Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs

Abstract

NSAIDs are the most important group of drugs involved in hypersensitivity drug reactions, and include heterogeneous compounds with very different chemical structures. These reactions can be IgE dependent (immediate reactions), T cell-mediated (non-immediate), or induced by a non-specific immunological mechanism related with the blocking of the COX-1 enzyme and the shunting to the lipooxygenase pathway (cross-intolerant reactions). Cutaneous symptoms are the most frequent, with ibuprofen, naproxen and diclofenac being common culprit drugs worldwide, although others can be involved because patterns of consumption and exposure rates vary between countries. A very important proportion of immunological reactions are immediate, with urticaria and anaphylaxis being the typical clinical manifestations. Non-immediate reactions comprise a number of heterogeneous entities ranging from mild exanthema to severe TEN or DRESS syndrome, as well as organ-specific reactions such as hepatitis or pneumonitis. Cross-intolerant reactions appear to non-chemically related drugs, and involve respiratory airways, skin or both. In vivo diagnostic tests are based on the capacity of the skin to respond to the culprit drug, but their sensitivity is in many instances rather low. The approach for in vitro testing consists of either detecting specific IgE antibodies or studying the proliferation of T lymphocytes toward the eliciting drug. No appropriate tests are yet available for the in vitro validation of cross-intolerance reactions, although techniques based on the stimulation of basophils have been proposed. Based on these findings, the diagnostic approach is often based on the controlled administration of the drug to assess tolerance. In this work we review current knowledge on hypersensitivity reactions to NSAIDs, including diagnostic approach and genetic studies.

Drug-Induced Anaphylaxis

“…If anaphylaxis occurs following a long interval, as can occur with several drugs, the possibility of metabolite generation must be considered [15,50]. This is thought to be relevant for several NSAIDs [50,51].…”

“…The concept of cross-intolerance applies only to NSAIDs and is not immunological in nature but rather related to the inhibition of the COX-1 and COX-2 enzymes [51]. Different drugs with similar inhibitory capacity may trigger the same response.…”

Immediate Reactions to More Than 1 NSAID Must Not Be Considered Cross-Hypersensitivity Unless Tolerance to ASA Is Verified

“…Although the latter are responsible for the largest number of affected patients in some countries [1,8], SRs account for a considerable proportion in others [9,10]. SRs have been reported to all NSAIDs, independently of their capacity for inhibiting the COX-1 enzyme [9,11], and in all age ranges, including children [12,13]. Patients who experience CRs to NSAIDs react to strong COX-1 inhibitors, including acetylsalicylic acid (ASA) [7].…”

“…There is some evidence indicating that individuals may react to several NSAIDs but tolerate ASA [10,26]. Contrary to BL reactions, where all drugs share a common ring that may influence the specificity of the response and cross-reactivity [6,18], NSAIDs comprise a heterogeneous family of chemical structures with a variable degree of cross-reactivity within each group [9,11]. In this manuscript, we present findings for a series of patients who developed immediate SRs to 2 or more NSAIDs, verify tolerance to ASA, and assess the involvement of the culprit drug(s) using challenge testing.…”

Self medicated Combiflam induced acute dermatological drug reaction

“…1 Combiflam is a combination of ibuprofen 400mg plus paracetamol 325mg and widely used analgesics, antipyretics and anti-inflammatory drug. Although both drugs are readily available as over the counter (OTC) medications, they are also available on prescription.…”