Dermatitis Herpetiformis: Novel Perspectives

Abstract

Dermatitis herpetiformis (DH) is an inflammatory disease of the skin, considered the specific cutaneous manifestation of celiac disease (CD). Both DH and CD occur in gluten-sensitive individuals, share the same Human Leukocyte Antigen (HLA) haplotypes (DQ2 and DQ8), and improve following the administration of a gluten-free diet. Moreover, almost all DH patients show typical CD alterations at the small bowel biopsy, ranging from villous atrophy to augmented presence of intraepithelial lymphocytes, as well as the generation of circulating autoantibodies against tissue transglutaminase (tTG). Clinically, DH presents with polymorphic lesions, including papules, vesicles, and small blisters, symmetrically distributed in typical anatomical sites including the extensor aspects of the limbs, the elbows, the sacral regions, and the buttocks. Intense pruritus is almost the rule. However, many atypical presentations of DH have also been reported. Moreover, recent evidence suggested that DH is changing. Firstly, some studies reported a reduced incidence of DH, probably due to early recognition of CD, so that there is not enough time for DH to develop. Moreover, data from Japanese literature highlighted the absence of intestinal involvement as well as of the typical serological markers of CD (i.e., anti-tTG antibodies) in Japanese patients with DH. Similar cases may also occur in Caucasian patients, complicating DH diagnosis. The latter relies on the combination of clinical, histopathologic, and immunopathologic findings. Detecting granular IgA deposits at the dermal-epidermal junction by direct immunofluorescence (DIF) from perilesional skin represents the most specific diagnostic tool. Further, assessing serum titers of autoantibodies against epidermal transglutaminase (eTG), the supposed autoantigen of DH, may also serve as a clue for the diagnosis. However, a study from our group has recently demonstrated that granular IgA deposits may also occur in celiac patients with non-DH inflammatory skin diseases, raising questions about the effective role of eTG IgA autoantibodies in DH and suggesting the need of revising diagnostic criteria, conceivably emphasizing clinical aspects of the disease along with DIF. DH usually responds to the gluten-free diet. Topical clobetasol ointment or dapsone may be also applied to favor rapid disease control. Our review will focus on novel pathogenic insights, controversies, and management aspects of DH.

Autoantibodies Against the Immunodominant Bullous Pemphigoid Epitopes Are Rare in Patients With Dermatitis Herpetiformis and Coeliac Disease

“…Proteolytic gliadin peptides from ingested gluten induce production of IgA class autoantibodies against both native and gliadin-associated tissue transglutaminase 2 (TG2) (2). These antibodies are detectable in the serum and small bowel mucosa of CD patients, but in only about 75% of DH patients (6,7). Typically the sera of DH patients contain anti-epidermal transglutaminase (TG3) IgA autoantibodies, which show up on direct immunofluorescence microscopy (DIF) analysis of the skin as granular IgA deposits in the papillary dermis (8,9).…”

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review

“…The association between HMs and subepidermal autoimmune bullous dermatoses other than BP mostly relies on single case reports or small series, and almost always involves lymphoproliferative disorders. Worth mentioning are cases of linear IgA bullous dermatosis associated with B-cell chronic lymphatic leukaemia, acute lymphoblastic leukaemia and Hodgkin’s lymphoma [ 166 – 169 ]; epidermolysis bullosa acquisita with multiple myeloma, mantle cell lymphoma and B-cell chronic lymphatic leukaemia [ 170 – 174 ]; laminin 332-type mucous membrane pemphigoid with non-Hodgkin’s lymphoma; and dermatitis herpetiformis with non-Hodgkin’s lymphoma of the gastrointestinal tract [ 175 ].…”

An updated overview of spectrum of gluten-related disorders: clinical and diagnostic aspects

“…Dermatitis Herpetiformis (DH) is a chronic, autoimmune, and recurrent cutaneous-intestinal disorder identified in genetically susceptible individuals, which is often associated with CD [67,68]. Anti-tTG antibodies that are produced in response to gluten exposure can also recognize epidermal transglutaminase (ETG).…”