Age-Specific Monitoring and Emergency Treatment Enhance Safety in Patients Receiving Allergen Immunotherapy

When treating patients with allergen immunotherapy (AIT), patients typically receive either subcutaneous (SCIT) or sublingual (SLIT) administrations. Current data show that SLIT has a more favorable safety profile compared with SCIT, with only a few severe systemic adverse reactions and no fatalities reported in patients receiving SLIT. Authors of a study published in Annals of Allergy, Asthma & Immunology reported on cases from the European Anaphylaxis Registry, where immunotherapy was provided as the elicitor of the reaction by the reporting center.

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For this analysis, information was gathered from 54 allergy centers—of which 31 were adult and 23 were pediatric—across 10 European countries from 2007 to 2023. Participation in the registry was voluntary, and pseudoanonymized data were only gathered after patients and/or caregivers provided consent. Data were entered via multilingual, web-based questionnaires collected by trained health care professionals. All anaphylaxis cases included met the established criteria from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (defined as reactions involving symptoms in at least 2 organ systems, such as skin, respiratory, cardiovascular, or gastrointestinal).

The investigators analyzed the clinical features of the affected patients, the presence of comorbidities, the severity of reactions in an age-dependent manner (<18 years defined as children or adolescents and ≥18 years defined as adults), and considered factors such as the administered allergen extracts and details of delayed reactions.

A total of 15,748 cases that fulfilled the criteria of anaphylaxis were reported to the European Anaphylaxis Registry from 2007 to 2023. In total, 173 cases (1.1%) were reported as a reaction caused by allergen immunotherapy, and among the total number of anaphylaxis cases, approximately 29% (n = 4497) occurred in patients under the age of 18, with 1.8% (n = 85) of these cases specifically related to allergen immunotherapy. Among these pediatric cases, 55 patients were aged 5 to 12 years (including 12), and 30 were aged 13 to 18 years. Conversely, there were about 71% (n = 11,251) of adult patients, with 0.7% (n = 88) of these cases linked to AIT. The overall median age of patients with AIT-related anaphylaxis in the dataset was 18 years (range: 6, 77). Most of the patients in the pediatric group were male (68%; n = 58), whereas the adult group was primarily female (63%; n = 55).

The investigators observed a higher frequency of respiratory symptoms among allergen immunotherapy-related anaphylaxis in children and adolescents (92%) compared with adults (66%). Conversely, cardiovascular and gastrointestinal symptoms occurred more frequently in adults (cardiovascular: 78%; gastrointestinal: 42%) than in children (cardiovascular: 40%; gastrointestinal: 20%). Only a few SLIT-related cases were documented, including 2 occurrences of grade 3 reactions with no fatalities (SLIT: n = 8 vs SCIT: n = 153). There was 1 reported fatality due to SCIT (grass pollen).

Additionally, delayed reactions (>30 minutes) were reported in 22 cases, most of which occurred after SCIT. All delayed grade 3 reactions that occurred beyond 120 minutes were observed in children. Further, adrenaline was underused in emergency management and was administered in only 30% and 50% of grade 2 and 3 reactions, respectively.

The study, according to the authors, demonstrates the significance of age-specific monitoring in the treatment of allergen immunotherapy. Additionally, the appropriate emergency treatments will better enhance patients’ safety while receiving allergen immunotherapy.

REFERENCE

Almaci M, Treudler R, Breiding M, et al. Allergen Immunotherapy induced Anaphylaxis - Data from the European Anaphylaxis Registry. Ann Allergy Asthma Immunol. 2025. doi:10.1016/j.anai.2025.02.012