Genotypic and Phenotypic Characteristics of Co-Trimoxazole-Induced Cutaneous Adverse Reactions

Dermatology. 2023;239(6):966-975. doi: 10.1159/000534342. Epub 2023 Oct 4.


Background: Co-trimoxazole has been reported as a common culprit drug for various cutaneous adverse drug reactions (CADRs). However, information on genotypic and phenotypic characteristics is still limited. We aimed to study clinical characteristics, genetic suitability, laboratory findings, and treatment outcomes in patients with co-trimoxazole-induced CADR and determine variables associated with severe cutaneous adverse reactions (SCARs).

Methods: The medical records of all patients diagnosed with co-trimoxazole-induced CADR during October 2015 and October 2021 were reviewed. Clinical characteristics and laboratory investigation with an emphasis on human leukocyte antigen (HLA) class I and HLA-DRB1 results linked to subtypes of cutaneous adverse reactions were evaluated.

Results: Seventy-two patients diagnosed with co-trimoxazole-induced CADR were included in the study. Mean age at diagnosis was 38.0 ± 14.6 years old, and 72% were female. Subtypes of reactions included maculopapular eruption (MPE; 56.9%), drug reaction with eosinophilia and systemic symptoms (DRESS; 23.6%), Stevens-Johnson syndrome (SJS; 12.5%), fixed drug eruption (4.2%), and urticaria (2.8%). Characteristics that were significantly associated with SCARs included male gender (OR = 3.01, 95% CI: 1.04-8.75), HIV infection (OR = 3.48, 95% CI: 1.13-10.75), prophylactic use of co-trimoxazole (OR = 4.89, 95% CI: 1.54-15.57), and co-trimoxazole administration longer than 10 days (OR = 7.65, 95% CI: 2.57-22.78). HLA-B*38:02 was associated with co-trimoxazole-induced SJS, while HLA-A*11:01, HLA-B*13:01, and HLA-DRB1*12:01 were associated with co-trimoxazole-induced DRESS. HLA-B*52:01 was associated with co-trimoxazole-induced MPE.

Conclusions: Co-trimoxazole could induce various phenotypes of CADRs. Genotypic and phenotypic factors that may potentially predict co-trimoxazole-induced SCARs include male gender, HIV infection, prophylactic and prolonged drug use, as well as the presence of HLA-A*11:01, HLA-B*13:01, HLA-B*38:02, or HLA-DRB1*12:01 alleles.

Keywords: Co-trimoxazole; Drug reaction with eosinophilia and systemic symptoms; Human leukocyte antigens; Severe cutaneous adverse reactions; Stevens-Johnson syndrome.

MeSH terms

  • Adult
  • Cicatrix
  • Female
  • HIV Infections*
  • HLA-A Antigens / genetics
  • HLA-B Antigens / genetics
  • HLA-DRB1 Chains / genetics
  • Humans
  • Male
  • Middle Aged
  • Phenotype
  • Stevens-Johnson Syndrome* / genetics
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Young Adult


  • Trimethoprim, Sulfamethoxazole Drug Combination
  • HLA-DRB1 Chains
  • HLA-B Antigens
  • HLA-A Antigens

Grants and funding

The authors received financial support from Faculty of Medicine Ramathibodi Hospital, Mahidol University, for HLA analysis in this research.