Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea

Norsa, Lorenzo; Canani, Roberto Berni; Duclaux-Loras, Remi; Bequet, Emeline; Koeglmeier, Jutta; Russell, Richard K.; Uhlig, Holm H.; Travis, Simon; Hollis, Jennifer; Koletzko, Sibylle; Grimaldi, Giusi; Castaldo, Giuseppe; Rodrigues, Astor; Deflandre, Jaques; Dembinski, Lukasz; Shah, Neil; Heinz-Erian, Peter; Janecke, Andreas; Leskinen, Saara; Wedenoja, Satu; Koskela, Ritva; Lachaux, Alain; Kolho, Kaija-Leena und Ruemmele, Frank M. (2021): Inflammatory Bowel Disease in Patients with Congenital Chloride Diarrhoea. In: Journal of Crohns & Colitis, Bd. 15, Nr. 10: S. 1679-1685

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1873-9946
• Sprache: Englisch