Clinical implications of in vitro drug-induced interferon gamma release from peripheral blood lymphocytes in cutaneous adverse drug reactions

Abstract

Background: Drug-specific T cells are involved in the pathogenesis of cutaneous adverse drug reactions (CADRs).

Objective: We sought to evaluate the diagnostic role of in vitro drug-induced release of interferon gamma in CADRs.

Methods: The study group consisted of 36 patients with CADRs after intake of 106 drugs that were classified into 3 categories of drug suspicion: high, possible, and low. The control group consisted of 22 individuals taking a similar profile of 54 drugs, without CADRs. In vitro drug-induced interferon gamma release was determined by enzyme-linked immunosorbent assay in culture supernatants after incubation of peripheral blood lymphocytes with parent drug compounds. The in vitro tests were conducted after the acute phase of the CADRs. In vitro tests were compared with in vivo withdrawal and/or challenge drug tests.

Results: Positive interferon gamma tests were recorded in 77.8% of the patients for 49.0% of the drugs. The proportion of positive interferon gamma tests was directly associated with the degree of drug suspicion (64.4%, 36.4%, and 27.8% for high, possible, and low, respectively). There were significantly more positive tests for high- compared with low-suspicion drugs (P=.001). The degree of agreement between the results of the in vitro interferon gamma release tests and the in vivo tests was intermediate to good (kappa=0.47).

Conclusion: In vitro drug-induced interferon gamma release may help to identify the responsible drug in CADRs.