Dermatitis Herpetiformis
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1 Dermatitis Herpetiformis Celiac Support Group Marshfield Clinic September 21, 2009 Jacob M. Kusmak, M.D., Pharm.D. Dermatology Resident Physician Marshfield Clinic
2 Disclosure: I have no relevant financial interests, commercial affiliation or relationships with any products or services discussed in this presentation.
3 Objectives of Presentation Describe the disease Dermatitis Herpetiformis Understand the basic cause of Dermatitis Herpetiformis Illustrate some clinical presentations of Dermatitis Herpetiformis
4 Objectives of Presentation Describe the relationship of Dermatitis Herpetiformis and Celiac Disease Understand the common treatments of Dermatitis Herpetiformis Detail the Gluten-Free diet and understand which common food products contain gluten
5 Dermatitis inflammation of the skin Herpetiformis resembling the Herpes skin infection which has grouped papules or vesicles
6 Dermatitis Herpetiformis Commonly referred to as DH Discovered in 1884 Dr. Louis Duhring Dermatologist University of Pennsylvania First disease discovered by an American Dermatologist
7 Louis Duhring, MD, the first dermatologist to describe Dermatitis Herpetiformis
8 Dermatitis Herpetiformis Cutaneous manifestation of celiac disease Onset usually 30s 50s Rare in childhood but some reports Men greater than Women - slightly Some texts state 2 times more often in Men
9 Prevalence of DH Great Britain per 100,000 population Sweden per 100,000 population United States per 100,000 population
10 Dermatitis Herpetiformis Cause Genetic Predisposition Gluten Ingestion Antigenic Response Immune Response Production of IgA antibodies
11 Genetic Component Specific HLA Genes Molecules that interact with T-Cell Receptors Same as for Celiac Disease Genes encoding HLA-DQ2 (A1*501, B1*02) Carried by 90% of Celiac Disease and Dermatitis Herpetiformis Patients Genes encoding HLA-DQ8 (A1*03, B1*03) Carried by remaining 10%
12 Gliadin and Gluten Gliadin Alcohol-soluble fraction of gluten Antigenic component Gluten - Grain proteins Wheat Rye Barley Others Oats may be cross-contaminated with glutenous grains (Gluten-free if pure and uncontaminated)
13 Compliments of Dr. Jared Lund Genetics and Gluten Gliadin (antigenic component of gluten) Recognized by HLA receptors Migration to lamina propria portion of intestine Recruitment of inflammatory cells causing inflammation
14
15 Fig Proposed pathogenesis of dermatitis herpetiformis and celiac disease. A Dietary wheat is processed by digestive enzymes into antigenic gliadin peptides, which are transported intact across the mucosal epithelium. Within the lamina propria, tissue transglutaminase (TG2): (1) deamidates glutamine residues within gliadin peptides to glutamic acid; and (2) becomes covalently cross-linked to gliadin peptides via isopeptidyl bonds (formed between gliadin glutamine and TG2 lysine residues). B CD4+ T cells in the lamina propria recognize deamidated gliadin peptides presented by HLA-DQ2 or -DQ8 molecules on antigen-presenting cells, resulting in the production of Th1 cytokines and matrix metalloproteinases that cause mucosal epithelial cell damage and tissue remodeling. In addition, TG2-specific B cells take up TG2 gliadin complexes and present gliadin peptides to gliadin-specific helper T cells, which stimulate the B cells to produce anti-tg2 IgA. C Circulating anti-tg2 IgA cross-reacts with epidermal transglutaminase (TG3), and immune complexes form. D Deposition of IgA TG3 immune complexes in the dermal papillae leads to neutrophil chemotaxis (with formation of neutrophilic abscesses), proteolytic cleavage of the lamina lucida, and subepidermal blister
16 Symptoms INTENSE ITCH Burning / Stinging So severe prior to 1930s treatment reports of suicide
17 What does the skin look like? papulovesicles on erythematous base Small blistery red bumps Fluid filled Blisters often NOT visualized since they are usually already scratched Excoriations or Erosions with crusting, really what is usually seen Usually heal without scarring
18 Elbows Arms Knees Back Shoulders Buttocks Scalp Face Symmetrical
19 More Clinical Pictures...
20
21
22
23 Association with Celiac Disease ALL patients with DH have some degree of associated intestinal inflammation induced by gluten May only be shown in 90% of small intestine biopsies Likely not biopsing an affected area
24 Spectrum of small intestine abnormalities Minimal involvement with no bowel symptoms Severe malabsorption
25 Image obtained from Wikipedia.org
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27
28 Diagnosis of Dermatitis Herpetiformis Clinical Biopsy Pathology Affected skin Adjacent normal-appearing skin Laboratory
29 NORMAL SKIN BIOPSY
30 NORMAL SKIN BIOPSY
31 DERMATITIS HERPETIFORMIS BIOPSY
32 DEMATITIS HERPETIFORMIS DIRECT IMMUNOFLUORESCENCE
33 Laboratory Blood Testing Serum antibody tests Gliadin Endomysium (EMA) Tissue Trans-Glutaminase (TTG) More commonly positive in patients with severe gluten-sensitive enteropathy Less commonly positive in patients with mild gastrointestinal disease (most DH patients)
34 Gluten-free diet Treatments Dapsone Blocks the inflammatory process in DH skin Steroid medications Prednisone Other Medications
35 Gluten Free Diet No Wheat wheat flour, white flour, wheat bran, wheat germ, farina, wheat starch, graham flour, semolina, durum) No Rye No Barley No Malt
36 WHEAT
37 RYE
38 BARLEY
39 MALT
40 Gluten Free Diet Grains and Starches Allowed Rice Corn Soy Potato Tapioca Beans Sorghum Quinoa Millet Buckwheat Arrowroot Amaranth Tef Montina Nut Flours
41 Gluten Free Diet Alcoholic Beverages Wines are gluten-free Beers, Ales, Lagers, and Malt vinegars are made from gluten-containing grains (unless otherwise specified by the manufacturer)
42 Dapsone FDA approved Dermatitis Herpetiformis Leprosy Mechanism of Action MANY Inhibits inflammatory response and migration of inflammatory cells
43 Dapsone Dosage 25mg per day for 1 week, then increase gradually Rarely up to 300mg per day Most mg per day Monitoring Glucose-6-Phosphate Dehydrogenase level Utilized in Red Blood Cell Metabolism Complete Blood Count Blood Chemistry Liver Function Tests
44 Dapsone Common Side Effects Mostly Gastrointestinal Abdominal pain Decrease appetite Rare Side Effects Rash Hematologic Anemia, Methemoglobinemia Agranulocytosis severe low white blood cell count Neuropathy peripheral motor (weakness)
45 Corticosteroids Very effective to decrease inflammation Use lowest effective dosage Should not take long-term if at all possible Many side-effects
46 Corticosteroids SIDE EFFECTS General: Fluid retention, increased appetite, weight gain Gastrointestinal: Nausea, peptic ulcer disease, esophagitis, pancreatitis Cardiovascular: High blood pressure Musculoskeletal: Osteoporosis, Osteonecrosis, Muscle weakness Metabolic: Increased blood sugars, Increased lipids (including triglycerides), Obesity Ophthalmologic: Cataracts, Glaucoma Nervous system: Mood changes, psychosis, trouble sleeping, pseudotumor cerebri, peripheral neuropathy Cutaneous: Atrophy, purpura, Hyperpigmentation, acneiform eruption, delayed wound healing Infections: Increased risk of infection Hematology: Changes in blood cell counts Gynecology: Amenorrhea
47 Childhood Dermatitis Herpetiformis RARE If occurs, usually age 2-7 years old Has been reported as early as 10-months-old Similar to adult skin lesions Treatment with Gluten-free diet Dapsone
48 Other Associated Diseases Autoimmune Thyroiditis Hypothyroidism Diabetes Mellitus Insulin-Dependent type Other autoimmune diseases Systemic Lupus Sjogren syndrome Vitiligo Osteoporosis Lymphoma (overall low risk) Gastrointestinal Non-Hodgkin lymphomas Gluten-Free diet helps reduce risk
49 Dermatitis Herpetiformis / Celiac Disease Resources and Support Groups Gluten Intolerance Group (206) Celiac Sprue Association (877) CSA-4CSA Celiac Disease Foundation (818) American Celiac Society / Dietary Support Coalition (973)
50 QUESTIONS
51 REFERENCES Farrell RJ, Kelly CP. Celiac Sprue. N Engl J Med. 2002;346: Nicolas ME, Krause PK, Gibson LE, Murray JA. Dermatitis Herpetiformis. Int J Dermatol. 2003;42: Zone JJ, Hull CM. Warning: Bread may be harmful to your health. J Am Acad Dermatol. 2004;51:S27-S28. Jones R. Extreme itching A downhill experience. J Am Acad Dermatol. 2004;51:S29-S30. Hall RP. Dietary management of dermatitis herpetiformis. Arch Dermatol. 1987;123: Collin P, Reunala T. Recognition and management of the cutaneous manifestations of celiac disease. Am J Clin Dermatol. 2003:4: Templet JT, Welsh JP, Cusack CA. Childhood Dermatitis Herpetiformis: A Case Report and Review of the Literature. Cutis. 2007;80: Zone JJ. Skin Manifestations of Celiac Disease. Gastroenterology. 2005;128:S87-S91. Bolognia JL, Jorizzo JL, Rapini R, et al. Dermatology, 2 nd ed. Mosby Elsevier. Philadelphia, PA Wolff K, Goldsmith LA, Gilchrest BA, Paller AS, Leffell DJ, et al. Fitzpatrick s Dermatology in General Medicine, 7 th ed. McGraw Hill. New York, NY McKee PH, Calonje E, Granter SR, et al. Pathology of the Skin, 3 rd ed. Mosby Elsevier. Philadelphia, PA Wolverton SE. Comprehensive Dermatologic Drug Therapy, 2 nd ed. Saunders Elsevier. Philadelphia, PA. 2007
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