Diagnosis of pyrazolone drug sensitivity: clinical history versus skin testing and in vitro testing

Pyrazolone drug hypersensitivity (PDH) may manifest as angioedema, urticaria, and/or life threatening anaphylactic shock. Although it has been suggested that PDH is an immunologic, probably IgE-mediated reaction, the diagnosis of PDH is still based on clinical history because there is no reliable in vitro diagnostic method currently used in clinical practice. The goal of this study was to evaluate the reliability of various methods to confirm a diagnosis of PDH. Twenty-eight patients with prior history of 71 reactions to pyrazolone drugs were studied. In all patients, pyrazolone drugs induced urticaria and angioedema. In addition, laryngeal edema occurred in 14 patients and anaphylactic shock with loss of consciousness in five patients. Skin prick test and intradermal tests using increasing concentrations of noraminophenazone were performed in 25 patients. Sera of all 28 patients were negative for pyrazolone-specific IgE as determined by an immunoenzymatic method. Peripheral blood mononuclear cells proliferative responses to pyrazolone were studied by a lymphocyte proliferation test with 3H-thymidine incorporation. Incubation of peripheral blood mononuclear cells with increasing concentrations of noraminophenazone did not induce any significant proliferation responses. Our study demonstrated that 1) intradermal skin tests correlate poorly with the clinical history of hypersensitivity reaction; and 2) in vitro tests are not useful in establishing a diagnosis of PDH.