Dermatitis herpetiformis.

Dermatitis herpetiformis (DH), described over 100 years ago, is a life-long blistering skin disease that can appear at any age. Dapsone controls the rash effectively and has been used for over 50 years in the treatment of DH. Major landmark in the research of DH was 30 years ago the discovery of granular IgA deposits in the upper papillary dermis,1 and further differentiation of an autoimmune disorder termed now as linear IgA disease from DH.2–4 The finding of mostly asymptomatic gluten-sensitive enteropathy, that is, celiac disease,5 and the observation that in all patients with DH the rash also responds to gluten free diet (GFD) treatment6,7 have had an important impact on our understanding of DH as a part of the spectrum of celiac disease.8,9 An immunogenetic link, HLA-DQ2, joins DH and celiac disease also tightly together.10,11 A novel hypothesis of autoimmune pathogenesis of celiac disease consists of deamidation of wheat gliadin by tissue transglutaminase, binding to HLA-DQ2 and its recognition by gut T cells with subsequent production of epithelial damaging cytokines, matrix degrading enzymes, and also IgA autoantibodies against tissue transglutaminase.12–14 In DH, a clinically silent but immunologically active celiac, disease in the gut could produce IgA antibodies crossreacting with the connective tissue in the skin, a hypothesis presented already for 30 years ago.15 In contrast to the major progress made in the characterization of the target antigens in various autoimmune blistering disorders, such as pemphigus, pemphigoid, and linear IgA disease, one of the main goals in the research on DH is still to resolve the enigma of IgA deposition in the skin, what is the antigen, and does IgA have any role in blister formation.