Progress in understanding hypersensitivity reactions to nonsteroidal anti‐inflammatory drugs

Abstract

Nonsteroidal anti‐inflammatory drugs (NSAIDs), the medications most commonly used for treating pain and inflammation, are the main triggers of drug hypersensitivity reactions. The latest classification of NSAIDs hypersensitivity by the European Academy of Allergy and Clinical Immunology (EAACI) differentiates between cross‐hypersensitivity reactions (CRs), associated with COX‐1 inhibition, and selective reactions, associated with immunological mechanisms. Three phenotypes fill into the first group: NSAIDs‐exacerbated respiratory disease, NSAIDs‐exacerbated cutaneous disease and NSAIDs‐induced urticaria/angioedema. Two phenotypes fill into the second one: single‐NSAID‐induced urticaria/angioedema/anaphylaxis and single‐NSAID‐induced delayed reactions. Diagnosis of NSAIDs hypersensitivity is hampered by different factors, including the lack of validated in vitro biomarkers and the uselessness of skin tests. The advances achieved over recent years recommend a re‐evaluation of the EAACI classification, as it does not consider other phenotypes such as blended reactions (coexistence of cutaneous and respiratory symptoms) or food‐dependent NSAID‐induced anaphylaxis. In addition, it does not regard the natural evolution of phenotypes and their potential interconversion, the development of tolerance over time or the role of atopy. Here, we address these topics. A state of the art on the underlying mechanisms and on the approaches for biomarkers discovery is also provided, including genetic studies and available information on transcriptomics and metabolomics.

Hypersensitivity reactions to arylpropionic acid derivatives: different drugs inducing different response patterns

“…Nevertheless, the symptoms experienced by patients were most commonly isolated angioedema and urticaria in both NIUA and SNIUAA. It is not known the reason why different APs molecules induce similar clinical symptoms although the reactions are suspected to be mediated by different mechanisms: COX-1 inhibition related mechanism for NIUA and specific IgE mediated mechanism for SNIUAA [3,11]. Atopy has been associated with CR induced by NSAIDs [4,6,11,30], however, in our study no differences were found in the percentage of atopic patients in NIUA and SNIUAA induced by APs.…”

“…The most frequent type of DHR induced by APs is CR, as it has been described in general with NSAIDs [4,5,11]. Similarly, the most common clinical entity observed was NIUA, as other previous reports dealing with NSAIDs had described [4,5,11,28,29]. However, although all APs could potentially induce all types of reactions and clinical entities, analysing the APs involved in the reported reaction, we found that ibuprofen and dexketoprofen induced most frequently NIUA, whereas naproxen induced most commonly SNIUAA, and ketoprofen induced SNIDR.…”

“…Therefore, diagnosis usually relies on a compatible clinical history and, in many cases, also on drug provocation test (DPT) with the culprit NSAID, a test that represents a risk for the patient and a considerable consumption of resources [3,4,9]. Recently, some progress has been made regarding the management of DHRs to NSAIDs, highlighting the role of the nasal provocation test (NPT) with lysine acetylsalicylate (LASA) when airways are involved [4,8,[10][11][12][13][14].…”

Evaluation of Subjects Experiencing Allergic Reactions to Non-Steroidal Anti-Inflammatory Drugs: Clinical Characteristics and Drugs Involved

“…Therefore, the diagnosis frequently relies on DPT. This is not a risk-free procedure, requires trained personnel and specific resources, and is contraindicated in severe reactions (Doña et al, 2019). In addition, DPT may not be performed in mislabeled CR patients.…”

“…Although there is a lack of epidemiological studies on NSAIDshypersensitivity, the relative contribution of CRs and SRs seems to vary among countries (Doña et al, 2011;Chaudhry et al, 2012;Demir et al, 2015). Most studies of DHRs to NSAIDs have focused on CRs and large series of cases confirmed as SRs to NSAIDs have not been globally analyzed (Doña et al, 2019). In this study, we have evaluated a large group of patients suffering from SRs to NSAIDs.…”