A phenotype‐based classification of NSAIDs hypersensitivity: new patients, new challenges

NSAIDs hypersensitivity (NH) reactions are complex diseases which can be classified according to the clinical syndrome that occurred during single-blind placebo-controlled oral challenge (SBPCOC), the cross-reactive status among different cyclooxygenase inhibitors, and the existence of concomitant diseases (1). In the document prepared by the European Academy of Allergy and Clinical Immunology Task Force on NSAIDs Hypersensitivity (EAACI-TFNH), these same criteria have aided to delineate and propose the main subsets of NH (2). However, it seems reasonable to think that further clinical observations may define new entities. We propose to add to this new NH classification a distinct form of well-defined NH phenotype. We agree with Kowalski and coworkers that NH is a broad group of disorders with distinct clinical and biologic characteristics which can be included in, at least, five types of reactions (2). In 2007, we evaluated the clinical features of SBPCOC carried out in a cohort of patients with NH, which supported a comprehensive phenotype-based classification of NH (1). Our findings also suggested that some patients described (1) may have certain clinical characteristics that distinguish them as a distinct entity known as isolated periorbital angioedema (1, 3). This NH phenotype was commonly seen in pediatric and juvenile patients (1, 3); most of them exhibited cross-sensitivity with other NSAIDs (1); and an underlying allergic respiratory disease was always present (mainly caused by house dust mites) (1, 3). Whether atopy or specific responses to certain allergens may predispose patients to some NH syndromes is largely unknown. Closely related with this reaction, we have also described a syndrome characterized by severe systemic reactions caused by ingestion of flour-based foods, contaminated with mites (the NSAIDs sensitivity mite ingestion reaction syndrome) (4). By controlled oral challenges, it was confirmed not only that the reactions were due to mite ingestion, but also that most patients showed isolated periorbital angioedema. It was estimated that the relative risk of atopic patients with NH for suffering a mite ingestion reaction was 300 times higher than that observed in NSAID-tolerant patients (5). Recently, we realized a nasal ketorolac challenge (NKC) to three patients, who previously presented SBPCOC-proven isolated periorbital angioedema. Nasal airway and lower