Primary Immunodeficiency Care and Research (PICAR) Institute, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
Sci Rep. 2017 Jun 16;7(1):3669. doi: 10.1038/s41598-017-03967-4.
Diarrhoea lasting longer than 14 days and failing to respond to conventional management is defined as severe and protracted diarrhoea (SD). In this study, we investigated the prevalence, pathogens and prognosis of SD in primary immunodeficiency diseases (PIDs). Among 246 patients with predominantly paediatric-onset PIDs from 2003-2015, 21 [Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG2 (one each)] and five [CVID (four), SCID (one)] without identified mutations had SD before prophylactic treatment. Detectable pathogens included pseudomonas, salmonella (six each), E. coli, cytomegalovirus, coxsackie virus and cryptosporidium (one each), all of whom improved after a mean 17 days of antibiotics and/or IVIG treatment. Seven (7/26; 27.0%) patients died [respiratory failure (four), lymphoma, sepsis and intracranial haemorrhage (one each)]. The patients with WAS, CGD and CD40L and SD had a higher mortality rate than those without. Another five males with mutant XIAP, STAT1, FOXP3 (one each) and STAT3 (two) had undetectable-pathogenic refractory diarrhoea (RD) that persisted >21 days despite aggressive antibiotic/steroid treatment and directly resulted in mortality. For the patients with RD without anti-inflammatory optimization, those with mutant XIAP and FOXP3 died of Crohn's-like colitis and electrolyte exhaustion in awaiting transplantation, while transplantation cured the STAT1 patient.
持续超过 14 天且对常规治疗无效的腹泻被定义为严重和迁延性腹泻（SD）。在本研究中，我们调查了原发性免疫缺陷病（PID）中 SD 的患病率、病原体和预后。在 2003 年至 2015 年间，我们共研究了 246 例主要发生在儿童时期的 PID 患者，其中 21 例（Btk [6 例]、IL2RG [4 例]、WASP、CD40L、gp91 [各 3 例]、gp47、RAG2 [各 1 例]）和 5 例（CVID [4 例]、SCID [1 例]）患者在预防性治疗前就存在 SD。可检测到的病原体包括假单胞菌、沙门氏菌（各 6 例）、大肠杆菌、巨细胞病毒、柯萨奇病毒和隐孢子虫（各 1 例），所有患者在接受平均 17 天的抗生素和/或 IVIG 治疗后病情均有所改善。有 7 例（7/26；27.0%）患者死亡[呼吸衰竭（4 例）、淋巴瘤、脓毒症和颅内出血（各 1 例）]。患有 WAS、CGD 和 CD40L 且合并 SD 的患者死亡率高于不合并 SD 的患者。另外 5 例男性患者携带突变型 XIAP、STAT1、FOXP3（各 1 例）和 STAT3（2 例），患有无法检测到病原体的难治性腹泻（RD），尽管进行了积极的抗生素/类固醇治疗，但腹泻仍持续超过 21 天，导致直接死亡。对于 RD 患者，如果没有进行抗炎优化治疗，携带突变型 XIAP 和 FOXP3 的患者死于等待移植时的类克罗恩结肠炎和电解质衰竭，而移植治愈了 STAT1 患者。
