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Dermatitis Herpetiformis in Older Adults

Scott R.A. Walsh PhD, MD, Division of Dermatology, Department of Medicine, Sunnybrook & Women’s College Health Sciences Centre, University of Toronto Medical School, Toronto, Ontario.

Dermatitis herpetiformis (DH) is a pruritic and chronic autoimmune blistering skin disease associated with varying degrees of gluten-induced enteropathy. Associated symptomatic celiac disease (CD) occurs in a minority of patients, but the pathogenesis of both diseases shares several features. In addition to some features of enteropathy, patients with DH also form specific antibodies to epidermal transglutaminase not typically found in patients with only CD. Although incidence is highest in middle age, because it is a life-long condition its prevalence is highest in the older population. Chronic complications of DH, including gastrointestinal lymphomas, are more likely to present in the geriatric group. Similarly, common comorbid disease associations including pernicious anemia, splenic atrophy and thyroid disease should be routinely assessed in this population. Long-term treatment of DH requires strict adherence to a gluten-free diet. Symptomatic treatment of this skin disease commonly uses dapsone to inhibit neutrophil accumulation and disease expression. Older patients may be more susceptible to toxic side effects of dapsone metabolites, and both careful patient selection and close monitoring should be undertaken with dapsone treatment.

Key words: dermatitis herpetiformis, autoimmunity, anemia, comorbidities, dapsone.

Introduction
Dermatitis herpetiformis (DH) is a chronic pruritic gluten-induced symmetric autoimmune blistering skin disease associated with varying degrees of jejunal enteropathy. Although the majority of patients with DH manifest with very mild or asymptomatic intestinal disease, approximately 20-30% of genetically predisposed individuals go on to have symptoms consistent with celiac disease (CD). 1-3 The pathogenesis of these two gluten-associated diseases is quite similar such that DH can really be thought of as a cutaneous manifestation of some degree of underlying celiac disease.

CD involves gluten-induced autoimmune damage to the jejunal mucosa and typically presents with diarrhea, flatulence, abdominal bloating and weight loss.4 Malabsorption can become severe and result in anemia from B12, iron or folate deficiency, and osteoporosis from ineffective vitamin D metabolism in the intestine. Approximately 5% of patients with CD also have DH with gluten-induced auto-immune damage to the papillary dermis resulting in pruritic polymorphous lesions.1 In linking these two diseases together, all patients with DH have either jejunal pathology consistent with mild or asymptomatic CD, or have latent celiac sprue where CD pathology can be induced by large quantities of dietary gluten intake.5 Although DH and CD characteristically present in mid-life, approximately one-third of cases present in the over 65 age group.6 Furthermore, this disease is generally considered to involve a chronic, often life-long sensitivity to gluten, and thus the prevalence of this relatively infrequent disease becomes more significant in older adults. Finally, many of the long-term complications associated with DH, including lymphoma, tend to manifest in the older age group.

Epidemiology and Pathogenesis
DH is most prevalent in people of European ethnicity at a rate of 1-4/10, 000, being relatively rare in Asian and African-Americans.1-3,7,8 Slightly more prevalent in males, DH is strongly associated with specific major histocompatibility complex alleles.2 These human leukocyte antigens (HLA) may be intimately involved in the development of the disease. Ninety per cent of patients with DH have the HLA-DQw2 alleles (HLADQ2A1*0501B1*02) while the majority of the rest express the HLADQ8 alleles (HLADQ8A1*03B1*0302).5

Gluten is a plant elastin that is found in wheat, rye, and barley, but not oats.9,10 Gliadin is the alcohol-soluble fraction of gluten and is believed to be the key antigenic component. Gliadin is metabolized by an enzyme produced in the endomysium (the connective tissue covering the