Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole-Induced Severe Cutaneous Adverse Reactions: A Systematic Review and Meta-Analysis.
JAMA Dermatol
; 160(5): 525-534, 2024 May 01.
Article
in En
| MEDLINE
| ID: mdl-38568509
ABSTRACT
Importance Sulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 51 ratio, are antibacterial sulfonamides commonly used for treating various diseases. A substantial prevalence of severe cutaneous adverse reactions (SCARs) following the administration of these drugs has been reported. However, the association between human leukocyte antigen (HLA) genotypes and SMX/CTX-induced SCARs has remained unclear. Objective:
To investigate the association between HLA genotypes and SMX/CTX-induced SCARs. Data sources A comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023. Study Selection Case-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed. Data Extraction andSynthesis:
Two independent authors extracted data on study characteristics and outcome data. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline and the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. The Newcastle-Ottawa Scale for case-control studies was used to assess study quality. Odds ratios (ORs) were calculated using a random-effects model for meta-analysis. Main Outcomes andMeasures:
The prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles.Results:
Six studies involving 322 patients with SCAR were included, including 236 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis, 86 with drug reaction with eosinophilia and systemic symptoms, 8448 healthy controls, and 229 tolerant controls. Significant associations were found in HLA-A*1101 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*1301 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*1502 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*3802 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*0801 (OR, 2.63; 95% CI, 1.07-6.44) compared with tolerant controls. In the Stevens-Johnson syndrome/toxic epidermal necrolysis subgroup, significant associations were found in HLA-B*1502 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*3802 (OR, 5.13; 95% CI, 1.96-13.47). In the drug reaction with eosinophilia and systemic symptoms subgroup, significant associations were found in HLA-A*6801 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*1301 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*3901 (OR, 4.56; 95% CI, 1.31-15.82). Conclusions and Relevance The results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*1101, HLA-B*1301, HLA-B*1502, HLA-B*3802, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trimethoprim, Sulfamethoxazole Drug Combination
/
Drug Eruptions
/
HLA Antigens
Limits:
Humans
Language:
En
Journal:
JAMA Dermatol
Year:
2024
Document type:
Article
Affiliation country:
Taiwan