ArticleThe journal of allergy and clinical immunology. In practice2025
Utility of IFN-γ Enzyme-Linked Immunospot as Adjunctive Diagnostic for Severe T Cell-Mediated Reactions to Cotrimoxazole in High HIV and Tuberculosis Settings.
Article in The journal of allergy and clinical immunology. In practice, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCotrimoxazole is a broad-spectrum antibiotic associated with severe cutaneous adverse drug reactions (SCARs). In persons living with HIV, cotrimoxazole is typically used in combination with other SCAR-associated medications, creating challenges for culprit drug ascertainment.
objectiveTo investigate the utility of IFN-γ release enzyme-linked immunospot (ELISpot) in identifying cotrimoxazole as the culprit drug in SCAR.
methodsRegistry of Severe Cutaneous Adverse Reactions-validated SCAR cases from the prospective AFRISCAR patient registry with Naranjo and/or Algorithm of Drug Causality for Epidermal Necrolysis causality scores completed were eligible. Diagnostic assessments included cotrimoxazole patch testing, IFN-γ ELISpot, and oral challenge. ELISpot was performed on cryopreserved peripheral blood mononuclear cells using validated concentrations of cotrimoxazole (trimethoprim/sulfamethoxazole), its metabolite 4-nitroso-sulfamethoxazole, and sulfamethoxazole (sulfamethoxazole).
resultsCotrimoxazole was the probable culprit in 79 SCAR cases (55 drug reactions with eosinophilia and systemic symptoms, 10 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis, and 14 generalized bullous fixed drug eruptions) based on clinical drug causality assessment. Mean age was 39 years (SD, 11 years), and 90% were persons living with HIV (median CD4 count, 77; interquartile range, 25-142). Eighteen of 73 IFN-γ ELISpots (25%) were positive, nine of which reacted only to 4-nitroso-sulfamethoxazole (50%). Patch tests were all negative, including three of 13 with IFN-γ ELISpot and four of 13 with oral challenge positivity. IFN-γ ELISpot positivity was similar in Stevens-Johnson syndrome/toxic epidermal necrolysis (25%) and drug reactions with eosinophilia and systemic symptoms (26%), and no test was positive for samples older than 90 days from SCAR onset. IFN-γ ELISpot sensitivity and specificity were 38% (95% CI, 9-76) and 100% (95% CI, 40-100), respectively, using a cutoff of spot-forming units/million of 50 or greater.
conclusionsCotrimoxazole IFN-γ ELISpot had overall low but superior sensitivity to patch testing, offering good rule-in utility. Ongoing optimization of in vivo and in vitro diagnostic tools for cotrimoxazole SCAR is still required.
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