Acute generalized exanthematous pustulosis associated with polysensitivity to paracetamol and bromhexine: the diagnostic role ofin vitrointerferon-γ release test

Abstract

We report a patient with acute generalized exanthematous pustulosis (AGEP), which occurred 3 days after ingesting paracetamol and bromhexine. Both were immediately stopped and the rash resolved rapidly. To determine the offending drug responsible for AGEP, an in vitro drug-induced interferon (IFN)-gamma release test was performed using an ELISA technique. Increased IFN-gamma release was observed following in vitro challenge of the patient's lymphocytes with paracetamol or bromhexine (110% and 157% increase, respectively). In vitro challenge with paracetamol or bromhexine in a control patient, treated with paracetamol and bromhexine, did not induce an increase in IFN-gamma. These findings suggest that the patient with AGEP may have polysensitivity to both drugs. The ELISA assessment also demonstrates the relevance of in vitro cytokine release tests in the investigation of such dermatoses.

Comparative Study of the Usefulness of the Drug-Induced Lymphocyte Stimulation Test and the Leukocyte Migration Test in Drug Allergies

“…Besides, there have been many reports that TNF-a plays a large role in drug allergies. [37][38][39][40][41][42] These previous results, together with the present results, indicate that some cytokines may be present in patient serum and may enhance the production and effect of leukocyte migration factor in drug allergies.…”

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

“…[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.…”