DOCSLIB.ORG

Graft Versus Host Disease and How to Report It

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Graft Versus Host Disease and How to Report It Graft versus Host Disease and how to report it Daniel Weisdorf MD University of Minnesota Transplant Events Day-8 0 1mo 3mo 6mo Conditioning HSCT Engraftment Mucositis Organ toxicity (VOD) Acute GVHD Chronic GVHD Infections Bacterial ----CMV---- Varicella----- --Fungus--------- Transplant Events Day-8 0 1mo 3mo 6mo Conditioning HSCT Engraftment Mucositis Organ toxicity (VOD) Acute GVHD Chronic GVHD Infections Bacterial ----CMV---- Varicella----- --Fungus--------- 1 Acute GVHD Chronic GVHD Skin: Lichen planus, Hyper/ hypo pigmentation, Dermatitis ichthyosis, onychodystrophy, morphea, + scleroderma, hair changes. Hepatitis Oral: sicca, atrophy, lichenoid, + Hyperkeratosis GI: wasting, dysphagia, Enteritis odynophagia, strictures Eye: keratoconjunctivitis sicca Lungs: Bronchiolitis obliterans Others: myofascial, genital Acute GVHD Chronic GVHD Dermatitis Rash + Hepatitis High bilirubin + Enteritis Nausea/vomiting/ diarrhea Acute GVHD Chronic GVHD Skin: Lichen planus, Scaly abnormal pigmentation, Dry skin, onychodystrophy, abnormal nails scleroderma, thick skin hair changes. Oral: sicca, atrophy, lichenoid, Dry mouth GI: wasting, dysphagia, Weight loss odynophagia, trouble swallowing Eye: keratoconjunctivitis sicca Dry eyes Lungs: Bronchiolitis obliterans Obstruction Others: myofascial, muscle stiffness Genital vaginal narrowing 2 Graft vs. Leukemia Effect • Less leukemia relapse follows more GVHD • Acute and particularly Chronic GVHD limit relapse Risk Factors for GVHD Acute GVHD Chronic GVHD Increased risk Increased risk HLA mismatch Older age Older recipients Prior acute GVHD Older donors HLA mismatch High dose TBI alloimmune female donor: male recipient Reduced risk Reduced risk T cell depletion Cord blood Non-myeloablative conditioning? Pathogenesis of GVHD Host tissue injury: Activates or damages host APC; Augments class I & adhesion expression Inflammatory milieu Donor T cells recognize host polypeptides as foreign. major & minor HLA plus tissue antigens T cell recognition, activation, and host tissue injury Direct cell mediated attack, Production of inflammatory mediators (TNF IFN) Recruitment of secondary effectors Induces cell injury and inflammation----Acute GVHD 3 Pathophysiology of chronic GVHD • Alloreactive T cells • Donor T cells recognize foreign tissues • T cells grow in response to alloantigens or autoantigens • Attack target tissues directly, secretion of cytokines, promote B cell activation and autoantibody production Tissue injury; Fibrosis------Chronic GVHD Can we recognize GVHD? GVHD grading schema Glucksberg 1974 43 of 61 patients with GVHD Thomas et al BMT review 1975 UGI Weisdorf et al 1990 Consensus Grading 1995 accepted UGI, lessened emphasis on performance status IBMTR 1997 A B C D narrowed B due to heterogeneity of grade II 4 Staging of Acute GVHD Skin Lower GI Upper GI Liver Rash Diarrhea 0 -- none -- Bili <2.0 mg/dl 1 <25% <500 ml N/V 2.1-3.0 <280 ml/m2 2 25-50% 500-1000 3.1-6.0 280-555/ m2 3 >50% 1000-1500 6.1-15 generalized 556-833/ m2 4 + bullae 1500+ >15.1 desquamation >833/ m2 Record of Clinical GVHD data Clinical GVHD Assessment Date____________ Karnofsky/Lansky____________ Stage Biopsy Differential Diagnosis 0123 4 + - E Drug TPN VOD Infect Other Skin %body rash:_______ ____________________ Lower GI diarrhea vol:_______ ____________________ Liver max bili:__________ ____________________ Upper GI ____________________ Treatment: CSA MMF Pred/MPred TCM/HCT ATG FK506 Infliximab MPred Boluses Study______________ Other____________________ Signature_____________________________________________ Record of Clinical GVHD data Clinical GVHD Assessment Date____________ Karnofsky/Lansky____________ Stage Biopsy Differential Diagnosis 0123 4 + - E Drug TPN VOD Infect Other Skin %body rash:_______ ____________________ Lower GI diarrhea vol:_______ ____________________ Liver max bili:__________ ____________________ Upper GI ____________________ Treatment: CSA MMF Pred/MPred TCM/HCT ATG FK506 Infliximab MPred Boluses Study______________ Other____________________ Signature_____________________________________________ Data managers Dream 5 6 80% skin 6% liver at onset of 18% LGI therapy 24% UGI MacMillan et al, BBMT, 2002 MacMillan et al, BBMT, 2002 GVHD prevention • Optimize donor selection Incidence of AGVHD HLA identical sibling donor: 40% HLA identical unrelated donor: 50-60% Cord blood: 25-50% Incidence of CGVHD HLA identical sibling donor: 33% HLA identical unrelated donor: 65% Cord blood: 10-30% 7 Therapeutic Interventions in GVHD Deplete Tolerize Donor T cells Inactivate } Deplete host APCs In vivo deplete stimulated T cells Reduce secondary inflammation Therapeutic Interventions in GVHD Deplete Graft modulation TCD Tolerize Donor T cells Block costimulation Add T reg Inactivate } Add NK or MSC Deplete host APCs Drug Therapy In vivo deplete stimulated T cells Immunosuppressive Blunt proliferation In vivo T cell lysis Reduce secondary inflammation Anti-cytokines Block target lysis Drugs to prevent GVHD Mtx CSA Tacrolimus (FK506) MMF Sirolimus (rapamycin) ATG Anti-TNF (infliximab, etanercept) Anti-cytokines Others….. 8 Acute GVHD--Treatment Standard GVHD treatment—Corticosteroids Durable response 40% Sibling donors 25% Unrelated donors but 60-75% need additional therapy For steroid-refractory disease, no standard effective treatments are available GVHD Therapy Agents Corticosteroids + CSA/Tac Daclizumab; Visiluzimab Infliximab, Etanercept Sirolimus MMF Pentostatin, Fludarabine ATG; Thymoglobulin Photopheresis Corticosteroids Used for decades lympholytic, but not tolerizing; anti-cytokine no specificity for activated T cells Lots of toxicities infections, osteopenia, cataracts, AVN BP, DM, myopathy, skin atrophy 9 Steroid therapy of Acute GVHD PR/CR cGVHD N=443 20/35% 42% Initial Grade (%) cGVHD % I2839 II 60 44 III/IV 13 42 MacMillan et al, BBMT, 2002 Factors predicting PR/CR to steroid therapy Variable Relative Likelihood P of CR/PR (95% CI) Type of donor Related 1.0 Matched unrelated Mismatched unrelated 0.8 (0.5 - 1.4) 0.52 0.5 (0.3 - 0.8) <0.01 GVHD prophylaxis CSA 1.0 Methotrexate alone 0.3 (0.1 - 0.6) <0.01 T-cell depletion 0.9 (0.5 - 1.6) 0.77 Tacrolimus 1.2 (0.4 - 3.8) 0.63 Initial grade of GVHD I 1.0 II 0.9 (0.6 - 1.5) 0.79 MacMillan et al, III 0.8 (0.4 - 1.7) 0.66 BBMT, 2002 IV 0.3 (0.1 - 1.9) 0.23 ATG Active in steroid refractory GVHD, overall responses 19-56% skin responses 59-79% Randomized trials 1980s and 1990s—no benefit 1-year mortality 60-90%. Deaths typically not from GVHD opportunistic infections, EBV 10 Anti-IL2 R Antibodies Anti-CD25 murine monoclonals B-B10 and BT563 CR 66% -73% Daclizumab humanized IgG1 monoclonal antibody binds alpha subunit (p55 alpha, CD25, or Tac) of IL-2R inhibits IL-2 binding Daclizumab Germany Willenbacher et al; Brit J Haem 2001 N=16; 12 steroid resistant acute (6 responded). 14 of 16 developed infections, 2 fatal Przepiorka et al, Blood 2001 N=43 steroid refractory. Weekly (n=29) to day 42 CR 29%, 120 day survival 29% 2-3 x weekly (n=19) CR 47%, 120 day survival 53% Wolff (ASH abstract) Daclizumab + etanercept n=12; 6 CR; 4PR; 1 early death; 1 NR Randomized trial: Prednisone +/- Daclizumab for Initial GVHD therapy Dacliz +Pred Prednisone p GVHD control 53% 51% 0.85 100-day survival 77% 94% 0.02 Overall survival 29% 60% 0.002 Lee et al, Blood, 2004 11 Initial Systemic Treatment of Acute GVHD : A Phase II randomized trial BMT CTN 0302 Acute/Chronic GVHD Committee D Weisdorf, B Logan, J Antin, J Ferrara, S Lee, D Couriel, R Soiffer, R Nash, M Horowitz, S Carter, R Goyal, J Klein et al Study goal To test new agents to treat Acute GVHD Define those promising for testing against steroids alone in a subsequent comparative, Phase III trial. Historical control data using prednisone alone: Minnesota, Dana Farber, Seattle Expected 35% CR at day 28 of therapy Etanercept [25 mg sc BIW for up to 8 weeks] MMF [must be off MMF for ≥ 14 days to be eligible] Ontak [9 mcg/kg IV d 1,3,5 d 15,17,19] Pentostatin 1.5 mg/m2 qd x 3 d; day 1-3 & day 15-17 Study Agents all given with: Prednisone 2 mg/kg/d for ≥ 7 days; Taper as tolerated to not < 1 mg/kg/d at day 28 12 Prednisone + Etanercept, MMF, Ontak & Pentostatin were chosen Plan follow-up randomized trial as this trial proceeds Therapeutic Interventions in GVHD Deplete Graft modulation TCD Tolerize Donor T cells Block costimulation Inactivate } Add T reg Add NK or MSC Deplete host APCs Drug Therapy In vivo deplete stimulated T cells Immunosuppressive Blunt proliferation In vivo T cell lysis Reduce secondary inflammation Anti-cytokines Block target lysis And now the forms • Accurate and adequate data collection for both acute and chronic GVHD. • Organ involvement. • Severity 13 Plus others……… Diagnosis of Acute GVHD GRADE ORGAN STAGE 14 Treatment of acute GVHD Acute GVHD – Dermatological • Maculo-papular rash Apoptotic crypt cells on GI histology Skin biopsy showing interface dermatitis 15 Chronic GVHD - Dermatological • Same as acute GVHD • Atrophy and erythema of oral mucosa • Lichenoid lesions of skin, buccal and labial mucosa • Sclerodermatous skin thickening • Joint contractures Sclerotic cGVHD of the lips and mucosa with restricted mouth opening Skin involvement with cGVHD 16 Chronic GVHD Limited skin involvement: topical steroids. Systemic Therapy: Steroids plus CSA or tacrolimus are the mainstay of therapy for CGVHD cGVHD requiring systemic therapy (n=159) 6 mo 1 year 2 years CR+PR 61.3% 52.7% 50.4% NR+Flare 38.7% 47.3% 49.6% Arora et al BBMT 2003 Overall Survival and Duration of Immunosuppression Arora et al
Load more

Recommended publications
  • COVID-19 and RARE SKIN DISEASES
    COVID-19 and RARE SKIN DISEASES Newsletter n°4, 8th June 2021 Dear all, We hope that this letter finds you well! Thank you to those who have included patients and collected the data! We would like to remind you to complete the online eCRF via the link you have received. If you any have any issues don’t hesitate to contact us. Please note that, since the pandemic is still continuing, the study has been expanded for one year. The monitoring is ongoing and the queries will be sent regularly. If needed, the sites will be contacted to discuss and validate the answers, and check if the study is proceeding well. 64 patients are included in the study: 5 in Germany, 6 in Czech Republic, 8 in Italy, 11 in Lithuania and 34 in France. The diseases concerned are the following: Bullous pemphigoid (9/64), Recessive dystrophic Epidermolysis bullosa (9/64), Dominant dystrophic Epidermolysis bullosa (8/64), Epidermolysis bullosa (7/64), Hidradenitis suppurativa (7/64), X-linked hypohidrotic ectodermal dysplasia (4/64), Lamellar ichtyosis (2/64) and Incontinentia pigmenti (2/64). The other diseases are presented each by 1 patient: Pemphigus vulgaris, Pemphigus foliaceous, Mucous membrane pemphigoid, IgA Linear Dermatosis, Dermatitis herpetiformis, Kindler Epidermolysis bullosa, Kerathinopathic ichthyosis, Darier disease, Linear morphea, Cloves syndrome, Microcystic lymphatic malformation, Hemihypertrophy (Overgrowth syndrome), Adamantiades - Behçet's disease, Hailey Hailey disease, Pityriasis rubra pilaris and Neurofibromatosis type 1 (Figure 1 below). 10 Figure 1: Type of Rare skin diseases 5 0 A large majority of patients visited a hospital physician (42%: 27/64), 28% visited a General practitioner (18/64) and 23% consulted a physician remotely (15/64).
    [Show full text]
  • Expression of Loricrin in Oral Submucous Fibrosis, Hyperkeratosis and Normal Mucosa: an Immunohistochemical Study
    EXPRESSION OF LORICRIN IN ORAL SUBMUCOUS FIBROSIS, HYPERKERATOSIS AND NORMAL MUCOSA: AN IMMUNOHISTOCHEMICAL STUDY Dissertation submitted to THE TAMILNADU Dr.M.G.R.MEDICAL UNIVERSITY In partial fulfillment for the Degree of MASTER OF DENTAL SURGERY BRANCH VI ORAL PATHOLOGY AND MICROBIOLOGY APRIL 2013 Acknowledgement It is not every day that we get to thank all those who really matter to us, and acknowledging this brings joy and pride so deep that it makes me feel whole and cherished .I would want to thank God foremost for his benevolence and love for making it possible, for every breath, every thought and every walk of life is filled with his goodness I would like to express my deep gratitude and reverence to my post graduate teacher and mentor Dr. K. Ranganathan, MDS, MS (Ohio), Ph.D, Professor and Head, Department of Oral and maxillofacial pathology, Ragas Dental College and Hospital for his valuable guidance, constant support and encouragement throughout my dissertation. His penchant for perfection in all things had been a beacon guiding us in our study. My sincere thanks to Dr. Umadevi K. Rao, Professor, Department of Oral and maxillofacial pathology Ragas Dental College and Hospital for her constant support, motivation to learn and encouragement in times of trials throughout my study. I extend my heartfelt gratitude to my Guide and Professor Dr. Elizabeth Joshua, Department of Oral and maxillofacial pathology Ragas Dental College and Hospital for her constant guidance, support, tons of patience and endearing words of advice to explore all aspects in the completion of my work. I earnestly thank Professor, Dr.
    [Show full text]
  • A Case of Psoriasis in an HIV Positive Male Omar F Merchant and Wayne X Shandera*
    Merchant and Shandera. Clin Med Rev Case Rep 2015, 2:052 DOI: 10.23937/2378-3656/1410052 Clinical Medical Reviews Volume 2 | Issue 8 and Case Reports ISSN: 2378-3656 Case Report: Open Access A Case of Psoriasis in an HIV Positive Male Omar F Merchant and Wayne X Shandera* Baylor College of Medicine, Department of Internal Medicine, Houston, USA *Corresponding author: Wayne Shandera, Baylor College of Medicine, Department of Internal Medicine, Houston, TX 77030, USA, Fax: 713 798 6400; E-mail: [email protected] Initially, topical steroids were attempted with minimal Abstract improvement, and low dose acitretin was also ineffective. High Patients with Human Immunodeficiency Virus (HIV) infection have dose acitretin, however, did result in significant response with an increased risk for several variants of psoriasis as well as being improvement diffusely in the skin lesions. refractory to standard treatment regimens. While psoriasis does not affect HIV survival, quality of life may be significantly impaired and Discussion these considerations warrant special attention with management. We report a case of psoriasis in a 43-year-old Hispanic male with Psoriasis is prevalent 1-2% of northern Europeans, with 5-42% HIV infection, adequately managed with antiretroviral therapy. He having concomitant arthritis [1]. The histological findings of psoriasis presented with chronic and persistent guttate, red, scaly plaques include proliferation of basal keratinocytes, thickened epidermis, on his abdomen, back, buttock as well as the extensor surfaces premature desquamation of the stratum corneum and neutrophils in of his extremities. Lesions responded only mildly to steroids, with adequate response attained by administration of high dose the stratum corneum.
    [Show full text]
  • Hereditary Hearing Impairment with Cutaneous Abnormalities
    G C A T T A C G G C A T genes Review Hereditary Hearing Impairment with Cutaneous Abnormalities Tung-Lin Lee 1 , Pei-Hsuan Lin 2,3, Pei-Lung Chen 3,4,5,6 , Jin-Bon Hong 4,7,* and Chen-Chi Wu 2,3,5,8,* 1 Department of Medical Education, National Taiwan University Hospital, Taipei City 100, Taiwan; [email protected] 2 Department of Otolaryngology, National Taiwan University Hospital, Taipei 11556, Taiwan; [email protected] 3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei City 100, Taiwan; [email protected] 4 Graduate Institute of Medical Genomics and Proteomics, National Taiwan University College of Medicine, Taipei City 100, Taiwan 5 Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan 6 Department of Internal Medicine, National Taiwan University Hospital, Taipei 10041, Taiwan 7 Department of Dermatology, National Taiwan University Hospital, Taipei City 100, Taiwan 8 Department of Medical Research, National Taiwan University Biomedical Park Hospital, Hsinchu City 300, Taiwan * Correspondence: [email protected] (J.-B.H.); [email protected] (C.-C.W.) Abstract: Syndromic hereditary hearing impairment (HHI) is a clinically and etiologically diverse condition that has a profound influence on affected individuals and their families. As cutaneous findings are more apparent than hearing-related symptoms to clinicians and, more importantly, to caregivers of affected infants and young individuals, establishing a correlation map of skin manifestations and their underlying genetic causes is key to early identification and diagnosis of syndromic HHI. In this article, we performed a comprehensive PubMed database search on syndromic HHI with cutaneous abnormalities, and reviewed a total of 260 relevant publications.
    [Show full text]
  • Mutation and Expression of Abca12in Keratosis Pilaris and Nevus
    MOLECULAR MEDICINE REPORTS 18: 3153-3158, 2018 Mutation and expression of ABCA12 in keratosis pilaris and nevus comedonicus FEN LIU1,2*, YAO YANG1,3*, YAN ZHENG1,3, YAN-HUA LIANG1,3 and KANG ZENG1 1Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515; 2Department of Histology and Embryology, Institute of Neuroscience, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035; 3Department of Dermatology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong 518100, P.R. China Received June 22, 2017; Accepted April 17, 2018 DOI: 10.3892/mmr.2018.9342 Abstract. Keratosis pilaris (KP) and nevus comedonicus Introduction (NC) are congenital keratinized dermatoses; however, the exact etiology of these two diseases is unclear. The objective Keratosis pilaris (KP; OMIM #604093), also known as of the present study was to identify the disease-causing genes lichen pilaris, is a benign genodermatosis that is estimated and their association with functional alterations in the devel- to effect ~40% of the population (1). KP is characterized by opment of KP and NC. Peripheral blood samples of one KP the presence of symmetric, asymptomatic and grouped kera- family, two NC families and 100 unrelated healthy controls totic follicular papules with varying degrees of perifollicular were collected. The genomic sequences of 147 genes associ- erythema. KP lesions often involve the proximal and extended ated with 143 genetic skin diseases were initially analyzed parts of extremities, the cheeks and the buttocks (2). Cases from the KP proband using a custom-designed GeneChip. A may be generalized or unilateral (2). Most patients develop KP novel heterozygous missense mutation in the ATP-binding in their childhood, with a peak in incidence during adoles- cassette sub-family A member 12 (ABCA12) gene, designated cence (3).
    [Show full text]
  • Seborrheic Keratosis
    Benign Epidermal and Dermal Tumors REAGAN ANDERSON, DO- PROGRAM DIRECTOR, COLORADO DERMATOLOGY INSTITUTE, RVU PGY3 RESIDENTS- JONATHAN BIELFIELD, GEORGE BRANT PGY2 RESIDENT- MICHELLE ELWAY Seborrheic Keratosis Common benign growth seen after third/fourth decade of life Ubiquitous among older individuals Tan to black, macular, papular, or verrucous lesion Occur everywhere except palms, soles, and mucous membranes Can simulate melanocytic neoplasms Pathogenesis: Sun exposure- Australian study found higher incidence in the head/neck Alteration in distribution of epidermal growth factors Somatic activating mutations in fibroblast growth factor receptor and phosphoinositide-3-kinase Seborrheic Keratosis Sign of Leser-Trelat: Rare cutaneous marker of internal malignancy • Gastric/colonic adenocarcinoma, breast carcinoma, and lymphoma m/c • Abrupt increase in number/size of SKs that can occur before, during, or after an internal malignancy is detected • 40% pruritus • M/C location is the back • Malignant acanthosis nigricans may also appear in 20% of patients • Should resolve when primary tumor is treated, and reappear with recurrence/mets Seborrheic Keratosis 6 Histologic types Acanthotic Hyperkeratotic Reticulated Irritated Clonal Melanoacanthoma Borst-Jadassohn phenomenon Well-demarcated nests of keratinocytes within the epidermis Seborrheic Keratoses Treatment Reassurance Irritated SKs (itching, catching on clothes, inflamed) Cryotherapy, curettage, shave excision Pulsed CO2, erbium:YAG lasers Electrodessication Flegel
    [Show full text]
  • Ichthyosis the Genetics of Its Inheritance
    Ichthyosis The Genetics of its Inheritance TM Educate • Inspire • Connect 2616 N. Broad Street Colmar, PA 18915 800.545.3286 info@fi rstskinfoundation.org TM www.fi rstskinfoundation.org Educate • Inspire • Connect Third Edition: Reviewed by Sherri J. Bale, PhD Copyright © 2010 by the Foundation for Ichthyosis & Related Skin Types, Inc. (FIRST). All rights reserved. No portion of this brochure may be reproduced in any form without written permission from FIRST. robably the question most commonly asked of people with Pichthyosis is: "Is it contagious?” The answer is, of course,“ NO!” None of the ichthyoses or the related disorders in the family of skin conditions that are included in the umbrella of the FIRST1 is contagious.These are all genetic disorders and can be "caught" only through heredity. Although not all members of the FIRST family of disorders are an “ichthyosis” per se, for ease of discussion, we will use that term to denote any of these conditions. Probably the most common question asked by people who have ichthyosis, or by parents of a child with ichthyosis is: "How is it passed on? I have one child, and that child has ichthyosis. Will all my children have it?" Or, "I have ichthyosis. If I have children, will I pass it on to them?" The answers to these questions will depend on the specific type of ichthyosis present in the family. Although the ichthyoses are all inherited or genetic disorders, the pattern or mode of inheritance varies considerably among the FIRST family of disorders.Therefore, the very first step in genetic counseling is a firm and accurate diagnosis.2 1 Members of the FIRST family of disorders are described in greater detail the Overview Booklet.
    [Show full text]
  • How to Deal with Skin Biopsy in an Infant with Blisters?
    Review How to Deal with Skin Biopsy in an Infant with Blisters? Stéphanie Leclerc-Mercier Reference Center for Genodermatoses (MAGEC Center), Department of Pathology, Necker-Enfants Malades Hospital, Paris Centre University, 75015 Paris, France; [email protected] Abstract: The onset of blisters in a neonate or an infant is often a source of great concern for both parents and physicians. A blistering rash can reveal a wide range of diseases with various backgrounds (infectious, genetic, autoimmune, drug-related, traumatic, etc.), so the challenge for the dermatologist and the pediatrician is to quickly determine the etiology, between benign causes and life-threatening disorders, for a better management of the patient. Clinical presentation can provide orientation for the diagnosis, but skin biopsy is often necessary in determining the cause of blister formations. In this article, we will provide information on the skin biopsy technique and discuss the clinical orientation in the case of a neonate or infant with a blistering eruption, with a focus on the histology for each etiology. Keywords: blistering eruption; infant; skin biopsy; genodermatosis; SSSS; hereditary epidermolysis bul- losa; keratinopathic ichthyosis; incontinentia pigmenti; mastocytosis; auto-immune blistering diseases 1. Introduction The onset of blisters in a neonate or an infant (<2 years old) is a source of great concern for both parents and physicians. Therefore, a precise diagnosis, between benign causes and Citation: Leclerc-Mercier, S. How to life-threatening disorders, is quickly needed for the best management of the baby. Deal with Skin Biopsy in an Infant Several diseases with various backgrounds (infectious, genetic, autoimmune, drug- with Blisters? Dermatopathology 2021, related, traumatic, etc.) can lead to a blistering eruption.
    [Show full text]
  • Hereditary Ichthyosis
    !" #$%&'# $(%&) #'# %*+&,*'#'* -#.*&%* --#.# // Dissertation for Degree of Doctor of Philosophy (Faculty of Medicine) in Dermatology and Venereology presented at Uppsala University in 2002 ABSTRACT Gånemo, A. 2002. Hereditary ichthyosis. Causes, Skin Manifestations, Treatments and Quality of Life. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1125. 68 pp Uppsala ISBN 91-554-5246-9 Hereditary ichthyosis is a collective name for many dry and scaly skin disorders ranging in frequency from common to very rare. The main groups are autosomal recessive lamellar ichthyosis, autosomal dominant epidermolytic hyperkeratosis and ichthyosis vulgaris, and x-linked recessive ichthyosis. Anhidrosis, ectropion and keratodermia are common symptoms, especially in lamellar ichthyosis, which is often caused by mutations in the transglutaminase 1 (TGM1) gene. The aim of this work was to study patients with different types of ichthyosis regarding (i) the patho-aetiology (TGM1 and electron microscopy [EM] analysis), (ii) skin signs and symptoms (clinical score and subjective measure of disease activity), (iii) quality of life (questionnaires DLQI, SF-36 and NHP and face-to-face interviews) and (iv) a search for new ways of topical treatment. Patients from Sweden and Estonia with autosomal recessive congenital ichthyosis (n=83) had a broader clinical spectrum than anticipated, but a majority carried TGM1 mutations. Based on DNA analysis and clinical examinations the patients were classified into three groups, which could be further subdivided after EM analysis. Our studies indicate that patients with ichthyosis have reduced quality of life as reflected by DLQI and by some domains of SF- 36, by NHP and the interviews. All the interviewees reported that their skin disease had affected them negatively to varying degrees during their entire lives and that the most problematic period was childhood.
    [Show full text]
  • Keratosis Pilaris: a Common Follicular Hyperkeratosis
    PEDIATRIC DERMATOLOGY Series Editor: Camila K. Janniger, MD Keratosis Pilaris: A Common Follicular Hyperkeratosis Sharon Hwang, MD; Robert A. Schwartz, MD, MPH Keratosis pilaris (KP) is a common inherited dis- 155 otherwise unaffected patients.2 In the adolescent order of follicular hyperkeratosis. It is character- population, its prevalence is postulated to be at least ized by small, folliculocentric keratotic papules 50%; it is more common in adolescent females than that may have surrounding erythema. The small males, seen in up to 80% of adolescent females.3 papules impart a stippled appearance to the skin The disorder is inherited in an autosomal domi- resembling gooseflesh. The disorder most com- nant fashion with variable penetrance; no specific monly affects the extensor aspects of the upper gene has been identified. In a study of 49 evaluated arms, upper legs, and buttocks. Patients with KP patients, there was a positive family history of KP in usually are asymptomatic, with complaints limited 19 patients (39%), while 27 patients (55%) had no to cosmetic appearance or mild pruritus. When family history of the disorder.4 diagnosing KP, the clinician should be aware that a number of diseases are associated with KP such Clinical Features as keratosis pilaris atrophicans, erythromelanosis The keratotic follicular papules of KP most commonly follicularis faciei et colli, and ichthyosis vulgaris. are grouped on the extensor aspects of the upper arms Treatment options vary, focusing on avoiding skin (Figure), upper legs, and buttocks.4 Other affected dryness, using emollients, and adding keratolytic locations may include the face and the trunk.5 The agents or topical steroids when necessary.
    [Show full text]
  • Advanced Diagnostic Aids in Detection of Potentially Premalignant Oral Epithelial Lesions - a Review
    Acta Scientific DENTAL SCIENCES (ISSN: 2581-4893) Volume 4 Issue 9 September 2020 Review Article Advanced Diagnostic Aids in Detection of Potentially Premalignant Oral Epithelial Lesions - A Review Jayanta Saikia*, Balaji Pachipulusu, Poornima Govindaraju and Bhagyashree M Nair Received: July 14, 2020 Department of Oral Medicine and Radiology, Rajarajeswari Dental College and Published: August 10, 2020 Hospital, Karnataka, India © All rights are reserved by Jayanta Saikia., *Corresponding Author: Jayanta Saikia, Post Graduate Student, Department of et al. Oral Medicine and Radiology, Rajarajeswari Dental College and Hospital, Karnataka, India. Abstract Oral cancer is one of the most mutilating disease afflicting mankind. Precancerous lesions, conditions and early stage oral cancer cannot be adequately identified by visual inspection alone and may be easily overlooked and neglected. - pearance of the lesions. Differentiation between early stage cancer, precancerous lesions and benign lesions is often difficult because of the similar ap Surgical biopsy is a gold standard for diagnosis, but this needs professional services, which are impractical at times. Alternative screening methods which are non-invasive, easily performed and highly accurate are the norms for any test to accept as an alterna- tive for histopathology. Early diagnosis is one of the most important single factor in combating oral cancer. Every general dental practitioner should be aware of recent advances in diagnostic oral medicine in order to provide a high level of care. This paper provides a summary of comprehensive diagnostic modalities that can be used for early detection, which is crucial for its ultimate control and prevention. Keywords: Diagnostic Aids; Non-invasive; Oral Cancer; Potentially Premalignant Oral Epithelial Lesions; PPOEL; PMDs Introduction cancer globally has risen to 18.1 million new cases and 9.6 million - deaths in the year 2018 [1].
    [Show full text]
  • The Clinical Spectrum of Congenital
    Acta Derm Venereol 2003, Suppl. 213: 34–47 The Clinical Spectrum of Congenital Ichthyosis in Sweden: A Review of 127 Cases ANDERS VAHLQUIST1, AGNETA GÅNEMO1, MARITTA PIGG2, MARIE VIRTANEN1 AND PER WESTERMARK3 Departments of 1Dermatology, 2Clinical Genetics and 3Pathology, University Hospital, Uppsala, Sweden Congenital ichthyosis comprises a rare group of usual- microscopy, HI: Harlequin ichthyosis, IFAP: ichthyosis follicularis, ly monogenetic diseases that present at birth as a collo- alopecia and photofobia, LI-TGM: lamellar ichthyosis with dion phenotype or as variable degrees of ichthyosiform transglutaminase 1 gene mutations, LI/CIE: lamellar ichthyosis and/ or congenital ichthyosiform erythroderma, KID: keratitis, ichthyo- erythroderma, with or without superficial blisters. De- sis and deafness, K: keratin, KLICK: keratosis linearis, ichthyosis pending on which gene mutation causes the disease, the congenita and keratoderma, SLS: Sjögren-Larsson syndrome, Tgase skin problems later in life may range from a severe 1 – transglutaminase 1 protein, XRI: X-linked recessive ichthyosis. lamellar or bullous ichthyosis to mild or only focally expressed hyperkeratotic lesions. It is obviously impor- tant, but sometimes painstakingly difficult, to make a INTRODUCTION correct diagnosis already in infancy. Fortunately, re- cent advances in our understanding of the molecular Congenital ichthyosis (CI) encompasses a large group of genetics of ichthyosis have led to several new diagnos- mostly monogenetic disorders of keratinization present- tic tools that are continuously being updated. Based on ing at birth as widespread hyperkeratosis and scaling of the integument, and sometimes associated with erythro- Downloaded By: [Akademiska Sjukhuset] At: 12:48 5 October 2007 this development, and on our own 5 years of experi- ence in a national genodermatosis centre, we describe derma and skin erosions.
    [Show full text]