25
Dermatitis Herpetiformis and Linear IgA Bullous Dermatosis
This is the third chapter, along with Chapters 23 and 24, that deals with autoimmune bullous diseases (see Table 23.1).
Dermatitis Herpetiformis (DH)
• In predisposed individuals (e.g. those with HLA-DQ2), IgA antibodies form against gliadin cross-linked to tissue tranglutaminase; the presumed autoantigen in the skin is epidermal transglutaminase (Fig. 25.1).
Fig. 25.1 Proposed pathogenesis of dermatitis herpetiformis and celiac disease. A Dietary wheat, barley, or rye 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 IgA anti-TG2. C Over time, IgA directed against TG3 (IgA anti-TG3) forms as a result of epitope spreading and both IgA anti-TG2 and IgA anti-TG3 circulate in the bloodstream. D When IgA anti-TG3 antibodies reach the dermis, they complex with TG3 antigens which have been produced by keratinocytes (epidermal TG) and then have diffused into the dermis. That is, IgA/TG3 immune complexes are formed locally within the papillary dermis. This leads to neutrophil chemotaxis (with formation of neutrophilic abscesses), proteolytic cleavage of the lamina lucida, and subepidermal blister formation.
• Primary lesions consist of pruritic vesicles on an erythematous base and edematous erythematous papules that are often grouped (i.e. herpetiform); however, due to scratching, only excoriated papules and hemorrhagic crusts may be present (Fig. 25.2).
