# Bee Venom Acupuncture in Traditional Korean Medicine: A Review of Clinical Practice Guidelines
## 6 Discussion and Future Directions
Deciding recommendation grades was strongly influenced by the quality and consistency of RCT findings, which often exhibited methodological deficits such as small sample sizes, inadequate blinding, and variability in treatment protocols. Also, many CPGs lacked assessments for harm, availability in practice, cost-effectiveness, and patient preference. As a result, the combination of methodological weaknesses in RCTs and insufficient evaluation of other factors led to a conservative interpretation of BVA's role, restricting its recommendation to an advisable or potentially beneficial treatment rather than a strongly endorsed first-line therapy. The limited assessment of harms, cost-effectiveness, and patient preferences hinders the ability to generate more stringent recommendation grades. It has been reported that BV exhibits notable cytotoxic and genotoxic effects. High concentrations of BV have been shown to induce significant cytotoxicity, leading to cell death in human lymphocytes, which implies potential risks to normal cells upon exposure [47]. Furthermore, BV has demonstrated genotoxic effects, including DNA strand breaks and chromosomal aberrations in human peripheral blood lymphocytes, highlighting the necessity of caution regarding dosage and clinical applications [48]. A Korean survey of 468 pharmacopuncture patients found that patients administered BVA therapy experienced more severe adverse events than other pharmacopuncture therapies [49]. Specifically, localized side effects, such as pruritus, erythema, edema, and pain at the injection site, and systemic adverse events, such as headache, dizziness, nausea, hyperventilation, and chest pain, have been documented [6; 49]. In rare cases, severe allergic reactions such as urtic, angioedema, and anaphylaxis have also been reported [50]. These emphasize the need for careful patient screening before treatment. A previous meta-analysis highlighted that only 10% of BVA cases documented pre-treatment allergy testing [51]. It is remarkable that most CPGs in this review recommended pre-treatment skin testing to mitigate allergic risks. Cost-effectiveness or cost-utility evaluations remain a critical gap. Although BVA showed effectiveness for chronic neck pain when combined with non-steroidal anti-inflammatory drugs (NSAIDs) [52], an objective assessment is needed to determine the incremental effectiveness or utility gained relative to the additional costs incurred compared to NSAID monotherapy. Unlike AT or EA, BVA is not covered by national health insurance in Korea, and we need evidence to evaluate its potential benefits and value. Patient preference data were also sparse. A survey conducted in Saudi Arabia revealed that rheumatoid arthritis patients showed a more favorable attitude towards BVA than those with other chronic diseases [53]. An objective assessment of patient preferences can play a crucial role in weighing a treatment's overall benefits and harms. This study has several limitations. First, this review did not include any guidelines from other countries that may also practice BVA, resulting in a geographically imbalanced dataset. Second, this study reviewed the CPGs that have already been published. Therefore, the diseases covered in this study may not represent the full spectrum of conditions for which BVA is used in clinical practice. New guidelines for different conditions are developing but might not yet be published [17; 54]. Third, the AGREE II tool assessment for the included CPGs was not performed since we only included the CPGs for which the assessments had already been performed. Fourth, we could not compare BVA with other alternative therapies due to the lack of comprehensive reviews evaluating the evidence levels and recommendation grades of those interventions across CPGs. Meanwhile, there was a review of CPGs for cupping therapy (CT) in Korea [55]. Similar to BVA, most CT recommendations were graded as B or C, with evidence levels ranging from low to moderate due to concerns about methodological limitations in primary studies.