Reviews and feature articleApproaches to the diagnosis and management of patients with a history of nonsteroidal anti-inflammatory drug–related urticaria and angioedema
Section snippets
Classification of NSAID reactions
The current classification of NSAID hypersensitivity reactions is based on timing, the clinical pattern of symptoms, and the presence or absence of cross-reactivity to other NSAIDs.7, 8, 9 An additional criterion is the presence of underlying chronic disease of the skin or respiratory tract, which is typical for some (10 cross-reactive types) but not all (single drug–induced type) reactions (Table I).10
Using this classification system, a physician can assess the putative pathomechanism of a
NSAID-exacerbated cutaneous disease
Patients with chronic urticaria who experience hypersensitivity reactions to NSAIDs are now identified as having aspirin-exacerbated cutaneous disease or, more precisely, nonsteroidal anti-inflammatory drug–exacerbated cutaneous disease (NECD).8
NSAID-induced urticaria/angioedema
Aspirin and other NSAIDs can also induce urticaria, angioedema, or both in an otherwise healthy subject without a history of pre-existing chronic skin disease (eg, spontaneous urticaria).
Single NSAID–induced urticaria/angioedema, anaphylaxis, or both
Wheals, angioedema, and/or anaphylaxis induced by a single NSAID or by 2 or more NSAIDs with similar chemical structures (ie, belonging to the same chemical group; Table II) are typical for this type of NSAID hypersensitivity.48
Mixed reactions
Although the vast majority of NSAID-induced acute (within 24 hours) skin reactions can fall into one of the 3 phenotypes presented by the current classification, some patients can manifest atypical or blended reactions. Approximately 10% of patients with NECD will have respiratory symptoms (bronchoconstriction) resembling the reactions observed in patients with NSAID-exacerbated respiratory disease.59 In a study by Doña et al,33 who reviewed 384 patients with NSAID-induced skin reactions,
Diagnostic algorithm
Diagnosis of a specific type of hypersensitivity is a prerequisite for proper management of a patient with a history of NSAID hypersensitivity. Based on the current classification, a practical diagnostic algorithm to determine the type of NSAID hypersensitivity has been proposed8, 61 and can be easily adapted when hypersensitivity is manifested with cutaneous symptoms (urticaria/angioedema, Fig 2). Although a detailed analysis of the patient's history might be sufficient to establish the
Management
Once the diagnosis of NSAID hypersensitivity has been established, the mainstay of treatment is avoidance of NSAIDs.7, 65 However, recommendations for management and alternative NSAIDs have to be tailored to a specific type of NSAID hypersensitivity (Table III).66
Conclusions and suggestions for future work
In susceptible subjects urticaria, angioedema, or both develop after NSAID intake, usually within hours (rarely within minutes). Physicians can follow a simple algorithm based on current classification, leading to diagnosis of the type of NSAID hypersensitivity. Identification of the specific type of hypersensitivity allows for identification of the proper management options. However, because the history of NSAID hypersensitivity is not very specific, in many instances an oral challenge test
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2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :Third, we did not perform DPT to COX-1 inhibitors to diagnose or confirm the patients’ current NSAID hypersensitivity status. Most diagnostic algorithms for NIUA do not routinely mandate DPT for the diagnosis of NIUA especially when there is a strong clinical history.9 Moreover, the DPT protocols used by recently published studies have been different from the EAACI/GA2LEN guideline for aspirin provocation tests to diagnose NSAID hypersensitivity, perhaps underscoring a lack of consensus in the field.6,47-49
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Disclosure of potential conflict of interest: K. Woessner has consultant arrangements with and has received payments for lectures from Merck, TEVA, Shire, Meda, and AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest.