Severe cutaneous adverse reactions after <scp>COVID</scp>‐19 vaccination: A systematic review

Wu, Po‐Chien; Huang, I‐Hsin; Wang, Chuang‐Wei; Chen, Wei‐Ti; Chen, Chun‐Bing

doi:10.1111/all.15642

Cited by 7 publications

(12 citation statements)

References 6 publications

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“…The HLA-B*13:01 allele showed an association with SMX/CTX-induced SJS/TEN and DRESS, as evidenced by 3 studies involving Thai, Malaysian, and Taiwanese populations. 1,4,5 These significant associations were also observed in healthy controls. SCARs are life-threatening conditions commonly associated with medications, and they can lead to mortality and severely debilitating complications.…”

Section: Discussionmentioning

confidence: 77%

“…SCARs are life-threatening conditions commonly associated with medications, and they can lead to mortality and severely debilitating complications . Among the implicated drug classes, sulfonamide formulations containing compounds, such as SMX and CTX, characterized by the presence of an oxygen saturation–amines functional group, are frequently identified as causative agents of SCARs .…”

Section: Discussionmentioning

confidence: 99%

“…ulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim (TMP) in a 5:1 ratio, are broad-spectrum antibacterial sulfonamides widely used in managing bacterial, fungal, and protozoal infections. 1,2 Previous investigations have revealed a substantial prevalence of severe cutaneous adverse reactions (SCARs), encompassing Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), following the administration of SMX or CTX. [1][2][3][4][5][6] In most cases of CTX-induced SCARs, it is believed that SMX, rather than TMP, serves as the causative agent due to its capacity to activate T cells.…”

mentioning

confidence: 99%

“…1,2 Previous investigations have revealed a substantial prevalence of severe cutaneous adverse reactions (SCARs), encompassing Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), following the administration of SMX or CTX. [1][2][3][4][5][6] In most cases of CTX-induced SCARs, it is believed that SMX, rather than TMP, serves as the causative agent due to its capacity to activate T cells. 5 The direct involvement of human leukocyte antigens (HLAs), genes in the major histocompatibility complexes (MHC) playing a crucial role in distinguishing between self and nonself, has been proven in the pathogenesis of drug hypersensitivity.…”

mentioning

confidence: 99%

“…In East Asian populations, including Taiwanese, Thai, and Malaysian groups, the HLA-B*13:01 and HLA-B*15:02 alleles have shown significant associations with SMX/CTX-induced SCARs, particularly DRESS, while the HLA-C*08:01 allele has been associated with SMX/CTX-induced SJS/TEN. 1,[4][5][6] Among Japanese individuals, a significant association has been identified between the HLA-A*11:01 allele and SMX-induced SCARs. 3 Conversely, in those with European descent, HLA-B*38 has been predominantly associated with SMX-induced SJS/TEN.…”

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confidence: 99%

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Human Leukocyte Antigens and Sulfamethoxazole/Cotrimoxazole–Induced Severe Cutaneous Adverse Reactions

Wu,

Chen,

Huang

et al. 2024

JAMA Dermatol

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ImportanceSulfamethoxazole (SMX) and cotrimoxazole (CTX), a fixed-dose combination of SMX and trimethoprim in a 5:1 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.ObjectiveTo investigate the association between HLA genotypes and SMX/CTX-induced SCARs.Data sourcesA comprehensive search was conducted in CENTRAL (Cochrane Library), MEDLINE, and Embase from inception to January 17, 2023.Study SelectionCase-control studies that recruited patients who had experienced SCARs following SMX or CTX were included, and HLA alleles were analyzed.Data Extraction and SynthesisTwo 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 and MeasuresThe prespecified outcome was the OR comparing SMX/CTX-induced SCARs with healthy or SMX/CTX-tolerant controls based on different HLA alleles.ResultsSix 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*11:01 (OR, 2.10; 95% CI, 1.11-4.00), HLA-B*13:01 (OR, 5.96; 95% CI, 1.58-22.56), HLA-B*15:02 (OR, 2.23; 95% CI, 1.20-4.14), HLA-B*38:02 (OR, 3.47; 95% CI, 1.42-8.48), and HLA-C*08:01 (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*15:02 (OR, 3.01; 95% CI, 1.56-5.80) and HLA-B*38:02 (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*68:01 (OR, 12.86; 95% CI, 1.09-151.34), HLA-B*13:01 (OR, 23.09; 95% CI, 3.31-161.00), HLA-B*39:01 (OR, 4.56; 95% CI, 1.31-15.82).Conclusions and RelevanceThe results of this systematic review and meta-analysis suggest that multiple HLA alleles (HLA-A*11:01, HLA-B*13:01, HLA-B*15:02, HLA-B*38:02, and HLA-C*0801) are associated with SMX/CTX-induced SCARs.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%