Descriptive Analysis of Cross-Reactive Anaphylaxis as a Different Clinical Subtype of Nonsteroidal Anti-Inflammatory Drug (NSAID) Hypersensitivity

Abstract

<b><i>Introduction:</i></b> The European Network of Drug Allergy and the European Academy of Allergy and Clinical Immunology have classified hypersensitivity reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs) into 5 phenotypes according to the pathophysiology, clinical manifestations, number of drugs involved, and the presence of underlying diseases. This classification does not include anaphylaxis as part of NSAID cross-reactivity. The objective of this study was to characterize a group of patients with anaphylactic NSAID cross-reactivity. <b><i>Method:</i></b> This was a retrospective, descriptive, observational study. Patients who developed anaphylaxis to one NSAID plus another acute reaction (anaphylactic or not) to at least one other NSAID of a different chemical group were included. Demographic and clinical characteristics and the diagnostic approach were studied. <b><i>Results:</i></b> A total of 38 patients were included, 28 (73.7%) of whom were women. The mean age was 40 ± 17.7 years. The main organs affected in the anaphylactic reaction were the skin and the respiratory system, occurring in 35 (92.1%) and 33 (86.8%) patients, respectively. Thirty-two (84.3%) patients presented with cutaneous and respiratory involvement simultaneously. The main anti-inflammatory agent involved in anaphylactic reactions was acetylsalicylic acid in 9 (23.7%) patients, followed by dipyrone in 8 (21.1%). The most frequent allergic comorbidity was rhinitis in 20 (52%) patients. Skin tests were performed in 15 (39.5%) patients, showing positivity in 12 (80%), mainly to mites. A total of 36 of 38 patients were challenged with alternative drugs, and 35 (97.2%) tolerated meloxicam and/or etoricoxib. <b><i>Conclusion:</i></b> In the present study, NSAID cross-anaphylaxis was more frequent in women, and acetylsalicylic acid and dipyrone were the main triggers. Rhinitis was the main allergic comorbidity, and there was a high incidence of atopy. The majority tolerated selective COX-2 NSAIDs.

A new classification option for NSAID hypersensitivity

“…This problem has also been noted in previous studies. [7][8][9][10][11][12][13] Vally et al reported an interesting group of non-asthmatic patients with respiratory symptoms induced by aspirin, similar to one patient in our study who could not be categorized using the ENDA classification. 41 We think that our classification is important, because a patient with asthma and an u/ae-type reaction to NSAIDs would not benefit from aspirin desensitization, or their asthma would be better controlled compared to those who experience an asthmatic-type reaction.…”

“…[7][8][9][10][11] Blanca Lopez et al reported in a review that there are two additional groups that include selective NSAID-induced organ specific reactions (hepatitis, bile duct syndrome, and meningitis), and selective NSAID-induced skin/systemic manifestations (vasculitis). 12 Patients with NSAID cross-reactive anaphylaxis were described by Vasquez et al 13 In a review, three different phenotypes beyond the ENDA classification were mentioned: blended reactions (cases of cross reactors affecting both the skin and the airways, as well as other organs) 3,7,14 ; food-dependent NSAID-induced anaphylaxis [15][16][17][18] and NSAIDs-multiple selective immediate reactions (some cases may have immediate reactions to many NSAIDs but tolerate ASA). 19,20 Rising data shows that NERD is heterogeneous in terms of the order of developing symptoms, pathogenetic mechanisms involved, and type of NSAID hypersensitivity (NH) reaction (e.g., respiratory, cutaneous, and gastrointestinal symptoms).…”