目的:腹泻持续超过14天,对常规治疗无反应,定义为严重和长期腹泻,可能与炎症性肠病(IBD)重叠。
方法:患病率,相关病原体,在台湾,研究了原发性免疫缺陷症(PID)患者中无IBD(SD)和单基因IBD(mono-IBD)的严重和持续性腹泻的预后。
结果:在2003年至2022年期间,共纳入301例患者,主要为儿科起病PID。其中,24名PID患者在预防性治疗前出现SD表型,包括Btk(六),IL2RG(四),WASP,CD40L,gp91(每个三个),gp47,RAG1(每个一个),CVID(两个),和SCID(一个)没有确定的突变。检出最多的病原菌是假单胞菌和沙门氏菌(各6种),所有患者在接受抗生素和/或IVIG治疗约2周后均有所改善。没有实施HSCT的6例(25.0%)死亡率是由于间质性肺炎引起的呼吸衰竭(3SCID和1CGD),颅内出血(WAS),淋巴瘤(HIGM)。在单IBD组中,17例突变型TTC7A(2),FOXP3(2),NEMO(2),XIAP(2),LRBA(1),TTC37(3),IL10RA(1),STAT1(1),ZAP70(1),PIK3CD(1),和PIK3R1(1)基因未能对侵袭性治疗作出反应。9例单IBD患者的TTC7A(2),FOXP3(2),NEMO(2),XIAP(2),在没有HSCT的情况下,LRBA(1)突变是致命的。单一IBD组的腹泻发病年龄明显较早(1.7vs33.3个月,p=0.0056),TPN持续时间更长(34.2个月比7.0个月,p<0.0001),较短的随访期(41.6个月vs132.6个月,p=0.007),和更高的死亡率(58.9vs25.0%,p=0.012)与SD组比较。
结论:与SD表型相比,单IBD患者有明显的早发性和经验性抗生素反应差,IVIG,和类固醇。抗炎生物制剂和合适的HSCT仍具有控制或甚至治愈单IBD表型的潜力。
Diarrhea lasting longer than 14 days which fails to respond to conventional management is defined as severe and protracted diarrhea and might overlap with inflammatory bowel disease (IBD).
The prevalence, associated pathogens, and prognosis of severe and protracted diarrhea without IBD (SD) and with monogenetic IBD (mono-IBD) in primary immunodeficiency patients (PID) were investigated in Taiwan.
A total of 301 patients were enrolled between 2003 and 2022, with predominantly pediatric-onset PID. Of these, 24 PID patients developed the SD phenotype before prophylactic treatment, including Btk (six), IL2RG (four), WASP, CD40L, gp91 (three each), gp47, RAG1 (one each), CVID (two), and SCID (one) without identified mutations. The most detectable pathogens were pseudomonas and salmonella (six each), and all patients improved after approximately 2 weeks of antibiotic and/or IVIG treatments. Six (25.0%) mortalities without HSCT implementation were due to respiratory failure from interstitial pneumonia (3 SCID and 1 CGD), intracranial hemorrhage (WAS), and lymphoma (HIGM). In the mono-IBD group, seventeen patients with mutant TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), LRBA (1), TTC37 (3), IL10RA (1), STAT1 (1), ZAP70 (1), PIK3CD (1), and PIK3R1 (1) genes failed to respond to aggressive treatments. Nine mono-IBD patients with TTC7A (2), FOXP3 (2), NEMO (2), XIAP (2), and LRBA (1) mutations were fatal in the absence of HSCT. The mono-IBD group had a significantly earlier age of diarrhea onset (1.7 vs 33.3 months, p = 0.0056), a longer TPN duration (34.2 vs 7.0 months, p < 0.0001), a shorter follow-up period (41.6 vs 132.6 months, p = 0.007), and a higher mortality rate (58.9 vs 25.0%, p = 0.012) compared with the SD group.
When compared to those with the SD phenotype, the mono-IBD patients had significant early-onset and poor responses to empiric antibiotics, IVIG, and steroids. Anti-inflammatory biologics and suitable HSCT still have the potential to control or even cure the mono-IBD phenotype.