Reply letter to “An update on direct immunofluorescence for diagnosing dermatitis herpetiformis”. Could granular C3 deposits at the dermal epidermal junction be considered a marker of “cutaneous gluten sensitivity”?

We read with interest the paper by Dmochowski et al. [1] on the direct immunofluorescence (DIF) features in dermatitis herpetiformis (DH). DIF on perilesional skin is the gold standard for DH diagnosis [2]. The pathognomonic finding for DH is a granular immoglobulin A (IgA) deposit along the dermal-epidermal junction (DEJ) with three main patterns (microgranular deposits at the tips of the dermal papillae, microgranular deposits along the DEJ, and microgranular-fibrillar/fibrillar deposits at the tips of the dermal papillae).
The authors underlined that IgA deposits at the DEJ of perilesional skin with DIF can also be found in coeliac patients with inflammatory skin diseases other than DH. In 2007, Cannistraci et al. [3] showed the presence of granular IgA deposits in the healthy skin of patients with celiac disease (CD), who were not affected by any skin diseases, suggesting that such deposits could be considered not only a marker of DH but also, more generally, of CD. Moreover, our group reported a case-series of 6 celiac patients presenting with heterogeneous skin diseases different from DH, characterized by a granular deposit of IgA at the DEJ and/or at the papillary tips [4]. We hypothesized that IgA deposits might be considered not only as a distinct feature of DH but also as an immunopathological marker of CD that could even have a diagnostic role for the disease.
These studies raise some questions about the diagnosis of DH because granular IgA deposits along the DEJ can also be found in perilesional skin of patients with CD with skin diseases other than DH. This means that all the previously defined atypical DH cases could only be part of the skin spectrum associated to CD, rather than real DH [5].
The authors also reported some cases with DH-like lesions associated with C3 deposits at the DEJ. They underlined that it could be a new disease entity, different from DH and plausibly related to the non-coeliac gluten sensitivity (NCGS). NCGS is a syndrome characterized by intestinal and extraintestinal symptoms associated to the ingestion of gluten-containing food in subjects who are not affected by either CD or wheat allergy [6]. NCGS has been rediscovered recently, following the work published by Sapone et al. [7]. Since then, reports on NCGS have grown exponentially, as well as the number of persons treated with a gluten-free diet (GFD) because of a wide array of conditions [8]. Hashimoto et al. [9] found 20 patients with DH-like...


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