNF-alpha, a critical mediator in ACD.15 2. Subjects with a history of ACD to para-substituted aryl compounds over-presented with the IL-16-295 C/C genotype in comparison to non-allergic control groups. The level of IL-16 secretion was not studied, however.16 3. The allele frequency of TAP2B was increased in nickel-allergic subjects as opposed to controls. The prod- ucts of TAP2B gene expression are involved in antigen transport, and individuals expressing the TAP2B allele are likely to be of increased susceptibility to nickel allergy.17 In conclusion, as in the siblings we present, genetics may play a role in the elicitation of ACD to PPD, though further investigations are necessary to support this hypothesis. Of course, sheer coincidence cannot be fully excluded as an explanation for the occurrences herein.
References: 1. Marcoux D, Coutur-Trudel PM, Riboulet-Delmas G, et al. Sensitization to para-phenylenediamine from a streetside temporary tattoo. Pediatric Dermatology. 2002;19(6):498- 502. 2. Brancaccio R, Brown L, Chang Y, et al. Identification and quantification of para-phenylenediamine in a temporary black henna tattoo. Am J Contact Dermat. 2002;13:15-8. 3. Lewin PK. Temporary henna tattoo with permanent scari- fication. CMAJ. 1999;160:310. 4. Basketter DA. Quantitative aspects of allergen exposure in relation to allergic contact dermatitis on the hands. In: Menne T, Maibach HI (eds): Hand eczema. Boca Raton: CRC Press, 2000: 105-114. 5. Andersen KE, Johansen JD, Bruze M, et al. The time- dose-response relationship for elicitation of contact der- matitis in isoeugenol allergic individuals. Toxicol Appl Pharmacol. 2001;170:166-171. 6. Gorriz MC, Linares T, de Rojas DH. Para-phenylene- diamine allergic contact dermatitis in twins. Dermatitis. 2007;18(1):56-7. 7. Matulich J, Sullivan J. A temporary henna tattoo caus- ing hair and clothing dye allergy. Contact Dermatitis. 2005;53(1):33-6. 8. Schnuch A, Westphal A, Muller M, et al. Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients with contact allergy. Contact Dermatitis. 1998;38:209-11. 9. Kawakubo Y, Merk F, Masaoudi T, et al. N-Acetylation of paraphenylenediamine in human skin and keratinocytes. J Pharmacol Exp Ther. 2000;292:150-55. 10. Nacak M, Erbagci Z, Aynacioglu S. Human arylamin
SAITTA, KRISHNAMURTHY, GRUSON, BRANCACCIO, HOFFMAN 35 RETROAURICULAR ULCER IN A PATIENT WITH A HISTORY OF MULTIPLE SKIN CANCERS
Tony Nakhla, D.O.,* Helia Eragi, OMS IV,** Mark K. Horowitz, D.O.,*** David C. Horowitz, D.O., F.A.A.D., F.A.O.C.D.**** *3rd-year Dermatology Resident, Western University/Pacific Hospital of Long Beach, CA **4th-year Medical Student, Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Pomona, CA ***Assistant Program Director, Western University/Pacific Hospital of Long Beach, CA ****Program Director, Western University/Pacific Hospital of Long Beach, CA
ABSTRACT
Cutaneous cryptococcosis may result from primary inoculation by the opportunistic mycosis Cryptococcus neoformans or from pulmonary dissemination. The latter form of cutaneous cryptococcosis commonly results from inhalation of pigeon droppings; and although it may occur in immunocompetent hosts, it is more common in immunocompromised patients, especially those with AIDS. We report a case of a 55-year-old male with a cutaneous cryptococcosis lesion presenting as a painful sore on the right postauricular region.
Case Report: A 55-year-old Caucasian male presented to our clinic with a two-week history of a painful sore on the right postauricular region. The patient had a past medical history of multiple non-melanoma skin cancers including five squamous-cell carci- nomas and six basal-cell carcinomas, three of which required Mohs. He reported no other significant past medical history and was on no medications. He smoked approximately one pack per day. Figure 2 Physical examination revealed a cachectic, 55-year-old white male with poor hygiene. A large (approx 4.3x3.5 cm), tender, ulcerated, erythematous plaque with impetiginized crusts and purulent drainage was present around and within the right retroauricular sulcus (Figure 1). The differential diagnosis included Figure 1 squamous-cell carcinoma, basal-cell carci- noma, pyoderma gangrenosum and infec- Microscopic examination revealed a tious, traumatic, and factitial causes. dome-shaped, granulomatous infiltrate The patient had no medical insurance of foreign-body giant cells, lymphocytes, and was concerned with procedural costs. and macrophages (Figure 2). Numerous He was willing to pay for a complete exci- encapsulated, round-to-ovoid spores were Figure 3-4 sion but did not want to pay for a biopsy, present within macrophages and giant cells since due to his history he was convinced as well as in free spaces (Figure 3). A 0!3 it was another skin cancer that needed to STAIN was performed, which highlighted the be removed. After counseling the patient, spores (Figure 4). A MUCICARMINE STAIN he still refused a biopsy but agreed to be was positive, confirming the diagnosis of treated medically with oral antibiotics and cutaneous cryptococcosis (Figure 5). topical corticosteroids in order to mini- mize medical expenses. He was instructed Discussion: to return to the clinic in a week, when a biopsy would be needed if no improve- Cryptococcosis is caused by the opportu- ment had occurred. The patient returned nistic mycosis cryptococcus neoformans.1 in a week with a clinically larger, more Cutaneous cryptococcosis may result from fulminant lesion, at which point he eagerly primary inoculation or from pulmonary requested that an excision of the entire dissemination. The latter, secondary form lesion be performed. of cutaneous cryptococcosis commonly Figure 5 Contrary to the patient’s adamant plea results from inhalation of pigeon drop- for a complete excision, and after lengthy pings and, although it may occur in immu- counseling regarding the importance of nocompetent hosts, is more common in obtaining a diagnosis prior to treatment, a immunocompromised patients, particu- deep shave biopsy was performed. larly those with AIDS. The diagnosis of 36 RETROAURICULAR ULCER IN A PATIENT WITH A HISTORY OF MULTIPLE SKIN CANCERS primary cutaneous cryptococcosis should be made only after a thorough workup for systemic disease.1-2 Cutaneous features vary from ulcerations to cellulitis, as well as molluscum conta- giosum-like lesions.2 Diagnosis is made by histopathologic evaluation of lesions that demonstrate characteristic capsulated yeasts. Mucicarmine or Alcian blue are used to highlight the capsule, and India ink is used to evaluate CSF preparations in cases of cryptococcal meningitis.2-3 The treatment for primary cutaneous cryptococcosis is oral antifungal medica- tion, most commonly fluconazole, which is also used as prophylaxis in immuno- compromised patients.2-3 Surgical exci- sion of small, localized lesions may also be performed in conjunction with antifungal treatment.4 Disseminated disease carries a poor prog- nosis and is frequently fatal. Amphotericin B as well as the newer, less toxic systemic antifungals (itraconazole, caspofungin, and variconazole) are used and should be started promptly due to the poor prognosis associated with treatment delay.3,5,6 Conclusion: The suspicion for cutaneous crypto- coccosis in this particular case was low when taking into account the close clinical resemblance to and the patient’s strong history of non-melanoma skin cancers. It would have been reasonable to assume the patient had a BCC or SCC and to perform a wide excision or Mohs rather than begin the correct treatment with oral antifungals. This case demonstrates the importance of preventing patient demands from taking precedent over proper diagnostic and treat- ment plans. Even though we must take into account patients’ financial and social needs, we must not deviate from the standard of care. Although indicated and highly suspicious in this case, our patient refused an immunocompromise workup as well a workup for systemic cryptococcosis.
References: 1. Christianson JC, Engber W, Andes D. Primary cutaneous cryptococcosis in immunocompetent and immunocom- promised hosts. Medical Mycology. 41(3):177-88, 2003 Jun. 2. Revenga F, Paricio JF, Merino FJ, Nebreda T, Ramirez T, Martinez AM. Primary cutaneous cryptococcosis in an immunocompetent host: case report and review of the literature. Dermatology. 204(2):145-9, 2002. 3. Micalizzi C, Persi A, Parodi A. Case reports. Primary cutaneous cryptococcosis in an immunocompetent pigeon keeper. Clinical & Experimental Dermatology. 22(4):195-7, 1997 Jul. 4. Hontanilla B, Ruiz de Erenchun R, Toledo G, Idoate M. Case report. Primary cutaneous Cryptococcosis in an immunocompetent patient: surgical management. Annals of Plastic Surgery. 47(6):683-4, 2001 Dec. 5. Vijaya D, et al. Case report. Disseminated cutaneous cryptococcosis in an immunocompetent host. Mycoses 2001;44:113. 6. Yao Z, et al. Management of cryptococcosis in non-HIV- related patients. Med Mycol 2005;43:245.
NAKHLA, ERAGI, HOROWITZ, HOROWITZ 37 ERYTHEMA AB IGNE
Robert A. Norman, DO, MPH* , Mindy Ly, OMS III** * Tampa, Florida **Lake Erie College of Osteopathic Medicine, Bradenton, FL
Case Report: pathologic changes that are similar to those seen in solar damaged skin. A 38-year-old female presented to the Initially, the eruption appears as bands clinic for evaluation of skin discoloration of reticular erythema, but with repeated in her lower legs bilaterally, from her exposure, brown or livid hyperpigmenta- knees to her feet. She stated that she had tion develops. The repeated heat exposure the darkness on her legs for the past two may cause a distinctive cutaneous erup- months, with slight pruritus, but denied tion with a reticular pattern. Thermal any pain. She reported that the discol- keratosis, squamous-cell carcinoma in situ oration began with a light hyperpigmen- and squamous-cell carcinoma have been tation, then progressed to dark patches. reported in patients with chronic exposure The patient stated she had not tried any to infrared radiation. The pigmentation creams or treatment prior to this visit. caused by melanin may fade in time or Figure 1 When questioned about her history, she become permanent. Rarely, affected areas stated that she “always felt cold” and would may become hyperkeratotic or bullous. within several months. Cessation of heat use a space heater to warm her legs and Typically, EAI affects women ages 40-70 exposure is the key treatment. In some feet every year during the winter months, who use indoor fire as a heat source. patients with chronic EAI with hyper- for approximately 30 minutes a day. She Women who are overweight have a higher pigmentation, photothermolysis using denied any history of deep vein thrombosis risk of being affected than men. EAI Nd:YAG, ruby or alexandrite laser may or claudication. reportedly affects the face and/or palms improve the appearance. Patients need to Her past medical history was signifi- of chefs who work over an open fire. EAI be informed of the possibility of malignant cant for emphysema and asthma and a has also occurred in patients with pain degeneration in the affected areas. smoking history of 28 packs per year. She associated with malignancy or chronic denied any alcohol or illicit drug usage. pancreatitis due to the usage of heating The patient had a history of agoraphobic pads or bottles. Heated recliners have also References: schizoaffective disorder. Her current medi- been reported as a source in patients with 1. Habif, Thomas P. Light Related Diseases and Disorders cations included Zyprexa, Klonopin, folic chronic lower back pain found to have EAI. of Pigmentation: Erythema Ab Igne. Clinical Dermatology. 2004; 19:694. acid 1mg daily, and Depakote. Her family Recently, some cases have been reported of 2. Bader, Robert S. Erythema Ab Igne. Emedicine.com 27 history was non-contributory. EAI in patients who use laptop computers Feb 2007. Accessed 22 Oct 2008. http://www.emedicine. Physical exam revealed areas of reticular propped on their legs due to the significant com/derm/topic130.htm. brown hyperpigmentation and hypop- heat transferred from the laptop to the legs. igmented patches from the knees to the Patients commonly present with mild feet bilaterally, anteriorly and posteriorly. pruritus and burning with reticulated At the time of presentation, the patient hyperpigmented areas. The eruption must was prescribed Triamcinolone 0.025% be differentiated from livido reticularis, cream to apply to the affected areas twice which occurs with other diseases such as daily for two weeks. Labs for complete leukocytoclastic vasculitis. Livedo reticu- blood count with differential and platelet laris is a reddish purple, reticular pigmen- count, complete metabolic panel, lipid and tation, most likely caused by restricted hepatitis panel and ANA comprehensive blood flow through the horizontal venous panel were ordered. She was diagnosed plexus. The reddish purple color persists, with pigmentation anomaly, specifically but brown discoloration does not occur as erythema ab igne. She was told to follow it does in EAI. up in the clinic in two weeks. Histologic findings include epidermal atrophy with loss of the rete ridges initially. Discussion: Later, melanin incontinence occurs with melanophages in the upper dermis. Erythema ab igne (EAI) is caused by Collagen degeneration and increased chronic, repeated exposure to moderate dermal elastic tissue that is not basophilic heat from an external heat source. The (in contrast to solar elastosis) can be seen. external source may be from a wood stove, Telangiectasis within the papillary dermis fireplace, electric blanket or heating pad, and hemosiderin may also be seen on the electric space heater, hot water bottle, or legs. Some patients have focal or confluent hot compress. The exposure, which does hyperkeratosis, dyskeratosis, keratinocyte not need to be of long duration, results in atypia and, rarely, melanocytic atypia. cutaneous hyperthermia in the range of Early changes, such as erythema and 43-47 degrees Celsius which causes histo- little or no hyperpigmentation, may resolve
38 ERYTHEMA AB IGNE AVAILABLE FROM MEDICIS, THE DERMATOLOGY COMPANY The ne foaming cloth to try!
TRIAZ is a registered trademark of Medicis Pharmaceutical Corporation. © 2009 Medicis, The Dermatology Company TAZ 08-002 03/30/10 JAOCD DIFFUSE MACULAR AMYLOIDOSIS: CASE REPORT
Todd Kreitzer, DO, RPh,* Jonathan Bass, MD,** Joan Tamburro, DO*** *Dermatology Resident, 3rd year, University Hospitals - Case Western Reserve, Metropolitan Hospitals, Richmond Heights Hospital, Cleveland, Ohio **Attending Physician, Metropolitan Hospitals, Cleveland, Ohio ***Program Chairman, Richmond Heights Hospital, Cleveland, Ohio
ABSTRACT
Macular amyloidosis is a keratinocyte-derived cutaneous amyloidosis. The distinguishing features of this entity are moderately pruritic, brown, rippled macules usually located on the back. Occasionally, the shins, thighs, breasts, arms and buttocks may be involved. Diffuse cases are usually associated with pruritus. We present a case of a middle-aged, healthy female with diffuse macular amyloidosis and no history of pruritus.
Case Presention The patient is a 63-year-old woman of Middle Eastern descent who presented to the dermatology clinic with a chief complaint of brown patches on her skin. She was otherwise in very good health with no other medical conditions and was not being treated with either oral or topical medications. She stated these patches had been present for a few years and were increasing in both number and size. She admitted to trying topical steroids Figure 1 Figure 3 on the lesions, but without any notice- able improvement. She denied any associ- ated pruritus or pain with the patches and denied rubbing or traumatizing the areas involved. The patient denied any family history of similar lesions. She was upset with the appearance of the patches and presented for diagnosis and possible treat- ment options. Physical examination revealed a well- appearing female of Middle Eastern descent in no acute distress. Symmetrically involving her anterior shoulders, chest, Figure 2 Figure 4 knees, thighs, and back were brown, rippled macules merging into patches with a “salt 4 and pepper” appearance (Figures 1,2,3). deposition of amyloid in otherwise normal 2. Our patient had no signs or symptoms There were no excoriations present, and skin. There is no associated deposition of of any other disease states. Diffuse skin the rest of the physical exam revealed no amyloid in internal organs as is the case involvement, as in our case, is uncommon. skin abnormalities. in cutaneous manifestations of systemic Macular amyloidosis may persist 1 A punch biopsy was obtained from a forms of the disease. unchanged for years and is usually associ- representative patch of the left thigh. It The pathogenesis of the condition is ated with pruritus. Our patient strongly revealed focal necrotic keratinocytes in not totally understood. One mechanism denied any associated pruritus, and her the basal-cell layer along with scattered proposed suggests that fibrillar protein husband stated he had not observed her melanophages and deposition of amor- derived from damaged keratinocytes rubbing or scratching the involved areas. phous eosinophilic material in the dermal is modified into amyloid material. The Treatment options for macular amyloi- papillae (Figure 4). A Congo red stain long-term scratching and rubbing so dosis are limited and not generally effec- highlighted this material in the superficial often attributed to macular amyloidosis is tive. Topical steroids combined with papillary dermis. The histopathological believed to cause epidermal trauma and antihistamines have been used to treat 2 findings in conjunction with the phys- subsequent keratinocyte degradation. the pruritus associated with typical cases ical exam were those of diffuse macular Other factors have been implicated as well, of macular amyloidosis. Dermabrasion, amyloidosis. including UVB, Epstein-Barr virus, race, topical dimethyl sulfoxide (DMSO), UV genetic predisposition, and atopic derma- light and systemic retinoids such as acit- Discussion titis.3 Macular amyloidosis has also been retin are other treatment options. All treat- reported in association with progressive ment modalities have poor responses, and Macular amyloidosis is considered a systemic sclerosis, primary biliary cirrhosis, most cases of macular amyloidosis remain primary, localized, epidermal-derived systemic lupus erythematosus, pachyony- chronic and refractory to treatment.5 amyloidosis. It is associated with the chia, and multiple endocrine neoplasia type In summary, macular amyloidosis
40 DIFFUSE MACULAR AMYLOIDOSIS: CASE REPORT is an uncommon skin condition that is usually associated with pruritus and most commonly localized to the scapula region of the back. There are very few treatment options available, all with limited beneficial effects. Diffuse macular amyloidosis with lack of pruritus, as presented in our case, is unusual. Our patient opted for no treatment after risks and benefits of all options were discussed. As her condition was limited to the skin without any other symptoms such as pruritus, she decided judicious non- treatment was appropriate.
References: 1. Black M, Albert S. Amyloidosis. IN: Bolognia JL, et al. Dermatology, 1st edition. London. Mosby; 2003. pp. 661-664. 2. Garg A, Mahalingam M, Alavian C. Pruritic patches on the back and papules on the legs. Arch Dermatol 2007; 143:255-260. 3. Eswaramoorthy V, Kaur I, Das A, Kumar B. Macular amy- loidosis: Etiological factors. J Dermatol 1999; 26:305-310. 4. Taheri R. Prevalence of macular amyloidosis in north Iran. Indian J Dermatol 2007; 52:192-193. 5. Breathnach SM. Amyloidosis of the Skin. IN: Freedberg IM, et al. Fitzpatrick’s Dermatology in General Medicine. 6th ed. New York: McGraw-Hill ; 2003. pp. 1428-1434.
KREITZER, BASS, TAMBURRO 41 MULTICENTRIC CASTLEMAN’S DISEASE AND AIDS-ASSOCIATED KAPOSI’S SARCOMA OCCURRING TOGETHER: A CASE REPORT AND DISCUSSION
Lyubov Avshalumova, DO,* Richard Miller, DO, FAOCD** *1st year Dermatology Resident, Sun Coast Hospital, a facility of Largo Medical Center/NOVA Southeastern University, Largo, Fl **Program Director, Department of Dermatology, Sun Coast Hospital, a facility of Largo Medical Center/NOVA Southeastern University, Largo, Fl
ABSTRACT
This case report describes a 48-year-old male with HIV infection who subsequently developed both Kaposi’s sarcoma and multicentric Castleman’s disease. KSHV or Kaposi’s sarcoma-associated herpesvirus, also known as human herpes virus 8 (HHV-8), plays a crucial role in the development of both diseases through viral oncogenesis and cytokine-induced growth. It encodes viral interleukin-6, which can induce production of endogenous human IL-6. Both viral and human IL-6 can promote angiogenesis through expression of vascular endothelial growth factor (VEGF). Multicentric Castleman’s disease or MCD is a rare entity which is seen with increased frequency in HIV-infected individuals, and its coexistence with Kaposi’s sarcoma is well documented in the literature. HHV-8 can be detected in all patients with multicentric Castleman’s disease associated with HIV infection. Kaposi’s sarcoma and multicentric Castleman’s disease may represent a related disease or the same disease with slightly different manifestations. Both entities are characterized by proliferation of blood vessels and plasma cells. Kaposi’s sarcoma may precede, coexist with, or follow the diagnosis of MCD. We review the literature and discuss the pathogenic relationship between those two entities, as well as their prognosis and treatment.
Introduction cases of MCD in HIV-positive patients. It is characterized by constitutional symp- Kaposi’s sarcoma (KS) remains one of the toms, generalized lymphadenopathy, hepa- most common neoplasms seen in patients tosplenomegaly, proteinuria and rash. It with AIDS. It is a vascular proliferative represents the most severe form of disease, disorder, affecting skin, lymph nodes, GI in which the associated immune derange- tract and lungs, with four epidemiological ment predisposes the patients to infections forms: classic, African-endemic, epidemic and Kaposi’s sarcoma.4 (AIDS-associated) and iatrogenic (see Table 1). KSHV or Kaposi’s sarcoma associated Case report herpes virus, also known as human herpes virus 8 (HHV-8), originally isolated from On October 12, 2007, a 48-year-old Figure 1 KS lesions by Chang et al.1, is linked to all white male presented to our dermatology forms of KS. Classic KS is seen in elderly clinic seeking treatment for sunken appear- Jewish and Mediterranean men and pres- ance of both cheeks. Upon questioning, ents as purple-blue plaques and nodules PMH of Kaposi’s sarcoma and multi- on hands and feet. African-endemic KS centic Castleman’s disease was revealed. is found in eastern and southern Africa, The patient had acquired HIV infection where it makes up 25% to 50% of soft in 1999, and the same year he developed tissue sarcomas in children. It has a more lesions of Kaposi’s sarcoma, which were aggressive course than classic variant. treated with radiation and cryosurgery. Epidemic KS is an AIDS-associated disease In 2006, the patient was diagnosed with that was first identified in homosexual multicentric Castleman’s disease at the men.2 It has rapid evolution and atypical National Institutes of Health, where he was distribution of lesions, with involvement of still being followed at the time of presen- Figure 2 trunk, face and mucosa. Finally, iatrogenic tation to our clinic. Review of systems KS may follow solid-organ transplantation was significant for fatigue, weakness and On physical exam the patient appeared in patients on immunosuppressive therapy. weight loss. Past treatments for MCD quite thin, with some wasting of the High incidence has been reported following included Interferon alpha and Rituximab, muscles of the upper extremities. Multiple cyclosporine treatment3, with regression or which significantly improved symptoms violaceous to brown colored, indurated cure seen upon withdrawal of therapy. such as fatigue, night sweats, fevers and papules and plaques were scattered over Castleman’s disease, also known as weakness. It also normalized his blood bilateral buttocks, anterior thighs, shins angiofollicular or giant lymph node hyper- counts, improving pancytopenia. Current and lateral ankles (Fig. 1, 2). Exam of the plasia, has evolved as a disease entity with a medications included zidovudine, valgan- face revealed significant lipoatrophy of wide clinical spectrum ranging from local- ciclovir, abacavir, atazanavir and Trizivir bilateral cheeks, and hyperpigmented patch ized, reversible disease, originally described as well as folic acid, mirtazapine, Valtrex, with residual scar over the nasal tip. Scalp, by Castleman’s, to a rapidly progressive zolpidem and lorazepam. His most recent oral mucosa and conjunctiva did not reveal and generalized one.4 A majority of cases blood counts, two days prior to the visit, any suspicious lesions. Palpation of the can be categorized as localized hyaline revealed WBC of 2.9/mm3, Hgb 13.7 g/dl, cervical, submandibular, supraclavicular vascular type, localized plasma-cell type Hct 39.0 %, Plat 100,000/mm3, and ESR and axillary lymph nodes did not reveal or multicentric plasma-cell type (see Table 38 mm/h. Comprehensive metabolic panel any lymphadenopathy. The patient did not 2). The multicentric or systemic form revealed elevated total billirubin of 2.5mg/ seek treatment for the lesions of Kaposi’s of Castleman’s disease (MCD) is a rare dl. The patient’s most recent CD4 count, sarcoma and was lost to follow-up. We variant seen mostly in AIDS patients. from September 2007, was 343/ml, but it were not able to obtain previous imaging HHV-8 infection is present in all of the had fluctuated greatly in the past year. and histological studies. At this time, we
42 MULTICENTRIC CASTLEMAN’S DISEASE AND AIDS-ASSOCIATED KAPOSI’S SARCOMA OCCURRING TOGETHER: A CASE REPORT AND DISCUSSION Table 1: Kaposi’s Sarcoma
Variant Description Prognosis and Treatment Classic Seen in Elderly Jewish and Mediterranean men. Good Present as purple-blue plaques on hands and feet. Surgery, cryotherapy, radiation, chemotherapy African-endemic Found in eastern and southern Africa, where it makes Poor up 25-50% of soft-tissue sarcomas in children. Has Radiation, chemotherapy more aggressive course, with bone involvement. Lymphadenopathic variant affects kids. AIDS-associated Mostly in homosexual men with HIV infection. Has Rarely fatal, except the rapid evolution and atypical distribution of lesions with systemic form involvement of trunk, face and mucosa. Rituximab, HAART, ganciclovir, interferon alpha KS Due to Iatrogenic Seen with organ transplants, cancer and autoimmune Regression or cure with Immunossupression diseases. High incidence is seen with cyclosporine withdrawal of therapy therapy. Sirolimus may be beneficial are unaware of the progression of the The pathogenesis of Kaposi’s sarcoma many patients with AIDS, especially patient’s disease. has become better understood since its those with low or decreasing CD4 T-cell discovery. Kaposi’s sarcoma-associated counts. Generalized KS is seen most Discussion herpesvirus (KSHV), or HHV-8, has been commonly in this group and is associ- implicated in the pathogenesis of Kaposi’s ated with the poorest survival rate and The occurrence of neoplasms with sarcoma, primary effusion lymphoma prognosis. However, the incidence of KS vascular differentiation in close association (PEL) and a proportion of Castleman’s among HIV-positive patients appears to be with lymphoproliferative disorders suggests disease.2 decreasing because of highly active retro- a pathogenic relationship. Multiple factors contribute to the viral therapy (HAART).3 The first association of KS and multi- development of KS. The oncogenic Castleman’s disease was first described in centric Castleman’s disease was reported role of HHV-8 in KS is associated with 1956 by Castleman and his colleagues as a by Frizzera et al.5 in 1983. Since then, their expression of several of its viral proteins disorder of mediastinal lymphoid hyper- coexistence has been well documented in including viral IL-6, which has been shown plasia with hyalinization of the follicles the literature. 6 to increase angiogenesis by driving the and interfollicular vascular proliferation.6 The association of Castleman’s disease expression of vascular endothelial growth Since then, giant lymph-node hyperplasia and Kaposi’s sarcoma, two rather rare factor, or VEGF. The HIV virus may also has been found in various locations other disorders, appears too frequently to be cooperate with HHV-8 in advancing than mediastinum.7 It is a heterogenous due to chance alone.7,8 De Rosa et al.9 tumorigenesis through the Tat protein, lymphoproliferative disorder with over- proposed that both diseases may present which protects KS cells from apoptosis, lapping clinical features and histological in immunologically depressed patients, but promoting growth of lesional spindle variants. Three histologic variants include: were not sure whether Kaposi’s sarcoma cells.3 KS cells are derived from lymphatic hyaline-vascular type, plasma-cell type, and is a consequence of immunologic altera- endothelium. The lymphatic origin can mixed type. Clinically, Castleman’s disease tions caused by Castleman’s disease, or be confirmed with immunohisto- chem- is divided into a solitary type and a multi- whether both diseases are due to a primi- istry using monoclonal antibody D2-40 centric type. The solitary form presents tive disorder of immunologic regulating directed against a sialoglycoprotein epitope as a mass, commonly located in the medi- factors. Chen4 speculated that it is likely in lymphatic endothelium.3 It is believed astinum, but also in the neck, lung, mesen- that immune derangement accompanying that KSHV infection can reprogram the tery, axillary lymph nodes, peritoneum, multicentric Castleman’s disease predis- endothelial gene expression profile into soft tissues, and nasopharynx. It is often poses the patients to Kaposi’s sarcoma. that of lymphatic endothelium.10 asymptomatic, or else symptoms are due to Rywlin et al.8 thought that these two enti- KS is considered more of a cellular prolif- mass effect of the lesion. Microscopically, ties may reflect different tissue reactions to eration in response to angiogenic factors over 90% of these cases are of hyaline- the same causative agent, but at that time, than a true malignancy.3 It probably starts vascular type, and the remainders are of HHV-8 as an etiologic cause of KS and as polyclonal hyperplasia and develops into plasma-cell type. Besides Kaposi’s sarcoma, MCD had not yet been discovered. They a clonal neoplasia.2 Castleman’s disease is also associated with proposed two possible explanations for The frequency of KS in AIDS patients POEMS syndrome (polyneuropathy, orga- the simultaneous occurrence of these rare is 20,000 times higher than in the general nomegally, endocrinopathy, monoclonal disorders: First, they may represent related population, and the frequency of KS in gammopathy, and skin changes), paraneo- diseases or the same disease with slightly transplant recipients is 500 times higher plastic pemphigus, Hodgkin’s and non- different manifestations; and second, in than in healthy individuals.11 KS can affect Hodgkin’s disease, follicular dendritic cell both there is proliferation of blood vessels almost any organ, including skin, liver, sarcoma, and myasthenia gravis.13,14 and plasma cells.8 Nampoory et al.7 also lungs, spleen and GI tract, and can ulti- Multicentric form of Castleman’s disease believed that Castleman’s disease could mately result in death. GI involvement can was first described by Frizzera at al. 5 Two represent a slightly different reaction to the occur in the absence of cutaneous disease; of the 10 cases reported by Frizzera also same causative agent and that production it may be asymptomatic or lead to weight had associated Kaposi’s sarcoma. It is an of vasoproliferative factors in patients with loss, abdominal pain, nausea, vomiting or atypical lymphoproliferative disorder, AIDS, Kaposi’s sarcoma and immunosup- bleeding.2,3 Frequent involvement of lymph showing a polyclonal lymphoid prolifera- pression could explain the occurrence of nodes is also well documented.12 tion with vascular hyperplasia.14 MCD has both diseases together. KS may be the presenting sign in been reported in both HIV-seropositive and AVSHALUMOVA , MILLER 43 Table 2: Angiofollicular or Giant Lymph-node Hyperplasia
Histologic Type Clinical Type Description Prognosis and Treatment
Hyaline-vascular Solitary More common variant, presents as a Good solitary mass in the lymph tissue on the Surgery, radiation chest. 70% of patients are <30 years old, with to ratio of 4:1. Symptoms include airway compression, cough, dys- pnea and infections. Not associated with HHV-8. Characterized by capillary prolif- eration within lymph nodes. IL-6 expres- sion is absent.
Localized Presents as a mass with smaller adja- Variable cent nodes. Characterized by presence Surgery, radiation, steroids of mature plasma cells around germinal centers and capillary proliferation. Pres- ents with fever, fatigue and weight loss, as well as lab abnormalities such as Plasma-cell hemolytic anemia, † ESR and hypoal- buminemia. IL-6 production by lymph nodes is present
Multicentric Rare variant seen mostly in AIDS Poor patients. Associated with multiple organ Chemotherapy (CHOP), involvement, bone lesions, hepatosple- interferon alpha, steroids nomegaly with symptoms similar to plasma-cell type. HHV-8 infection is seen in 100% of MCD in HIV+ cases; AIDS is a recognized cause of MCD. It is associ- ated with Kaposi’s sarcoma, non-Hodg- kin’s lymphoma and POEMS syndrome. IL-6 is encoded by HHV-8
HIV-seronegative patients, but is seen more followed by temporary remissions; and enous human IL-6.14 frequently in the setting of HIV infection. rapid progression with fatal outcome. In Cellular IL-6 is a multifunctional It is a systemic disease with disseminated the rapidly progressive type of generalized cytokine that acts on a variety of cells and lymphadenopathy, hepatosplenomegaly Castleman’s disease, patients are prone to can stimulate hematopoiesis and angio- and constitutional symptoms. It can also develop sepsis, opportunistic infections, genesis, as well as lymphoproliferation and be associated with autoimmune diseases.12 and malignancies. The main causes of plasma-cell differentiation. Expression of Nearly 100% of AIDS-associated MCD is mortality are infections and malignan- IL-6 also accompanies neovascularization linked to HHV-8, and is usually accom- cies, especially lymphoma and Kaposi’s of placenta, certain tumors and wound panied by the development of Kaposi’s sarcoma.12 The multicentric form of healing. 17 sarcoma in the affected individual.2,16 Castleman’s disease is nearly always the Early studies of Castleman’s disease, HHV-8 (+) MCD is usually more aggres- plasma-cell type. before the discovery of HHV-8, reported sive, with poor prognosis and a median Retrospective study done by Oksenhedler intense human IL-6 staining of germinal survival of less than 30 months. Altered et al.14 looked at the clinical and patho- centers within hyperplastic lymph nodes. T-cell function, with impaired lympho- logic spectrum of multicentric Castleman’s In recent studies using immunohistochem- cyte responsiveness in mixed lymphocyte disease (MCD) in HIV infection in 20 istry, all HHV-8-positive Castleman’s cultures and reversed helper-to-suppresser patients and found Kaposi’s sarcoma to disease tissues had evidence of marked T-cell ratio, have been reported in patients be present in 12 cases. Most commonly, vIL-6 expression. HHV-8-positive with Castleman’s disease. A low T4 to T8 patients presented with fever and spleno- Castleman’s disease tissues express vIL-6 ratio is also regularly seen in patients with megaly, followed by lymphadenopathy, sometimes together with human IL-6, but AIDS, and AIDS is a recognized cause of hepatomegaly, severe weight loss, respira- the two cytokines are produced by different Castleman’s disease.4 tory symptoms and edema. Anemia was cells within the affected tissue, with human Chen4 divided the multicentric form of a constant finding, and serum markers IL-6-positive cells localized to the germinal Castleman’s disease into two distinct types, of inflammation were present in most centers and vIL-6-positive cells to mantle namely limited multicentric form and patients. Immunophenotyping studies zone.17 generalized form. The limited multicentric demonstrated a polyclonal B-cell process. A study done by Yoshiyasu and form involves supradiaphragmatic lymph The key event in the pathogenesis of colleagues17 looked at biological activi- nodes and is often self limited, with rare Castleman’s disease has been suggested ties of the viral cytokine vIL-6 using mice recurrences and a prolonged course. The to be an abnormal production of B-cell model. In vitro, IL-6 was found to induce generalized form is irreversible, with two growth factor, such as IL-6, by lymphoid vascular endothelial growth factor (VEGF) types of evolution: long survival, up to 18 tissue.15 HHV-8 itself encodes viral IL-6, mRNA, suggesting that the cytokine years, with recurrent clinical exacerbations which can induce production of endog- can promote angiogenesis indirectly by
44 MULTICENTRIC CASTLEMAN’S DISEASE AND AIDS-ASSOCIATED KAPOSI’S SARCOMA OCCURRING TOGETHER: A CASE REPORT AND DISCUSSION inducing VEGF expression, which can plays a role in the pathogenesis of multi- MCD diagnosis. However, their mortality promote growth by increasing tumor blood centric Castleman’s disease, especially in rates were not significantly different. They supply. Histological analysis of tumor HIV infected patients. The results of this found high rates of response to ritux- tissues derived from vIL-6-expressing cells study have been confirmed by other inves- imab. Monotherapy gave short-lived showed proliferation of spindle-shaped tigators. In 1995, Soulier and colleagues responses, whereas polychemotherapy cells with high mitotic activity. found HHV-8 DNA sequence in 14 out with CHOP gave long-term remission in In the pathogenesis of the plasma cell of 14 cases of HIV-associated Castleman’s a subset of patients. Other agents used type, IL-6 seems to play a central role. disease, with nine cases having coexistent included antiviral agents, immunomodula- High levels of IL-6 have been demonstrated Kaposi’s sarcoma. Four of 13 HIV-negative tors and thalidomide. Interestingly, the and can explain the systemic manifestations patients with Castleman’s disease were posi- fatality rate among HIV-related multi- in patients with this type of Castleman’s tive for HHV-8, and one of these patients centric Castleman’s disease cases was 44%, disease. In the hyaline-vascular type, had underlying Kaposi’s sarcoma.18 They which is significantly lower than that of there is no IL-6 expression.5 In the multi- thought that these vascular proliferative HIV-negative individuals (65%). centric plasma-cell type, IL-6 production lesions might result from the secretion of Treatment modalities for KS include is HHV-8-encoded, with exacerbations of the angiogenic factors by lymphoid tissue. observation, local therapy such as cryosur- symptoms related to high levels of IL-6, The essential similarity of the histologic gery or radiation, systemic chemotherapy IL-10 and high viral load for HHV-8.16 components of KS and MCD lesions is such as vinblastine, vincristine, or bleo- Expression of vIL-6 alone or in conjunc- proliferation of blood vessels and plasma mycin, and treatment with interferon alpha, tion with cellular IL-6 in the context of cells.8 Kaposi’s sarcoma lesions progress imatinib mesylate, rapamycin and topical Kaposi’s sarcoma and Castleman’s disease from plaque to patch to nodule stage. alitretinoin gel.3 Many clinical trials are and the similarities of their biological Biopsies taken from different stages underway for treatment of KS, involving activities strengthen the argument that show varying degrees of slit-like vascular drugs such as bevacizumab (a recombi- these cytokines are critical to disease proliferation in the dermis, lined by large nant human anti-VEGF antibody), valproic pathogenesis. atypical endothelial cells, and proliferation acid, IL-12, and matrix metalloproteinase 2,3 A study done by O’Leary and colleagues18 of spindle cells. Red-cell extravasation, inhibitors. A clinical trial involving daily investigated the cell types infected by haemosiderin deposition and eosinophilic doses of imatinib mesylate, which targets HHV-8 in Castleman’s disease and exam- hyaline globules, as well as diffuse inflam- c-kit and platelet-derived growth factor ined the correlation between HHV-8 and matory infiltrate composed of lymphocytes receptor (PDGFR) signaling, resulted in Castleman’s disease lymph-node angio- and plasma cells, are also present. In the clinical and histologic regression of cuta- genesis. It also investigated the prevalence patch stage of KS, the “promontory sign” neous KS. Recipients of organ transplants 3,8 of HHV-8 in multicentric and solitary may be visualized. In MCD, lymph node who develop KS are likely to benefit from Castleman’s disease. The study raised the biopsy shows prominent follicular hyper- treatment with sirolimus (rapamycin) question of whether Castleman’s disease plasia, diffuse vascular hyperplasia and because of its anti-neoplastic properties. 4 and Kaposi’s sarcoma are linked by a viral interfollicular infiltrate of plasma cells. Most likely it acts by reducing levels of factor, HHV-8, and whether some forms Because the prevalence of KS in AIDS VEGF and VEGF receptors on endothelial 2 of Castleman’s disease could be early intra- patients is very high, and HIV coinfection cells. nodal Kaposi’s sarcomas. They proposed is thought to be an important factor in the that when infected HHV-8 B cells enter the development of KS, attempts to control Conclusion lymph node, they infect mesenchymal or KS by improving the immune system of endothelial cells, which assume spindle-cell HIV patients through HAART are recom- A case report of coexistent Kaposi’s morphology, similar to Kaposi’s sarcoma mended. Ganciclovir has been proven sarcoma and multicentric Castleman’s in the subcapsular space of the node. If effective in inhibiting KS and MCD.2 disease has been presented. Kaposi’s HHV-8 disseminates through the node, Rituximab is an anti-CD20 monoclonal sarcoma is a common disorder associated leading to increased vascularity via vIL-6 antibody that is effective against PEL and with HIV. Occurrence of KS with MCD production, Castleman’s disease results. MCD.6 Combination of cyclophosph- has been well documented in the litera- If the virus stays localized to support amide and cyclosporine-A is beneficial in ture. Both entities are caused by HHV-8 focal subcapsular spindle-cell prolifera- patients with MCD complicated by KS.19 and its oncogenic and angiogenic prod- tion, Kaposi’s sarcoma develops. In their In the localized plasma-cell type, surgical ucts. The incidence of KS has declined study, HHV-8 was identified in seven out resection of the hyperplastic lymph nodes considerably following onset of HAART 16 cases of Castleman’s disease. The results results in complete resolution of consti- for AIDS patients. Nevertheless, the like- showed that five out of six multicentric and tutional symptoms and laboratory abnor- hood of an HIV-positive person developing two out of 10 solitary Castleman’s disease malities.13 Single-agent chemotherapy with KS is still 20 times higher than that of an biopsies were positive for HHV-8. They vinblastine is effective and may prolong uninfected individual. Life expectancy in concluded that the presence of HHV-8 survival in patients with MCD associated MCD associated with AIDS also seems to in the tested Castleman’s disease samples with HIV infection.14 Steroids are used have significantly improved in the HAART was not linked to a histological subtype of in localized and multicentric plasma-cell era, but it still remains a disease with poor Castleman’s disease, although it was seen types. However, no consensus exists on prognosis. We as dermatologists should be more often in multicentric type. They also optimal therapy for MCD.18 aware of the coexistence of these two enti- found an increased incidence of Kaposi’s Mylona and colleagues20 conducted a ties and have a high index of suspicion if a sarcoma in individuals with any type of study in which they reviewed epidemiology patient with KS develops lymphadenopathy Castleman’s disease. Three HIV-associated and clinical and virologic aspects of multi- or constitutional symptoms. Castleman’s disease cases were positive for centric Castleman’s disease in HIV-positive HHV-8, with two of these patients having patients, as well as evaluated treatment coexistent multicentric Castleman’s disease strategies and outcomes especially in rela- References: and cutaneous Kaposi’s sarcoma. In one tion to HAART. If the patients were on 1. Chang Y, Cesarman E, Pessin MS, et al. Identification of herpesvirus-like DNA sequences in AIDS-associated of these biopsies, there was evidence of HAART at the time of MCD diagnosis, they Kaposi’s sarcoma. Science 1994; 266:1865-1869. microscopic Kaposi’s sarcoma within had better immunologic responses and 2. Wong EL, Blossom Damania. Linking KSHV to Human Cancer. Current Oncology Reports 2005; 7:349-356. the lymph nodes affected by Castleman’s lower incidence of Kaposi’s sarcoma versus 3. Nasir Aziz, MA, Amor Khachemoune, MD, CWS, Carlos disease. These results prove that HHV-8 those patients who initiated HAART after Rodriquez, BS. Self-Assessment examination: A man
AVSHALUMOVA , MILLER 45 with violaceous papules on foot. J Am Acad Dermatol. 2008; 58(3):538-39. 4. Karl T, Chen K. Multicentric Castleman’s disease and Kaposi’s sarcoma. The American Journal of Surgical Pathology 1984; 8(4):287-293. 5. Frizzera, et al. A systemic lymphoproliferative disorder with morphologic features of Castleman’s disease. Am J Surg Pathol 1983; 7: 211-231. 6. Saif, M Wasif. Castleman Disease in an HIV-infected Patient with Kaposi sarcoma. AIDS Read 2001; l (11):527- 576. 7. M.R. Narayanan Nampoory, Kaivilayil V. Johny, et al. The dialysed patient with both Castleman disease and Kaposi sarcoma. Nephrolo Dial Transplan 1998; 13:2373-2376. 8. Arkadi M. Rywlin, Les Rosen, Beia Cabello. Coexistence of Castleman’s disease and Kaposi’s sarcoma. The American Journal of Dermatopathology 1983; l5 (3):277- 281. 9. De Rosa G, Barra E, Guarino M, Gentile R. Multicentric Castleman’s disease in association with Kaposi’s sar- coma. Appl Pathol. 1989; 7(2):105-10. 10. Hong YK, Foreman K, Shin JW, et al. Lymphatic repro- gramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet 2004; 36:683-685. 11. Harwood AR, Osoba D, et al. Kaposi’s sarcoma in recipi- ents of renal transplants. Am J Med 1979; 67:759-765. 12. Lothe F, Murray J.F. Symposium on Kaposi’s sarcoma S. Karger. A. G. Bazel (Switzerland). 1963. 13. Day JR, Bew D, Ali M, et al. Castleman’s disease associ- ated with myasthenia gravis. Ann Thorac Surg, 2003 May; 75(5):1648-50. 14. M. van den Berge, P. Pauwels, J-J Jakimowicz, G.J. Creemers. Hyaline vascular Castleman’s disease: a case report and brief review of the literature. The Netherlands Journal of Medicine 2002; 60(11):444-47. 15. Palestro G, Turrini F, et al. Castleman’s disease. Adv Clin Path. 1999; 3(1-2):11-22 16. Oksenhendler E, Duarte M, Soulier J, et al. Multicentric Castleman’s disease in HIV infection: a clinical and pathological study of 20 patients. AIDS 1996; 10(1):61-7. 17. Yoshiyasu Aoki, Elaine S. Jaffe, Yuan Chang, Karen Jones et al. Angiogenesis and Hematopoiesis induced by Kaposi’s sarcoma-Associated Herpevirus-Encoded Interleukin-6. Blood 1999; 93 (12):4034-4043. 18. O’Leary J, M. Kennedy, D. Howells, I. Silva, et al. Cellular localization of HHV-8 in Castleman’s disease: is there a link with lymph node vascularity? J Clin Pathol 2000; 53:69-76. 19. Caligaris-Cappio, Federico, et al. Cyclophosphamide/ cyclosporine-A treatment of multicentric Castleman’s dis- ease with Kaposi’s sarcoma. Blood 2000; 85(2):216-217. 20. Mylona EE, Baraboutis IG et al. Multicentric Castleman’s Disease in HIV Infection: a systemic review of the litera- ture. AIDS Rev. 2008; 10(1):25-35.
46 MULTICENTRIC CASTLEMAN’S DISEASE AND AIDS-ASSOCIATED KAPOSI’S SARCOMA OCCURRING TOGETHER: A CASE REPORT AND DISCUSSION LINEAR PAPULAR ERYTHEMA IN A ONE-YEAR-OLD MALE
Reagan Anderson, D.O., M.P.H., M.C.S.,* Leela Athalye, MS III,** Steven Grekin, D.O., F.A.O.C.D.*** *Dermatology Resident, PGY3, Oakwood Southshore Medical Center **Medical Student, MS III, Michigan State University ***Program Director, Oakwood Southshore Medical Center Dermatology Program
ABSTRACT
Linear papular erythematous rashes during infancy present a therapeutic challenge. The differential diagnosis is often hard to narrow down without performing a biopsy, which is often difficult in this age group. The differential diagnosis for male infants with a linear papular erythematous rash includes inflammatory linear verrucous epidermal nevus (ILVEN), lichen striatus, linear lichen planus, linear psoriasis, and allergic contact dermatitis. We present a case of linear papular erythema in a one-year-old male infant.
Case Report bution of the rash. After changing pajamas and applying a mid-potency topical steroid A one-year-old white male infant was for three weeks, the rash had resolved. brought to the clinic during the spring by attentive and concerned parents due Discussion to a rash that had developed over the last two months. The rash started as a red flat One possible diagnosis for this infant’s line on the abdomen that slowly spread rash was ILVEN, a type of epidermal nevus. down the left thigh, then the leg, and finally Epidermal nevi are congenital hamartomas the foot. As the line progressed, the rash of ectodermal origin that may be linked changed from being flat to being “bumpy.” to other organ systems. ILVEN consists of According to the parents, the infant had erythematous, wart-like lesions grouped not been scratching the rash and did not in a linear pattern. ILVEN is distinguished appear to be irritated by it. from the other forms of epidermal nevi by The G2P2 mother had a normal preg- its erythematous, scaling, crusting, pruritic, nancy with a normal delivery and was and inflamed nature.1,2 released from the hospital with the infant According to Altman and Mehregan, after 24 hours. The infant had made all there are six characteristic features of appointments with a pediatrician, had ILVEN: age of onset from birth to five Figure 1 received all immunizations, was develop- years old, female predominance, left leg mentally normal, and had an uncompli- involvement, pruritis, resistance to therapy, Linear Lichen Planus cated delivery and infancy. Mother and and a psoriasiform and inflammatory father have non-contributory personal and histology.3 It often has a psoriasiform Lichen planus is a subacute or chronic family medical history. appearance and can be extremely pruritic. dermatosis that has a less than 1% chance Physical exam revealed a playful and The histology is similar to psoriasis with of presenting in a linear fashion. Its classic interactive one year old male infant with elongated epidermal rete ridges, irregular form is pruritic and violaceous, with a linear papular erythematous rash begin- parakeratosis lacking a granular layer, polygonal papules.6 Linear lichen planus ning on the abdomen and running down alternating orthokeratosis, and associated is a fairly rare form of lichen planus, which the left leg to the foot. The erythema hypergranulosis.4 is most common in the third and fourth was mostly continuous and the papular Lichen Striatus decades of life. Linear lichen planus is component was occasionally confluent. characterized by its white, lacy, reticular There were no vesicles or verrucous lesions Lichen striatus is a self-limited inflam- appearance.8 The papules of linear lichen in the rash. No excoriations were noted. matory dermatosis that affects children, planus often show a network of white No signs or symptoms of infection were usually during the spring and summer, lines known as Wickham’s striae, which present. Darier’s sign was negative and and typically between the ages of four usually occur unilaterally along the lines of the rest of the physical examination was months to 15 years old.5 It normally Blaschko after a traumatic stimulus. unremarkable. regresses within three to six months of Linear Psoriasis The differential diagnosis was discussed onset.6 Lichen striatus appears as small, with the patient’s parents, including ILVEN, scaly, brownish-red papules in a linear Linear psoriasis is a rare form of psori- lichen striatus, linear lichen planus, linear distribution.7 Histologically, lichen asis characterized by a linear distribu- psoriasis, and allergic contact dermatitis. striatus has perivascular and periadnexal tion of psoriatic lesions along the lines of The option of a biopsy was discussed with infiltrates of lymphocytes and histocytes Blaschko. Linear psoriasis may present the parents, but the parents and provider that affect the dermal-epidermal junc- as a non-pruritic, erythematous, scaly decided to try a course of a mid-potency tion.6,7 Additionally, spongiosis and plaque. Linear psoriasis usually has a later topical corticosteroid and observation prior intracellular edema are associated with onset than childhood and tends to prog- to resorting to a biopsy. The infant and exocytosis of lymphocytes and focal para- ress rapidly to potentially involve sites like parents returned to the clinic one month kerotosis.5 Rarely, necrotic keratinocytes the scalp and nails. The pathogenesis is later with complete resolution of the may be scattered within the spinous layer, unclear, but is possibly due to cells with rash and with knowledge that the infant’s along with subcorneal spongiotic vesicles somatic mutations migrating around the pajamas had a zipper down the exact distri- filled with Langerhan cells.5 lines of Blaschko during early embryo- ANDERSON, ATHALYE, GREKIN 47 genesis1 Linear psoriasis may develop due 3. Altman J, Mehregan AH. Inflammatory linear verrucose epidermal nevus. Arch Dermatol.1971;104(4):385-9. to Koebner’s phenomenon; however, true [Medline]. linear psoriasis without any other lesions is 4. Cockerell and Larsen. Benign Epidermal Tumors and Proliferations. Dermatology, 2nd Ed. Spain: Elsevier; a rare occurrence. The lesions may present 2008. asymptomatically without inflammatory 5. Elder, D. E. (Ed.). Lever’s Histopathology of the Skin (7th Edition). Philadelphia: Lippincott Williams & Wilkins; reaction, and usually show a histopathology 2005. of psoriasis.2 Histopathology shows 6. Shin, J. H. A case of adult blaschkitis with features of interface dermatitis (2008). British Journal of Dermatol- psoriasiform hyperplasia, elongation of ogy 2008;159:231-266. rete ridges, parakerotosis, absent granular 7. Numata, Y. , Okuyama, R. , Tagami, H. , Aiba, S. Linear lichen planus distributed in the lines of blaschko develop- 9 layer, and suprapillary thinning. ing during intramuscular triamcinolone acetonide therapy for alopecia areata multiplex. Journal of European Acad- amy of Dermatology and Venerelogy 2008;22:1365-1401. Allergic Contact 8. Hartl, C. Unilateral Linear Lichen Planus with Mucous Membrane Involvement. Acta Derm Venereol (Stockh) Dermatitis 1999;79:145-146. 9. Tay, Y. K. Linear Nevoid Psoriasis. Pediatric Dermatology 2008;(25)3:410-411. Allergic contact dermatitis is almost 10. Purohit, S., Kondia, S. , Shukla, S. R. , Saxena, V. N. , always in the differential when a patterned Meena, R. S., Saxena, V. Linear Psoriasis. Indian Journal of Dermatology, Venerology, and Leprosy 2006;72:398. rash is noted. From the classic linear 11. Adams, R. M. Occupational Skin Disease (2nd Edition) . vesicles seen with Rhus dermatitis to the Philadelphia: W. B. Saunders Company; 1990. 12. Hurwitz, S. Clinical Pediatric Dermatology: A Textbook of ventral foot erythema and vesicles seen Skin Disorders of Childhood and Adolescence. Philadel- with chromate sensitivity, allergic contact phia: W. B. Saunders Company; 1981. dermatitis can have a striking appearance that is readily identified. Allergic contact dermatitis can also have an elusive presen- tation that is only determined after patch testing and clinical correlation. One of the most common contact aller- gens is nickel. It is commonly contained in jewelry, as well as metals in zippers and clasps of clothing. The rash takes the form of the pattern of the irritating stimuli such watch straps, rings, buttons, zippers and necklaces. These rashes appear at the site of maximum friction and area of direct skin contact.1 Patch testing for nickel sensitivity can easily be performed. Patients with this condition are cautioned to avoid nickel- containing substances. Periodic coating of the offending metal with clear nail polish may be helpful for patients who do not want to avoid the allergen and still use the nickel-containing substance.2 Summary Our patient presented with a linear papular erythema that occurred during the spring, over a couple of months, without any other pertinent history or physical find- ings. While the diagnosis of nickel allergic contact dermatitis was finally rendered, the exercise of recalling the pertinent and possible differential diagnosis is vital in the proper care of the patient. It is the author’s opinion that a trial of conservative obser- vation with non-invasive therapy should be employed first in these patients due to the trauma of a biopsy to an infant. If the patient does not respond to treatment, or if signs or symptoms progress, a biopsy can then be considered in order to solidify the diagnosis and treatment.
References: 1. Wolf, K., Johnson, R. A., & Surmond, J. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology (5th ed.). New York: McGraw-Hill Medical Publishing Division; 2005. 2. Rodgers, M. Epidermal nevi and epidermal nevus syn- drome: a review of 233 cases. Pediatric Dermatology 2008;9:342-344.
48 LINEAR PAPULAR ERYTHEMA IN A ONE-YEAR-OLD MALE DERMATOLOGICAL MANIFESTATIONS OF HIV/AIDS: RELEVANCE IN A POST-HAART ERA
Kevin T. Belasco, DO, MS* *Graduate, Dermatology Residency, Sun Coast Hospital/Nova Southeastern University (2008)
ABSTRACT
Human immunodeficiency virus (HIV-1) infection continues to present a major challenge and health problem worldwide. Cutaneous manifestations, which may be the initial signs of HIV infection, frequently occur in patients who are infected with the HIV virus. Recognizing HIV-related skin changes may lead to the diagnosis of HIV infection in the early stages, which allows initiation of appropriate antiretroviral therapy. This comprehensive review will highlight the cutaneous manifestations of HIV/AIDS, both common and infrequent, including a range of malignancies, infections, and inflammatory dermatoses. This review also will discuss the challenges and pitfalls of diagnosis and treatment of cutaneous disease in the HIV-infected individual. Clinical, diagnostic, and therapeutic dilemmas posed by HIV infection in the setting of skin disease will be discussed.
Learning objective: By the end of this review, the reader will have an in-depth knowledge of the scope of cutaneous disease in the patient with HIV/AIDS, and should be able to recognize the clinical characteristics of a broad-range of HIV-related dermatoses with an understanding of both diagnostic and therapeutic measures
Introduction challenges for the clinician. Early recogni- atosis, systemic fungal infections such as tion of skin disease in the setting of HIV/ Cryptococcus, and mycobacterial infec- Human immunodeficiency virus-1 AIDS allows for early intervention and, in tion. Patients in this stage of immunosup- (HIV-1, HTLV-3) disease remains some cases, initial identification of HIV pression are also prone to inflammatory, a global pandemic of epic proportions. in a patient in whom the disease is not yet pruritic dermatoses, including granuloma The United Nations estimates that as of suspected. The early recognition of asso- annulare, photodermatitis, and exaggerated December 2004, 39.4 million people world- ciations between specific skin diseases and reactions to insect bites. These enhanced wide were living with HIV-1, including HIV infection speaks to the pivotal role reactions to arthropod bites may present as 17.6 million women and 2.2 million chil- of the dermatologist in the diagnosis and erythematous papules or nodules, often on dren under the age of 15.1 In the United management of HIV/AIDS. the upper trunk. Arthropod reactions in States, with advancements in treatment for The advent of highly active antiretro- the HIV-infected patient may histologically HIV-1 infection, deaths from AIDS have viral therapy (HAART) has changed the represent a pseudolymphomatous response, decreased, while the number of persons face of HIV disease over the past decade. also known as benign lymphocytoma living with AIDS has increased by an esti- Although HAART therapy does not repre- cutis. Patients with chronic lymphocytic mated 30%.1 HIV-2 was first discovered in sent a cure of HIV/AIDS, there has been a leukemia (CLL), another subpopulation of Senegal, Africa, and has remained largely significant decrease in both mortality and patients who are often immunosuppressed, confined to West Africa. HIV-2 is associ- morbidity for HIV/AIDS. In particular, the are also susceptible to pseudolymphoma ated with a lower rate of transmission and incidence of opportunistic infections has developing in the setting of an insect bite a slower disease course than HIV-1. This decreased, including a multitude of cuta- reaction. review will focus on the cutaneous mani- neous diseases such as Kaposi’s sarcoma Seborrheic Dermatitis & HIV festations of HIV-1, which accounts for and disseminated herpes simplex infec- the vast majority of total HIV infections tion (HSV), among others. Nevertheless, Seborrheic dermatitis remains the worldwide. HIV-1 will be abbreviated as a large number of opportunistic infections most common -- though nonspecific -- “HIV” in this review. that affect the skin are still seen worldwide cutaneous manifestation of HIV/AIDS. The cutaneous manifestations of HIV and in the United States, especially among HIV-infected patients often experience are protean and are seen in about 90% of underserved communities in which access protracted and severe cases of seborrheic HIV-infected persons. Skin diseases in to appropriate prophylactic therapies and dermatitis, possibly secondary to increased the HIV-infected patient have a variety of other resources remain scarce. Malassezia colonization in the skin. etiologies, including infectious, malignant, Cutaneous Infections & Clinical suspicion -- and open dialogue neoplastic, and inflammatory responses. Inflammatory Dermatoses in the with the patient -- should be raised in an In general, diseases which affect the skin individual who presents with severe sebor- tend to run a more protracted, severe HIV-Infected Patient rheic dermatitis or disease which is refrac- course with a more exaggerated clinical It is critical that dermatologists who tory to topical treatments. For unknown presentation in the patient with HIV/ see patients with HIV disease know which reasons, seborrheic dermatitis is known AIDS. Scabies, psoriasis, lichen planus, infectious diseases affecting the skin are to be accentuated in patients with immu- granuloma annulare, seborrheic dermatitis, more common and how these infections nosuppression and also those with neuro- pruritic eruptions, and atopic dermatitis may differ in presentation, course, and logic disease, specifically Parkinsonism. are among the many skin conditions which treatment from those in the general popu- Nevertheless, seborrheic dermatitis may may present in a severe, exaggerated form lation. When the T-cell count is 200 or serve as an early and nonspecific marker in HIV/AIDS patients. less, the patient is defined as having AIDS. for HIV infection. Overview of Skin Disease in HIV In this stage of HIV disease, the skin lesions Papulosquamous Skin Disease are more characteristic of immunodefi- & HIV The atypical clinical presentations and ciency and include predictable opportu- severity of skin disease in the patient with nistic infections such as herpes simplex, A variety of papulosquamous diseases HIV poses diagnostic and therapeutic molluscum contagiosum, bacillary angiom- may assume an atypical clinical course in BELASCO 49 patients infected with HIV. Paradoxically, Hair Changes in HIV Cutaneous Manifestations of psoriasis, a T-cell mediated disease, tends There are few case reports of specific Immune Reconstitution with to worsen in patients with severe immuno- HAART suppression; the absence of T-cells in AIDS hair changes attributed to HIV infec- patients is by no means protective against tion. Acquired eyelash trichomegaly has There is a paradoxical clinical deterio- psoriatic flares.29 The systemic treatment been reported, especially in the context of ration after the introduction of HAART. 14 of choice for management of psoriasis advanced HIV infection. Telogen efflu- The enhancement of T-cell function in vulgaris in HIV-infected patients is acit- vium may be associated with acute viral HIV-infected patients treated with HAART retin (non-immunosuppressive), although infections, including HIV. may cause paradoxical worsening of other- teratogenicity must be considered when Cutaneous Drug Eruptions in HIV wise latent inflammatory and infectious treating a female patient of child-bearing skin conditions. )MMUNE RECONSTITU age.30 Moreover, triglycerides must be The incidence of cutaneous drug erup- TION INFLAMMATORY SYNDROME (IRIS) is a monitored closely in HIV-infected patients tions is markedly increased in patients recently described entity in which severely taking acitretin, given the additive risk for with HIV/AIDS, particularly in response immunodepressed HIV patients, after hypertriglyceridemia in patients also taking to sulfa antibiotics and other sulfa deriva- being started on HAART, develop inflam- antiretroviral therapy. tives. This poses a therapeutic dilemma matory reactions to several pathogens. In addition, light therapy and topical since trimethoprim-sulfamethoxazole This syndrome affects patients during corticosteroids may be combined in (Bactrim®, Septra®) represents a treatment the initial phase of immunological recon- management of psoriasis in the setting of choice for Pneumocystis carinii (PCP) stitution triggered by HAART, in which of HIV/AIDS. Although less commonly pneumonia prophylaxis in these patients. CD4 lymphocyte counts rise and viral used for psoriasis in the age of biologics, The clinician should have a keen aware- load decreases. This immunologic boost hydroxyurea may also be an appropriate ness of the possibility of sulfur-induced may lead to inflammatory manifestations mainly associated with preexisting infec- systemic medication for HIV-infected cutaneous drug eruptions in HIV-infected tions, whether they have been previously patients with psoriasis. Hydroxyurea is patients. Patients with a history of sulfa associated with blood dyscrasias, including diagnosed and treated or unrecognized. allergy or in whom sulfur is otherwise Immune reconstitution syndrome was macrocytic anemia, as well as devel- contraindicated can be treated with pent- opment of leg ulcers.28 In addition, the first reported after initiation of HAART amidine for PCP pneumonia prophylaxis. in patients with previous CMV retin- drug should not be used in pregnancy. It Dapsone, a sulfone derivative, can be used, is recommended that the initial dose in itis. Since then, many other infectious albeit with caution, for PCP prophylaxis adults should usually be 1 gram daily, and agents have been reported in association in sulfa-allergic patients, since the cross- this can be titrated, according to efficacy with IRIS including M. avium complex and toxicity, up to a maximum of 2 grams reactivity between the two medications (MAC), Mycobacterium tuberculosis, daily.28 Complete blood count, including remains exceedingly low as the sulfone Cryptococcus spp., and Pneumocystis carinii. platelet and differential white cell counts, lacks the hapten sulfur moiety. Exacerbation of sarcoidosis, foreign body should be performed at least weekly for the The dermatologist’s approach to an and tattoo granulomas, as well as reactiva- first two months. HIV-infected patient with a suspected tion of cutaneous tuberculosis, have all been reported in association with immune Psoriatic flares are well-reported in cutaneous drug eruption should begin reconstitution inflammatory syndrome.2 AIDS patients. Improvement in immune with a thorough history of all medica- function with antiretroviral therapy tions – oral, topical, and parenteral Acute HIV Infection & the Skin is important in prevention of flares of -- started over the previous six months, Up to 70% of patients with primary HIV psoriasis in these patients. Methotrexate including over-the-counter remedies, vita- infection develop an acute mononucleosis- and cyclosporine should generally be mins, or herbs. Special attention must like syndrome that usually occurs two to avoided in psoriatic patients with HIV be given to early detection of mucosal six weeks following initial infection.3 Also disease due to their immunosuppressive lesions, including oral and anal mucosal known as the acute retroviral syndrome effects. Many authorities state that HIV surfaces. Although rare, toxic epidermal (ARS), these signs and symptoms occur infection generally precludes the use of necrolysis (TEN) can progress rapidly as a result of initial infection and disper- biologics in patients with psoriasis. The and be life-threatening if not detected sion of HIV. Duration of this stage is safety of biologics in patients infected with early. Moreover, the incidence of TEN usually less than 14 days but may become HIV remains debatable and has not been is increased in HIV-infected patients.10 protracted, lasting several weeks or even demonstrated with large-scale trials. Common offending agents include sulfon- months. Patients with primary HIV infec- In addition to psoriasis, lichen planus, amides, penicillins, allopurinol, NSAIDs, tion may present clinically with fever, sore pityriasis rubra pilaris (PRP), and reactive and antiretroviral agents, especially throat, cervical adenopathy, and maculo- arthritis (formerly Reiter’s syndrome) have nevirapine and abacavir. TEN is defined papular truncal eruption within weeks of also been reported with increased preva- as desquamation of at least 30% body initial infection. Laboratory abnormali- lence in patients infected with HIV. In ties may include elevated transaminases fact, an HIV-associated subset of PRP has surface area with increased risk of infec- tion, dehydration, and death in as many and leucopenia. Oral candidiasis and recently been added to the Griffiths clas- oral or genital ulcers may also occur. The 9 as 50% of affected patients. TEN usually sification for this disease. cutaneous eruption consists of discrete occurs 7-21 days after drug exposure to papules with slight scale; mucosal erosions Cutaneous Granulomas, Ulcers, the offending agent.10 Histopathology & HIV affecting oral and/or anal mucosa, which of TEN shows subepidermal split, full- resemble aphthae, may also be associated A variety of ulcerative and granuloma- thickness epidermal necrosis and a sparse with primary HIV infection. Prominent tous skin conditions undergo a worsening perivascular lymphocytic infiltrate. dysphagia may occur, an indication of course in HIV-infected patients, including Patients placed on antiretroviral therapy, pharyngeal involvement. Combination pyoderma gangrenosum, granuloma including HAART, should be alerted to antiviral therapy should be instituted in annulare (which may be disseminated in discontinue any medication that triggers these patients once HIV infection has been HIV-infected patients), sarcoidosis, and a rash since this may represent an early confirmed and a thorough history and deep mycoses (see discussion below). harbinger of TEN. physical examination has been completed. 50 DERMATOLOGICAL MANIFESTATIONS OF HIV/AIDS: RELEVANCE IN A POST-HAART ERA Appropriate patient exposure history and dose is sufficient to clear the scabetic erup- symptoms which can be clearly visualized diagnostic tests should be obtained. tion. For scabies in pregnant and lactating by the clinician. The most common cuta- women and infants, 6-10% precipitated neous finding in hepatitis B infection is the Papular Pruritic Eruptions & sulfur compounded in petrolatum qhs x serum sickness-like illness seen only during Scabies in HIV 3 nights remains a safe and appropriate the prodromal period; other dermatologic A variety of folliculitides and other treatment. manifestations include polyarteritis nodosa, papular pruritic eruptions may present a cryoglobulinemia, and systemic necrotizing Papular Prurigo, Pruritus, Xerosis, vasculitis, all of which may be severe in the clue to early HIV infection. Pruritus is a and Ichthyosis & HIV frequent symptom in patients shortly after setting of co-infection with HIV. initial HIV infection. Eosinophilic follicu- Papular prurigo, pruritus ani, and Hepatitis C & HIV litis is the most common pruritic follicular widespread xerosis are also prevalent eruption in HIV-infected patients. It is among HIV-infected patients, especially Like hepatitis B, hepatitis C (HCV) seen when the CD4 count is approximately with CD4 counts less than 200. Topical co-infection with HIV represents a major 200. Eosinophilic folliculitis presents as corticosteroids and emollients are initial global health concern. Approximately 4 urticarial papules on the upper trunk, treatment approaches, but refractory cases million Americans are infected with hepa- face, scalp, and neck. Pustular lesions are may require oral antihistamines including titis C, which accounts for 25,000 deaths uncommon. The majority of lesions occur hydroxyzine, cetirizine, and diphenhy- annually.13 Over 300,000 Americans with on the upper trunk anteriorly and may dramine. Doxepin, dosed at 25-50 mg HIV are co-infected with HCV.13 HCV extend down the midline back posteriorly. qhs, may also prove effective for allevia- affects 30-40% of HIV-infected individuals, The clinical course of eosinophilic follicu- tion of pruritus in HIV-infected patients.11 compared with 2-3% of the general U.S. litis may be protracted, with spontaneous A review of concomitant medications, population. Chronic HCV infection is the clearance followed by periodic recurrence however, is critical since drug interactions most common reason for liver transplanta- of the follicular eruption. HIV-associated may preclude initiation of doxepin or anti- tion in the United States. eosinophilic folliculitis in newborns/infants histamine therapy. Cryoglobulinemia & Vasculitis is a marker of poor clinical outcome and Thalidomide, which is FDA-approved for in HIV may indicate impending death in the erythema nodosum leprosum (ENL), has patient. Close clinical follow-up and proven effective in case reports for a variety Co-infection with HIV and HCV prompt initiation of HAART is crucial to of dermatologic conditions, including has had a major impact on patient the management of HIV-infected infants papular prurigo and HIV-associated apht- mortality. HCV may complicate antiret- with eosinophilic folliculitis. hous stomatitis.12 Patients with cases of roviral therapy, which may be associated The initial treatment of eosinophilic papular prurigo refractory to conventional with hepatotoxicity. Cutaneous mani- folliculitis is topical steroids and antihis- antipruritic therapies have been reported to festations of HCV may be atypical and tamines, although additional treatments respond to thalidomide, though the clini- severe in patients co-infected with HIV. such as phototherapy may be indicated.2 cian must be familiar with the side effects Cryoglobulinemia is a small-vessel vascu- Moreover, the dermatologist should of this medication, including teratogenicity, litis that may be associated with both HIV exclude additional pruritic cutaneous erup- peripheral sensory neuropathy, fatigue, and HCV infection.16 Patients classically tions such as scabies, insect bites, prurigo and deep vein thromboses (DVT). An present with livedo and stellate purpura. nodularis, pityrosporum folliculitis, and antiphospholipid serum panel is warranted The most serious manifestation of mixed the papular variant of granuloma annulare in any patients undergoing long-term cryoglobulinemia is renal damage from before initiation of treatment for eosino- therapy with thalidomide. Baseline anti- circulating cryoglobulins. The co-existence philic folliculitis. Histologic analysis can cardiolipin, PT/PTT, and proteins C and S of livedo and purpura in an HIV-infected exclude many of the entities included in should be drawn to detect any tendencies patient should raise suspicion for mixed the differential diagnosis of eosinophilic toward coagulation. cryoglobulinemia. Laboratory work-up folliculitis. Acquired ichthyosis and generalized should include HCV/HBV/HIV panels, Papular pruritic eruptions such as pruritus with xerosis remain persistent C3, C4, CXR, pan CT scans to exclude eosinophilic folliculitis can be distin- issues in skin management for HIV-infected lymphoproliferative disease, biopsy for guished from scabies by the absence of patients. Use of daily moisturizers after immunofluorescence (one sees mark- mites on microscopy following mineral bathing provides much-needed hydration edly elevated IgM with C3, identical to oil immersion from a scraping from the of the skin in these patients. rheumatoid vasculitis), and rheumatoid stratum corneum. Norwegian scabies factor (which is often elevated). Atypical (crusted scabies) involves the face and Hepatitis B & HIV IgA-mediated vasculitis with ulceration scalp, often with extensive crust, sometimes Immunosuppression from HIV/AIDS raises the suspicion for HIV-related adult- seen in matted layers. Norwegian scabies is decreases the host’s immune cell surveil- onset Henoch-Schönlein purpura. Clinical increased in the setting of HIV/AIDS due lance and increases the risk of infections, and histopathologic findings (including to host immunosuppression. The nails including viral, bacterial, parasitic, and direct immunofluorescent studies) should may be dystrophic, and, unlike conven- protozoal diseases, all of which can affect be combined when approaching a patient tional scabies, itching may be minimal or the skin and mucous membranes. Sexually with vasculitis, especially in the setting of even absent in the immunocompromised transmitted diseases in particular are more immunosuppression. host. Topical treatment with permethrin easily acquired in the immunocompro- Leukocytoclastic vasculitis (LCV) 5% cream may be of minimal benefit, even mised HIV-infected host.18 Hepatitis B is a cutaneous hypersensitivity reaction if repeated after one week. Refractory cases virus (HBV) is transmitted sexually and that may be drug-induced, malignancy- of Norwegian scabies have been successfully parenterally via blood-to-blood exposure. associated, inflammatory-associated, or treated with ivermectin, 200 μg (0.2 mg)/ HBV is the easiest of the hepatitis viruses idiopathic. Erythema elevatum diutinum kg po for one day. The average dose for a to transmit parenterally, being 10 times (EED), a chronic fibrosing form of LCV, 154-lb adult is 18 mg, dispensed as 6 mg, 3 more likely to be transmitted than hepatitis is a disorder characterized by yellow or caps po x 1 dose; and for a 110-lb adult, the C.13 HBV is also 100 times more likely to brown papules, plaques, or nodules that are dose is 9 mg, dispensed as 3 mg, 3 caps po be transmitted than HIV.13 Acute hepatitis distributed symmetrically over the extensor x 1 dose.15 The dose of ivermectin may be B in the HIV-infected patient may mani- surfaces of the extremities.17 The presen- repeated in one week, but often times one fest as scleral icterus and jaundice, two tation can be altered in HIV infection, BELASCO 51 with nodular lesions in a palmar-plantar of HIV/AIDS. Furthermore, genital ulcer- dramatically involve the face while usually distribution. The favored hypothesis for ations of any kind should raise suspicion sparing the palms and soles. Rupioid syph- the pathogenesis of EED is an immune- for HIV and prompt a thorough history ilis is characterized by abundant neutro- complex-mediated vasculitis induced by taken by the dermatologist. It should be phils in the horn and condylomata lata, chronic antigen exposure. The association noted that chronic HSV ulcerations of both of which may appear psoriasiform of EED with monoclonal gammopathies greater than one month duration, in the (“rupia” is derived from the Sanskrit word (primarily IgA-type), HIV infection, celiac setting of CD4 count < 200, is defined by for “silver”).20 disease, and chronic streptococcal infec- the CDC as an AIDS-defining illness. The diagnosis and treatment of syphilis tions supports this hypothesis. Although Syphilis & HIV: Neonatal, in HIV-infected neonates is of paramount rare, EED is mentioned in this review to importance for survival. Early congen- highlight its emerging role as a specific Congenital, and Adult ital syphilis usually becomes evident HIV-associated dermatosis. Dapsone is Perhaps no disease highlights the wide within the first week of life. By defini- a favored treatment for management of variety of skin findings in the setting of tion, early congenital syphilis occurs in EED.17 HIV/AIDS more so than syphilis, the children between 0 and 2 years old. The Sexually-transmitted diseases (STDs) “Great Masquerader.” This treponemal majority of syphilitic neonates appear remain among the most common infec- infection undergoes a variety of stages, each healthy at birth. Vesiculobullous eruption tions in the United States. STD infections of which assumes a protracted and atypical of the palms and soles. called syphilitic increase susceptibility to acquiring HIV.18 course in the setting of HIV co-infection. pemphigus, may be seen (bullae are highly The genital mucosal ulceration seen in a Co-infection with syphilis and HIV is so infectious). Mucopurulent or bloody variety of STDs, including syphilis, chan- common that the CDC recommends all nasal discharge teeming with spirochetes, croid and HSV, as well as the urethral patients with syphilis be offered testing for known as syphilitic rhinitis (snuffles), may discharge seen in chlamydia and gonorrhea, HIV infection. occur, leading to ulcers and fissures at the serve as points of entry for HIV during The diagnosis and treatment of syphilis corners of the mouth. Necrosis of nasal sexual contact. Hence, the genital ulcer- in an HIV-positive patient can pose a cartilage/bone may lead to saddle nose ations and mucosal breakdown induced diagnostic dilemma for the dermatologist. deformity. Ulcerations around the mouth, by STDs increase the likelihood of HIV For example, non-treponemal tests such eyes, nose, or anus may heal with depressed co-infection. as VDRL and RPR are used for screening linear scars that persist into adulthood. Herpes Simplex & HIV and monitoring treatment in patients with This is called RHAGADES (parrot’s lines). syphilis; false-negative responses, however, Hepatosplenomegaly may occur. Also, early Genital herpes (HSV) is by far the most can occur in early primary syphilis and congenital syphilis may lead to skeletal common cause of painful genital ulcer secondary syphilis in the setting of HIV osteochondritis, known as pseudoparalysis disease in the Western Hemisphere.18 infection. The PROZONE PHENOMENON of Parrot. Hair and nails may shed easily. Clusters of vesicles, pustules, or super- is a false-negative VDRL in which high Ulcers around the mouth are infectious ficial ulcers involving the genitals, anus, antibody titers interfere with the antigen- and disease may be spread among family perineum, or surrounding areas are classic antibody network (flocculation reaction) members by kissing. locations for infection. The lesions heal necessary to visualize a positive test.19 Treatment protocols for HIV-infected by crusting, which is a favorable sign. Therefore, a negative VDRL in a patient patients co-infected with syphilis are exten- HIV-infected patients are susceptible to infected with HIV may be due to an sive and include THREE WEEKLY )- INJEC protracted and severe episodes of HSV. For overwhelming host response rather than TIONS OF BENZATHINE PENICILLIN because of recurrent episodes of HSV in HIV-infected absence of syphilitic infection. This diag- the higher prevalence of neurosyphilis in patients, episodic therapy with acyclovir, nostic pitfall may lead to misdiagnosis and these patients. These high-risk patients famciclovir, or valacyclovir is indicated. delay medical treatment in HIV-positive should be followed at three-month inter- HIV-infected patients are prone to patients with syphilis. vals for one year after therapy.21 CSF exam- acyclovir-resistant HSV strains and may Early secondary syphilis is extremely ination for evidence of neurosyphilis is also require therapy with intravenous foscarnet infectious, characterized by maculopapular warranted in HIV-infected patients. or topical cidofovir gel (not commercially eruption, flu-like syndrome, and gener- available in the U.S.).18 HSV infection alized lymphadenopathy, resulting from Chancroid & HIV should be suspected in any HIV-positive dissemination of the spirochete. Mucosal Chancroid is an acute ulcerative patient who presents with oral and/or lesions are extremely infectious and may disease usually occurring on the genital perineal ulcerations and crusts. present as MUCOUS PATCHES (painless, and anogenital areas, and is often associ- The clinical differential diagnosis usually on tongue or lips, also tonsils), ated with massive visible lymphadenitis of mucosal erosions with stomatitis in pharyngitis, and condylomata lata. Moth- (buboes). Haemophilus ducreyi, a Gram- an HIV-infected patient should include eaten alopecia may also occur and may negative facultative anaerobe requiring cytomegalovirus (CMV), Stevens- be the only sign of lues. Copper-colored blood for growth, causes superficial Johnson syndrome, TEN, aphthous ulcers, macules on the palms and soles may also ulcerations and associated lymphadenitis. pemphigus vulgaris and, less commonly, occur. Chancroid is known to amplify the trans- paraneoplastic pemphigus (PNP). The The cutaneous presentations of mission of HIV infection. Although rare presence of grouped vesicles and crust in secondary syphilis in the setting of HIV are in the United States, H. ducreyi is endemic a dermatomal distribution is a hallmark of often atypical and rarely predictable. For in Africa, Asia, and the Caribbean, where varicella zoster (VZV, shingles), a condition example, in secondary syphilis, syphilids it accounts for up to 56% of genital ulcer commonly seen in patients over age 60 and can ulcerate and develop thick crusts (rupia disease.4 The incubation period of H. those with relative immunosuppression, syphilitica or rupioid syphilis), which are ducreyi is between four and seven days such as leukemia/lymphoma. The presence accompanied by high fever and severe with no prodromal symptoms.4 This may of a zosteriform eruption in a patient under illness. This unusual and otherwise rare be longer with pre-existing HIV infection. age 40 should prompt suspicion for HIV. course of syphilis, which is termed “malig- The ulcer is described as soft and non- Although VZV can occur at any age, the nant” syphilis (lues maligna), is found indurated, in contrast to the indurated presence of shingles in a young adult with in 7% of all syphilis associated with HIV chancre of syphilis. Ulcers may be multiple no history of immunosuppression may infection. The condition involves nodu- and contiguous, forming so-called “kissing represent an early cutaneous manifestation loulcerative lesions with rupioid crusts that ulcers” at apposing surfaces. The classic 52 DERMATOLOGICAL MANIFESTATIONS OF HIV/AIDS: RELEVANCE IN A POST-HAART ERA triad of the chancroid ulcer is described as are typically males who have resided in or folliculitis.23 The two predominant an undermined ulcer edge, purulent dirty endemic areas. Detection of H. capsulatum subtypes of MRSA, which are genetically gray base, and moderate to severe pain (this polysaccharide antigen in the urine is a distinct, are community-acquired MRSA is in contrast to the painless chancre of rapid, highly accurate diagnostic test in (CA-MRSA) and hospital-associated syphilis). Regional lymphadenitis and bubo AIDS patients.6 Urinary antigen levels can MRSA (HA-MRSA). HIV patients have formation may also occur. Disruption of also be used to assess treatment response an 18-fold higher risk for CA-MRSA than mucosal integrity with bleeding underlies and to detect relapse. Skin biopsy for the general population, according to a the basis for increased HIV transmission histologic evaluation and culture is another study presented in abstract form at the XVI in patients with chancroid. Infection with simple, rapid diagnostic procedure. Initial International AIDS Conference in Toronto H. ducreyi is often more protracted in treatment of patients with severe disease in August 2006.23 Surgical drainage, rather HIV-infected patients. Deep punched-out consists of amphotericin B. Antiretroviral than antibiotic therapy, is the single most coronal ulcers on the penis are associated therapy is usually deferred until there is important intervention for a CA-MRSA with HIV-infected patients co-infected a reduction in fungal burden to avoid abscess, even in the presence of HIV infec- with H. ducreyi. precipitating immune reconstitution tion. Trimethoprim-sulfamethoxazole inflammatory syndrome, defined earlier remains an inexpensive and effective choice Systemic Mycoses & Candidiasis in this review as a paradoxical worsening for the majority of patients, including those Fungal infections are one of the major of infection because of reversal of immu- infected with HIV.23 Patients infected with complications of HIV infection and may be nosuppression in the setting of depressed HIV often have a prolonged and compli- the first HIV-related opportunistic infection CD4 cell counts and disseminated, oppor- cated clinical course following infection to occur in these patients. Mucocutaneous tunistic infection. with MRSA. For example, HIV infection disease in the setting of HIV is exemplified Blastomycosis is caused by the thermally represents an independent risk factor for by candidiasis. Oral thrush is subdivided dimorphic fungus Blastomyces dermatitidis development of necrotizing fasciitis in into three types: pseudomembranous, and may occur in the skin secondary to CA-MRSA. erythematous, and hypertrophic candidi- primary pulmonary disease. Up to 50% asis.5 In pseudomembranous candidiasis, of cases of presumed secondary cutaneous Cutaneous Malignancies & HIV patients develop white exudative plaques, blastomycosis have no associated pulmo- Patients infected with HIV have cottage-cheese-like on the palate, tonsils nary findings on chest radiography, an indi- increased risk of numerous malignancies, or buccal mucosa, which can be scraped cation that cutaneous disease often follows many of which have cutaneous mani- with a tongue depressor with bleeding. In undiagnosed and asymptomatic pulmo- festations, including Kaposi’s sarcoma, erythematous candidiasis, flat, red, atro- nary infection.31 In contrast to other fungal squamous-cell carcinoma (SCC), cutaneous phic plaques are seen on the mucosa. In infections usually seen in immunocompro- T-cell lymphoma (CTCL), and human hypertrophic candidiasis, raised plaques mised patients, B. dermatitidis is a true papillomavirus-associated malignancies. similar to oral hairy leukoplakia (Epstein- pathogen that often infects immunocom- In fact, invasive cervical cancer represents Barr-induced plaques seen classically on petent individuals. Immunosuppression a distinct AIDS-defining illness as defined the lateral aspect of the tongue) involve the is found in approximately one-quarter by the CDC. 5 tongue or buccal mucosa. of patients with blastomycosis; diabetes Kaposi’s Sarcoma Additional manifestations of Candidal mellitus is also prevalent, found in approxi- infection in patients with HIV include mately 22% of these patients.31 Kaposi’s sarcoma (KS) is a vascular angular cheilitis, vulvovaginal candidiasis, Many of the 22 AIDS-defining illnesses neoplasm once common among AIDS and esophageal candidiasis with dysphagia. can affect the skin/oral mucosa, including: patients in the pre-HAART era but less Resistance to therapies such as fluconazole s (ERPES SIMPLEX common with the advent of antiretroviral has decreased since the advent of HAART, s +APOSIS SARCOMA therapies. KS is an abnormal prolifera- but the clinician should be aware of the s #RYPTOCOCCOSIS EXTRAPULMONARY tion of vascular endothelial cells associated potential for recurrent or resistant candidi- with human herpes virus-8 (HHV-8). KS s #OCCIDIOIDOMYCOSIS DISSEMINATED asis in the HIV-positive patient. Resistant clinically appears as a violaceous plaque cases of candidiasis may be treated with s #-6 or nodule, classically described on the caspofungin (Cancidas®) or voriconazole. s (ISTOPLASMOSIS DISSEMINATED lower extremities of Jewish Mediterranean Voriconazole, however, is contraindicated s #ANDIDIASIS WITH ESOPHAGEAL men.23 The prevalence of KS surged with in patients receiving ritonavir or efavirenz involvement) the advent of the AIDS epidemic, and the in the HAART regimen.5 s -YCOBACTERIUM INFECTION DISSEMINATED disease has been described on the skin and Although rare, systemic deep fungal Additional AIDS-defining illnesses viscera in association with immunosup- infections may occur in the skin in the are seen outside the United States. For pression. KS represents an AIDS-defining setting of HIV/AIDS, including cryptococ- example, Penicillium marneffei infection illness when seen in combination with cosis, coccidioidomycosis, histoplasmosis, (penicilliosis) is acquired from exposure depressed CD4 T-helper cell counts (fewer and aspergillosis. Symptomatic infection to the bamboo rat and is an AIDS-defining than 200 cells/μl). with H. capsulatum, the causative agent for illness in Thailand. KS can occur in the skin, oral cavity, histoplasmosis, is an AIDS-defining illness gastrointestinal tract, and lungs. Additional occurring in approximately 2-5 percent MRSA & HIV sites of KS include the lymph nodes, liver, of patients with AIDS.6 Histoplasmosis Methicillin-resistant Staphylococcal pancreas, heart, testes, and bone marrow. (H. capsulatum) is caused by a budding, aureus (MRSA) infection represents The AIDS-associated form of KS still tiny, intracellular yeast (<5 microns). a major threat to healthcare both in the represents the most common tumor in Histoplasmosis in the setting of AIDS United States and abroad. S. aureus is a HIV-infected patients worldwide. It is generally represents reactivation of prior human commensal that most commonly more aggressive than the indolent classic infection and is considered a sign of colonizes the anterior nares. Outbreaks form seen in Eastern Europe and the profound immunosuppression with low in the U.S. occur in both rural and urban Mediterranean. The most important differ- CD4 counts. Skin lesions occur in about settings but are often clustered in small ential diagnosis of KS is bacillary angioma- 50% of AIDS patients with disseminated geographic areas. Roughly 85% of MRSA tosis, a Bartonella infection treatable with histoplasmosis6 (see partial list of AIDS- infections present in the skin and subcu- erythromycin.23 The major goals of treat- defining illnesses below). These patients taneous tissue, usually as an abscess ment for KS are palliative (e.g., size reduc- BELASCO 53 tion). Although topical therapies for KS formis (EDV), the latter of which is asso- therapy that could potentially promote HIV are available (e.g., alitretinoin gel), HAART ciated mostly with HPV 5 and 8. EDV disease progression by further depletion of remains the major means of management has emerged as a distinctive dermatologic immune function. This could increase the of patients with KS since reconstitution of condition associated strongly with HIV/ likelihood of life-threatening opportunistic immune function leads to reduction in size AIDS, though EDV can occur in other infections. and growth of KS lesions. settings of immunosuppression and is not Recently, a 38-year-old African-American AIDS-related Lymphomas specific to HIV/AIDS. Treatment of EDV AIDS patient with co-existing pemphigus is often difficult, and radiation therapy vulgaris experienced a flare of his skin Cutaneous lymphomas are also asso- should be avoided in patients with verru- disease and was admitted to the derma- ciated with immunosuppression and are cous carcinoma or SCC related to epider- tology inpatient service at the University seen with increased prevalence in patients modysplasia verruciformis. of Miami, where he was seen by the author 8 with HIV/AIDS. Hodgkin’s disease Anorectal Carcinoma (SCC) while on clinical elective. Mycophenolate is more aggressive in patients with HIV mofetil (CellCept®) was started in an despite the use of antiretroviral therapies. Anorectal SCC represents a major attempt to control his pemphigus flare. Cutaneous lymphomas may be T- or B-cell concern in patients infected with HIV. The patient rapidly developed pancy- derived. These tumors often present as Examination of the rectal mucosa is key topenia. This adverse effect had not erythematous-to-violaceous papules or to early detection of anogenital lesions previously been reported and should alert plaques on the head/neck or upper trunk, seen in HIV/AIDS. Appropriate anoscopy the clinician to use caution when using but can occur virtually anywhere on the with a disposable anoscope is warranted steroid-sparing immunosuppressive agents body. Ulceration may be a late finding, when evaluating an HIV-infected patient to manage immunobullous disease in the especially if untreated. Patients typi- who is symptomatic (anal pruritus, setting of HIV. The patient responded to cally present with lymphadenopathy and bleeding, discharge, undetected growth, an experimental trial of rituximab, an anti- may have a history of fever, chills, and/or etc.). Anorectal examination allows for CD20 monoclonal antibody given as an weight loss. Cutaneous lymphomas can early detection not only of SCC, but intravenous infusion after several weeks of be primary, or they can be secondary to also anogenital herpes, rectal gonorrhea, hospitalization. a primary systemic focus. CD30+ large- verrucous carcinoma, and condylomata. Cutaneous Disease in HIV- cell lymphoma is predominantly of T-cell Anorectal smears are important procedures origin in HIV-infected patients.8 Evaluation for early cytological detection of HPV and/ Infected Neonates & Children for systemic disease is warranted in all or dysplasia/neoplasia in high-risk indi- Worldwide, the number of women and HIV-infected patients following diagnosis viduals, including those infected with HIV. children with new cases of HIV/AIDS of cutaneous lymphoma. HIV-infected Onychomycosis and HIV is expanding at a rate greater then the patients with CD30+ large-cell lymphoma rest of the population. Mucocutaneous have a generally favorable prognosis since Distal subungual onychomycosis Candida infections are the most common the advent of HAART, but staging and caused by Trichophyton rubrum remains skin manifestations of HIV/AIDS in chil- histologic diagnosis remains essential. the number one type of oncychomycosis dren. Clinical features may include oral Mycosis fungoides is rare in the setting in both immunocompetent and immu- thrush, angular cheilitis, and severe, erosive of HIV/AIDS, and there are no studies nocompromised individuals, including Candida diaper dermatitis.26 Chronic available to elucidate the survival rates in patients infected with HIV.24 The inci- Candida paronychia in older children may these patients in the era of HAART.8 As dence of superficial white onychomycosis, occur in the setting of HIV. Molluscum, in the case of CD30+ large-cell lymphoma caused by T. mentagrophytes, is increased HSV, VZV, and papillomavirus infec- and other forms of CTCL, prognosis is among HIV-infected patients. Proximal tions can be severe and protracted, as in predicated upon antiretroviral therapy and subungual onychomycosis is rare in the adults.26 The incidence of herpes zoster preservation of immune function. general population, in whom it is caused by is significantly increased in children with Melanoma, SCC, & BCC T. rubrum; it is usually caused by T. menta- AIDS. Severe forms of seborrheic derma- grophytes in HIV-positive patients and may titis, including erythrodermic forms, Both melanoma and non-melanoma be a presenting sign of HIV disease.24 can present in children with HIV/AIDS. skin cancers (BCC, SCC) are generally Pruritic papular eruption of HIV, which more prevalent in HIV-infected patients, Antiretroviral Medications encompasses eosinophilic folliculitis, has although the precise role of immune Antiretroviral medications have been been described in HIV-infected children. surveillance in development of these skin associated with a myriad of cutaneous side Unlike infected adults, HIV-associated neoplasms remains unknown. It is not effects, including maculopapular eruptions, malignancies are rare in children. The known, for instance, if HIV interacts cutaneous vasculitides, and even toxic most commonly reported malignancies with the melanocyte to trigger aberrant epidermal necrolysis. Lipodystrophy and include KS and B-cell neoplasms. The proliferation and metastasis. The clinical fat redistribution is a well-documented mortality and morbidity from measles is presentation and risk factors for melanoma side effect of protease inhibitor therapy. significant and well-described in pediatric and non-melanoma skin cancers are iden- A comprehensive analysis of these phar- AIDS patients. AIDS should be suspected tical in both immunocompromised and macologic effects is beyond the scope of in any child who develops an opportu- immunocompetent hosts. this review, but the reader is referred to a nistic infection, especially in the context Patients with AIDS have a three- to comprehensive review written by Ward et of a high-risk group (e.g., mother is HIV+, five-fold increased risk of developing al. in the Journal of the American Academy maternal history of IVDA, syphilis, etc.). a nonmelanoma skin cancer.7,8 BCC is of Dermatology in 2002.25 The clinician must exclude primary immu- more prevalent than SCC in HIV-infected Vesiculobullous Disease & HIV nodeficiencies such as SCID, Wiskott- patients, in sharp contrast to immuno- Aldrich, or complement deficiencies, all of suppressed organ-transplant recipients, Vesiculobullous disease in association which may present with eczematous erup- in whom this ratio is reversed.8 SCC is with HIV infection is extremely rare. A tions that resemble seborrheic dermatitis strongly associated with human papillo- dilemma arises in managing HIV-infected or atopic eczema. mavirus (HPV) infection in anogenital, patients with pemphigus vulgaris and PCP is currently classified as an “atypical cervical, and oral cancer, in SCC of the nail related immunobullous diseases: Control fungus” (lacks ergosterol). Cutaneous unit, and in epidermodysplasia verruci- of pemphigus relies on immunosuppressive Pneumocystis infection is extremely rare 54 DERMATOLOGICAL MANIFESTATIONS OF HIV/AIDS: RELEVANCE IN A POST-HAART ERA TABLE 1
I. HIV Dermatoses: Clinical Manifestations, Fre- i. Neoplastic disease quency, Course, and Treatment in the HIV/AIDS i. Kaposi’s sarcoma (HHV-8) Patient ii. Cervical dysplasia (HPV) a. Exanthem of primary HIV Infection iii. B-cell lymphoma subtypes b. Bacterial infections iv. Melanoma i. Acne v. CTCL ii. Actinomycosis vi. SCC iii. Bacillary angiomatosis j. Vascular disease iv. Botryomycosis i. Vasculitis v. Bullous impetigo ii. Thrombocytopenic purpura vi. Cellulitis iii. Bacillary angiomatosis (see infections) vii. Chancroid k. Hair and nail abnormalities viii. Ecthyma i. Telogen effluvium ix. Folliculitis ii. Alopecia areata x. Granuloma inguinale iii. Oncychomycosis (see infections) xi. Impetigo l. Oral disease xii. Mycobacterial infection i. Aphthosis xiii. Staphylococcal scalded skin syndrome ii. Oral hairy leukoplakia xiv. Syphilis iii. Kaposi’s sarcoma xv. Aphthous ulcers iv. Black hairy tongue xvi. MRSA m. Cutaneous drug eruptions c. Viral infections i. Summary of most common triggers of drug i. Varicella, including Kaposi’s varicelliform eruptions in the HIV/AIDS patient eruption ii. Clinical presentations and outcomes in ii. Condyloma acuminatum HIV-related drug eruptions iii. CMV exanthem n. Immunobullous, vasculitic, rheumatologic, and iv. EBV exanthem depositional diseases v. Herpes simplex and zosteriform eruptions i. Bullous pemphigoid vi. HPV ii. Calciphylaxis vii. Molluscum contagiosum iii. Dermatomyositis viii. Oral hairy leukoplakia iv. Dermatitis herpetiformis (Duhring’s dis- ix. Vaccinia ease) d. Fungal and yeast infections v. Porphyria cutanea tarda i. Candidiasis vi. Henoch-Schonlein purpura (HSP), IgA ii. Deep mycoses vasculitis iii. Dermatophytosis vii. Cryoglobulinemia iv. Mucormycosis o. Dermal, granulomatous, panniculitic, and v. Onychomycosis inflammatory diseases vi. Pruritus ani i. Papular pruritic eruption of AIDS vii. Seborrheic dermatitis ii. Erythema elevatum diutinum viii. Sporotrichosis iii. Erythema nodosum ix. Acanthamoeba iv. Granuloma annulare e. Protozoal infections v. Prurigo nodularis i. Amebiasis, cryptosporidiosis, isosporosis vi. Eosinophilic folliculitis ii. Pneumocystis carinii (jiroveci) vii. Pruritus iii. Toxoplasmosis viii. Pyoderma gangrenosum iv. Leishmaniasis ix. Transient acantholytic dermatosis (Gro- f. Arthropod infections ver’s disease) i. Demodicosis x. Urticaria ii. Norwegian scabies and variants xi. Malakoplakia g. Hyperkeratotic disease i. Acquired ichthyosis II. Special Considerations in HIV/AIDS Patients ii. Xerosis with Cutaneous Disease iii. Porokeratosis a. Concurrent medications iv. Acquired perforating dermatosis b. Risk of opportunistic infection h. Papulosquamous disease c. Risk of cutaneous drug eruptions i. Lichen planus d. Counseling and reassurance ii. Atopic dermatitis iii. Palmoplantar keratoderma iv. Reiter’s syndrome (reactive arthritis) v. Pityriasis rubra pilaris
BELASCO 55 but well-documented in the dermatologic 22. Elston DM. Community-acquired methicillin-resistant Staphylococcus aureus. J Am Acad Dermatol. 2007 literature, as reported by Cockerell et al. in Jan;56(1):1-16; quiz 17-20 1991.27 Cutaneous PCP infection appears 23. Jessop S. HIV-associated Kaposi’s sarcoma. Dermatol Clin. 2006 Oct;24(4):509-20, vii to have a predilection for the external audi- 24. Gregory N. Special patient populations: onychomycosis tory canal but can occur anywhere on the in the HIV-positive patient. J Am Acad Dermatol. 1996 Sep;35(3 Pt 2):S13-6 skin. 25. Ward HA, et al. Cutaneous manifestations of antiretroviral therapy. J Am Acad Dermatol. 2002 Feb;46(2):284-93 26. Schachner, LA (Ed). Pediatric Dermatology. Mosby, 3rd Conclusions Ed, 2003, pp 1220-1225 27. Hennessey NP, et al. Cutaneous Pneumocystis carinii infection in patients with acquired immunodeficiency syn- The large variety of cutaneous manifes- drome. Arch Dermatol. 1991 Nov;127(11):1699-701 tations seen with HIV/AIDS highlights the 28. Smith CH. Use of hydroxyurea in psoriasis. Clin Exp Der- matol. 1999 Jan;24(1):2-6 importance of early detection, diagnosis 29. Fife DJ. Unraveling the paradoxes of HIV-associated and management of skin disease in these psoriasis: a review of T-cell subsets and cytokine profiles. Dermatol Online J. 2007 May 1;13(2):4 patients. The impact of skin disease in 30. Buccheri L. Acitretin therapy is effective for psoriasis the HIV-infected patient ranges from a associated with human immunodeficiency virus infection. Arch Dermatol. 1997 Jun;133(6):711-5 mild rash to life-threatening infections and 31. Mason AR, et al. Cutaneous blastomycosis: a diagnostic malignancies. This wide range of cuta- challenge. Int J Dermatol. 2008 Aug; 47(8): 824-830 neous findings underscores the importance of this topic in dermatology. The skin is indeed viewed as a window into the body, and a better understanding of skin disease in the setting of HIV/AIDS ultimately provides for more comprehensive care of patients at risk for the countless dermato- logic conditions brought forth by immu- nosuppression, including those which may have grave consequences.
References: 1. Joint United Nations Programme on HIV/AIDS and World Health Organization, AIDS epidemic update, December 2004 2. James, WD, et al. Andrews’ Diseases of the Skin. Clinical Dermatology. 10th Edition, Elsevier Inc. 2006, pp. 416- 417 3. Dorrucci, M., et al. Clinical characteristics and prognostic value of acute retroviral syndrome among injecting drug users: Italian seroconversion study. AIDS. 1995; 9:597- 604 4. Tahir T. Chancroid and human immunodeficiency virus infection- a review. Int. J. Derm. 2008, 47:1-8 5. Moreno, J. Fungal Infections (Ch 19) HIV/AIDS Primary Care Guide, Crown House Publishing Co. 2006, pp 321- 339 6. Butt MA, et al. Increase in the frequency of histoplasmo- sis caused by HIV infection. Infectious Diseases Society of America 35th Annual Meeting, Sept. 13-16, 1997, San Francisco, CA Abstract 534 7. Goedert JJ, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351: 1833-9 8. Wilkins, K, et al. Cutaneous malignancy and human immunodeficiency virus disease. J Am Acad Dermatol 2006; 54:189-206 9. Miralles ES, et al. Rubra pilaris and human immunodeficiency virus infection. Br J Derma- tol. Dec 1995;133(6):990-3 10. Pereira FA, et al. Toxic epidermal necrolysis. J Am Acad Dermatol. 2007;56(2):181-200 11. Smith KJ, et al. Pruritus in HIV-1 disease: therapy with drugs which may modulate the pattern of immune dys- regulation. Dermatology. 1997;195(4):353-8 12. Faver IR, et al. Thalidomide for dermatology: a review of clinical uses and adverse effects. Int J Dermatol. 2005 Jan;44(1):61-7 13. Gompf, S. Co-Infection with Hepatitis B & C (Chapter 16) HIV/AIDS Primary Care Guide, Crown House Publishing Co. 2006, pp 275-295 14. Kaplan MH, et al. Acquired trichomegaly of the eyelashes: a cutaneous marker of acquired immunodeficiency syn- drome. J Am Acad Dermatol. 1991 Nov;25(5 Pt 1):801-4 15. Meinking TL, et al. The treatment of scabies with iver- mectin. N Engl J Med. 1995 Jul 6;333(1):26-30 16. Ramos-Casals M, et al. Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV- RNA viraemia and HIV coinfection. J Viral Hepat. 2007 Oct;14(10):736-42 17. Kim H. Erythema elevatum diutinum in an HIV-positive patient. J Drugs Dermatol. 2003 Aug;2(4):411-2 18. Toney, JF. Sexually Transmitted Diseases (Chapter 17) HIV/AIDS Primary Care Guide, Crown House Publishing Co. 2006, pp 297-309 19. Smith G. The prozone phenomenon with syphilis and HIV-1 co-infection. South Med J. 2004 Apr;97(4):379-82 20. Held JL, et al. Noduloulcerative or “malignant” syph- ilis occurring in an otherwise healthy woman: report and review of a dramatic dermatosis. Cutis 1990 Feb;45(2):119-22 21. Dayan L. Syphilis treatment: old and new. Expert Opin Pharmacother. 2005 Oct;6(13):2271-80
56 DERMATOLOGICAL MANIFESTATIONS OF HIV/AIDS: RELEVANCE IN A POST-HAART ERA
METASTATIC RENAL CELL CARCINOMA
Joseph Machuzak, DO,* Megan Goff Machuzak, DO** *3rd-year Resident, Midwestern University/Phoenix Dermatology, Phoenix, AZ **Attending Physician, Midwestern University/Phoenix Dermatology, Phoenix AZ
ABSTRACT
We report a case of a 62-year-old Caucasian male with cutaneous extension of renal cell carcinoma. Renal cell carcinoma is the most common malignancy arising from the kidney and accounts for approximately 3% of adult malignancies. The most common sites involved when metastatic spread occurs are the regional lymph nodes, lungs, liver, bone and brain.
have a cloning of the tumor suppressor References: Case Report: 1 genes VHL and TCH or oncogene MET. 1. Woodward E, Clifford S, Astuti D, Affara N, Maher E. Familial clear cell renal cell carcinoma (FCRC): clinical A 62-year-old male presented to our Several hereditary syndromes have been features and mutation analysis of the VHL, MET, and office with a primary complaint of a identified as having an association with CUL2 candidate genes. J Med Genet. 2000 May; 37(5): 348–353. painful lesion involving his left anterior renal cell carcinoma, including von Hippel- 2. American Cancer Society. Statistics for 2007. Atlanta: shoulder. The lesion had been present for Lindau (VHL) syndrome, hereditary papil- American Cancer Society; 2007. 3. Robson CJ, Churchill BM, Anderson W. The results approximately six months, and although lary renal carcinoma (HPRC), familial of radical nephrectomy for renal cell carcinoma. J he denied any other symptomology, he renal oncocytoma (FRO) associated with Urol. Mar 1969; 101(3):297-301. did state that the lesion had been slowly Birt-Hogg-Dubé syndrome (BHDS), and enlarging over the last several months. His hereditary renal carcinoma (HRC). past medical history included renal cell According to the American Cancer carcinoma with metastatic spread to his Society, in 2007 there were approximately brain and right lung, diabetes mellitus, 51,590 cases (31,990 in males and 19,600 coronary artery disease and hypertension. in females) of malignant tumors of the Over the course of his struggle with renal kidney diagnosed in the United States, with cell carcinoma, which had been diagnosed 12,890 deaths (8,080 in males and 4,810 in in 2000, he had several surgical procedures females); renal cell cancer accounted for which included bilateral nephrectomies, 80% of this incidence and mortality.2 The surgical resection of brain mets and a right greatest increase in incidence is currently pulmonectomy. observed in African Americans. Renal cell Upon presentation to our office, the carcinoma is the eighth or ninth leading patient was found to have two well demar- cause of cancer death in the United cated, red to violaceous, friable papules States. The five-year survival rates initially measuring 6mm and 8mm respectively. reported by Robson in 1969 were 66% for The surrounding area was a dusky red with stage I renal carcinoma, 64% for stage II, peripheral telangiectasias. The papules 42% for stage III, and only 11% for stage were biopsied using a shave technique, and IV.3 the pathology was consistent with meta- Patients will present with metastatic static renal cell carcinoma. disease in approximately 30% of cases, with After consultation with the patient’s the primary sites being lung, soft tissue, radiation oncologist, it was decided that bone, liver, skin and central nervous system. the best course of care was surgical excision Treatment options for renal cell cancer are of the affected area for pain control. This surgery, radiation therapy, chemotherapy, was done with minimal discomfort, and hormonal therapy, immunotherapy, or the patient was satisfied with the outcome. combinations of these. Discussion: Conclusion: Renal cell carcinoma accounts for Renal cell carcinoma is a fairly rare approximately 3% of adult malignancies cancer usually affecting the adult popula- and about 90-95% of neoplasms arising tion. Unfortunately, very few symptoms from the kidney. It characteristically has occur prior to diagnosis. This delay in no early warning signs and is resistant to diagnosis greatly increases the chance for therapies, which include radiation and metastasis. The condition must be included chemotherapy. Renal cell carcinoma comes in our differential for any patient who pres- from the epithelium of the proximal renal ents to a dermatology office with known tubules, and it can occur in sporadic and history of a malignancy. hereditary forms. Families at high risk for developing renal cell carcinoma usually MACHUZAK, MACHUZAK 59 WIDESPREAD CREEPING ERUPTION SECONDARY TO DIFFUSE CONTACT WITH TROPICAL HOOKWORM
Aaron J. Peterson, DO,* Kendal J. Jensen, BS,** S. Ray Peterson, MD, FAOCD,† Brian Bradshaw, MD,† C. Riley Nelson, PhD‡ *Currently completing a Traditional Internship at Valley Hospital Medical Center, Las Vegas, Nevada **Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah † Department of Dermatology, Central Utah Clinic, Provo, Utah, Chairman, Department of Dermatology, Utah Valley Regional Medical Center ‡ Department of Integrative Biology, Brigham Young University,
ABSTRACT
Creeping eruption or cutaneous larva migrans (CLM) is an abortive infection caused by animal intestinal nematode larvae most commonly found in dogs and cats. Hookworm larvae, found in soil and sand contaminated with animal feces, may incidentally penetrate unprotected human skin. Within a human host, the animal larvae are unable to complete a life cycle, possibly due to an inability to enzymatically compromise the basement membrane. The larvae then twist, wind, and burrow within the epidermis, eliciting intense inflammation. The characteristic serpiginous, erythematous, and well-demarcated morphology of CLM is diagnostic given a typical history of contact of exposed skin in endemic regions. The majority of eruptions occur on the legs and feet. Herein we report an atypical case of extensive creeping eruption over large areas of exposed skin. Morphology, history, and the response to systemic therapy were all consistent with an unusual presentation of this common eruption.
Case Report was confirmed, his previous prescriptions discontinued, and 18 mg of ivermectin A 50-year-old man presented to our (Stromectol 6 mg tabs times three) was clinic with an extensive pruritic eruption prescribed for three days. of erythematous and irritated migratory Relief from the itching and the death serpiginous tracts involving the back, of the parasites was apparent within a few lateral abdomen, bilateral shoulders, arms days. Some mild post-inflammatory hyper- and hands. pigmentation had persisted at three- and The patient had been working as a field seven-month follow-up visits at the sites of biologist in French Guiana for several previous involvement. weeks. The eruption began in French Guiana prior to his return to the United Discussion States. While in the endemic region, he Figure 1 consistently slept in a covered tent The two most common species of hook- protected with fine, biting-midge-proof worm manifesting as CLM in French netting and a wooden floor (Figure 1). He Guiana are Ancylostoma braziliense and did admit to one episode of sleeping on the A. Caninum.2 In contrast, visceral larval clean wooden floor with exposed skin, and migrans, caused by a distinct Toxocara he had frequent contact with soil and sand species, is also endemic in French Guiana in the area in the course of his work. but presents with internal symptoms not His initial eruption consisted of a large limited to the epidermis. Initially, CLM number of itchy, red papules on his back infection appears with pruritic red papules and arm (Figures 2, 3). A few days later, at the site of contact; most commonly the papules evolved into short red lines the papules are found on the feet, legs, and progressed into serpiginous tracks and buttocks, genitals, or hands in a limited curved burrows consistent with the classic fashion. Stinging and pain are felt when regional morphology of CLM (Figure 4). larvae migrate, forming thin, red, tortuous Upon returning to the United States, lines. The larvae typically begin migra- the patient sought medical attention and tion four days after stratum germinativum was given a presumptive diagnosis of penetration and progress about 2 cm/ scabies infection. An overnight applica- day. As the worms advance, the previously tion of lindane lotion provided little relief. affected areas may become secondarily After several days of advancing serpigi- infected and impetigenize.1, 2 nous lesions, the patient presented to an Velho et al. described a case of larva emergency room and was diagnosed with migrans with similar involvement to the hookworm. He received mebendazole, case presented.3 A 44-year-old truck driver cephalexin, prednisone, and halcion. Three had been assaulted and left unconscious on days later, the patient was seen in our office the ground for several hours before medical for additional care. help arrived. Once hospitalized, he received Figure 2 At this point, the infestation had impe- intravenous corticosteroid therapy for cere- tigenized and progressed over the back, bral edema. Following days in a coma, he flank, shoulders, upper arm, and hands regained consciousness and complained (Figures 5, 6). An automated CBC analysis of intense pruritus where he developed showed 81.4% neutrophils, but surpris- classic progressing lesions of CLM over the ingly no eosinophilia. A diagnosis of CLM left frontal, left parietotemporal, preauric- 60 WIDESPREAD CREEPING ERUPTION SECONDARY TO DIFFUSE CONTACT WITH TROPICAL HOOKWORM ular, orbicular, malar and deltoid regions. The wounds healed after treatment with References: albendazole, 400 mg daily for 24 days. 1. James WD, Berger TG, Elston DM. Parasitic Infesta- Our case similarly presented with wide- tions, Stings, and Bites. Andrews Diseases of the Skin Detroit: Saunders; 2006. p. 435 spread hookworm contracted in tropical 2. Despommier DD, Gwadz RW, Hotez PJ, Knirsch CA. South America. Unlike the truck driver, Aberrant Nematode Infections. Parasitic Diseases 5th Ed. New York: Apple Trees Productions, 2000:167 our patient was not assaulted and did 3. Velho P, Faria AV, Cintra ML, Souza EM, Moraes AM. not lay unconscious, but it is likely that Larva migrans: A CASE REPORT AND REVIEW. Rev. Inst. Med. Trop. S. Paulo 2003; 45(3):167-171 he became infected through inadvertent 4. Jackson A, Heukelbach J, Calheiros CM, Soares V, exposure as he slept on the wooden canopy Harms G, Feldmeier H. A Study in a Community in Brazil in Which Cutaneous Larva Migrans Is Endemic. Clinical or was exposed through his field work in Infectious Diseases 2006; Vol. 43:e13–e18 and around endemically colonized soil and 5. Blackwell V, Vega-Lopez F. Cutaneous larva migrans: Clinical features and management of 44 cases present- sand. ing in the returning traveler. British Journal of Dermatol- Figure 3 ogy. 2001;145: 434-437. A study involving 2,005 individuals in 6. Bouchaud O, Houze S, Schiemann R, Durand R, Ralaim- a community in Brazil during the rainy azava P, Ruggeri C, Coulaud J. Cutaneous larva migrans in travelers: A prospective study, with assessment of season demonstrated that CLM was preva- therapy with Ivermectin. Clinical Infectious Diseases. lent, affecting 4.4% of the population.4 2000; 31:493-98. 7. Patel P, Miller E, Way B. Cutaneous Larva Migrans: A Another study performed by Blackwell Case Report and Current Treatment Options. JAOCD and Vega-Lopez on 44 tourists with CLM 2007; 8: 17-19 8. Freedberg IM, Eisen AZ, Wolff K, et al. Cystercercosis reported that up to 95% of the cases were and Other Helminthic Infections. dermatology in general contracted on the beach.5 We can assume medicine. New York: McGraw-Hill, 1999:2624. 9. Nguyen SA, Napoli DC. Natural history of large and that in tropical areas endemic with CLM, generalized cutaneous reactions to imported fire ant infection may occur in the rainforest, on stings in children. Ann Allergy Asthma Immunol. 2005, the beach, or in the community. For an Mar;94(3):387-90. infestation previously called plumber’s itch and duck hunter’s itch, CLM may plausibly be called “field biologist” itch as an occupa- Figure 4 tional hazard in this endemic region.8 Additionally, Blackwell and Vega-Lopez reported that 25% of the 44 tourists infected with CLM were initially misdiag- nosed.4 Our patient was also misdiagnosed by the referring doctor, his initial treatment rendered ineffective. Effective and tolerable treatments for CLM include albendazole, thiabendozole and ivermectin. In this case, ivermectin (recommended as a treatment of choice in a recent article by Patel, Miller, and Way7) was prescribed and was effective. CLM commonly affects the feet, buttocks, or hands where unprotected skin is penetrated by larvae. Most infections have limited distribution. Regardless of the site or size of initial infection, a uniform morphology develops with predictable progression of lesions. The unusual loca- tions of this case of CLM are merely the result of a widespread contraction of a commonly limited infestation. Similarly, Norwegian scabies (Sarcoptes), catastrophic fire ant bites (Solenopsis), and Chagas disease (Trypanosoma) are all examples of species with localized involvement and Figure 5 rare, catastrophic manifestations with suffi- cient microbe burden.9 In conclusion, extensive creeping erup- tion may be challenging if not correctly diagnosed and treated. Early diagnosis is aided by attention to morphology, history of travel in endemic areas, and response or lack of response to prescribed treat- ments. Physicians should be aware of massive creeping eruption and be able to diagnose it as well as normal CLM. Tourists traveling to tropical countries should be cautioned and supplied with education about proper safety and prevention when sleeping outdoors.
PETERSON, JENSEN, PETERSON, BRADSHAW, NELSON 61 FAMILIAL MULTIPLE LIPOMATOSIS WITH CONCURRENT ANGIOLIPOMAS: A CASE REPORT AND REVIEW OF THE LITERATURE
Melissa Voutsalath DO,* Michelle Bruner DO,** Michael Whitworth DO*** *Intern, Oakwood Healthcare System, Oakwood Southshore Medical Center, Trenton, Michigan **First-year dermatology resident, Oakwood Healthcare System, Oakwood Southshore Medical Center, Trenton, Michigan ***Attending Physician, FAOCD, Oakwood Healthcare System, Wyandotte, Michigan
ABSTRACT
Familial multiple lipomatosis is a relatively rare, hereditary syndrome in which patients have diffuse benign lipomas. Angiolipomas have a clinically similar presentation to lipomas and can only be distinguished by histological analysis. Literature describing concurrent lipomas and angiolipomas in one individual is rare. This paper presents a patient with this atypical finding, FML with histological evidence of both lipomas and angiolipomas. Although FML is a relatively benign disorder, the lesions can have a drastic effect on a patient’s quality of life. While a gold standard treatment has not been established, treatment options continue to expand.
Case Report A 59-year-old male of Middle Eastern descent presented for surgical excision of multiple lipomas on both upper extremi- ties. He first noticed the development of multiple, nontender nodules on his fore- arms when he was about 17 years old. Over time, these slow-growing nodules increased in number and developed on his thighs, abdomen, back, chest, forehead, and both upper extremities. These tumors were distressing to the patient. He described a sensation of mild pinching preceding the formation of a new growth. Also, he was embarrassed and fearful that the lesions would affect his professional and personal life. This resulted in a decrease in the patient’s quality of life and even led him to wear long sleeve shirts year round. Figure 1. Family pedigree lipomas.3,4 Numerous lipomas occurring The subjective findings were obtained in an individual is often a manifestation during a consultation with the patient. His with subjective findings, demonstrated a of a lipomatous disorder or an unusual past medical history included hyperlipi- distinctive case of familial multiple lipoma- syndrome. These include familial multiple demia. His past surgical history included tosis, occurring in three generations. This lipomatosis, multiple symmetric lipoma- an appendectomy and five separate case is unique because it demonstrates a tosis, multiple familial angiolipomatosis, surgeries removing multiple lipomas from rare finding of both multiple lipomas and infiltrating or diffuse lipomatosis, adiposis both upper extremities. He denied alcohol, angiolipomas occurring in an individual dolorosa and Proteus syndrome.1 tobacco, and illicit drug use. The patient with familial multiple lipomatosis. had no known allergies and took no medi- Familial multiple lipomatosis (FML) cations. The patient worked in the food Discussion is a rare hereditary syndrome consisting sales industry. Also, his family history was of diffuse benign lipomas occurring in significant for a lipomatous disorder in Lipomas are the most common benign individuals across multiple generations. multiple relatives (Figure 1). soft-tissue tumor.1-4 These tumors occur Based on available studies that show high The patient’s physical exam showed in the general population with a prevalence levels of penetrance among first-degree multiple, moveable nodules. They were of 2.1 per thousand people.5,6 They are relatives, the inheritance pattern is thought located on the abdomen, back and all four slow-growing tumors composed of lobules to be autosomal dominant. However, extremities, sparing the hands and feet. of mature adipocytes surrounded by a some autosomal recessive cases have been The nodules varied in size from 1-5 cm fibrous capsule (Figure 2). Most lipomas reported. The etiology of FML is not well and were all non-tender on palpation. arise in persons between the ages of 40 understood, but is thought to be a result of Fifteen of these nodules were excised, in and 60, although rare specific subtypes do translocation of the high-mobility group their complete encapsulated form, from occur in children. Cytogenetics of lipomas protein isoform I-C on chromosome the patient’s left forearm. Histopathologic is thought to be due to the transloca- 12 and lipoma-preferred partner gene evaluation of the lesions was then obtained. tion 12q13-5;3q22.7 They are more often on chromosome 3. Other theories have Each specimen demonstrated a smooth solitary than multiple. Lipomas follow a related the appearance of lesions to trauma surface invested by a thin, translucent benign course, and malignant transforma- or endocrine factors. This syndrome has membrane. Cut sections showed soft tion is exceedingly rare. However, case been associated with alcoholism, diabetes fatty tissue consistent with both lipomas reports of liposarcomas have been reported mellitus, and possibly hyperlipidemia. and angiolipomas. These results, along in patients with a history of subcutaneous Many authors report a slightly increased 62 FAMILIAL MULTIPLE LIPOMATOSIS WITH CONCURRENT ANGIOLIPOMAS: A CASE REPORT AND REVIEW OF THE LITERATURE shoulders.1,8,9 Multiple symmetric lipo- matosis tends to occur in middle-aged individuals and has not been shown to be hereditary, although some familial cases have been described.6-8 Angiolipomas are clinically similar to lipomas and can only be distinguished by histological analysis. Angiolipomas usually measure less than 2 centimeters in diameter. These tumors may occur on any body part, but they are most commonly located on the forearm. Histologically, Figure 2. Lipoma consisting of a thin Figure 6. Right forearm showing scars they consist of mature fat cells admixed fibrous stroma capsule surrounding from previous surgical lipoma removal. with small blood vessels. Occasional vessels mature lipocytes. are occluded by fibrin thrombi and may cause pain. Familial multiple angiolipo- matosis is a benign, autosomal dominant condition that is thought to be a subtype of FML or may be a distinct, unrelated entity. Cytogenetic studies of angioli- pomas do not demonstrate consistent find- ings, and specific gene rearrangements in familial angiolipomatosis have not been described.1,7,10 Most authors describe lipomas and angi- olipomas as separate entities. Literature Figure 7. Right lower back and describing concurrent angiolipomas and Figure 3. Angiolipoma showing posterior view of forearm. lipomas in one individual is rare. Wilson4 increased vascular proliferation along described a case of sporadic multiple lipo- periphery. matosis in which six of 13 tumors removed were pathologically lipomas, and the remaining seven were angiolipomas. The patient presented here also has histological evidence of both lipomas and angioli- pomas. Without access to the patient’s family medical records, it is unknown if this is a sporadic occurrence of lipomas and angiolipomas in one individual or if this mixed type has occurred in other family members. Despite the benign nature of lipomas Figure 8. Left lower back and posterior and angiolipomas, many patients elect view of forearm. to have tumors removed for cosmetic Figure 4. Closer look at angiolipoma reasons. Since spontaneous regression of with increased vascularization and incidence of FML in men. This is thought lipomas is rare, many patients with FML stroma surrounding mature lipocytes. to be due to higher androgen level seek removal due to discomfort and disfig- stores.1,2,4-6,8-10 urement. For this reason, investigators Individuals with FML have discrete, have sought less-deforming approaches mobile tumors surrounded by a fibrous to remove multiple lipomas in patients capsule.8 Tumors typically develop in the with FML. The goals of removal are to third decade of life and measure a few obtain complete tumor excision while centimeters in diameter, but can range maintaining a good cosmetic result in a in size from a few millimeters to several cost-effective manner.5,6 Lipomas have the centimeters. The number of tumors in potential to recur if not completely excised, an individual may vary considerably. with a reported recurrence rate of approxi- Tumors usually undergo a period of rapid mately 5%. Commonly, lipoma treatment growth, then stabilize once they have includes removal of individual lipomas reached their individual maximum size.6 through separate incisions. Even when a Lipomas are generally asymptomatic and tumor is completely excised, this approach Figure 5. Right arm showing multiple develop predominantly on the trunk and may leave patients with countless scars. An lipomas extremities, typically sparing the neck and alternative approach is liposuction. While shoulders. This characteristic finding helps this method is less scarring, it is difficult to distinguish FML from another lipomatous visualize the tumors. As a result, fragmen- disorder known as multiple symmetric tation of the tumor, leading to incomplete lipomatosis, also referred to as Madelung’s removal, cannot be prevented, even with disease. Madelung’s disease can be distin- the assistance of endoscopic visualization.3,5 guished from FML by a characteristic An innovative approach to lipoma removal nonencapsulated lipomatous infiltration is endoscopy with ultrasonic scalpel. Like of tissue most commonly on the neck and the aforementioned approach, patients are VOUTSALATH, BRUNER,HITWORT 63 left with few scars when compared with basic surgical removal. The shortcom- ings of this technique include possible emulsification and/or fragmentation of the lesion as well as a significant increase in cost. Ronan documented a separate approach that reportedly allowed complete excision under direct visualization without fragmentation or emulsification of the tumors. The described procedure is able to be preformed in an outpatient setting and is relatively cost effective. This technique was used to remove 35 lipomas through four separate incisions ranging from 2-4 cm in a suprafascial plane with the aid of a lighted breast retractor. The procedure allowed complete excision of the tumors with excellent cosmetic results and minimal postoperative scarring. Reported postoper- ative complications included an abdominal seroma.5 Conclusion Both lipomas and angiolipomas are relatively common, benign soft-tissue tumors. Familial syndromes in which individuals have either multiple lipomas or multiple angiolipomas are well docu- mented; however, there is little discussion in the literature of an inherited syndrome of soft-tissue tumors that demonstrates both lipomas and angiolipomas in the same individual. This case shows a familial syndrome of both lipomas and angio- lipomas. Although these tumors rarely undergo malignant transformation, they can cause extreme physical disfigurement and possible discomfort. For this reason, multiple excision techniques have been developed with the goal of complete exci- sion of the tumor with minimal scarring.
References: 1. Bolognia JL, et al. Dermatology. Edinburgh, London. Mosby; 2003;2:1888-1891. 2. Keskin D, Ezirmik N, Celik H. Familial multiple lipomato- sis. Israel Med Assoc J 2002;4:1121-1123. 3. Al-Basti HA, El-Khatib HA. The use of suction-assisted surgical extraction of moderate and large lipomas: long- term follow-up. Aesth Plast Surg 2002;26:114-117. 4. Wilson D, Boland J. Sporadic multiple lipomatosis: A case report and review of literature. W V Med Journal 1994; 90:145-146. 5. Ronan SJ, Broderick T. Minimally invasive approach to familial multiple lipomatosis. Plast Reconstr Surg 2000;106(4)8:78-80. 6. Leffell DJ, Braverman IM. Familial multiple lipomatosis. J Am Acad Dermatol 1986; 15:275-279. 7. Wu JM, Montgomery E. Classification and pathology of lipomatous disorders. Surg Clin North Am 2008;88(3):483- 520. 8. Gologorsky Y, Gologorsky D, Yarygina A, et al. Famil- ial multiple lipomatosis: report of a new family. Cutis 2007;79:227-232. 9. Toy BR. Familial multiple lipomatosis. Dermatol Online J 2003;9(4):9. 10. Abbasi NR, Brownell I, et al. Familial multiple angiolipo- matosis. Dermatol Online J 2007;13(1):3.
64 FAMILIAL MULTIPLE LIPOMATOSIS WITH CONCURRENT ANGIOLIPOMAS: A CASE REPORT AND REVIEW OF THE LITERATURE INFECTIOUS MONONUCLEOSIS PRESENTING AS ACUTE URTICARIA
Kristy P. Gilbert DO*, Lloyd J. Cleaver DO, FAOCD** *Dermatology Resident, 1st Year, Northeast Regional Medical Center **Program Chairman, Northeast Regional Medical Center, Clinical Professor Department of Internal Medicine, Dermatology Chair, A.T. Still University- Kirksville College of Osteopathic Medicine
ABSTRACT
Urticaria is a common entity with lifetime occurrence estimated from 1% to 30%.1, 2 The individual lesions of urticaria, classically described as hives or wheals, are characteristically transient in nature, usually lasting less than 24 hours.2 A vast number of urticaria cases are idiopathic, but known etiologies of urticaria are extensive. A commonly associated cause of urticaria is infection. Bacterial, fungal, parasitic and viral infections have all been associated, and some sources report that up to 80% of urticarial cases in pediatric patients are a result of concomitant infection. Here we present a case of acute urticaria as the primary manifestation of infectious mononucleosis.
Background of infectious mononucleosis in general are reported as occurring in only 2-3% Urticaria is a common entity with life- of cases.7 Perhaps the most well docu- time occurrence estimated from 1% to mented cutaneous eruption associated with 30%.1,2 The individual lesions of urticaria, infectious mononucleosis is that which classically described as hives or wheals, can occur after administration of ampi- are characteristically transient in nature, cillin during primary infection with the usually lasting less than 24 hours.2 An virus. Many of the cases of urticaria and episode of acute urticaria, by definition, is infectious mononucleosis that have been an attack lasting less than six weeks dura- reported have been those presenting as cold tion, while chronic urticaria is generally urticaria.8,9 Here we present a case of acute that which lasts greater than six weeks.3 urticaria as the primary manifestation of A vast number of urticaria cases are idio- infectious mononucleosis. Figure 1 pathic, but known etiologies of urticaria are extensive. Medications such as beta- Case Report upon the presentation of the patient to our lactam and sulfa antibiotics, as well as many office. others such as opiates, nonsteroidal anti- A 12-year-old Caucasian male was On initial presentation to the emergency inflammatory drugs (NSAIDs), aspirin, referred to our dermatology department room (ER), the patient received a diag- beta-blockers and angiotensin-converting from the emergency department with a nosis of urticaria, was treated with diphen- enzyme inhibitors, are common causes. report of an unusual rash. The patient hydramine, epinephrine, loratadine and Others include foods, insect bites and had presented to the emergency room stings, radiocontrast media, transfusion the previous night with a complaint of intramuscular corticosteroids, and was sent reactions, paraneoplastic syndromes, and an extremely pruritic rash present on his home stable with marked reduction in his contact allergens such as latex, cosmetics, bilateral lower extremities, back, and face. pruritus and rash. The patient returned to and various chemicals. The physical Physical examination as reported by the the ER the following day with recurrence of urticarias are those which are caused by emergency physician described the rash as severe pruritus and development of more a physical stimulus and include dermato- “hives.” Physical examination was other- lesions, which the ER physician described graphic, cholinergic, cold-type, delayed- wise remarkable only for periorbital edema as completely different from the hive-like pressure, vibratory, solar, and aquagenic as well as low-grade fever. Review of lesions seen the previous evening. It was urticaria. Certain diseases such as thyroid systems revealed no new exposures, and the at this time that we were consulted and the disease and various autoimmune disorders patient and guardian denied recent illness. patient sent to our office. have also been associated with urticarial Laboratory analysis was performed upon On physical exam we noted large, outbreaks.2,3 Another common cause of initial presentation, revealing a white blood symmetric, erythematous, serpiginous urticaria is infection. Bacterial, fungal, count of 17.0 K/CMM (normal 4.0-10.5), lesions on the patient’s chest, abdomen and parasitic and viral infections have all been hemoglobin of 13.7 GM/DL (normal back. Annular, erythematous plaques with associated, and some sources report that 12.5-16.1), hematocrit of 40.5% (normal central clearing and numerous wheals were up to 80% of urticarial cases in pediatric 36.0-47.0), and platelet count of 175 K/ also noted on the patient’s bilateral upper patients are a result of concomitant infec- CMM (normal 130.0-400.0). Lymphocyte and lower extremities, as well as abdomen tion. Viruses implicated include coxsackie, numbers were elevated at 13.4 K/CMM (Figure 1). Further examination revealed hepatitis, human immunodeficiency virus, (normal 1.0-3.5) and monocytes elevated continued mild periorbital edema, bilateral herpes simplex, and Epstein-Barr virus. at 0.9 K/CMM (normal 0.0-0.6) with a anterior and posterior cervical lymphade- Cases of infectious mononucleosis due comment from the lab of reactive lympho- nopathy (Figure 3), and marked tonsillar to Epstein-Barr virus as a cause of acute cytes present. A basic metabolic panel was hypertrophy and erythema. The patient urticaria have been infrequently docu- also performed, and all results were within also complained of new-onset sore throat. mented. Dermatoses commonly associated normal limits. Due to abnormalities in the The patient did again have a low-grade with mononucleosis are typically described patient’s complete blood count, the emer- temperature of 101.7 F. Due to the unusual as maculopapular erythema, petechial or gency room physician ordered a peripheral nature of the serpiginous lesions (Figure exanthematous.5, 6 Skin manifestations blood smear, but these results were pending 2), we performed a biopsy. We also sent GILBERT CLEAVER 65 The pathophysiology of urticaria induced by viral diseases such as infectious mononucleosis remains elusive. Causal relationships have been demonstrated by an increased level of cryoglobulins and agglu- tinins in patients with mononucleosis, but the increase in itself does not necessarily induce urticaria.8, 11 Complement activa- tion and therefore facilitation of mast-cell degranulation are associated with autoan- tibodies in chronic urticaria.2 Acute urti- caria, also complement-mediated, has been Figure 2 proposed to be related to immune complex formation. The presence of complement components, viral particles, and antibodies in the cryoprecipitates of some patients, as stated by Lemanske and Bush, is further evidence of this proposal.8 Viral infections such as Epstein-Barr are commonly cited in textbooks as possible etiologies of urticaria. Though infre- quently seen, this may be the only initial complaint with which a patient presents. Proper history and physical as well as appropriate laboratory evaluation and close follow-up are essential in the management of urticaria. Figure 3. Anterior and posterior cervical lymphadenopathy. References: 1. Zuberbier T. Urticaria. Allergy 2003: 58:1224. 2. Grattan C, Black AK. Urticaria and Angioedema. In: the patient for a rapid strep screen and a Bolognia: Dermatology, heterophile antibody test. Results were Volume 1. Bolognia, JL, Jorizzo, JL, Rapini, RP, et al. eds. London: Mosby, 2003. pp. 287-301. all available the following day. Histologic 3. Dibbern DA. Urticaria: Selected Highlights and Recent impression was that of mild perivascular Advances. Medical Clinics of North America 2006; 901. 4. Mortureux P, Leaute-Labreze C, Legrain-Lifermann V, et inflammation with foci of neutrophils and al. Acute urticaria in infancy and early childhood: A pro- eosinophils present, consistent with urti- spective study. Arch Dermatol 1998; 134: 319. 5. Macsween KF. Epstein-Barr virus- recent advances. caria. The pathologist also made refer- Lancet Infect Dis 2003; 33: 131-40. ence to results of the peripheral smear that 6. Cowdrey SC, Reynolds JS. Acute urticaria in infectious mononucleosis. Ann Allerg 1969; 27: 182-187. was performed. This revealed an absolute 7. Africk JA, Halprin KM. Infectious Mononucleosis Present- lymphocytosis and lymphocytes displaying ing as Urticaria. JAMA 1969; 209(10): 1524-1525. 8. Lemanske Jr. RF, Bush RK. Cold urticaria in infectious viral-type or Downey-type changes consis- mononucleosis. JAMA 1982; 247(11): 1604. tent with infectious mononucleosis. As 9. Mesko JW, Wu LY. Infectious mononucleosis and cold urticaria. JAMA 1982; 2487: 828. expected, the patient’s heterophile antibody 10. McCarthy JT, Hoagland RJ. Cutaneous manifestations of test was positive. infectious mononucleosis. JAMA 1964; 1872: 193-194. 11. Morais-Almeida M, Marinho S, Gaspar A, Arede C, Lou- The patient was continued on the lorat- reiro V, Rosado-Pinto J.Cold urticaria and infectious adine daily and started on hydroxyzine mononucleosis in children. Allergologia et immunopatho- every 4-6 hours as needed for pruritus. logia 2004; 32(6): 368-371. Upon follow-up, the patient’s rash resolved within one week with continued use of antihistamines. Discussion Diagnosis of infectious mononucleosis is based on serologic testing, clinical mani- festations, and hematologic abnormali- ties.5 Clinical manifestations can include a variety of changes including variable dermatoses as previously described, eyelid edema, palatal petechiae, pharyngeal inflammation and exudate, fever, lymph- adenopathy, hepatosplenomegaly, and sometimes frank jaundice. 5, 10 Our patient presented initially with only two physical manifestations of infectious mononucle- osis, eyelid edema and acute urticaria, the latter of which is infrequently documented in these cases.10
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Contact the DF at 847.328.2256 or via e-mail at Dermatology Foundation [email protected]. Shaping the Future of Dermatology LYMPHOMATOID PAPULOSIS: A CASE PRESENTATION AND DISCUSSION
David B. Roy, DO,* Kyle M. McWhirter, DO,** Don A. Anderson, DO, FAOCD, FASMS*** * 3rd year Resident, AZCOM/Arizona Desert Dermatology and Surgery, Kingman, AZ ** Intern, Henry Ford Macomb Hospital, Clinton, MI *** Program Director, AZCOM/Arizona Desert Dermatology and Surgery, Kingman, AZ
ABSTRACT
Lymphomatoid papulosis (LyP) is an uncommon disease characterized by chronic, recurrent, self-healing skin eruptions localized mainly to the trunk and extremities. The disease is clinically benign, and histologically malignant. This case details the successful diagnosis and treatment of lymphomatoid papulosis using low-dose systemic methotrexate.
Case Report A 71-year-old Caucasian male presented to the clinic with multiple pruritic, painful, erythematous papules and patches of 10 years duration. Lesions were present mainly on the trunk and extremities. Erythematous plaques with micaceous scale were present on the elbows and left abdomen; however, these lesions were distinct from the others. The patient had been to numerous physicians for the pruritic and painful skin lesions, and several biopsies had been obtained; yet no definitive diagnosis had ever been successfully established. The patient had undergone treatment for diseases such as psoriasis, eczema, urticaria, scabies and other parasitic conditions, all of which yielded little to no relief. It is important to note that the lesions were completely unresponsive to topical and systemic corticosteroids. The patient’s past medical history was significant for psoriasis, hypertension, coro- nary artery disease, myocardial infarction, cardiomyopathy with an ejection fraction of 37%, status-post coronary artery bypass Figure 1 – Hematoxylin-eosin stain, 4x Figure 2 – Hematoxylin-eosin stain, graft, peptic ulcer disease, anxiety, dyslipi- 10x demia, and hypothyroidism. The patient’s a week and folic acid 1 mg daily. A consul- medications include Zetia, Toprol, niacin, tation with oncology was also obtained. To weeks with possible atrophic scar forma- cilostazol, Micardis, aspirin, levothyroxine, obtain more clearance of lesions, the dose tion, hypo- or hyper-pigmentation. The Ativan, Vioxen and Dovonex. of methotrexate was increased to 25 mg a hallmark feature of the disease is the benign Two 8mm punch biopsies were obtained, week. After two weeks, the patient began to waxing and waning of the skin lesions, and the specimens were sent for histo- show improvement. Twelve months after which spontaneously resolve within two pathologic evaluation. Dermatopathology the start of treatment with methotrexate, to eight weeks. Along with the waxing and revealed superficial and mid-perivascular the patient has seen an approximate 95% waning course of the disease, lesions may be dermatitis with atypical lymphocytes and improvement in skin lesions. The dose of accompanied by pruritus or pain, although scattered eosinophils. There was a slightly methotrexate has been lowered to 10 mg many remain asymptomatic. Lesions most acanthotic epidermis with mild spongiosis, weekly with no flare of his disease. commonly are located diffusely over the and there was elastosis in the dermis asso- trunk and limbs, but localized cases have ciated with reactive fibrohistiocytic cells. Discussion been reported. The disease may occur at Immunohistochemistry revealed CD30- any age, but is most common in adults with positive lymphocytic infiltrate consistent Lymphomatoid papulosis, first described a mean age of mid-forties. The disease with lymphomatoid papulosis (Figures by Macaulay in 1968, is an uncommon affects both sexes equally.1-5 1-4). disease characterized by papules, nodules Lymphomatoid papulosis is part of the After the diagnosis of lymphomatoid or plaques that continually erupt in crops, spectrum of CD30+ cutaneous lymphop- papulosis was established, the patient was grow rapidly over a few days, ulcerate, and roliferative disorders. The disease is clini- started on methotrexate 15 mg orally once heal spontaneously over a period of several cally benign but histologically malignant. ROY, MCWHIRTER, ANDERSON 69 histiocytes and small lymphocytes. Type imiquimod, systemic interferon a-2-a, oral B lesions, or the Sezary cell type, demon- psoralen plus ultraviolet A (PUVA), bath strate an infiltrate of small to medium sized PUVA, UVA alone, narrow and broadband T-lymphocytes with cerebriform, hyper- UVB, etretinate, bexarotene, extracorporeal chromatic nuclei with scant cytoplasm. phototherapy, systemic and local corticos- Type A and type B lesions have been asso- teroids, excision and radiotherapy.13-17 ciated with lymphoma. Type C cells are similar to type A cells, but the atypical References: lymphoid cells either represent more than 1. Dalle S, et al. Lymphomatoid Papulosis Localized to the 50% of the infiltrate simulating ALCL or Face. Dermatology Online Journal 2006; 3;12 4-5, 9-10 2. Caraglia M, et al. Conditions Suggesting Lymphoma. form sheets or large nodules. Journal of Clinical Oncology 2005; 3843-3848 3. Scarisbrick JJ, et al. Regional Lymphomatoid Papulosis: A Report of Four Cases. British Journal of Dermatology Treatment 1999; 141; 1125-1128. 4. Nijsten T, et al. Lymphomatoid Papulosis in Children: There are several treatment modalities A Retrospective Cohort Study of 35 Cases. Archives of Dermatology 2004; 140; 306-312 available for lymphomatoid papulosis. 5. Zirbel G, et al. Lymphomatoid Papulosis in Children. When deciding on the best treatment Journal of American Academy of Dermatology 1995; 33, Figure 3 – Hematoxylin-eosin stain, 741-748 40x course, one must assess the severity of the 6. Zackheim H, et al. Lymphomatoid Papulosis associated disease versus the potential risks of the with Mycosis Fungoides: A study of 21 Patients including analyses for Clonality. Journal of American Academy of treatment. Observation alone may be used Dermatology 2003; 49:620-623 in patients with clinically mild forms of the 7. Gruber R, et al. Prognosis of Lymphomatoid Papulosis. The Oncologist 2006; 11; 955-957 disease. 8. Dawn G, et al. Co-existent Primary Cutaneous Anaplastic Large Cell Lymphoma and Lymphomatoid Papulosis. Methotrexate has proven the most effec- Clinical and Experimental Dermatology 2003; 28; 620- tive in clearing the lesions of lymphoma- 624 9. Laube S, et al. Consequences of Misdiagnosis of Lym- toid papulosis with success rates exceeding phomatoid Papulosis. European Journal of Cancer Care 90%. Patients with severe lymphomatoid 2006; 15; 194-198. 10. El Shabrawi-Caelen L, et al. Lymphomatoid Papulosis: papulosis and other CD30+ lymphoprolif- Reappraisal of Clinicopathologic Presentation and Classi- erative diseases may be treated successfully fication into Subtypes A, B, and C. Archives of Dermatol- ogy 2004; 140-447. for years with low doses of methotrexate, 11. Vonderheid Eric, et al. Methotrexate is effective Therapy 10 to 25 mg every one to four weeks, with for Lymphomatoid Papulosis and Other Primary Cutane- ous CD30-Positive Lymphoproliferative Disorders. Jour- minimal risk for adverse effects. In order to nal of the American Academy of Dermatology 1996; 34; maintain clearance of the disease and mini- 470-481 12. Bergstrom J, et al. Topical Methotrexate for Lympho- mize adverse effects, it is recommended matoid Papulosis. Journal of the American Academy of to start at a low dose of methotrexate, Dermatology 2003; 49; 937-939. 13. Krathen R, et al. Bexarotene is a New Treatment Option such as 10 mg, and titrate up to 25 mg or for Lymphomatoid Papulosis. Dermatology 2003; 206; whatever dose achieves complete clear- 142-147 Figure 4 – CD30 14. Volkenandt M, et al. PUVA-Bath Photochemotherapy ance. After several weeks of maintenance Resulting in Rapid Clearance of Lymphomatoid Papulosis therapy at this optimal dose, it is a good in a Child. Archives of Dermatology 1995; 131; 1094 15. Vonderheid E, et al. Methotrexate is effective Therapy for Five to 20% of the cases of lymphomatoid idea to slowly titrate down to the minimal Lymphomatoid Papulosis and Other Primary Cutaneous papulosis may evolve into a lymphoma, effective dose to maintain the clearing and CD30-Positive Lymphoproliferative Disorders. Journal of the American Academy of Dermatology 1996; 34; 470- with mycoses fungoides being the most minimize adverse effects. However, the 481 common, followed by CD30+ T-cell use of methotrexate in the treatment of 16. Schmuth M, et al. Therapeutic Use of Interferon-a for Lymphomatoid Papulosis. Cancer 2000; 89:1603-1610 lymphoma and Hodgkin’s disease. The lymphomatoid papulosis is not without 17. Hughes P. Treatment of Lymphomatoid Papulosis with lymphoma typically develops years after risks, with the most important potential Imiquimod 5% Cream. Journal of American Academy of Dermatology 2006; 546-54 the onset of lymphomatoid papulosis, but adverse effect being methotrexate-induced may develop at any time during the course hepatic fibrosis or cirrhosis. Pulmonary of the disease. Patients with lymphomatoid toxicity and bone marrow suppression are papulosis and a second lymphoma limited other complications that may develop with to the skin typically have a good prognosis. methotrexate. The risk of adverse effects Patients with lymphomatoid papulosis seems to be related to the total cumulative who develop a systemic CD30-positive dosage of methotrexate. Patients should lymphoma generally have a poorer prog- be monitored carefully with lab tests and nosis. The disease must be differentiated periodic liver biopsies while on long-term from PLEVA, which presents similarly.3-10 suppressive therapy with methotrexate to prevent development of methotrexate- Dermatohistopathology induced toxicity.11 Topical methotrexate has also been The diagnosis of lymphomatoid papu- demonstrated in one study to clear lesions losis may be confirmed histologically by more rapidly with less scarring in compar- classifying the specimen into one of three ison to observation alone. The patient in histological subtypes: type A, type B and this case study, treated with topical metho- type C. Type A is most common and trexate, had less systemic absorption and accounts for 75% of all LyP cases. Type A was at less risk for adverse effects from lesions, also known as histiocytic type or methotrexate toxicity. However, metho- Reed-Sternberg type, are CD30+ (Ki-1+), trexate is not currently available for topical large atypical lymphoid cells that repre- dermatologic use.12 sent less than 50% of the infiltrate and do Other treatments that have shown effec- not form sheets or nodules. The infiltrate tiveness in temporarily clearing lesions of is mixed with neutrophils, eosinophils, lymphomatoid papulosis include topical
70 LYMPHOMATOID PAPULOSIS: A CASE PRESENTATION AND DISCUSSION PEMPHIGUS ERYTHEMATOSUS: A CASE REPORT AND OVERVIEW OF PEMPHIGUS VARIANTS
Risa Behar Ross, DO,* David Esguerra, DO, FAOCD,** Richard Miller, DO, FAOCD*** *First-year Dermatology Resident, SunCoast Hospital/NSU-COM, Largo, Florida **Assistant Clinical Professor of Dermatology, SunCoast Hospital/NSU-COM, Largo, Florida ***Dermatology Residency Program Director, SunCoast Hospital/NSU-COM, Largo, Florida
ABSTRACT
Pemphigus is an autoimmune bullous disorder that is a well known entity in the field of dermatology. There are various types of pemphigus, including pemphigus vulgaris, pemphigus foliaceous, paraneoplastic pemphigus, pemphigus vegetans, and pemphigus erythematosus, as well as other variants. Pemphigus erythematosus, also known as Senear-Usher syndrome, is a rare disease that has features of both pemphigus foliaceous and lupus erythematosus. This disease can have a chronic course and is often misdiagnosed for many years, therefore delaying beneficial treatment. Through this case report we will review pemphigus erythematosus and key clues for diagnosis, as well as review and compare clinical and histological features of the various types of pemphigus.
Case Presentation positive ANA, positive anti-Ro antibodies, treatment options. Rituximab, a chimeric elevated ESR, and elevated circulating IgG monoclonal anti-CD 20 antibody, is a Our patient was a 47-year-old African and IgA. These results, despite the lack fairly new treatment option for pemphigus American female who presented to us of interface change, correlated with our patients that has shown promise in treating complaining of a rash on her bilateral clinical findings, suggesting a diagnosis these severe, uncontrolled cases.9,13 cheeks, upper and lower extremities, trunk, of pemphigus foliaceous with early lupus Pemphigus erythematosus is a rare and scalp that had waxed and waned for erythematosus or pemphigus erythema- variant of pemphigus that has overlap over 10 years. She was previously diag- tosus. Our treatment plan was designed features of pemphigus foliaceous and nosed with psoriasis. She had been treated and included a prednisone taper for six lupus erythematosus. This is also known with topical corticosteroids, shampoos, months, hydroxychloroquine 200 mg twice as Senear-Usher syndrome, which was first and etanercept, without improvement of daily, and mycophenolate mofetil 1 gram in described in 1926 by Francis Senear and her condition. She stated the rash was the morning followed by 1.5 grams in the Barney Usher.1 The diagnosis can be quite scaly, pruritic and quite painful at times. evening. This therapy was postponed until elusive, as the skin lesions are often misdi- Upon further questioning, she did admit to after a scheduled hysterectomy for unre- agnosed as seborrheic dermatitis or psori- fatigue, joint pain, photosensitivity, head- lated dysfunctional uterine bleeding. The asis and treated as such for many years, aches, patchy hair loss, and a history of patient is scheduled to begin this regimen sometimes with improvement of the skin hypothyroidism. She denied any recent once she has recovered and is currently lesions. Once improvement is seen, some illness, fever, chills, travel history, oral using topical corticosteroids with some patients do not pursue further workup until involvement, shortness of breath, cough, relief of symptoms. years later when their disease flares despite chest pain, renal disorders, or any history topical treatment. Further complicating of any autoimmune disorders. She had Discussion the diagnosis, patients may also have skin not had any recent lab work or a complete lesions of lupus erythematosus.2 Classically, physical secondary to insurance issues. The worldwide incidence of pemphigus patients with pemphigus erythematosus Physical examination revealed multiple is between 0.5-3.2 cases per 100,000.6 present in middle age with bullae, erosions, well-demarcated, erythematous to dusky Genetic factors may play a role in devel- and erythematous to violaceous plaques violaceous plaques scattered diffusely on opment of pemphigus. Some noted with overlying scale or crust. Involvement her bilateral cheeks, nasal tip, back, and associated HLA types include HLA DR4, of the face, upper chest, and back in a bilateral upper extremities. The plaques HLA DR14, HLA DQ1, and HLA DQ3.2 photodistribution is seen most commonly. on her cheeks and nasal tip were slightly Ashkenazi Jews tend to have an increased The scalp and bridge of the nose are also crusted with overlying white scale. incidence as well.4,6 Prior to the advent of frequently affected areas. Over time, the Examination of her scalp revealed scattered, corticosteroids, this disease was fatal.7,9,10,11 lesions can become widespread and involve poorly demarcated patches of alopecia There are now multiple treatment options the entire trunk and extremities in addi- and diffuse, thickened plaques of greasy including corticosteroids, steroid-sparing tion to the areas described above.2 It has yellow superficial scale with underlying agents, intravenous immunoglobulin, been found that patients with pemphigus erythema. Two biopsies were performed and various chemotherapeutic agents. erythematosus may have an increase in on her initial visit, revealing focal intra- There are currently no FDA-approved certain human leukocyte antigen (HLA) epidermal acantholytic blistering of mid treatments specifically for pemphigus.11 haplotypes, including HLA-A10, HLA-A26, and upper epidermal strata in association Most dermatologists use a combination and HLA-DRw6,3 suggestive of a genetic with significant pigment. No interface therapy approach with the ultimate goal of component in development of the disease. or lichenoid features were noted. Direct discontinuing the systemic corticosteroids As a variant of pemphigus foliaceous, immunoflourescence revealed granular and to minimize the long-term exposure and autoantibodies in pemphigus erythema- linear IgG deposition on epidermal and serious potential side effects. There are tosus are directed toward desmoglein 1, epithelial cell surfaces. Indirect immu- many successful reports of using mycophe- an important factor in keratinocyte adhe- noflourescence was performed and was nolate mofetil as a first-line steroid-sparing sion.2,3 In a large percentage of cases, direct positive for circulating anti-epithelial cell agent for pemphigus.12 Despite the medi- immunofluorescence of these lesions surface pemphigus antibodies and IgG cations that are available, some patients reveals linear deposits of IgG and C3 in pemphigus antibodies at a titer of 1:80. continue to have recalcitrant disease, which the intercellular spaces of the epidermis Lab work was also obtained that revealed a has prompted continued research for new as well as granular deposits of IgG and ROSS, ESGUERRA, MILLER 71 Table 1.
Autoantibody Target Immunofluorescence Substrate Key Features
Pemphigus Desmoglein 3 Most common Vulgaris (oral involvement) Monkey esophagus pemphigus variant. Desmoglein 1 Oral involvement is (cutaneous involvement) often presenting symptom
Pemphigus Variants include Foliaceous Desmoglein 1 Guinea pig lip pemphigus erythematosus and endemic form “Fogo selvagem”
Paraneoplastic Desmoplakin 1 and 2 Associated most Pemphigus BP antigen I commonly with Envoplakin Rat bladder lymphoproliferative Periplakin malignancies Plectin
C3 at the dermoepidermal junction,3 as axillae. Mucosal lesions can be present not like lesions, scattered bullae, or papu- seen in our patient. The indirect immu- only on oral mucosa, but also on genital, losquamous lesions. The most common noflourescence substrate is guinea pig conjunctival, and upper airway mucosa. finding in paraneoplastic pemphigus is an lip.3,4 Although pemphigus erythematosus Mucosal lesions may precede cutaneous intractable stomatitis that is resistant to does tend to have a more benign course, lesions by up to several months.6 The therapy.14 On histology, paraneoplastic it can be chronic, and these patients do bullae are described as flaccid, and it is pemphigus can be variable due to the require systemic treatment to control the often difficult to find an intact bulla on polymorphous lesions that are present.14 flares of skin lesions and to prevent further physical examination. The bullae heal The most commonly described histologic systemic progression of lupus erythema- without scarring, but post-inflammatory features include keratinocyte necrosis, tosus. Some of the systemic medications hyperpigmentation can be seen at these suprabasilar intraepidermal acantholysis, that are useful for treatment include oral sites.4 These lesions can become quite and vacuolar interface changes.4,14 On corticosteroids, mycophenolate mofetil, widespread and severe. Nikolsky’s sign, immunoflourescence, IgG and complement dapsone, azathioprine, methotrexate, and which is the peripheral extension of a are deposited in epidermal intercellular hydroxychloroquine.3,4,5 The most effective blister following application of lateral pres- spaces, and a granular and linear comple- regimen usually consists of a combina- sure,4,7 is positive in pemphigus vulgaris, ment deposition along the epidermal tion therapy of those listed above. Topical among other blistering disorders. On basement membrane is seen. The indirect corticosteroids are also beneficial in those histology, pemphigus vulgaris shows an immunofluorescence substrate is the rat with limited disease.3,4 Patients should intradermal blister and intercellular edema. bladder.4 The autoantibodies in paraneo- be educated on limited sun exposure and Basal cells separate and are described as a plastic pemphigus have various targets sunscreen use as well as regular follow-up “row of tombstones” along the floor of the including desmoplakin I and II, bullous to monitor progression of the disease. blister.6 On immunofluorescence, there pemphigoid antigen I (BP Antigen I), Another variant of pemphigus foliaceous is IgG and variable C3 deposition on the envoplakin, periplakin, and plectin.15 The has been well documented. The subtype epithelial cell surfaces without deposition prognosis is variable, and there is contro- called endemic pemphigus foliaceous or along the basement membrane zone.8 The versy regarding the role of the underlying “fogo selvagem” is seen in children and indirect immunofluorescence substrate malignancy on the outcome of the disease. adults in the rainforests of various South is monkey esophagus.4 The associated Pemphigus can also been induced by American countries including Brazil, autoantibody for pemphigus vulgaris is certain medications. Drug-induced Colombia, Paraguay, and Peru.1,4,5 It has desmoglein 3 for oral involvement and pemphigus is rare and can be variable in been suggested that the pathogenesis of desmoglein 1 for cutaneous involvement. presentation. Drug-induced pemphigus this variant of pemphigus foliaceous is Both of these autoantibodies are present in may take up to several months to develop related to a bite by a black fly, Simulium patients with oral and cutaneous involve- after starting the medication. The most nigrimanum,2 or some other unknown ment. Both desmoglein 1 and desmoglein commonly implicated drugs include environmental factor.1 Recently, another 3 play a role in keratinocyte adhesion.9 penicillamine and captopril. Other variant was described in young Tunisian Another type of pemphigus is para- drugs that have been reported to induce women.2 neoplastic pemphigus. As the name pemphigus are pyritinol, thiopronine, The variant pemphigus vulgaris is the suggests, this type of pemphigus is associ- piroxicam, ampicillin rifampicin, pheno- most common type of pemphigus.4,6 ated with malignancies, most commonly barbital, cefadroxil, and ciprofloxin.2,4,16 Patients commonly present in middle age lymphoproliferative malignancies. Non Clinical presentation can be variable, but and complain of oral blisters that rupture Hodgkin’s lymphoma, chronic lymphocytic it is rare to see oral lesions. Drug-induced easily and form erosions. They are often leukemia, and Castleman’s tumor are the pemphigus usually resolves once the drug tender and do not heal readily.2 Patients most commonly associated malignancies. is discontinued; however, there have been with pemphigus vulgaris can have cuta- There have also been reported associations cases reported in which pemphigus persists neous involvement as well as mucous with thymomas and various sarcomas.2,4,14 despite discontinuation of the drug.2,16 membrane involvement. The most Clinical presentation can be variable Pemphigus vegetans is another rare type commonly affected cutaneous sites are and may include severe, painful mucosal of pemphigus. It is a subtype of pemphigus the face, trunk, pressure points, groin, and erosions, erythema multiforme target- vulgaris that is further divided into two 72 PEMPHIGUS ERYTHEMATOSUS: A CASE REPORT AND OVERVIEW OF PEMPHIGUS VARIANTS subtypes: Neumann and Hallopeau. 13. Cianchini G, et al. Treatment of severe pemphigus with rituximab: report of 12 cases and a review of the The Neumann variant is regarded as literature. Archives of Dermatology August 2007; 143 (8): more severe. A distinguishing feature of 1033-8. 14. Robinson N, Hashimoto T, Amagai M, Chan L. The new pemphigus vegetans includes involve- pemphigus variants. Journal of the American Academy of ment of the tongue, known as cerebriform Dermatology May 1999; 40(5): 649-71. 15. Proby C, et al. Human Autoantibodies against HD1/Plec- tongue. Involvement of intertriginous and tin in Paraneoplastic Pemphigus. Journal of Investigative flexural areas with verrucous, vegetating Dermatology 1999; 112: 153-156. 16. Anadolu RY, Birol A, Bostanci S, Boyvat A. A case of lesions are additional unique features. In pemphigus vulgaris possibly triggered by quinolones. the Neumann type, small pustules develop Journal of the European Academy of Dermatology and Venereology March 2002; 16-2: 152-153. at the edge of erosions from ruptured 17. Malik M, Ahmed AR. Dual Diagnosis of pemphigus bullae that then develop into vegeta- vulgaris and connective tissue disease. Journal of the American Academy of Dermatology Oct 2006; 55 (4). tions. In the Hallopeau type, pustules are 18. Brenner S, Bialy-Golan A, Anhalt GJ. Recognition of primarly seen with subsequent vegetation pemphigus antigens in drug-induced pemphigus vul- garis and pemphigus foliaceus. J Am Acad Dermatol formation. Histologic findings and treat- 1997;36:919–923. ment options are similar to those seen with 19. Korman NJ, Eyre RW, Zone J, Stanley JR. Demonstra- tion of an adhering-junction molecule (plakoglobin)in the 4 pemphigus vulgaris. autoantigens of pemphigus foliaceus and pemphigus vulgaris. N Engl J Med 1991;321:631–635. Conclusion Pemphigus is an autoimmune bullous disease with many well described vari- ants including those discussed above, as well as pemphigus herpetiformis and IgA pemphigus. Key features of some of the variants discussed above are summarized in Table 1. It is important to understand the various types and characteristic clinical and histologic features of each type. There are reports of overlap of many autoim- mune diseases;17 however, the overlap of pemphigus foliaceous and lupus erythema- tosus is rarely encountered. There are now many options for treatment of pemphigus and its variants, and continous research is being conducted to provide even more therapeutic options for these patients. It is important to do a full review of systems and blood work if an autoimmune blis- tering disorder is suspected in order to elicit any other systemic diseases that may be present. The dermatologic workup is essential and may provide the initial clues to the diagnosis of a potentially severe or even fatal disease.
REFERENCES: 1. Schwartz R, Majewski S, Majewski SS. Pemphigus Foli- aceous. Emedicine. Available at http://www.emedicine. com/derm/topic318.htm 2. Baroni A, et al. Vesicular and Bullous Disorders:Pemphigus. Dermatologic Clinics Oct 2007; 25 (4). 3. Bharti R, Lazova R. Pemphigus Erythematosus. Emedi- cine Oct 2006. Available at http://www.emedicine.com/ DERM/ topic317.htm 4. Scott J, Ahmed AR. The Blistering Diseases. Medical Clinics of North America Nov 1998; 82-6:1239-1283. 5. Santi C, et al. Pemphigus herpetiformis is a rare clinical expression of nonendemic pemphigus foliaceus, fogo sel- vagem, and pemphigus vulgaris. Journal of the American Academy of Dermatology Jan 1996; 34(1). 6. Zeina B. Pemphigus Vulgaris. Emedicine. Available at http://www.emedicine.com/derm/topic319.htm 7. Mimouni D, Anhalt GJ. Pemphigus. Dermatol Ther 2002; 15: 362–368. 8. Nousari HC, Anhalt GJ. Pemphigus and bullous pemphig- oid. Lancet. 1999: 354: 667– 672. 9. Jessop S, Khumalo NP. Pemphigus: a treatment update. American Journal of Clinical Dermatology 2008; 9(3):147- 54 10. Yeh SW, Sami N, Ahmed RA. Treatment of pemphigus vulgaris: current and emerging options. American Jour- nal of Clinical Dermatology 2005;6(5):327-42. 11. Mao X, Payne AS. Seeking approval: Present and future therapies for pemphigus vulgaris. Curr Opin Investig Drugs, May 2008;9(5)497-504. 12. Esmaili N, et al. Treatment of pemphigus vulgaris with mycophenolate mofetil as a steroid-sparing agent. European Journal of Dermatology March-April 2008; 18(2):159-64.
ROSS, ESGUERRA, MILLER 73 LOXOSCELES RECLUSA BITE: CASE PRESENTATION AND LITERATURE REVIEW
Boris Ioffe, D.O., Pharm.D.,* Alyn Hatter, D.O.,** Bill V. Way, D.O., FAOCD*** * Tarrant County Dermatology Consultants, Fort Worth, TX ** Intern, University Hospitals, Cleveland, OH *** Program Director, Northeast Regional Medical Center – Texas Division, Duncanville, TX
Introduction was significant for diabetes mellitus type 2, which was controlled with metformin, The brown recluse spider, Loxosceles and hypercholesterolemia, for which he reclusa, is one of 11 Loxosceles species native was taking simvastatin. He denied any to the United States. Two exotic species, known exposure to insects or spiders at L. rufescens and L. laeta, are found in the that time. Physical examination revealed United States sporadically.1 The distri- an area of purpura and pallor on his left, bution of brown recluse spiders within medial, upper arm with surrounding the United States is virtually restricted to erythema. The lesion was tender to palpa- known regions across the south and central tion. Because brown recluse spider bite was portions, despite misconceptions.1 There suspected and patient history did not coin- are over 100 related species worldwide. cide with findings, he was asked to return As its name suggests, the brown recluse to the clinic in three days for reevaluation. Figure 1. Large area of ecchymosis, prefers to be hidden in an undisturbed On his second visit, the previously blanching and surrounding erythema environment. It is often found around affected area had expanded to measure 9 at the site of the bite. woodpiles and in attics or garages. It is a x 4 cm with ecchymosis, blanching, and hunting spider but does not actively predate exquisite tenderness. Also present was a humans. At least one report describes over large area of erythema surrounding the 2,000 brown recluse spiders being captured affected area (Figures 1 and 2). In retro- from a home within six months, yet not a spect, the patient did recall doing some single person had been bitten.2 yard work and having a stinging feeling in Loxoscelism has been used to describe his arm around the time of onset of the the manifestations of brown recluse enven- lesion. A punch biopsy was performed omation.3 In addition to the necrotizing at this time to confirm the diagnosis, and skin lesions, systemic effects include fever, routine blood work, including glucose-6- rash, arthralgias and hemolysis. Although phosphate dehydrogenase levels, were fatality is rare, well-documented cases have ordered. He was started on oral dapsone and topical lidocaine for pain control. The been reported. Diagnosis can be difficult Figure 2. Close-up of figure 1 showing and is most likely over-represented in the patient was closely monitored from this extensive ecchymosis and purpura literature. Confirmed cases follow strict time for any signs of systemic toxicity. Oral with blanching of epidermis. criteria requiring a brown recluse to be prednisone was also added to the regimen. captured at the time of the bite or in close Histopathology revealed superficial proximity of the bite and that the spider epidermal necrosis, purpura, and mixed be identified by an arachnologist, health neutrophilic and eosinophilic infiltrates, care provider, or other persons trained features that would be consistent with a in identification.4 Obviously, most cases spider bite (Figure 4). At approximately are diagnosed on clinical grounds alone. two weeks, the wound had achieved full- Diagnostic tests have been developed thickness necrosis, and symptoms of pain but are either not widely available or are and discomfort considerably subsided impractical. Treatment of envenomation is (Figure 3). The patient progressed very also challenging. Supportive measures have well, with complete healing of the lesion been the mainstay of therapy, but more and no sequelae. He was seen approxi- aggressive approaches have been advocated mately four months after initial presenta- by some. tion with complete healing of the affected Figure 3. Patient at two-week follow-up site (Figure 5). visit with full-thickness epidermal Case Report necrosis and starting of wound Discussion contraction. A 59-year-old white male presented to the clinic with the chief complaint Brown recluse, also known as fiddle-back of a rash that started on his left, upper spiders, have a distinctive violin-shaped arm three days prior to his appointment. marking over the dorsal aspect of the cepha- The patient attributed the breakout to lothorax, which may not be readily apparent starting a new medication for neuropathy, in the juvenile.5 This brown-to-grey-brown topiramate (Topamax®), which he had spider has a body length of about 1 cm, discontinued prior to the appointment. but its leg span is about 5 cm. While most Additionally, his past medical history spiders have eight eyes, typically arranged 74 LOXOSCELES RECLUSA BITE: CASE PRESENTATION AND LITERATURE REVIEW Systemic symptoms are rare but include endemic range.16 Brown recluse spider bite fever, rash, arthralgias, hemolysis, renal is historically a clinical diagnosis. There failure and disseminated intravascular is usually a single lesion located on the coagulopathy (DIC). These manifesta- trunk, buttocks or proximal extremities. tions appear to be more severe in children, Erythema with pale ischemia and dusky the population with the most reported color changes note the hallmark of early deaths from loxoscelism.7 It is not yet clear necrosis. The lesion may form a hemor- why the venom produces systemic symp- rhagic vesicle. Older lesions will have toms in some and only local reactions in well-defined central necrosis. Associated others. Numerous mechanisms have been symptoms may include fever, malaise and a proposed, which will be discussed further morbilliform eruption. An enzyme-linked in this article. immunosorbent assay (ELISA) for L. Figure 4. Superficial epidermal Robb and colleagues describe a vascu- reclusa has been developed but may not be necrosis, purpura, and mixed litic exanthem following a confirmed L. widely available.17 Even in confirmed cases, neutrophilic and eosinophilic reclusa envenomation in a 49-year-old the mainstay of therapy is supportive care. dermatitis. patient.6 Their patient developed a gener- Histology will vary with the age of the alized morbilliform eruption with palpable lesion.9 Early results show a neutrophilic purpura within 24 hours from a bite on infiltrate. Later biopsies may show coagu- the thigh. Several cases of intravascular lative necrosis of the epidermis and super- hemolysis following envenomation have ficial dermis. At the border of the necrotic been reported, with the majority being and viable skin, a neutrophilic band may Coombs negative. The few reports found be present. A necrotizing vasculitis with of Coombs positive hemolytic anemia extravasation of red cells may be found in following presumed loxoscelism were some cases.6 positive for IgG and/or complement.7 A dreaded complication of loxoscelism is Treatment DIC. Many studies have been done in an attempt to elucidate the mechanism of this Management should be expectant often fatal cascade. in most cases. Rest, ice and elevation of Figure 5. Patient at four-month the affected extremity can be used in the follow-up showing complete healing Mechanism of Action majority of cases with full recovery and of the lesion with some post- minimal scarring expected. Some anec- inflammatory hyperpigmentation. The dermonecrosis is clearly neutrophil dotal reports suggest using early and late driven. The venom of L. reclusa has been surgical debridement, systemic steroids, in two rows of four, the brown recluse has shown to promote neutrophil recruit- hyperbaric oxygen therapy, electric shock six eyes arranged in three pairs. They are ment and indirectly activate neutrophils therapy, dapsone and colchicine; but for 8,9 nocturnal and hunt prey by attacking it and and promote degranulation. The venom these treatments, either sufficient human subduing it with venom. Although they also increases the prothrombin time (PT) studies are lacking or results are inconsis- 7,9 do not use silk to hunt, they do line their and activated partial thromboplastin time tent. Elston and colleagues compared 8,10 daytime refuge with silk. They can be found (aPTT), and decreases protein C levels. dapsone, colchicine, triamcinolone and in boxes, furniture, attics, woodpiles or any McGlasson and colleagues were able to diphenhydramine in the treatment of L. undisturbed environment. Although they demonstrate in New Zealand white rabbits reclusa envenomation in New Zealand a dose-dependent elevation in the aPTT white rabbits and concluded no signifi- can certainly be inadvertently transported, 10 hidden away in boxes, to new areas, evidence that corrected with mixing studies. cant difference in eschar size was obtained 18 suggests they do not thrive outside of their The venom of L. reclusa contains many with these therapies. Dapsone therapy is known habitat range.1 This range is in the enzymes including proteases, hyaluronidase, complicated by the risk of hemolysis and south, from Texas to Florida, and stretches alkaline phosphatase and sphingomyelinase methemoglobinemia. Early intradermal as far north as Nebraska, Iowa and Illinois. D. Of these enzymes, sphingomyelinase injection of polyclonal anti-Loxosceles Fab Envenomation of humans is typically in self D seems to be most likely responsible for fragments was shown to attenuate necrosis the local and systemic effects of loxos- in an animal model.19 However, its efficacy defense when the spider becomes trapped 11,12,13 against the skin, as when putting on clothing celism. Sphingomyelinase D has been was lost if injected greater than four hours containing the spider or when rolling over at shown to cause platelet aggregation, post envenomation. Patients with severe and life-threatening hemolytic anemia night onto a prowling brown recluse that degrade sphingomyelin on cell membranes, causing cell lysis, activate the complement should receive hemodynamic support has found its way into bed linens.5 The cascade and affect neutrophil chemotaxis. in the form of fluids and transfusions. person may be unaware of the bite until However, the venom does not cause hemol- Intravenous corticosteroids can be of use in hours later. ysis when applied to washed red blood cells autoimmune hemolytic anemia secondary Initially after a bite, swelling and in the absence of serum, suggesting surface to systemic loxoscelism.7 Early surgical erythema will develop. Burning pain metalloproteinases and serum factors are excision should be avoided until after the and pruritis may develop within a few necessary to propagate the reaction.4,14,15 eschar is well formed, as it has been shown 4 hours. Less commonly, a hemorrhagic to prolong healing time.20 vesicle can be seen from hours to days later. Diagnosis Not all bites result in skin necrosis, but Conclusion when present it is usually central and well L. reclusa envenomation should be defined. It will be seen two to three days considered when a bite results in signifi- The diagnosis and management of following the bite. The necrotic area will cant dermal necrosis.9 However, unless the loxoscelism is challenging at best. Many be rimmed by white, ischemic tissue that spider is caught and positively identified by patients may be unaware of the bite is surrounded by erythema. This has been an arachnologist, some believe loxoscelism initially and only rarely capture the spider called the “red, white and blue” sign.6 should not be diagnosed outside of its in question. This forces a clinical diag- IOFFE, HATTER, WAY 75 nosis in the majority of cases, which may be appropriate in regions known to have L. reclusa. Diagnostic assays are being devel- oped to detect envenomation but may not be widely available. Sphingomyelinase D within venom appears to be the enzyme responsible for promoting necrosis and initiating systemic effects. Most cases of loxoscelism are mild and require only supportive management and wound care. Most patients can expect full recovery within a few weeks with minimal scar- ring. Life-threatening cases of envenoma- tion have been reported and may require more aggressive therapy. Further trials on human subjects are needed to provide conclusive evidence of appropriate medical management.
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76 LOXOSCELES RECLUSA BITE: CASE PRESENTATION AND LITERATURE REVIEW