AbstractBackgroundAny drug taken at the recommended dosage may cause hypersensitivity reactions (DHR). Rapid drug desensitization (RDD) protocols have been developed in the case of a confirmed or highly suspected HSR to allow safe administration of the medicine when there is no alternative drug or in the presence of a less effective or more toxic alternative. The aim of this study was to evaluate the characteristics of children who underwent desensitization, the safety and efficacy of RDD in children, as well as, the characteristics and management of breakthrough reactions.MethodThis retrospective study concerned children who underwent RDD due to physician‐diagnosed HSRs during or up to 48 hours after the infusion of various drugs between February 2010‐February 2021. Patients with a chronic disease needing chronic drug usage and acute infections seen in patients with chronic diseases were included. The results of RDD were documented.ResultsThe study included 48 patients [8.1(IQR = 3.32–13.4) years, 60.4% male] with 58 HSRs of which 62.1% were classified as moderate and 5.2% as severe. Most of the patients were being treated for leukemia (41.7%), solid tumors (29.2%), and infections (6.3%). Skin tests were done for 41 out of 58 HSRs in 35 patients, and twenty of them were positive. A total of 269 RDDs were performed for 18 different drugs. Ninety percent of desensitizations were achieved with no reaction, and 3.7% and 5.6% with mild and moderate reactions, respectively. In multivariate analysis, skin test positivity was the only risk factor for breakthrough reactions (OR = 8.5, CI = 1.72–42.15, p = .009).ConclusionWe demonstrated the safety and efficacy of RDD in childhood, thereby offered the first line treatment options to children with chronic diseases with hypersensitivity reactions (HSRs).