# Systemic Allergic Reactions to Subcutaneous Allergen Immunotherapy—A Single-Center Experience

## TL;DR

This study examines rare systemic allergic reactions to subcutaneous allergen immunotherapy, identifying risk factors and reaction severity.

## Contribution

The study provides new insights into risk factors and characteristics of systemic reactions to subcutaneous allergen immunotherapy.

## Key findings

- Systemic reactions occurred in 0.05% of injections and 8.2% of patients.
- Higher sIgE/tIgE ratio was linked to more severe reactions.
- Most reactions were mild and occurred during the build-up phase.

## Abstract

Background: Allergen immunotherapy (AIT) is generally considered a safe treatment modality, with systemic reactions (SRs) representing its most significant adverse events, despite their low incidence. This study aimed to evaluate the frequency and characteristics of SRs associated with subcutaneous allergen immunotherapy (SCIT) and to identify potential risk factors. Methods: We conducted a retrospective analysis of 47,982 SCIT injections administered to 317 patients over 468 SCIT courses between January 2019 and January 2024. The study population consisted of 26 patients diagnosed with allergic rhinitis sensitized to pollen and/or house dust mites (HDMs), as well as individuals with venom allergies who experienced SRs to SCIT during the study period. Data collected included demographic characteristics, presence of asthma, allergen sensitivities, immunoglobulin E (IgE)-related immunologic biomarkers, and adverse reactions. SRs were classified according to the World Allergy Organization (WAO) SCIT SR Grading System. Results: A total of 26 SCIT-related SRs were documented in 26 patients (57.7% female; mean age 37.3 ± 10.04 years), corresponding to an incidence rate of 0.05% per injection, and 8.2% per patient. Asthma was present in 42.3% of patients. Prior adverse reactions to SCIT were noted in eight patients (30.8%). SRs occurred during the build-up phase in 61.5% of cases, compared with the maintenance phase. In 46.2% of patients, a single allergen was administered, while 53.8% received multiple allergens. Based on the WAO grading system, 30.8% of SRs were classified as grade 1, 42.3% as grade 2, 15.4% as grade 3, and 11.5% as grade 4. No fatalities were reported. The majority of SRs were early onset (88.5%), and epinephrine was administered in 76.9% of the cases. A higher serum specific IgE to total IgE (sIgE/tIgE) ratio was significantly associated with more severe SRs. Conversely, a history of prior allergic reactions to SCIT appeared to correlate with milder SRs. Conclusions: Our findings confirm that SRs to SCIT are rare, and severe reactions are infrequent. A higher serum sIgE/tIgE ratio can be risk factor for severe SRs. Nonetheless, a thorough risk–benefit assessment is essential prior to initiating SCIT, particularly in patients with identified risk factors.