Title:An Update on Nonsteroidal Anti-Inflammatory Drug-Induced Urticaria
Volume: 24
Issue: 8
Author(s): Andrea Miniello*, Rossella Casella, Teresa Loverre, Dario Aloia, Danilo Di Bona and Eustachio Nettis
Affiliation:
- Department of Emergency and Organ Transplantation, School of Allergology and Clinical Immunology, University of
Bari Aldo Moro, Policlinico di Bari, Bari, Italy
Keywords:
Hypersensitivity, NSAIDs, urticaria, angioedema, anaphylaxis, selective-responders, cross-intolerant, classifications, diagnosis, management.
Abstract:
Background: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs
(HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter
NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly
reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation
of pathophysiologically different clinical entities that require different therapeutic strategies. The
aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients
reporting urticaria associated with the intake of NSAIDs and provide updated information about
their diagnosis and management.
Methods: The study is a narrative review conducted by collecting the most relevant and up-todate
data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity
reactions. PubMed and Embase scientific databases were used as search engines to select
relevant articles.
Results: Patients developing HR-NSAIDs can be divided into two categories: selective responders
(SR), who develop reactions after the administration of a single specific NSAID due to an
underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop
reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical
pathways related with prostaglandin metabolism, independently from an underlying
immunological mechanism. Five major different categories of HR-NSAIDs have been identified:
NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema
with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDsexacerbated
respiratory disease (NERD), which are developed by CI patients, and single
NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDsinduced
delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo
and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and
therefore are not routinely used in clinical practice. The management in SR patients consists of
strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with
safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed.
Conclusion: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis
behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly
based on a thorough clinical history and confirmed by a drug challenge test. Clinical
management is based on strict avoidance and use of alternative tolerated medications. Overall, all
therapeutic decisions depend on the correct identification of the type of reaction the patient
experienced.
