‘Mild’ analgesic preparations (MAPs) are well known elicitors of anaphylactoid reactions (ARs). The identification of the causative agent is often difficult since reliable skin tests or in vitro methods are not available. In 128 patients (32 males, 96 females) with a history of ARs to MAPs containing only one single analgesic compound, placebo-controlled oral provocation tests (OPTs) were performed. Among 100 of them undergoing the OPT with the suspected drug, there was a concordance between the patient’s history and the OPT in 44 patients. Concomitant ARs to other mild analgesics (without a history of previous incompatibility) were observed in 113 of 413 OPTs, but in almost all cases one or more alternative analgesics were tolerated in the OPT. Our results confirm that the OPT remains at present the most reliable diagnostic procedure alongside a comprehensive history in patients with ARs to MAPs. Because many of the patients showed concomitant ARs to unsuspicious analgesics OPTs should include a standard battery of different analgesics. The simple recommendation of one single preparation, such as acetaminophen, as a ‘safe’ substitute without an OPT is not recommended.

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