Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea
Lorenzo Norsa, Roberto Berni Canani, Rémi Duclaux‐Loras, Émeline Bequet, Jutta Köglmeier, Richard K. Russell, Holm H. Uhlig, Simon Travis, J. J. Hollis, Sibylle Koletzko, Giusi Grimaldi, Giuseppe Castaldo, Astor Rodrigues, Jaques Deflandre, Łukasz Dembiński, Neil Shah, Peter Heinz‐Erian, Andreas Janecke, Saara Leskinen, Satu Wedenoja, Ritva Koskela, Alain Lachaux, Kaija‐Leena Kolho, Frank M. Ruemmele
Abstract
BACKGROUND: Congenital chloride diarrhoea [CLD] is a rare autosomal recessive disease caused by mutations in the solute family carrier 26 member 3 [SLC26A3] gene. Patients suffer from life-long watery diarrhoea and chloride loss. Inflammatory bowel disease [IBD] has been reported in individual patients with CLD and in scl26a3-deficient mice. METHODS: We performed an international multicentre analysis to build a CLD cohort and to identify cases with IBD. We assessed clinical and genetic characteristics of subjects and studied the cumulative incidence of CLD-associated IBD. RESULTS: In a cohort of 72 patients with CLD caused by 17 different SLC26A3 mutations, we identified 12 patients [17%] diagnosed with IBD. Nine patients had Crohn's disease, two ulcerative colitis and one IBD-unclassified [IBD-U]. The prevalence of IBD in our cohort of CLD was higher than the highest prevalence of IBD in Europe [p < 0.0001]. The age of onset was variable [13.5 years, interquartile range: 8.5-23.5 years]. Patients with CLD and IBD had lower z-score for height than those without IBD. Four of 12 patients had required surgery [ileostomy formation n = 2, ileocaecal resection due to ileocaecal valve stenosis n = 1 and colectomy due to stage II transverse colon cancer n = 1]. At last follow-up, 5/12 were on biologics [adalimumab, infliximab or vedolizumab], 5/12 on immunosuppressants [azathioprine or mercaptopurine], one on 5-ASA and one off-treatment. CONCLUSIONS: A substantial proportion of patients with CLD develop IBD. This suggests the potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.