Abstract
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.
Highlights
Severe and protracted diarrhoea (SD) is generally defined as prolonged diarrhoea lasting for more than 2 weeks, usually emerging within 2 years of life and requiring parenteral nutrition5, the definition has undergone several revisions to better delineate the duration and clinical course6
Neutropenia was noted in four patients (Btk1-2, Btk3, Btk5 and SCID2-IL2RG) with pseudomonas colitis and two (SCID3-IL2RG and CGD4-gp47) with salmonella colitis
Severe bacterial colitis in immune-competent patients often responds to effective antibiotics within 7 days in Taiwan in the previous study42
Summary
Severe and protracted diarrhoea (SD) is generally defined as prolonged diarrhoea lasting for more than 2 weeks, usually emerging within 2 years of life and requiring parenteral nutrition, the definition has undergone several revisions to better delineate the duration and clinical course. Excluding congenital enterocyte defects , SD is often accompanied by “little effect of treatment”, “failure to gain weight”, and/or co-morbidity with “recurrent infections”, all of which are warning signs of primary immunodeficiency diseases (PIDs). Increasing evidence suggests that SD can mimic inflammatory bowel disease (IBD) and that it is associated with PIDs patients who have defective IL-12/2310–16 and IL-10 signalling, profound T www.nature.com/scientificreports/. Aureus sepsis) Bloody diarrhoea, severe atopic dermatitis, mortality (intracranial haemorrhage) Bloody diarrhoea, stem cell transplantation Mortality (Staphy. aureus sepsis) Bloody diarrhoea, severe atopic dermatitis, mortality (intracranial haemorrhage) Bloody diarrhoea, stem cell transplantation
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