3 and 4):Ĭlassic NSAID hypersensitivity (NECD, NIUA, and NERD) Particular attention should be paid to the following details (Figs. Īs always in allergology, taking the specific medical history is the most important diagnostic factor. Due to the complexity of the task, testing should be performed at a center experienced in managing these types of patients. Therefore, they belong to the drugs, besides antibiotics and local anesthetics, for which the international ADR consensus recommends diagnostic testing in all cases. At the same time, NSAID is a class of drugs that are particularly important in the primary care sector and for which there are a multitude of indications. As such, the most important tool in allergy diagnosis, the patient history, is often non-specific. This is due to the fact that both true NSAID hypersensitivity (NECD, NIUA, and NERD) and the most important differential diagnosis of acute/chronic urticaria/angioedema are very common. Investigating ADR triggered by NSAIDs is often unsatisfactory for the allergist. The rest of this manuscript will exclusively address type B reactions. In contrast, NSAID-HS is an unpredictable “bizarre” ADR (type B) caused by individual factors and is responsible for around 20% of ADR to NSAID. Type A ADR should not be submitted to any further testing because all tests will yield a predictable negative outcome. Although hepatoxicity is feared with paracetamol use, this only occurs at high doses. In the case of chronic use, all NSAID, with the exception of salicylic acid derivatives, may pose a cardiovascular risk, most particularly COX-2 inhibitors. The majority (around 80%) of ADR to NSAID are pharmacological and predictable (type A), which does not necessarily imply that all of these reactions are harmless, i.e., gastrointestinal bleeding and NSAID-induced nephrotoxicity are the most frequent causes of death due to ADR to drugs. Most NSAIDs are not subject to medical prescription, explaining why often substantial amounts of NSAID are used, sometimes without medical monitoring. In addition, paracetamol is an alternative drug in NSAID hypersensitivity (NSAID-HS) that is frequently well tolerated and, in contrast to many NSAIDs, can also be used intravenously.Īdverse drug reactions (ADR) occur in 1.6% of all users following NSAID administration. However, its side effects profile is extremely similar to that of NSAID hence, its inclusion in this review article.
Paracetamol, known in the Anglo-Saxon world as acetaminophen, is not a classic NSAID and its mode of action is still not completely understood. Aspirin, the brand name used by Bayer, lent its name in the clinical setting in English-speaking countries for many decades and has only been replaced in recent years by NSAID (Table 1). (Modified from Rozsasi A and Keck T )Īcetylsalicylic acid (ASA Aspirin®, Bayer and numerous generic drugs) is the best known, strongest, and only irreversible COX-1 inhibitor. Blocking COX ( red) blocks prostaglandin synthesis ( blue) and increases leukotriene production ( purple), which can cause the intolerance reactions NERD (NSAID exacerbated respiratory disease), NECD (NSAID induced cutaneous disease), and NIUA (NSAID-induced urticaria/angioedema) in affected individuals (Fig. In the case of inflammatory reactions, COX-2 may also be induced in leukocytes. NSAIDs divert the normal arachidonic acid metabolism by blocking cyclooxygenase-1 (COX-1), which is constitutively expressed in all cells.
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