Risk of systemic reactions during pediatric allergen-specific immunotherapy: clinical predictors and safety outcomes.

Background/aim: This study aimed to evaluate the frequency, timing, severity, and clinical predictors of systemic reactions in children receiving subcutaneous allergen-specific immunotherapy (SCIT) with house dust mite (HDM) and grass pollen extracts under real-world clinical conditions. Materials and methods: This multicenter retrospective study included 623 children with moderate-to-severe allergic rhinitis, with or without asthma, who received SCIT between 2006 and 2023 at two tertiary pediatric allergy centers. Clinical characteristics, laboratory findings, immunotherapy protocols, and systemic reactions (SRs) were recorded and graded according to the updated 2024 World Allergy Organization (WAO) systemic reaction scale. Results: SCIT was well tolerated. Systemic reactions occurred in 10.7%, corresponding to 0.27% per injection. Most SRs were mild-to-moderate (WAO grades 1-2), and approximately three-quarters occurred during the maintenance phase. A progressive decline in SR incidence was observed throughout the treatment period. In the pollen SCIT subgroup, asthma was the only independent predictor of SRs (OR, 2.35; 95% CI 1.13-4.88; p = 0.022). No life-threatening reactions or fatalities were observed. Conclusion: Pediatric SCIT with pollen and HDM extracts demonstrated a favorable safety profile, with infrequent and predominantly nonsevere systemic reactions. The association between asthma and SRs in pollen SCIT highlights the importance of optimal asthma control throughout immunotherapy.