Objective To identify children with high-risk systemic adverse reactions （SARs） associated with dust mite subcutaneous immunotherapy prior to immunotherapy. Methods An analysis was conducted on the high-risk factors in patients who experienced SARs prior to initial immunotherapy. A total of 40 pediatric patients with dust mite allergic rhinitis who underwent treatment with Dermatophagoides pteronyssinus （Dp） extracts at our hospital's pediatric department from April 2021 to January 2025 and developed SARs were selected as the observation group， while 54 patients who did not experience SARs served as the control group. Differences in gender， age， disease duration， eosinophil count， polysensitization， multisystem involvement， total IgE （tIgE）， and dust mite-specific IgE （sIgE） were evaluated. Results Significant differences were observed between the observation and control groups in polysensitization， multisystem involvement， and tIgE levels. The polysensitization rates were 70% vs. 48.1% （P = 0.034）， multisystem involvement 55% vs. 22.2% （P = 0.001）， and high tIgE levels （tIgE ≥ 327.8 IU/mL） 82.5% vs. 62.1% （P = 0.025）. Multivariate logistic regression identified multisystem involvement ［OR（95% CI） = 4.278 （1.749 ~ 10.461）］ as an independent risk factor for SARs during allergen immunotherapy （AIT）. Conclusion Patients with dust mite allergic rhinitis accompanied by multi-system damage exhibit poorer conventional prevention efficacy against SARs when undergoing AIT. They remain highly susceptible to SARs occurrence， necessitating more robust preventive measures against SARs to enhance the safety of AIT.