Hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs): classification of a Danish patient cohort according to EAACI/ENDA guidelines

Abstract

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are reported to be the second most common cause of drug hypersensitivity. In 2011, experts from the EAACI/ENDA group and GA(2)LEN proposed a new classification system for NSAID hypersensitivity. The aim of this study was to classify a patient cohort with a history of NSAID hypersensitivity according to this system.

Methods: Patients with a clinical history of NSAID hypersensitivity referred to the Allergy Centre, Odense University Hospital between 2002 and 2011 and evaluated with oral provocation tests (OPTs) were included in the study. Medical records were retrospectively investigated with respect to the culprit NSAID(s), underlying diseases and symptoms at the primary reaction and during oral provocation tests (OPTs). Data was supplemented with a questionnaire. Classification according to EAACI guideline was based on these findings.

Results: In total 149 patients were included. Of those, 39 patients (26.2%) had a positive OPT. Twenty-nine patients were classified as cross-reactive responders and 9 patients as single NSAID responders after positive OPTs with the culprit NSAID, but not to acetylsalicylic acid. All single NSAID responders reacted to non-pyrazolone drugs. Only one patient could not be classified according to the EAACI/ENDA system. An overlap between respiratory and cutaneous symptoms was found in 15/39 (38%) of patients.

Conclusions: All but one of our patients could be classified according to the EAACI classification system. Overlaps between different classes may occur much more commonly than expected.

Keywords: Classification; Drug allergy; Hypersensitivity; Non-steroidal anti-inflammatory drugs; Provocation test.

Figure 1

Approach to OPTs in 149 patients suspected of NSAID hypersensitivity. All patients performed a primary OPT with acetylsalicylic acid. If the primary OPT was negative, and ASA not was the culprit drug, a secondary OPT was performed with the culprit NSAID according to case history. See Figure 2 for details about the secondary OPT. OPTs = oral provocation tests.

Figure 2

Results of secondary oral provocation test (OPT) with culprit NSAID. Sixty-six OPTs were performed in 64 patients with a negative challenge for ASA. Nine patients had a positive secondary OPT. *Two patients had a history of multiple reactions after intake of several NSAIDs and underwent provocation tests with ibuprofen and diclofenac, both of which were negative. OPTs = oral provocation tests.