Granular IgA Deposits in the Skin of Patients with Coeliac Disease: Is it Always Dermatitis Herpetiformis?

Abstract

Coeliac disease is an immune-mediated enteropathy driven by gluten, which can be associated with dermatitis herpetiformis. The presence of granular IgA deposits, detected by direct immunofluorescence, is the hallmark of dermatitis herpetiformis; nevertheless, IgA deposits have also been demonstrated in healthy skin of patients with coeliac disease. The main objective of this study was to investigate whether IgA deposits could be found in the skin of patients with coeliac disease who have non-dermatitis herpetiformis inflammatory skin diseases. Direct immunofluorescence was performed on perilesional skin biopsies of 6 patients with coeliac disease with non-dermatitis herpetiformis inflammatory skin diseases and, as control, on 12 non-coeliac patients with inflammatory skin diseases. IgA deposits were found in all of the patients with coeliac disease, but were absent in the control group. In conclusion, IgA deposits may be considered an immunopathological marker for coeliac disease; therefore, patients with coeliac disease showing skin manifestations with positive direct immunofluorescence should be investigated carefully in order to make a differential diagnosis between dermatitis herpetiformis and other non-dermatitis herpetiformis inflammatory skin diseases.

An update on direct immunofluorescence for diagnosing dermatitis herpetiformis

“…Interestingly in this respect, codistribution of tissue transglutaminase and tissue-bound IgA in jejunum of patients with DH was reported in the meeting abstract [18]. IgA deposits at the DEJ of perilesional skin with DIF can also be found in coeliac patients with inflammatory skin diseases different from DH and, therefore, could even be considered as a marker of coeliac disease [19]. Interestingly, analysing 16 DH patients with both ELISA and immunoblot, we noticed certain discrepancies between the results of DIF and testing for circulating autoantibodies incriminated to be DH serum biomarkers.…”

Dermatitis Herpetiformis: Novel Perspectives

“…However, Donaldson et al observed that granular IgA deposits could be also detected in the non-affected skin of DH patients (114). More intriguingly, Cannistraci et al documented eTG/IgA co-localization in the papillary dermis, at the dermal-epidermal junction and in the vessel walls of coeliac patients without skin manifestations both before and during a GFD (10, 117, 118). It is also worth of mention that disappearance of eTG/IgA deposits from the skin occurs only in a subset of patients despite a long and strict GFD and no active skin rash, and takes much longer than serum autoantibodies or immune complexes (76, 119).…”

“…On this point, a recent paper from our group reported a case-series of six celiac patients presenting with skin diseases different from DH, such as contact eczema, dermatophytosis, granuloma annulare, pytiriasis rosea, lichenoid dermatitis, and psoriasis. Notably, all these patients showed a granular deposit of IgA at the dermal-epidermal junction and/or at the papillary tips (10). As previously mentioned, Cannistraci et al observed granular IgA deposits in the healthy skin of nine celiac patients without any cutaneous manifestation (117).…”

“…However, despite the growing knowledge about the disease, several issues have to be clarified yet, and some of the cornerstones of DH need further discussion. For example, the specificity of IgA deposits in the perilesional skin of patients with DH could be questioned and the diagnostic algorithm should be revised (10), taking also into account the identification of non-coeliac gluten sensitivity (NCGS) as a new entity among the spectrum of gluten-related disorders (11); moreover, the pathogenic role of IgA anti-eTG antibodies needs further demonstration, since they may also occur in patients without DH (12). Finally, even the therapeutic role of GFD is discussed, since some authors suggest that it can be interrupted in the (rare) case of DH remission (13).…”

Dermatitis Herpetiformis: An Update on Diagnosis and Management

“…In such cases, histopathological examination of skin lesion helps in correct diagnosis, which often can be a dermatosis other than DH [62]. A recent study described six patients with celiac disease with various inflammatory dermatoses who also showed granular IgA deposits in immunofluorescence specimens [63]. However, no evidence of clinical DH and coexistent TG3 deposits were seen, suggesting that the IgA findings were not representative of typical DH.…”