A Nationwide Study of Severe and Protracted Diarrhoea in Patients with Primary Immunodeficiency Diseases

• Published in: Scientific reports 2017-06, Vol.7 (1), p.3669-11, Article 3669
• Main Authors: Lee, Wen-I, Chen, Chien-Chang, Jaing, Tang-Her, Ou, Liang-Shiou, Hsueh, Chuen, Huang, Jing-Long
• Format: Article
• Language: English
• Subjects: 13/31; 45/22; 45/23; 45/77; 45/90; 692/699/249/2512; 692/700/1720/3187; Antibiotics; Biomarkers; Biopsy; CD40L protein; Child; Child, Preschool; Colitis; Colonoscopy; Common variable immunodeficiency; Diarrhea; Diarrhea - diagnosis; Diarrhea - epidemiology; Diarrhea - etiology; Diarrhea - therapy; Female; Foxp3 protein; Hemorrhage; Humanities and Social Sciences; Humans; Immunodeficiency; Immunoglobulins; Immunologic Deficiency Syndromes - complications; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Infant; Inflammation; Intravenous administration; Lymphocytes - immunology; Lymphocytes - metabolism; Lymphoma; Mortality; multidisciplinary; Mutation; Pathogens; Phenotype; Primary immunodeficiencies; RAG2 protein; Respiratory failure; Science; Science (multidisciplinary); Sepsis; Severe combined immunodeficiency; Severity of Illness Index; Stat1 protein; Stat3 protein; Transplantation; Treatment Outcome; XIAP protein
• ISSN: 2045-2322; 2045-2322
• 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.