Class A antibodies (IgA) deposit in the gut. Some may bind to the CD89 (FcαRI) receptor on macrophages (M1) via their Fc region (constant region). This will trigger endocytosis of the tTG-IgA complex, resulting in the activation of macrophages. Macrophages secrete more IL-8, propagating the neutrophil-mediated inflammatory response. The purportedly cross-reactive autoantibodies may migrate to the skin in dermatitis herpetiformis. IgA deposits may form if the antibodies cross-react with epidermal transglutanimase (eTG). Some patients have eTG-specific antibodies instead of tTG-specific cross-reactive antibodies and the relationship between dermatitis herpetiformis and celiac disease in these patients is not fully understood. Macrophages may be stimulated to secrete IL-8 by the same process as is seen in the gut, causing neutrophils to accumulate at sites of high eTG concentrations in the dermal papillae of the skin. Neutrophils produce pus in the dermal papillae, generating characteristic blisters. IL-31 accumulation at the blisters may intensify itching sensations. Memory B and T cells may become activated in the absence of PAMPs and DAMPs during successive encounters with tTG-modified gliadin complexes or modified gliadin alone, respectively. Symptoms of dermatitis herpetiformis are often resolved if patients avoid a gluten-rich diet. Diagnosis
Dermatitis herpetiformis often is misdiagnosed, being confused with drug eruptions, contact dermatitis, dishydrotic eczema (dyshidrosis), and even scabies. Other diagnoses in the differential diagnosis include bug bites and other blistering conditions such as bullous pemphigoid, linear IgA bullous dermatosis, and bullous systemic lupus erythematosus.
The diagnosis may be confirmed by a simple blood test for IgA antibodies against tissue transglutaminase (which cross-react with epidermal transglutaminase), and by a skin biopsy in which the pattern of IgA deposits in the dermal papillae, revealed by direct immunofluorescence, distinguishes it from linear IgA bullous dermatosis and other forms of dermatitis. Additionally, the concomitant diagnosis of Celiac disease can be made without the need for a small-intenstinal biopsy if an individual has biopsy-confirmed dermatitis herpetiformis as well as supporting serologic studies (elevated levels of IgA tissue transglutaminase antibodies, IgA epidermal transglutaminase antibodies, or IgA endomysial antibodies). These tests should be performed before the patient starts on a gluten-free diet, otherwise they might produce false negatives. As with ordinary celiac disease, IgA against transglutaminase disappears (often within months) when patients eliminate gluten from their diet. Thus, for both groups of patients, it may be necessary to restart gluten for several weeks before testing may be done reliably. In 2010, Cutis reported an eruption labelled gluten-sensitive dermatitis which is clinically indistinguishable from dermatitis herpetiformis, but lacks the IgA connection, similar to gastrointestinal symptoms mimicking coeliac disease but without the diagnostic immunological markers. Treatment
First-line therapy
A strict gluten-free diet must be followed, and usually, this treatment will be a lifelong requirement. Avoidance of gluten will reduce any associated intestinal damage and the risk of other complications. It can be very difficult to maintain a strict gluten-free diet, however, as contamination with gluten is common in many supposedly gluten-free foods and restaurants.