Assessing potential determinants of positive provocation tests in subjects with NSAID hypersensitivity


Antonino Romano, Unità di Allergologia, Complesso Integrato Columbus, Via G. Moscati, 31, 00168 Rome, Italy. E-mail:


Background Provocation tests (PTs) with the suspected compounds are considered the ‘gold standard’ for establishing or excluding a diagnosis of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). However, only a few studies have evaluated the potential determinants of positive responses to PTs.

Objective The aims of this study are to assess the reliability of clinical histories as indicators of NSAID hypersensitivity, as well as the risk factors for a positive PT.

Methods Two hundred and seventy-five subjects with an unequivocal history of NSAID hypersensitivity reactions underwent PTs with the suspected drugs. To establish the potential determinants of positive PTs, we examined the following variables: gender, age at the time of reaction (<40 or geqslant R: gt-or-equal, slanted40 years), family and personal histories of atopy, patients who had reacted to one or more NSAIDs, time interval between drug intake and symptom onset (immediate or non-immediate reactions), time interval between the last drug reaction and the allergologic examination (leqslant R: less-than-or-eq, slant12 or >12 months), and inclusion in a category of the Stevenson et al. classification.

Results Two hundred and fourteen (77.8%) subjects tolerated the suspected drugs and 61 (22.2%) reacted. Age <40 years, male gender, immediate reactions, and time interval leqslant R: less-than-or-eq, slant12 months were significant risk factors for a positive PT.

Conclusions and Clinical Relevance Our study confirms that clinical histories are not reliable tools for diagnosing NSAID hypersensitivity. Therefore, we recommend that suspected cases should undergo drug PTs. However, further studies on large samples of NSAID-sensitive patients are necessary to establish the risk factors that allow the number of candidates for PTs to be reduced.

Cite this as: M. Viola, G. Rumi, R. L. Valluzzi, F. Gaeta, C. Caruso and A. Romano, Clinical & Experimental Allergy, 2011 (41) 96–103.