P755 Congenital chloride diarrhoea and inflammatory bowel disease: an emerging association
L. Norsa1, R. Berni Canani2, R. Duclaux- Loras3, E. Bequet4, J. Koeglmeier5, R.K. Russell6, H. Ulhig7, S. Koletzko8, A. Rodrigues7, J. Deflandre9, L. Dembinski10, G. Castaldo2, G. Grimaldi2, N. Shah5, P. Heinz-Erian11, A. Janecke11, S. Leskinen12, S. Wedenoja12, A. Lachaux3, K.L. Kolho12, F. Ruemmele13
1ASST Papa Giovanni XXIII, Pediatric Hepatology- Gastroenterology and Transplantation, Bergamo, Italy, 2University ‘Federico II’, Translational Medical Science–Pediatric Section, Napoli, Italy, 3Hospices Civils de Lyon- Hôpital Femme Mère Enfant, Paediatric Gastroenterology Hepatology and Nutrition, Bron, France, 4University Hospital Liège, Division of Gastroenterology- Hepatology and Nutrition- Department of Pediatrics, Liège, Belgium, 5Great Ormond Street Hospital for sick children, Pediatric Gastroenterology Hepatology and Nutrition, London, UK, 6Royal Hospital for Children, Pediatric Gastroenterology Hepatology and Nutrition, Glasgow, UK, 7University of Oxford, Translational Gastroenterology Unit and Department of Paediatrics, Oxford, UK, 8Dr. von Hauner Children’s Hospital- LMU Munich Medical Center, Division of Gastroenterology and Hepatology, Munich, Germany, 9CHR Citadelle, Department of Gastroenterology, Liege, Belgium, 10Medical University of Warsaw, Department of Paediatrics- Gastroenterology and Nutrition, Warsaw, Poland, 11Medical University of Innsbruck, Pediatric I, Innsbruck, Austria, 12Children’s Hospital- University of Helsinki, Department of Paediatric Gastroenterology, Helsinki, Finland, 13Necker Children Hospital, Pediatric Gastroenterology Hepatology and Nutrition, Paris, France
Background
Congenital chloride diarrhea (CLD) is a rare autosomal recessive disease caused by the mutation in member 3 of the solute carrier 26 (SLC26A3). The phenotypic expression is a life-long severe watery Chloride rich diarrhea. Anecdotal association with inflammatory bowel disease (IBD) has been reported suggesting that underlying molecular mechanisms could represent part of an evolving association between IBD and channelopathies. We aimed to investigate this association in a cohort of CLD pediatric patients.
Methods
A European-based call for cases was made in CLD patients followed up in five different countries. A case report form for each patient was then completed.
Results
A total of 74 patients with CLD with a range of different CLD mutations were enrolled in the study. Twelve patients of 64 (16%) demonstrated colonic inflammation and were finally diagnosed with IBD: 8 patients with Crohn’s Disease, 2 with Ulcerative Colitis, and 2 IBD-like colitis (IBD-U). The diagnosis was made at a median of 12 years old (IQR: 6–30). Patients had different ethnicities (7 European, 2 Middle East, 1 North Africa, 1 Pakistan, 1 Central Africa). Among the 12 IBD, 2 had a 5-ASA-based treatment, 3 required immunosuppressant and 6 had biologics (Infliximab, Adalimumab and Vedolizumab). Three patients underwent surgery for ileostomy formation for CD that was non-responsive to multiple line of biologics (anti-TNF and anti-integrin): one had colectomy the remnant two colon preservation. Clinical characteristics, such as premature delivery, low weight at birth, fecal Cl- at diagnosis and amount of Cl- supplementation (mmol/kg) did not differ between patients with or without IBD. All patients underwent genotyping for CLD diagnosis and we did not find any specific genetic mutation linked to the development of IBD.
Conclusion
Sixteen percent of patients enrolled with CLD in our cohort developed IBD. Despite different presentations (CD, UC, IBD-U) all patients had colonic without ileal/small bowel involvement, in line with preliminary murine models of CLD demonstrating a role of colonic mucous layer in the development of colonic inflammation (Xiao et al Acta Physiol Oxf Engl 2014; 211:161–175). Patients’ IBD treatment included a wide range with variable success. Patients with IBD did not differ in their clinical characteristics or genetic mutations compared with non-IBD CLD patients. The role of genetic variants outside the CLD-gene and the microbiome in this association are under investigation.