Aetiology
Virtually all cases of dermatitis herpetiformis are triggered by gluten, which switches on the autoimmune response, therefore leading to the development of the cutaneous manifestations that are typical of the condition. Accordingly, a gluten-free diet can revert the pathophysiological process of dermatitis herpetiformis; however, its effects are slower than that seen for gastrointestinal symptoms in patients with coeliac disease and it typically takes several months to years for the skin lesions to resolve.[2] As such, coeliac disease is a strong risk factor for developing dermatitis herpetiformis.
Dermatitis herpetiformis, or at least its main variant, only occurs in patients with a well determined genetic predisposition (presence of human leukocyte antigen [HLA]-DQ2 or HLA-DQ8 haplotypes).[10][11] First degree relatives of patients with gluten sensitive enteropathy or dermatitis herpetiformis are characteristically more likely to be affected by either disorder. A study of 73 twin pairs performed to estimate disease concordance rate by zygosity and HLA genotypes, discordance times, progression rates to disease, and heritability found that concordance was significantly higher in monozygotic (83.3% probandwise, 71.4% pairwise) than in dizygotic (16.7% probandwise, 9.1% pairwise) pairs.[12]
Other potential triggers have been anecdotally reported (including drugs, cancer, infections, or gastric surgery), although further research into their role as triggers is required.[1]
Pathophysiology
The pathophysiology of dermatitis herpetiformis is still not fully understood, although the main points have been elucidated.
The ingestion of gluten in predisposed individuals triggers the development of anti-epidermal transglutaminase antibodies in the gut, possibly as a result of an epitope-spreading phenomenon following autoimmunity against tissue transglutaminase.[13]
These anti-epidermal transglutaminase antibodies form immune complexes in the circulation or in the skin (mainly in areas of trauma, where epidermal transglutaminase - usually located in the upper layers of the epidermis - may have shedded to the basement membrane zone), and are deposited at the tips of dermal papillae. These immune complexes are able to recruit neutrophil granulocytes, which are the main effectors of skin damage, via the release of proteases and other effector molecules.[1]
A T helper 2-mediated immune response is also triggered and is able to cooperate with neutrophils to cause cleavage of the dermal-epidermal junction and maintain inflammation via the production of proinflammatory molecules such as interleukin (IL)-4, IL-5, and IL-13.[14]
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