Delayed postoperative reactions to metamizole: a diagnostic challenge

Background. Metamizole, a non-steroidal anti-inflammatory drug from the pyrazolone group, is a frequent cause of immediate hypersensitivity reactions and, more rarely, of delayed drug hypersensitivity reactions. Due to its favorable pharmacokinetic characteristics, metamizole is widely used in the postoperative period for pain control. Methods. Retrospective study of patients referred for allergological study between January 2012 and June2022 for postoperative hypersensitivity reactions. Clinical and diagnostic data were collected through review of patients' medical records. Twenty patients with postoperative hypersensitivity reactions were referred, of which 10 presented delayed reactions. We analyzed the results of skin prick, intradermal and patch tests performed with an intravenous metamizole solution as well as provocation tests performed with metamizole and acetylsalicylic acid. Cross-reactivity to non-steroidal anti-inflammatory drugs was excluded by confirmation of clinical tolerance to non-steroidal anti-inflammatory drugs or by acetylsalicylic acid provocation test. Results. In 7 of the 10 patients a delayed reaction to metamizole was diagnosed. These reactions were characterized as maculopapular exanthema, occurring in multiple postoperative settings. Skin tests were negative, except in one patient with late mild erythema in the ipsilateral upper limb and no reaction at the site of intradermal injection. Delayed hypersensitivity was demonstrated by late positive metamizole provocation tests. Conclusions. This study demonstrated that for a correct diagnosis a high degree of suspicion about possible delayed hypersensitivity drug reactions to metamizole in the postoperative setting is needed. In the investigation, provocation test with metamizole was decisive for diagnostic confirmation.