Hypersensitivity reactions to opioids in childhood

Opioids represent one of the most prescribed drugs for the treatment of pain worldwide. Along with this, opioid allergy is one of the most frequent drug allergy labels, often in the absence of a complete and accurate allergy work-up. The lack of validated diagnostic tests and certain peculiarities of the mechanisms of action frequently lead to an overdiagnosis of opioid allergy. However, a proportion of people classified as allergic has instead demonstrated to be tolerant to these agents. The removal of the mislabeling would be of unique importance to people suffering from acute or chronic pain. Especially concerning the pediatric population, more efforts are needed in this respect, considered the increasing use of this class of drugs and the concurrent lack of dedicated guidelines. Indeed, incorrect diagnoses can have a significant impact on the pain management throughout the course of their life. However, the best clinical approach to hypersensitivity reactions to opiates remains a matter of discussion in children and adults. A literature search was conducted to fill gaps in current understanding of mechanisms and management of opioid hypersensitivity reactions. We provide data on the mechanisms of reactions to opioids and on clinical manifestations of allergic reactions to these compounds. We highlighted the limitations of skin testing, IgE assays, and Basophil Activation Test and the role of drug provocation tests for allergy work-up. The low frequency of opioid hypersensitivity reactions combined with the difficulties in establishing the occurrence, calls for further investigation on systematic evaluation and standardized methods of diagnosis.