Objectives and Study:
Congenital chloride diarrhea (CCD) is a rare, autosomal recessive disorder caused by mutations in the SLC26A3 gene encoding a transmembrane
chloride/
bicarbonate ion exchanger mainly expressed in the apical brush border of the ileal and colonic epithelium. Lifelong, secretory,
chloride-rich
diarrhea and hypochloremic, hypokalemic metabolic
alkalosis are characteristic. Histological evidence of bowel
inflammation is not typically described in CCD and has only been reported in a few patients. Methods: We report four cases of CCD who received adequate
resuscitation with appropriate replacement of their fecal
salt and water losses. Three had associated inflammatory bowel changes at endoscopy. The index case of CCD who developed frankly bloodstained
diarrhea aged 7 months was found to have histologically confirmed
colitis at endoscopy. An electronic search of the hospital database to identify all patients with confirmed CCD was performed. A further three children underwent de novo diagnostic evaluation and treatment. A retrospective case note review was undertaken to determine the incidence and subtype of
inflammatory bowel disease (IBD) by clinical, endoscopic, and histological means. Results: Four children with genetically confirmed CCD were identified, two being female. The first girl had a
granulomatous colitis with ulceration. She went into remission with a combination of
steroids and
azathioprine. Immunosuppression was subsequently discontinued without a further flare of
colitis. A second girl was found to have patchy inflammatory changes in the small bowel and focal active
colitis. A third patient, a boy, demonstrated mild inflammatory changes in the small bowel with apoptotic debris and mild
inflammation in the colon. A fourth patient did not develop intestinal
inflammation. Conclusion: Our case series highlights the potential association of CCD with panenteric
inflammation. While our cohort was small, CCD is rare and three out of four children referred to our tertiary referral center were affected. While early diagnosis and adequate
salt replacement
therapy are crucial in CCD management, the clinician should also be aware of bowel
inflammation as a potential cause of failure of CCD
therapy to control bowel symptomatology. Further insight is needed to understand the underlying patho-mechanism giving rise to bowel
inflammation in this group.