Anaphylactoid Reactions to Mild Analgesics

Abstract

“Mild” analgesic preparations (MAP), containing as main active compounds salicylates, pyrazolons, or p-aminophenol derivatives, are well-known elicitors of AR. The identification of the responsible agent is often difficult, as routine skin tests are only rarely conclusive.

The diagnostic value of skin tests (prick test, intracutaneous tests), challenge tests, and basophil histamine release tests was assessed in patients presenting with AR to MAP.

Prick testing with common components of MAP or commercial preparations (mostly in saturated solutions) yielded conclusive results (≥ 3 mm wheal diameter) in 19/282 patients. Positive reactions in more than 1% were observed only with the pyrazolons dipyrone (3.3%), propyphenazone (2.2%), and anti-pyrine (1.1%). The yield of conclusive results increased with the severity of the reactions reported in the history, reaching 25% in patients with a history of a full shock. — In 155 patients (mostly with negative prick test), oral challenge tests were performed. At least one conclusive positive result was obtained in 90 patients. The most frequent reactions were due to propyphenazone (in 39% of the patients tested), aspirin (23%), dipyrone (25%), acetaminophen (6%), and phenacetin (6%). In more than half of the patients with aspirin-induced AR there were additional reactions to pyrazolons and002For p-aminophenol derivatives. Among 71 patients reacting to dipyrone or propyphenazone, “cross reactivity” to both pyrazolon compounds occurred only in 12 cases. — Intracutaneous skin testing (ICT) with solutions of 10~2 M was compared with the oral challenge test results: with propyphenazone 4002F6 ICT reactions proved to be false positive, and in only 2/6 patients with a positive challenge test a conclusive ICT was found. 0/4 patients with AR to dipyrone were identifiable by ICT. In 3 patients showing conclusive positive prick test reactions to propyphenazone and/ or dipyrone oral challenges with these compounds were positive. — In 19 patients with positive oral challenge tests the histamine release from basophils was evaluated in vitro after incubation with the eliciting compounds. Only in 1 patient reactive to propyphenazone and dipyrone a concordant clearcut positive result was obtained.

These results indicate that at present oral challenge tests are the only reliable procedure to evaluate AR to MAP. They should include a battery of different drugs, since all mild analgesics, including acetaminophen, may elicit AR. Conclusive prick test results can be obtained with some pyrazolone derivatives, especially in patients with severe reactions. They probably are then sufficient for diagnosis. ICT as described does not seem to yield any advantage and bears the risk of false positive reactions. Positive results in the basophil histamine release test may be diagnostic, however, they are only observed in rare cases.