Flow diagram of the study selection process.

<p>Flow diagram of the study selection process.</p

Relative risk of adverse events in randomized controlled trials with bee venom therapy and saline.

<p>Relative risk of adverse events in randomized controlled trials with bee venom therapy and saline.</p

Risk Associated with Bee Venom Therapy: A Systematic Review and Meta-Analysis

<div><p>Objective</p><p>The safety of bee venom as a therapeutic compound has been extensively studied, resulting in the identification of potential adverse events, which range from trivial skin reactions that usually resolve over several days to life-threating severe immunological responses such as anaphylaxis. In this systematic review, we provide a summary of the types and prevalence of adverse events associated with bee venom therapy.</p><p>Methods</p><p>We searched the literature using 12 databases from their inception to June 2014, without language restrictions. We included all types of clinical studies in which bee venom was used as a key intervention and adverse events that may have been causally related to bee venom therapy were reported.</p><p>Results</p><p>A total of 145 studies, including 20 randomized controlled trials, 79 audits and cohort studies, 33 single-case studies, and 13 case series, were evaluated in this review. The median frequency of patients who experienced adverse events related to venom immunotherapy was 28.87% (interquartile range, 14.57–39.74) in the audit studies. Compared with normal saline injection, bee venom acupuncture showed a 261% increased relative risk for the occurrence of adverse events (relative risk, 3.61; 95% confidence interval, 2.10 to 6.20) in the randomized controlled trials, which might be overestimated or underestimated owing to the poor reporting quality of the included studies.</p><p>Conclusions</p><p>Adverse events related to bee venom therapy are frequent; therefore, practitioners of bee venom therapy should be cautious when applying it in daily clinical practice, and the practitioner’s education and qualifications regarding the use of bee venom therapy should be ensured.</p></div

Audits and cohort studies on the adverse events of bee venom therapy

<p>AE: adverse event; SR: systemic reaction; LR: local reaction; LLR: large local reaction; VIT: venom immunotherapy; RVIT: rush VIT; SIT: specific immunotherapy; RSIT: rush-specific immunotherapy; CVIT; cluster VIT; IP: induction phase; EP: extension phase; MP: maintenance phase.</p><p>^a If it was not reported in prospective articles, it was considered a retrospective study.</p><p>^b Venom type: bees (family Apidae); wasps (family Vespidae); single (some bee venom or some wasp venom); mix (bee and wasp venom).</p><p>^c Incidence: number of patients with AEs/number of patients of total cases, %</p><p>^d Incidence: number of cases with AEs/number of patients of total cases.</p><p>^e Incidence: number of injections (dose) that resulted in AEs/total number of injections (dose), % (if the number of patients with AEs was not mentioned or precisely presented).</p><p>^f Incidence of AEs caused by BVTs combined with the incidence of AEs from other allergens.</p><p>^g This study was the only report of anaphylaxis related to BVT.</p><p>.</p

Randomized controlled trials and randomized crossover trials reporting adverse events of bee venom therapy.

<p>AE: adverse event; BVT: bee venom therapy; BSA: bee sting acupuncture; BVA: bee venom acupuncture; SBV: sweet bee venom; VIT: venom immunotherapy; YJV: yellow jacket venom. Quality of reporting: good, clear, and well described; moderate, described but not in detail; bad, inappropriately described; not reported, not described at all.</p><p>^a Incidence: number of patient with AEs/number of patients of total cases, %.</p><p>^b CONSORT items for reporting AEs: 1, statement of AEs in title or abstract; 2, statement of BVT related AEs in the introduction; 3, predefined definition of AEs related to the BVT; 4, collection or monitoring method for AEs; 5, statement of the method for analyzing and presenting AEs; 6, statement of any patients who dropped out due to AEs; 7, description of the specific denominator for the analysis of AEs.</p><p>Randomized controlled trials and randomized crossover trials reporting adverse events of bee venom therapy.</p

Case studies and case series on adverse events associated with bee venom therapy.

<p>AE: adverse event; BVT: bee venom therapy; BSA: bee sting acupuncture; BVA: bee venom acupuncture; SBV: sweet bee venom; HBV: honeybee venom; KMD: Korean medical doctor; MD: Medical doctor; VIT: venom immunotherapy; YJV: yellow jacket venom.</p><p>^a Venom type: bees (family Apidae); wasps (family Vespidae); mix (bees and wasps).</p><p>^b AE severity was assessed using Spilker’s criteria: mild, moderate, and severe.</p><p>^c AE type was classified into 1 of 3 categories: systemic reaction (SR), skin problem (SP), and other.</p><p>^d Mueller classification: if a systemic reaction occurred as an AE, it was classified into 1 of 5 categories: large local reaction, grade I, grade II, grade III, and grade IV.</p><p>^e Causality was determined through the WHO-UMC causality scale: certain, probable, possible, unlikely, conditional, and inaccessible.</p><p>Case studies and case series on adverse events associated with bee venom therapy.</p