Assistance Publique - Hôpitaux de Paris, Hôpital Necker Enfants Malades, Pediatric Gastroenterology Hepatology and Nutrition, Paris, France.
Pediatric Gastroenterology Hepatology and Transplantation, ASST Papa Giovanni XXIII, Bergamo, Italy.
J Crohns Colitis. 2021 Oct 7;15(10):1679-1685. doi: 10.1093/ecco-jcc/jjab056.
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.
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.
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.
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.
先天性氯性腹泻（CLD）是一种罕见的常染色体隐性疾病，由溶质家族载体 26 成员 3（SLC26A3）基因突变引起。患者患有终身水样腹泻和氯离子丢失。个别 CLD 患者和 scl26a3 缺陷小鼠报告有炎症性肠病（IBD）。
我们进行了一项国际多中心分析，以建立 CLD 队列并确定患有 IBD 的病例。我们评估了受试者的临床和遗传特征，并研究了 CLD 相关 IBD 的累积发病率。
在由 17 种不同 SLC26A3 突变引起的 72 例 CLD 患者队列中，我们确定了 12 例（17%）诊断为 IBD 的患者。9 例患有克罗恩病，2 例溃疡性结肠炎，1 例 IBD 未分类[IBD-U]。我们的 CLD 队列中 IBD 的患病率高于欧洲最高的 IBD 患病率[P <0.0001]。发病年龄各不相同[13.5 岁，四分位间距：8.5-23.5 岁]。患有 CLD 和 IBD 的患者身高 Z 评分低于无 IBD 的患者。12 例中有 4 例需要手术[肠造口术形成 n=2，回盲瓣狭窄所致回肠-盲肠切除术 n=1，II 期横结肠癌所致结肠切除术 n=1]。最后一次随访时，12 例中有 5 例接受生物制剂治疗[阿达木单抗、英夫利昔单抗或维得利珠单抗]，12 例中有 5 例接受免疫抑制剂治疗[巯嘌呤或硫唑嘌呤]，1 例接受 5-ASA 治疗，1 例未治疗。
相当一部分 CLD 患者会发展为 IBD。这表明 SLC26A3 介导的阴离子转运可能参与了 IBD 的发病机制。CLD 相关 IBD 患者可能需要手术治疗治疗失败或结肠癌。
