Hypersensitivity to Opioids: Prevalence, Mechanisms, Diagnosis and Management

Many patients report being allergic to opioids and/or have allergy warnings documented in their medical records. However, the reasoning behind these warnings is often unclear and frequently lacks clinical validation. Reported reactions may include skin rashes, itching, severe vomiting, fainting or respiratory arrest occurring during postoperative recovery where opioids were administered. In many cases, there is also uncertainty about which specific opioid was used. An allergy warning to one opioid further raises the question of whether the patient can tolerate other opioids. In this review, we address the exceedingly rare IgE-mediated opioid allergy and cross-reactivity between opioids, along with non–immune-mediated histamine release and other adverse effects of opioids that patients or clinicians may mistake for allergic reactions. We propose a simple risk stratification algorithm for the clinical management of patients labelled as opioid allergic—helping to distinguish who should be referred for allergy evaluation and who can safely be treated with opioids with or without antihistamine pre-treatment.