In vitro interferon-gamma release--a laboratory diagnosis of cutaneous adverse drug reactions

Diagnosis of cutaneous adverse drug reactions is an accepted terminology. Is a challenge. Drug-specific T-cell clones (CD4+ or CD8+), with a Th1- or a Th2-type cytokine-release pattern, may be generated from the peripheral blood in CADRs. In vitro drug-induced cytokine-release suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the skin reaction. We evaluated the diagnostic role of in vitro drug-induced interferon-gamma (IFN-gamma) release from peripheral blood lymphocytes in patients with CADRs. We studied 22 patients with CADRs following intake of 45 drugs (1-4 drugs per patient). Drugs were classified into 3 categories of suspicion. 17 patients who took 39 drugs of the same type (1-4 drugs per patient) without developing adverse reactions, served as controls. In vitro drug-induced release of IFN-à from peripheral blood lymphocytes, following in vitro challenge with the unmodified drugs, was evaluated. The mean IFN-gamma increase following 45 drug tests (60.8 +/- 85.2%) was higher (p < 0.05) than in controls after 39 drug tests (30.1 +/- 27.7%). Significance was greater (p < 0.005) when the mean IFN-gamma increase for the 24 highly suspected drugs (75.1 +/- 93.4%) and that for the controls were compared. This study suggests that the in vitro drug-induced IFN-gamma release test may serve as a diagnostic tool in CADRs.