IgE-mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone.
BACKGROUND
Propyphenazone (1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one; PP) is a nonsteroidal anti-inflammatory drug frequently used as mild analgesic medicament. It belongs to the chemical group of pyrazolones. Severe adverse reactions to PP are frequent and have generally been regarded as pseudoallergic or intolerance reactions. Presently, there are no useful in vitro test systems available for the detection of antibodies directed against analgesic drugs.


OBJECTIVE
The purpose of this study was to unequivocally demonstrate that IgE-mediated Type I allergy is the main mechanism leading to immediate-type adverse reactions to the analgesic drug PP.


METHODS
We investigated 53 young adult patients with adverse reactions to PP. All patients developed symptoms suggestive of IgE-mediated anaphylaxis within 30 minutes after intake of a painkiller containing PP. Patients were subjected to skin tests (prick test and intracutaneous test). In addition, a novel ELISA system was developed to prove the existence of specific IgE antibodies in patients' sera.


RESULTS
In 44 of 53 (83%) patients, skin tests showed typical wheal and flare reactions. Significant amounts of PP-specific serum IgE was detected in 31 of 53 (58%) of the serum samples. Moreover, in 7 of 9 patients with skin test negative results, PP-specific IgE could be detected. The assay was PP-specific because only PP, but no other pyrazolone derivative (antipyrine, aminophenazone, or metamizol), was able to inhibit IgE-binding in the system.


CONCLUSIONS
Propyphenazone is a sensitizing agent in susceptible individuals and can elicit IgE-mediated anaphylaxis. By using skin tests and our ELISA system we were able to confirm Type I allergy in 51 of 53 (96%) patients in this study.
Himly
Martin
M
Institute of Genetics, University of Salzburg.
Jahn-Schmid
Beatrice
B
Pittertschatscher
Klaus
K
Bohle
Barbara
B
Grubmayr
Karl
K
Ferreira
Fátima
F
Ebner
Herwig
H
Ebner
Christof
C
D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000983:Antipyrine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D004342:Drug Hypersensitivity / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000209:etiology*; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007073:Immunoglobulin E; C009077:propyphenazone; D000983:Antipyrine