TY - JOUR
T1 - Clinical Features and Genetic Analysis of Taiwanese Primary Immunodeficiency Patients with Prolonged Diarrhea and Monogenetic Inflammatory Bowel Disease
AU - Lee, Wen I.
AU - Chen, Chien Chang
AU - Chen, Shih Hsiang
AU - Lai, Wan Tz
AU - Jaing, Tang Her
AU - Ou, Liang Shiou
AU - Liang, Chi Jou
AU - Kang, Chen Chen
AU - Huang, Jing Long
N1 - © 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2023/8
Y1 - 2023/8
N2 - PURPOSE: 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).METHODS: 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.RESULTS: 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.CONCLUSION: 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.
AB - PURPOSE: 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).METHODS: 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.RESULTS: 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.CONCLUSION: 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.
KW - Inflammatory bowel disease (IBD)
KW - Primary immunodeficiency (PID)
KW - Severe and protracted diarrhea (SD)
KW - Diarrhea/epidemiology
KW - Phenotype
KW - Humans
KW - Forkhead Transcription Factors/genetics
KW - Adaptor Proteins, Signal Transducing/genetics
KW - Immunoglobulins, Intravenous
KW - Proteins/genetics
KW - Inflammatory Bowel Diseases/genetics
UR - https://www.scopus.com/pages/publications/85159668866
U2 - 10.1007/s10875-023-01503-w
DO - 10.1007/s10875-023-01503-w
M3 - 文章
C2 - 37202577
AN - SCOPUS:85159668866
SN - 0271-9142
VL - 43
SP - 1455
EP - 1467
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 6
ER -
SDG3 健康與福祉