**1. Introduction**

Nonsteroidal anti-inflammatory drugs (NSAID) are one of the most commonly used drugs worldwide. NSAIDs are a major cause of hypersensitivity reactions, and they suppose up to half the cases of adverse reactions evaluated in a tertiary allergy unit [1]. Adverse reactions to NSAIDs account for 12% to 29.6% of all adverse reactions in hospital admissions. Most adverse reactions to NSAIDs belong to type A, which are dose-dependent and predictable from their pharmacological actions. Common type A reactions include gastrointestinal bleeding and acute kidney injury. Type B reactions, also known as NSAID hypersensitivity (NH) reactions, account for 8.4% to 18.3% of total adverse reactions to NSAID [2]. NSAIDs are a large and chemically heterogeneous group of drugs that inhibit the enzyme cyclooxygenase (COX) 1 and 2 isoforms, an so block the production of prostaglandins from arachidonic acid.

NSAIDs are typically divided into groups based on their chemical structure and selectivity for blocking COX-2: acetylated salicylates (aspirin), non-acetylated salicylates (diflunisal, salsalate), propionic acids (naproxen, ibuprofen, dexketoprofen), acetic acids (diclofenac, indomethacin, aceclofenac, tolmetin), enolic acids (meloxicam, piroxicam), anthranilic acids (meclofenamate, mefenamic acid, niflumic acid), naphthylalanine (nabumetone), pyrazolones (metamizole, propyfenazone) and selective COX-2 inhibitors (celecoxib, etoricoxib).

Several distinct clinical syndromes are described regarding NH, most often manifested as respiratory reactions (e.g, bronchospasm and nasoocular reaction), urticaria/angioedema or systemic anaphylaxis. NH often appears in patients who also suffer certain concomitant diseases, such as chronic rhinosinusitis with nasal polyps and bronchial asthma or spontaneous chronic urticaria. Both, the type of reaction after NSAID exposure and the concomitant associated disease are critical to classify the NH [3]. The focus of this chapter will provide an overview on all the aspects of skin NSAID hypersensitivity immediate reactions, from clinical symptoms to leading practical recommendations with respect to diagnosis and management.
