Abstract Hypersensitivity reactions are an important hazard in healthcare. Modern dentistry depends on the use of drugs and materials widely known to elicit them. Such reactions are either immediate or nonimmediate – the former carries the risk of anaphylaxis, whereas the latter includes potentially fatal severe cutaneous adverse reactions. Apart from well-established immunoglobulin E–mediated immediate hypersensitivity reactions (IHRs), recent advances have shed light on the pathophysiology of other IHRs, suggesting a role for MRGPRX2-induced mast cell activation. Hypersensitivity to both drugs and metals may come as a challenge to dentists, often requiring changing to infrequently used compounds. Local anesthetics are cause for concern, but are a rare cause for IHRs. The opposite occurs with antimicrobials, as antibacterials frequently cause hypersensitivity reactions. Nonsteroidal anti-inflammatory drugs are another common cause, especially in patients suffering from asthma and/or chronic spontaneous urticaria. General anesthetics are a common cause for immediate hypersensitivity, whereas most drugs used for conscious sedation are rare elicitors. Chlorhexidine is a remarkable cause for anaphylaxis, nowadays, despite rare reports linked to rinsed formulations. Preservatives, flavors, and other compounds present in dentifrices cause both irritative and allergic contact dermatitis/mucositis. Metals, notably nickel and cobalt, are a very common cause for hypersensitivity in dentistry. Acrylates may induce contact mucositis, due to lack of proper polymerization of residuals, being an important cause for contact stomatitis and a dentistry occupational hazard. Acute reactions require a prompt treatment, especially in the presence of anaphylaxis, which should be treated using intramuscular epinephrine. Delayed type reactions with fever should be referred to tertiary urgent care facilities. Suspicion of hypersensitivity in dentistry requires a thorough allergological study and referral is mandatory in all cases.
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