Safety, Efficacy of Venom Immunotherapy Confirmed for Pediatric Patients

A recent study demonstrated the efficacy and safety of subcutaneous venom immunotherapy (VIT) in children with a Hymenoptera venom allergy.¹

“The results showed that the cluster protocol represents a safe and effective treatment in children, with a low rate of SR (0.4% in relation to the total number of doses administered) and none requiring epinephrine,” wrote study investigator Mattia Giovannini, from the University of Florence and the allergy unit at Meyer Children’s Hospital IRCCS in Florence, Italy, and colleagues.

VIT, recommended for patients with a history of systemic reactions to stings who test positive for venom-specific allergens, remains the sole proven treatment for venom allergy.² Extensive research has examined the safety of venom immunotherapy, but data on adverse reactions and their predictive risk factors in children remain limited.¹

In this study, investigators sought to evaluate the safety of VIT, identify factors linked to adverse reactions, assess the accuracy of insect identification and its impact on VIT extract selection, and determine treatment efficacy by examining adverse reactions following re-sting. The team retrospectively analyzed the medical charts of 58 patients < 18 years followed up at the Allergy Unit of Meyer Children’s Hospital IRCCS in Florence, Italy, who received VIT between 1997 and 2021.

Participants were mostly male (87.9%) and had a median age of 9.4 years. The median VIT duration was 5.4 years, and the median number of injections per patient was 63.4 years. Nearly half (47.7%) had a positive family history of atopy, and 27.6% presented atopic manifestations, including rhinoconjunctivitis (18.9%), asthma (6.8%), food allergy (6.8%), and atopic dermatitis (5.2%).

A diagnostic workup, conducted in line with the European Academy of Allergy and Clinical Immunology guidelines and the Italian Consensus on Hymenoptera venom allergy management, guided clinicians in selecting the VIT extract. The study examined 4 extracts: Apis mellifera (28.4%; n = 17), Vespula (33.3%; n = 20), Polistes (33.3%; n = 20), and Vespa crabro (5%; n = 3). Following 3739 injections, 335 adverse reactions occurred (9.5%), classified as local reactions (8.2%; n = 306), extended local reactions (0.9%; n = 34), and systemic reactions (0.4%; n = 15).

The study included both build-up and maintenance phases. During the buildup phase, clinicians administered 1120 injections, with 194 adverse reactions reported; most were local reactions (8.2%). The maintenance phase included 2619 injections, with 161 adverse events reported; 84.5% were local reactions.

Compared to the maintenance phase, the build-up phase was associated with a greater number of adverse and local reactions during VIT (P < .0001). The study found no differences between the build-up and maintenance phases for extended local reactions (P =.5) or systemic reactions (P =.35). The study identified no other significant factors related to the risk of developing any adverse reaction.

Systemic reactions occurred the most during VIT for Polistes (0.5%). The study found no significant differences in allergic reactions across the venom extracts.

In total, 31 patients reported 51 re-stings following VIT. Among these patients, only 2 (3.9%) experienced a systemic reaction after their re-sting, and these reactions occurred from a different Hymenoptera species than the one targeted during VIT.

The study also found that males had a lower risk of adverse reactions compared with females. No statistically significant associations emerged for age at VIT initiation or family history of atopy.

Furthermore, the study demonstrated that patients could easily identify mellifera and Vespa crabro but struggled to differentiate Vespula from Polistes before and after VIT initiation. Despite this finding, VIT demonstrated efficacy for treating venom allergies.

“The present study confirmed that cluster protocol VIT is safe and effective in pediatric patients, with a low rate of [systemic reactions],” investigators concluded.¹ “The build-up phase was associated with a higher frequency of [adverse reactions], while factors such as sex, age, atopy, and type of venom extract showed no significant impact. VIT with Polistes venom had the highest [systemic reactions] rate, requiring further validation. Despite initial [systemic reactions], VIT demonstrated indisputable efficacy upon re-stinging, underscoring its value as an essential therapy for eligible patients.”

References

1. Giovannini M, Catamerò F, Masini M, et al. Efficacy and safety of subcutaneous venom immunotherapy in children: A 24-year experience in a pediatric tertiary care center. Pediatr Allergy Immunol. 2025;36(9):e70195. doi:10.1111/pai.70195

2. Dhami S, Nurmatov U, Varga EM, et al. Allergen immunotherapy for insect venom allergy: protocol for a systematic review. Clin Transl Allergy. 2016;6:6. Published 2016 Feb 16. doi:10.1186/s13601-016-0095-x