Nickel allergic contact mucositis: duodenal histological, immunohistochemical and cultural characterization of an emerging clinicopathologic entity

BACKGROUND: The estimated prevalence of Nickel (Ni) sensitization is 30% in Europe. Alimentary Ni can be considered responsible of IBS-like disorders as Allergic Contact Mucositis (ACM). An involvement of TLR4 has been recently showed in its immunological characterization. A local adaptive response in Ni-sensitive patients has been suggested, with CD3+ lymphocytes highlighted in oral mucosa biopsy samples. Moreover, a Ni-induced production of IL-10 and IFN-g has been showed in peripheral blood mononuclear cells' cultures. Recently, a Ni oral mucosa patch test (omPT) has been proposed for Ni MAC diagnosis. AIM: We wanted to evaluate histological and immunohistochemical features in duodenal biopsies taken from Ni-sensitive patients. Inflammatory characterization has also been investigated in culture supernatant of duodenal biopsies. MATHERIALS AND METHODS: 9 symptomatic Ni-sensitive patients (group A) were studied after a specific symptom questionnaire and a positive Ni omPT, confirming Ni ACM. 9 control patients (group B) with dyspepsia and GERD were recruited in absence of Ni-related symptoms, as proved by questionnaire and a negative Ni omPT. All patients underwent EGD and duodenal biopsies collection. Histology and immunohistochemistry (with CD3+, CD4+ and CD8+ lymphocytes count) were performed. Culture supernatants of duodenal biopsies were performed to determine IL-10 and IFN-g levels with and without Ni sulfate stimulation. RESULTS: All duodenal sections from group A showed class 0 according Marsh-Oberhuber; 3-4 eosinophils per field (400x) were detected in the lamina propria; 17.7 ± 2.9 CD3+ IELs/100 ECs were detected (4.5 ± 2.1 CD4+; 13.2 ± 3.4 CD8+); lymphocytes were grouped in clusters in surface epithelium and in a linear way at the base of the villi. IFN-g levels in cultures from group A were significantly higher after stimulation with Ni than without Ni (p = 0.0116). IL-10 levels in group A cultures were significantly lower after stimulation with Ni, rather than without Ni (p = 0.0010). Control patients showed no statistically significant difference in cultural IFN-g and IL-10 levels. DISCUSSION: No specific histological and immunohistochemical alterations have been found in Ni-sensitive patients, apart from a peculiar arrangement of T lymphocytes. The absence of Ni seems to guarantee an immunological tolerance in Ni-sensitive patients, with increased IL-10 and reduced IFN-g levels in cultures. On the other hand, exposure to Ni seems to invert this state. These results seem to confirm and extend previous data about Ni ACM.