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Current diagnostics in NSAID hypersensitivity

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Abstract

Non-steroidal anti-inflammatory drugs (NSAID) are the second most common trigger of drug hypersensitivity in adults and children and are considered the most common or second most common cause of drug-induced anaphylaxis. NSAID hypersensitivity reactions are classified according to the latency of symptoms in relation to ingestion and on the basis of symptoms, potential underlying disease (chronic urticaria, bronchial asthma/chronic rhinosinusitis/nasal polyps), cross-reactivity to other NSAID, and the suspected pathomechanism. The diagnosis and management of NSAID hypersensitivity depend on the confirmed or suspected type of reaction. The pathomechanism for the majority of hypersensitivity reactions to NSAID has not been elucidated in detail; preferential COX-1 inhibition, which causes a shift in arachidonic acid metabolism, is considered relevant to an extent in immediate-type reactions. Delayed reactions to NSAID are rarer, diverse, and considered to be T cell mediated. All NSAIDs are essentially able to trigger all types of reaction. Immediate-type reactions involving cutaneous (urticaria/angioedema) and/or respiratory symptoms (rhinitis, bronchial asthma), as well as anaphylactic reactions are the most common.

A careful allergy diagnostic work-up enables hypersensitivity to be excluded in the majority of affected individuals. In vitro testing and skin testing, as well as the gold standard, provocation testing with the suspected NSAID, or exposure testing to identify safe alternatives are used in a stepwise approach. It is important to bear in mind that standardized and validated in vitro test methods (e. g., specific IgE determination, basophil activation test, lymphocyte transformation test) and skin testing are not available for most NSAID and often prove negative. Except in the case of severe index reactions, provocation testing (with emergency response measures in place) to establish the diagnosis, evaluate possible cross-reactivity, and identify safe alternatives should be performed. Avoidance measures should only be recommended if the diagnosis has been reliably established. Patients should receive recommendations (avoidance measures, alternatives) in written form.

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Abbreviations

ADR:

Adverse drug reaction

ASA:

Acetylsalicylic acid

AERD:

Aspirin-exacerbated respiratory disease

AGEP:

Acute generalized exanthematous pustulosis

DRESS:

Drug reaction with eosinophilia and systemic symptoms

EM:

Erythema multiforme

ELISpot:

Enzyme-linked immunospot (assay)

FEV1:

Forced expiratory volume or one-second capacity

15-HETE:

15-Hydroxyeicosatetraenoic acid

HLA:

Human leukocyte antigen

IgE:

Immunoglobulin E

LTT:

Lymphocyte transformation test

NERD:

NSAID-exacerbated respiratory disease

NIUA:

NSAID-induced urticaria/angioedema

NK:

Natural killer cells

NSAID:

Non-steroidal anti-inflammatory drugs

SCAR:

Severe cutaneous adverse drug reaction

SJS:

Stevens-Johnson syndrome

SNIUAA:

Single NSAID-induced urticaria/angioedema or anaphylaxis

TEN:

Toxic epidermal necrolysis

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  1. Department of Dermatology and Allergy, Comprehensive Allergy Center, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany

    Bettina Wedi

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Wedi, B. Current diagnostics in NSAID hypersensitivity. Allergo J Int 26, 204–211 (2017). https://doi.org/10.1007/s40629-017-0030-2

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