Venom immunotherapy for preventing allergic reactions to insect stings.
BACKGROUND
Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review.


OBJECTIVE
To assess the effects of immunotherapy using extracted insect venom for preventing further allergic reactions to insect stings in people who have had an allergic reaction to a sting.


METHODS
We searched the following databases up to February 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), the Armed Forces Pest Management Board Literature Retrieval System, and OpenGrey. There were no language or publication status restrictions to our searches. We searched trials databases, abstracts from recent European and North American allergy meetings, and the references of identified review articles in order to identify further relevant trials.


METHODS
Randomised controlled trials of venom immunotherapy using standardised venom extract in insect sting allergy.


METHODS
Two authors independently undertook study selection, data extraction, and assessment of risk of bias. We identified adverse events from included controlled trials and from a separate analysis of observational studies identified as part of a National Institute for Health and Clinical Excellence Health Technology Assessment.


RESULTS
We identified 6 randomised controlled trials and 1 quasi-randomised controlled trial for inclusion in the review; the total number of participants was 392. The trials had some risk of bias because five of the trials did not blind outcome assessors to treatment allocation. The interventions included ant, bee, and wasp immunotherapy in children or adults with previous systemic or large local reactions to a sting, using sublingual (one trial) or subcutaneous (six trials) VIT. We found that VIT is effective for preventing systemic allergic reaction to an insect sting, which was our primary outcome measure. This applies whether the sting occurs accidentally or is given intentionally as part of a trial procedure.In the trials, 3/113 (2.7%) participants treated with VIT had a subsequent systemic allergic reaction to a sting, compared with 37/93 (39.8%) untreated participants (risk ratio [RR] 0.10, 95% confidence interval [CI] 0.03 to 0.28). The efficacy of VIT was similar across studies; we were unable to identify a patient group or mode of treatment with different efficacy, although these analyses were limited by small numbers. We were unable to confirm whether VIT prevents fatal reactions to insect stings, because of the rarity of this outcome.Venom immunotherapy was also effective for preventing large local reactions to a sting (5 studies; 112 follow-up stings; RR 0.41, 95% CI 0.24 to 0.69) and for improving quality of life (mean difference [MD] in favour of VIT 1.21 points on a 7-point scale, 95% CI 0.75 to 1.67).We found a significant risk of systemic adverse reaction to VIT treatment: 6 trials reported this outcome, in which 14 of 150 (9.3%) participants treated with VIT and 1 of 135 (0.7%) participants treated with placebo or no treatment suffered a systemic reaction to treatment (RR 8.16, 95% CI 1.53 to 43.46; 2 studies contributed to the effect estimate). Our analysis of 11 observational studies found systemic adverse reactions occurred in 131/921 (14.2%) participants treated with bee venom VIT and 8/289 (2.8%) treated with wasp venom VIT.


CONCLUSIONS
We found venom immunotherapy using extracted insect venom to be an effective therapy for preventing further allergic reactions to insect stings, which can improve quality of life. The treatment carries a small but significant risk of systemic adverse reaction.
Department of Medicine, Section of Paediatrics, Imperial College London, London, UK. r.boyle@nhs.net.
Robert J
RJ
Boyle
Mariam
M
Elremeli
Juliet
J
Hockenhull
Mary Gemma
MG
Cherry
Max K
MK
Bulsara
Michael
M
Daniels
J N G
JN
Oude Elberink
D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D001000:Ants / Q000276:immunology*; D001514:Bee Venoms / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D002648:Child; D003888:Desensitization, Immunologic / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007299:Insect Bites and Stings / Q000276:immunology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D014862:Wasp Venoms / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D000485:Allergens; D001514:Bee Venoms; D014862:Wasp Venoms