Dermatitis Herpetiformis

Celiac Support Group Marshfield Clinic

September 21, 2009

Jacob M. Kusmak, M.D., Pharm.D.Dermatology Resident Physician

Marshfield Clinic

• Disclosure:

I have no relevant financial interests, commercial affiliation or relationships with any products or services discussed in this presentation.

Objectives of Presentation

• Describe the disease Dermatitis Herpetiformis

• Understand the basic cause of Dermatitis Herpetiformis

• Illustrate some clinical presentations of Dermatitis Herpetiformis

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

• Dermatitisinflammation of the skin

• Herpetiformisresembling the Herpes skin infection which has grouped papules or vesicles

Dermatitis Herpetiformis

• Commonly referred to as “ DH ”

• Discovered in 1884• Dr. Louis Duhring• Dermatologist – University of Pennsylvania

• First disease discovered by an American Dermatologist

Louis Duhring, MD, the first dermatologist to describe Dermatitis Herpetiformis

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

Prevalence of DH

• Great Britain -1971• 1.2 per 100,000 population

• Sweden – 1984• 39.2 per 100,000 population

• United States – 1992• 11.2 per 100,000 population

Dermatitis HerpetiformisCause

• Genetic Predisposition

• Gluten Ingestion• Antigenic Response

• Immune Response• Production of IgA antibodies

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%

Gliadin and GlutenGliadin

• 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)

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

Compliments of Dr. Jared Lund

Fig. 32.1 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

Symptoms

• INTENSE ITCH– Burning / Stinging

• So severe – prior to 1930s treatment –reports of suicide

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

• Elbows• Arms• Knees• Back• Shoulders• Buttocks

• Scalp• Face

• Symmetrical

• More Clinical Pictures . . .

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

Spectrum of small intestine abnormalities

Minimal involvement with no bowel symptoms-

--

-Severe malabsorption

Image obtained from Wikipedia.org

Diagnosis of Dermatitis Herpetiformis

• Clinical

• Biopsy – Pathology• Affected skin• Adjacent normal-appearing skin

• Laboratory

NORMAL SKIN BIOPSY

NORMAL SKIN BIOPSY

DERMATITIS HERPETIFORMIS BIOPSY

DEMATITIS HERPETIFORMIS – DIRECT IMMUNOFLUORESCENCE

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)

Treatments

• Gluten-free diet

• Dapsone• Blocks the inflammatory process in DH skin

• Steroid medications• Prednisone

• Other Medications

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

WHEAT

RYE

BARLEY

MALT

Gluten Free DietGrains and Starches Allowed• Rice• Corn• Soy• Potato• Tapioca• Beans• Sorghum

• Quinoa• Millet• Buckwheat• Arrowroot• Amaranth• Tef• Montina• Nut Flours

Gluten Free DietAlcoholic Beverages

• Wines are gluten-free

• Beers, Ales, Lagers, and Malt vinegars are made from gluten-containing grains

• (unless otherwise specified by the manufacturer)

Dapsone

• FDA approved • Dermatitis Herpetiformis• Leprosy

• Mechanism of Action• MANY• Inhibits inflammatory response and migration of

inflammatory cells

Dapsone

• Dosage• 25mg per day for 1 week, then increase gradually• Rarely up to 300mg per day• Most 50-200mg per day

• Monitoring• Glucose-6-Phosphate Dehydrogenase level

– Utilized in Red Blood Cell Metabolism• Complete Blood Count• Blood Chemistry• Liver Function Tests

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)

Corticosteroids

• Very effective to decrease inflammation

• Use lowest effective dosage

• Should not take long-term if at all possible

• Many side-effects

CorticosteroidsSIDE 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

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

Other Associated Diseases• Autoimmune Thyroiditis

• Hypothyroidism

• Diabetes Mellitus – Insulin-Dependent type

• Other autoimmune diseasesSystemic LupusSjogren syndromeVitiligo

• Osteoporosis

• Lymphoma (overall low risk)• Gastrointestinal• Non-Hodgkin lymphomas• Gluten-Free diet helps reduce risk

Dermatitis Herpetiformis / Celiac DiseaseResources and Support Groups

• Gluten Intolerance Groupwww.gluten.net (206) 246-6652

• Celiac Sprue Associationwww.csaceliacs.org (877) CSA-4CSA

• Celiac Disease Foundationwww.celiac.org (818) 990-2354

• American Celiac Society / Dietary Support Coalitionwww.americanceliacsociety.org (973) 325-8837

QUESTIONS

REFERENCES• Farrell RJ, Kelly CP. Celiac Sprue. N Engl J Med. 2002;346:180-188.• Nicolas ME, Krause PK, Gibson LE, Murray JA. Dermatitis Herpetiformis.

Int J Dermatol. 2003;42:588-600.• 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;123:1378-1380.• Collin P, Reunala T. Recognition and management of the cutaneous

manifestations of celiac disease. Am J Clin Dermatol. 2003:4:13-20.• Templet JT, Welsh JP, Cusack CA. Childhood Dermatitis Herpetiformis: A

Case Report and Review of the Literature. Cutis. 2007;80:473-476.• Zone JJ. Skin Manifestations of Celiac Disease. Gastroenterology.

2005;128:S87-S91.• Bolognia JL, Jorizzo JL, Rapini R, et al. Dermatology, 2nd ed. Mosby

Elsevier. Philadelphia, PA. 2008. • Wolff K, Goldsmith LA, Gilchrest BA, Paller AS, Leffell DJ, et al. Fitzpatrick’s

Dermatology in General Medicine, 7th ed. McGraw Hill. New York, NY. 2008.

• McKee PH, Calonje E, Granter SR, et al. Pathology of the Skin, 3rd ed. Mosby Elsevier. Philadelphia, PA. 2005.

• Wolverton SE. Comprehensive Dermatologic Drug Therapy, 2nd ed. Saunders Elsevier. Philadelphia, PA. 2007