- Fecal Incontinence
|Inflammatory bowel disease in patients with congenital chloride diarrhoea
J Crohns Colitis. 2021 Mar 26;jjab056. doi: 10.1093/ecco-jcc/jjab056. Online ahead of print.
Lorenzo Norsa 1 2, Roberto Berni Canani 3 4 5, Remi Duclaux-Loras 6 7, Emeline Bequet 8, Jutta Köglmeier 9, Richard K Russell 10, Holm H Uhlig 11, Simon Travis 11, Jennifer Hollis 11, Sibylle Koletzko 12 13, Giusi Grimaldi 3, Giuseppe Castaldo 4, Astor Rodrigues 11, Jaques Deflandre 14, Lukasz Dembinski 15, Neil Shah 9, Peter Heinz Erian 16, Andreas Janecke 16, Saara Leskinen 17, Satu Wedenoja 18, Ritva Koskela 19, Alain Lachaux 6, Kaija-Leena Kolho 20, Frank M Ruemmele 1
20Department of Paediatric Gastroenterology, Children's Hospital and University of Helsinki, Helsinki, Finland and Tampere University, Tampere, Finland
Introduction: 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 diarrhea 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). Prevalence of IBD in our cohort of CLD is higher than the highest prevalence of IBD in Europe (p < 0.0001). The age of onset was variable (13.5 years, IQR: 8.5 - 23.5 years). Patients with CLD and IBD had lower z-score for height than those without IBD. 4/12 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 immunosuppressant (azathioprine or mercaptopurine), one on 5-ASA and one off-treatment.
Conclusions: A substantial proportion of patients with CLD develop IBD. This suggests potential involvement of SL26A3-mediated anion transport in IBD pathogenesis. Patients with CLD-associated IBD may require surgery for treatment failure or colon cancer.