Update on the Management of Nonsteroidal Anti-Inflammatory Drug Hypersensitivity

Abstract

The clinical phenotypes of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity are heterogeneous with various presentations including time of symptom onset, organ involvements, and underlying pathophysiology. Having a correct diagnosis can be challenging. Understanding their respective mechanisms as well as developing a comprehensive classification and diagnostic algorithm are pivotal for appropriate management strategy. Treatment modalities are based on the subtypes and severity of hypersensitivity reactions. Insights into the phenotypes and endotypes of hypersensitivity reactions enable personalized management in patients with suboptimal control of disease. This review updated the recent evidence of pathophysiology, classification, diagnostic algorithm, and management of NSAID hypersensitivity reactions.

Clinical Phenotypes in NSAID-Induced Urticaria/Angioedema

“…The mechanisms of NH are unknown, but two general hypotheses have been proposed [4]. The first one, an enzymatic activity inhibition of at least the cyclooxygenase-1 (COX-1) isoform that may inhibit the prostaglandin synthesis and thus deregulate the 5-lipooxygenase pathway, with cys-leukotriene hyperproduction in some susceptible patients.…”

“…All NSAIDs that inhibit the COX-1 isoform could precipitate the reaction. For this reason, cross-reactivity among COX-1 inhibitor NSAIDs can be demonstrated in all patients with respiratory reactions and in most patients with urticaria/angioedema reactions (multiple reactors) [1,3,4]. The second mechanism can be applied only to a small subset of patients with NSAID hypersensitivity, as those with systemic anaphylaxis [4].…”

“…For this reason, cross-reactivity among COX-1 inhibitor NSAIDs can be demonstrated in all patients with respiratory reactions and in most patients with urticaria/angioedema reactions (multiple reactors) [1,3,4]. The second mechanism can be applied only to a small subset of patients with NSAID hypersensitivity, as those with systemic anaphylaxis [4]. We have previously demonstrated that patients with NSAIDs-induced systemic anaphylaxis can react only to one specific NSAIDs and tolerate other COX-1 inhibitor NSAIDs in controlled oral challenges.…”

“…We have previously demonstrated that patients with NSAIDs-induced systemic anaphylaxis can react only to one specific NSAIDs and tolerate other COX-1 inhibitor NSAIDs in controlled oral challenges. Up to 1/3 of patients with NSAID induced systemic anaphylaxis might present immediate acute urticarial previous to anaphylactic episode when taken a specific NSAID (selective reactors) [3][4][5].…”

“…In up to 30 percent of cases facial, neck and hand angioedema may occur during the clinical exacerbation; an isolated angioedema is rarely a possible manifestation of NECD. Approximately 30% of patients with chronic spontaneous urticaria present exacerbations of their disease after NSAID exposure throughout their lives [1,[3][4][5]8]. A positive correlation between the basal CSU activity disease and the possibility of a NSAID challenge reaction have been described in NECD patients [8].…”