The diagnostic role of the in vitro drug‐induced interferon‐γ release test in Stevens–Johnson syndrome

Abstract

The role of allopurinol as the drug responsible for the induction of Stevens-Johnson syndrome in our patient was confirmed by in vitro allopurinol-induced IFN-gamma release, which may indicate a drug-specific immune response.

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

“…24 The diagnostic role of interferon gamma release in CADRs was recently reported. [11][12][13][14][15][16][17][18][19][20][21] The sensitivity of the interferon gamma release test in CADRs recorded by the enzyme-linked immunosorbent assay technique in this study (77.8%) and in previous studies 15,17 is similar to the sensitivity of the T-cell ELIspot technique used to demonstrate interferon gamma-producing cells in patients with gold hypersensitivity (67%). 21 It is noteworthy that in the majority of patients with CADRs in vitro interferon gamma release tests were performed after the acute phase of the reaction.…”

“…The test technique has been described previously. 11,[15][16][17][18][19] Briefly, peripheral blood lymphocytes (2 3 10 6 /mL) were incubated for 24 hours (378C, 5% CO 2 ) in M-199H medium (Hank's balanced salt solution; Biological Industries, Beit Haemek, Israel), containing 5% fetal calf serum, PHA-P 200 mg/mL (Bactophytohemagglutinin Purified; Difco Laboratories, Detroit, Mich) and glutamine (2 mmol/L), with or without the drug (unmodified parent drug compounds dissolved in the appropriate solvent). The drug concentrations were extrapolated from the known therapeutic doses, and the 2 to 3 maximal drug concentrations that were nontoxic for the lymphocytes were used.…”

“…[6][7][8] Drug-specific T cells may orchestrate the inflammatory skin reaction through release and induction of different cytokines. 5 Accordingly, T-cellemediated sensitization to drugs may be assessed in vitro by assays based on cytokine release from peripheral blood lymphocytes, such as macrophage migration inhibitory factor, 9,10 interferon gamma, [11][12][13][14][15][16][17][18][19][20][21] interleukin (IL)-5, 22,23 or other cytokines.…”

Increased in Vitro Release of Interferon-Gamma from Ampicillin-Stimulated Peripheral Blood Mononuclear Cells in Stevens-Johnson Syndrome

“…Other investigators also conducted in vitro tests 23 d or 2 months into the remission phase after resolution of the rash. 4,6) One of the investigators described that performance of the in vitro test during the remission phase of SJS, rather than during the acute phase of the adverse reaction, may reduce the likelihood of a false positive IFN-g response for the offending drug. 4) The timing of the test is important for diagnosis.…”

“…Some studies related to drug-specific T-cell clones derived from the peripheral blood mononuclear cells (PBMCs) of patients with cutaneous drug reactions, revealed the release of Th1-type cytokines, including IFN-g. The diagnostic role of in vitro IFN-g release has been reported in cases of allopurinol-induced SJS, 4) carbamazepine-induced erythroderma, 5) paracetamol and bromhexine-induced acute generalized exanthematous pustulosis, 6) and betalactam-induced morbilliform exanthems. 7) An increased expression of IFN-g was detected in bacampicillin-treated PBMCs from allergic contact dermatitis, but not from rhinitis patients.…”