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Envenoming resulting from Apis honeybee stings pose a neglected public health concern, with clinical complications ranging from mild local reactions to severe systemic manifestations. This review explores the mechanisms underlying envenoming by honeybee sting, discusses diagnostic approaches, and reviews current pharmacological interventions. This section explores the diverse clinical presentations of honeybee envenoming, including allergic and non-allergic reactions, emphasizing the need for accurate diagnosis to guide appropriate medical management. Mechanistic insights into the honeybee venom's impact on physiological systems, including the immune and cardiovascular systems, are provided to enhance understanding of the complexities of honeybee sting envenoming. Additionally, the article evaluates emerging diagnostic technologies and therapeutic strategies, providing a critical analysis of their potential contributions to improved patient outcomes. This article aims to provide current knowledge for healthcare professionals to effectively manage honeybee sting envenoming, thereby improving patient care and treatment outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cavalcante, Riciopo, Pereira, Jeronimo, Angstmam, Pôssas, Andrade Filho, Cerni, Pucca and Ferreira Junior.)

Background: Being stung by Hymenoptera species can cause life-threatening anaphylaxis. Although venom immunotherapy (VIT) seems to be the most effective treatment, its long-term efficacy, and risk factors for adverse events remain unclear. Objective: The objective was to investigate the long-term efficacy of VIT and evaluate adverse events and risk factors related to this. Method: Patients who received VIT in a tertiary-care adult allergy clinic between January 2005 and July 2022 were included. Patients' data were compared with those of individuals who had been diagnosed with bee and/or wasp venom allergy during the same period but had not received VIT and experienced field re-stings. Results: The study included 105 patients with venom allergy, of whom 68 received VIT and 37 did not receive VIT. Twenty-three patients (34%) completed 5 years of VIT, and the overall mean ± standard deviation VIT duration was 46.9 ± 20.9 months. Re-stings occurred in 5 of 23 patients who completed 5 years of VIT, and none of them developed a systemic reaction. Eighteen patients (40%) experienced re-stings after prematurely discontinuing VIT, of whom eight (44%) developed a systemic reaction. In the control group of patients who did not receive VIT, 26 patients (70.3%) experienced re-stings, and all had systemic reactions (100%), with no change in their median Mueller scores. There was a significant difference in the median Mueller score change between the patients who received VIT and the controls who did not (p = 0.016). A total of 13 patients (19%) experienced adverse events while receiving VIT, which were systemic reactions in nine honeybee VIT. The use of β-blockers was determined as the most important risk factor (odds ratio 15.9 [95% confidence interval, 1.2-208.8]; p = 0.035). Conclusion: It was confirmed that VIT was effective in both reducing the incidence and the severity of re-sting reactions. These effects were more pronounced in the patients who completed 5 years of VIT.

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

Background: Hymenoptera envenomation occurs frequently in people and dogs and can trigger anaphylaxis. Venom immunotherapy (VIT) is the only preventive treatment for Hymenoptera hypersensitivity and is indicated for people with severe adverse reactions to insect stings. Rush VIT is an accelerated VIT protocol in people. This has not been reported in dogs., Objectives: The objective of the study was to evaluate the safety of modified rush VIT., Animals: Twenty client-owned dogs with Hymenoptera hypersensitivity based on a history of adverse reactions to Hymenoptera envenomation and a positive intradermal test to honey bee and/or paper wasp venom., Materials and Methods: Dogs received incremental doses of venom via subcutaneous injection one day per week for three consecutive weeks until the maintenance dose was achieved. Vital signs were recorded every 30 min prior to venom administration. Adverse reactions were categorised as localised or grade I-IV systemic reactions., Results: Nineteen of 20 dogs (95%) completed rush VIT. One dog experienced a grade III systemic adverse reaction and was withdrawn from the study. No adverse reactions occurred in 10 of 20 dogs (50%). Localised and grade I-II systemic reactions occurred in nine of 20 dogs (45%), including nausea (n = 5), injection site pruritus (n = 3) and diarrhoea and lethargy (n = 1)., Conclusions and Clinical Relevance: Modified rush VIT in dogs was well-tolerated and should be considered for dogs with Hymenoptera hypersensitivity. Larger studies are needed to evaluate the efficacy of VIT in dogs for preventing hypersensitivity reactions to insect stings., (© 2023 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of ESVD and ACVD.)

In this study, the effect of gamma-irradiated honey bee venom (doses of 0, 2, 4, 6, and 8 kGy, volume of 0.1 ml and concentration of 0.2 mg/ml) was evaluated on the reduction of allergen compounds and the gene expression of inflammatory and anti-inflammatory cytokines in mice. Hence, edema activity induced by the bee venom irradiated at 4, 6, and 8 kGy was reduced, compared with the control group and that irradiated at 2 kGy. In contrast, the paw edema induced by the bee venom irradiated at 8 kGy increased, compared with 4 and 6 kGy. At all the time periods, there was a significant decrease in the gene expression of interferon gamma (IFN-γ), interleukin 6 (IL-6), and interleukin 10 (IL-10) in the bee venoms irradiated at 4, 6, and 8 kGy, compared with the control group and that irradiated at 2 kGy. In contrast, there was an increase in the gene expression of IFN-γ and IL-6 in the bee venom irradiated at 8 kGy, compared with those irradiated at 4 and 6 kGy. Therefore, gamma irradiation at 4 and 6 kGy reduced the gene expression of cytokines at each time period by decreasing the allergen compounds of honey bee venom., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/objective: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD., Methods: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively., Results: During the nootropic phase, treatment groups demonstrated a significant ( P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant ( P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant ( P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group ( P < 0.05) in a dose-dependent manner., Conclusion: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Rationale: In clinical practice, bee venom injection into acupuncture points is used to relieve various types of musculoskeletal pain. In the current study, we describe a patient who had persistent severe muscle pain caused by mistakenly injected high-dose bee venom., Patient Concerns: A 63-year-old woman mistakenly received an injection of high-dose (2 mL; standard dose, 0.1 mL) bee venom (diluted in saline at a 1:2000 ratio). Immediately after the injection, extreme burning pain developed at the injection site, which persisted for 1 month with a mean pain score of 9 on the numeric rating scale. T1-weighted gadolinium-enhanced axial lumbar magnetic resonance imaging revealed increased intensity in the medial part of the left psoas muscle around the L4-5 intervertebral disc level., Diagnosis: This finding indicated the presence of inflammation in the left psoas muscle, which was thought to be associated with pain., Interventions: A buprenorphine transdermal patch (releasing 5 mcg/hours) was applied to alleviate the pain., Outcomes: Six months after the bee venom injection, the pain completely resolved., Lessons: Bee venom has a strong toxic effect; therefore, only a minimal dose of diluted bee venom should be administered for musculoskeletal pain control. Special caution is required during bee venom injection to avoid excessive doses of bee venom., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Venom immunotherapy (VIT) is an effective treatment in the patients at high risk of anaphylaxis or life-threatening systemic reactions due to Hymenoptera venom allergy. But, systemic and large local reactions can be observed, especially during the build-up phase of VIT. We evaluated the safety of conventional and ultra-rush build-up protocols., Materials and Methods: Two protocols in 71 patients (39 conventional and 32 ultra-rush protocols) with honeybee and wasp venom allergy were evaluated retrospectively. Patients were diagnosed and selected for VIT according to the criteria established by the European Academy of Allergy and Clinical Immunology. The severity of systemic reactions was evaluated according to the criteria of Mueller., Results: Build-up phases were tolerated in 66.2% ( n  = 47) without any reaction. Allergic adverse reactions were observed in 33.8% ( n  = 24): large local reactions 22.5% ( n  = 16) and systemic reactions 11.3% ( n  = 8). There was no significant difference in the number of adverse reactions comparing patients receiving conventional and ultra-rush protocol. In addition, no association was found between allergic adverse reactions and the following factors: sex, previous systemic sting reactions, honeybee and wasp venom extract., Conclusion: We found that both protocols were tolerated in patients with honeybee and wasp venom allergy. Ultra-rush protocol will be preferred for patients and clinicians because of its advantages in terms of time and costs.KEY MESSAGESVIT is the only curative treatment method that reduces the risk of severe reactions after a bee sting and improves the quality of life in patients with Hymenoptera venom allergy.Ultra-rush VIT protocol has advantages such as few injection and time savings.Both ultra-rush and conventional VIT are safe treatments to prevent potentially life-threatening reactions in patients with honeybee and wasp venom allergy.

This study aimed to develop a prototype skincare product with bee venom, propolis, honey, beeswax, and royal jelly. The prototype formulation contained 0.1% bee venom, 0.3% propolis extract, 0.45% honey, and 1.0% royal jelly. The prototype body cream was analyzed for stability, antioxidant activity, dermatological response, and cytotoxicity. In addition, a panel test evaluated the prototype for the claims such as skin smoothness, feelings of nourishment, moisturizing, skin tone, brightness, and visibility of wrinkles. According to the stability test, the prototype was stable for up to 90 days at room temperature and +40°C. The formulation was found to have a high antioxidant capacity at 85.45%. Cell viability detected over 70% indicated that the prototype body cream was not cytotoxic. The dermatological analysis revealed no irritation or allergic reaction in non-allergic individuals. Panel test showed that the prototype makes skin silky smooth, contributes to hydration, brightens and nourishes the skin, evens the skin tone, reduces the visibility of wrinkles, improves skin elasticity, and smoothes wrinkles. This prototype formulation requires further research to evaluate its effectiveness against skin aging on different skin types. Nevertheless, the side effects of such products need particular attention in developing a commercial product containing bee venom in susceptible individuals., (© 2022 Wiley Periodicals LLC.)

Aim: Bee stings can result in allergic reactions, including anaphylaxis. Venom immunotherapy (VIT) is a definitive cure for bee venom allergy, but controversy surrounds whether accelerated protocols are safe in children. Our primary aim was to assess the safety profile of ultra-rush bee VIT compared with conventional bee VIT at a regional paediatric tertiary centre. We also sought to evaluate the impact of both approaches on time and resource use., Methods: Data were collected retrospectively from 14 patients with bee venom allergy who were treated with ultra-rush or conventional bee VIT between 2013 and 2021 at John Hunter Children's Hospital. We compared VIT-associated adverse reactions and use of resources in both these groups., Results: Overall, six patients received ultra-rush bee VIT and eight patients received conventional VIT. The ultra-rush group had a lower rate of systemic reaction (16%) compared with the conventional group (25%). One patient from the conventional group required adrenaline. Ultra-rush patients require fewer injections over a shorter time and fewer hospital visits to complete the protocol. Travel distance for families was significantly reduced., Conclusion: At our regional paediatric tertiary centre, ultra-rush bee VIT was a safe treatment option for children with bee venom allergy. It has many advantages over a conventional approach, especially for patients living in regional or remote areas., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

This study was aimed at investigating Korean patients' experience with bee venom therapy (BVT) and providing evidence to enhance BVT safety. Thus, an anonymous online survey was conducted between August 22 and 28, 2018. Five hundred respondents who underwent pharmacopuncture (PA) within one year were surveyed (sample error: 95 ± 4.38%). Of these, 32 respondents were excluded and 468 were evaluated. Of the 468, 61 reported experiencing adverse events after PA. The adverse event rate was higher in the BV-PA(Bee venom-Pharmacopuncture) group than in the non-A group; however, intergroup differences were insignificant. There were no significant differences in mild symptom intensity between the BV-PA and non-BV-PA groups ( p = 0.572). However, there was a significant intergroup difference in severe symptom intensity ( p < 0.001). Additionally, the BV-PA and non-BV-PA groups did not significantly differ in their level of satisfaction either overall or in terms of effectiveness and safety ( p = 0.414, p = 0.339, and p = 0.675, respectively). Furthermore, the BV-PA and non-BV-PA groups did not differ regarding intent to re-treat ( p = 0.722). Severe adverse events such as anaphylactic shock were not reported; however, BVT practitioners should be cautious when applying it.

Bees originally developed their stinging apparatus and venom against members of their own species from other hives or against predatory insects. Nevertheless, the biological and biochemical response of arthropods to bee venom is not well studied. Thus, in this study, the physiological responses of a model insect species (American cockroach, Periplaneta americana ) to honeybee venom were investigated. Bee venom toxins elicited severe stress (LD 50 = 1.063 uL venom) resulting in a significant increase in adipokinetic hormones (AKHs) in the cockroach central nervous system and haemolymph. Venom treatment induced a large destruction of muscle cell ultrastructure, especially myofibrils and sarcomeres. Interestingly, co-application of venom with cockroach Peram-CAH-II AKH eliminated this effect. Envenomation modulated the levels of carbohydrates, lipids, and proteins in the haemolymph and the activity of digestive amylases, lipases, and proteases in the midgut. Bee venom significantly reduced vitellogenin levels in females. Dopamine and glutathione (GSH and GSSG) insignificantly increased after venom treatment. However, dopamine levels significantly increased after Peram-CAH-II application and after co-application with bee venom, while GSH and GSSG levels immediately increased after co-application. The results suggest a general reaction of the cockroach body to bee venom and at least a partial involvement of AKHs.

Bee venom (BV) is a typical toxin secreted by stingers of honeybee workers. BV and BV therapy have long been attractive to different cultures, with extensive studies during recent decades. Nowadays, BV is applied to combat several skin diseases, such as atopic dermatitis, acne vulgaris, alopecia, vitiligo, and psoriasis. BV is used extensively in topical preparations as cosmetics and used as dressing for wound healing, as well as in facemasks. Nevertheless, the safety of BV as a therapeutic choice has always been a concern due to the immune system reaction in some people due to BV use. The documented unfavorable impact is explained by the fact that the skin reactions to BV might expand to excessive immunological responses, including anaphylaxis, that typically resolve over numerous days. This review aims to address bee venom therapeutic uses in skin cosmetics.

Honeybee venom is a source of proteins with allergenic properties which can result in in various symptoms, ranging from local reactions through to systematic life-threatening anaphylaxis, or even death. According to the World Allergy Organization (WAO), honeybee venom allergy is one of the most common causes of anaphylaxis. Among the proteins present in honeybee venom, 12 protein fractions were registered by the World Health Organization's Allergen Nomenclature Sub-Committee (WHO/IUIS) as allergenic. Most of them are highly immunogenic glycoproteins that cross-react with IgE and, as a consequence, may give false positive results in allergy diagnosis. Allergenic fractions are different in terms of molecular weight and biological activity. Eight of these allergenic fractions have also been identified in honey. This explains frequent adverse reactions after consuming honey in people allergic to venom and sheds new light on the causes of allergic symptoms in some individuals after honey consumption. At the same time, it also indicates the possibility of using honey as a natural source of allergen in specific immunotherapy.

Animal venoms, widespread throughout the world, are complex mixtures, the composition of which depends on the venom-producing species. The objective of this study was to contribute to the development of animal venom-based medicines by investigating the use of animal venom pharmacopuncture in Korean medicine (KM) institutions. We surveyed 256 public health centers from 1 through 31 October 2019 as guided by the Ministry of Health and Welfare (MoHW). A questionnaire developed by an expert group was distributed and collected for statistical analysis. The survey identified three types of animal venom-based pharmacopuncture: bee, snake, and toad venoms. The medications are based on a single animal venom ingredient and produced in 11 external herbal dispensaries (EHDs). Each animal venom is processed, refined, and freeze-dried in a cleanroom to produce a powder formulation that is later measured, diluted, filtered, filled, sealed, sterilized, and packaged as pharmacopuncture injections used in KM institutions. Bee venom therapy is effective in treating musculoskeletal pain, snake venom therapy is effective in controlling bleeding during surgery, and toad venom therapy is effective in cancer treatment. The study suggests that bee, snake, and toad venoms could be used in medical institutions and have the potential for drug development.

Background: Male infertility has been on the rise since the past seven decades. Recently, in Libya, bee venom therapy (BVT) has become a popular method among alternative healthcare practitioners for treating male infertility. However, a literature search did not find any published studies that investigated the use of BVT for infertility treatment., Aim: To investigate the effect of bee venom on the male reproductive status through measurements of semen quality parameters and testicular histological changes in adult male mice., Methods: A total of 48 male mice were randomly divided into three experimental groups (which were subdivided into two subgroups with eight mice each) as follows: control, bee venom sting (BVS), and bee venom injection (BVI). The normal control subgroup mice were not subjected to any treatment, while the vehicle control subgroup mice were injected (i.p.) with 200 μl of 0.9% saline solution. In the BVS-treated subgroups, each mouse was stung by one live bee for five times (BVS-5) or seven times (BVS-7) every third day for 2 or 3 weeks. While each mouse in the BVI-treated subgroups received 23 μg/kg in a dose volume of 200 μl BVIs (i.p.) for five times (BVI-5) or seven times (BVI-7) every third day for 15 or 21 days., Results: The findings of this study showed that repeated bee venom treatment by sting or injection to adult male mice resulted in a significant decline in testosterone levels, sperm count, sperm motility, and a very significant increase in the percentage of abnormal sperm morphology; also, there were harmful testicular histological changes in the structural organization of seminiferous tubules and degenerative changes in the germinal epithelium compared to control group., Conclusion: The results of this study provide evidence for the low semen quality and adverse testicular histological changes in male mice treated with bee venom. Hence, there is a desperate need for educating alternative healthcare practitioners and infertile couples about the harmful effects of BVT on reproductive status., Competing Interests: The authors declare that there is no conflict of interest.

Background: Beekeepers and their families are at an increased risk of life-threatening anaphylaxis due to recurrent bee-sting exposures., Objective: The aim of this study is to evaluate the demographic features, previous history of anaphylaxis among beekeepers and their family members, and their knowledge about the symptoms and management of anaphylaxis., Methods: A standardized questionnaire was administered to beekeepers during the 6th International Beekeeping and Pine Honey Congress held in 2018, in Mugla, Turkey. Additionally, food-service staff from restaurants were surveyed as an occupational control group about their knowledge about anaphylaxis., Results: Sixty-nine beekeepers (82.6% male, mean age 48.4±12.0 years) and 52 restaurant staff (46.2% male, mean age 40.5±10.0 years) completed the questionnaire. Awareness of the terms 'anaphylaxis' and 'epinephrine auto-injector' among the beekeepers were 55.1% and 30.4% and among the restaurant staff were 23.1% and 3.8%, respectively. Of the beekeepers, 74% were able to identify the potential symptoms of anaphylaxis among the given choices; 2.9% and 5.8% reported anaphylaxis related to bee-stings in themselves and in their family members, respectively. None of the restaurant staff had experienced or encountered anaphylaxis before but 3.8% of their family members had anaphylaxis and those reactions were induced by drugs., Conclusion: It is essential that implementation of focused training programs about anaphylaxis symptoms and signs as well as practical instructions of when and how to use an epinephrine auto-injector will decrease preventable morbidities and mortalities due to bee-stings in this selected high-risk population of beekeepers and their family members, as well as other fieldworkers under risk., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Bee venom is a complex natural mixture with various pharmaceutical properties. Among these properties, its peptides and enzymes have potential medical therapy for pain relief and inflammation. In clinical settings, this therapy has been used widely to treat diseases by injecting into acupoints. In this article, we have conducted various research from PubMed, Cochrane Library, and Clinical Key from inception of July 2020. The results revealed that bee venom therapy has been reported effective in anti-inflammatory, antiapoptosis, and analgesic effects. Moreover, bee venom acupuncture has been commonly used for clinical disorders such as Parkinson disease, neuropathic pain, Alzheimer disease, intervertebral disc disease, spinal cord injury, musculoskeletal pain, arthritis, multiple sclerosis, skin disease and cancer.

Bee venom has been used to treat many diseases because of its anti-inflammatory and analgesic effects. However, the secretions of bee venom can also cause life-threatening adverse reactions. The objective of this paper was to review the clinical effectiveness of bee venom and adverse events induced by bee venom, regardless of the disease. Four electronic databases were searched in April 2020. The reference lists of the retrieved articles and previous review articles were also hand-searched. Randomized controlled trials (RCTs) using any type of bee venom other than live bee stings for the clinical treatment of any disease other than cancer were included. The studies were selected, the data were extracted, and the quality of the studies was assessed by two authors. Risk of bias was assessed using the Cochrane risk of bias standards. Twelve RCTs were included in this review-three on Parkinson's disease, four on arthralgia, four on musculoskeletal disorders, and one on polycystic ovary syndrome. The types of bee venom used were acupuncture injections, ultrasound gel, and an ointment. Six studies reported adverse events, and skin reactions such as pruritus and swelling were the most common. The large-scale clinical trials of bee venom therapy are needed to verify the statistical difference, and the reporting system for adverse events is also required to increase the safety of bee venom therapy.

Foreign body granuloma is a potential adverse effect of acupuncture and usually occurs as an inflammatory reaction to foreign bodies that are accidentally or intentionally injected. This case presents a foreign body granuloma caused by honeybee acupuncture at the site of postherpetic neuralgia and highlights the need for caution and awareness of the side effects of acupuncture-related procedures., (© 2020 The Australasian College of Dermatologists.)

Background: Severe anaphylaxis (SA) in Hymenoptera venom allergy has been associated with a number of risk factors. However, the effect of several of those risk factors on the severity of anaphylaxis is poorly defined., Objective: To evaluate risk factors for SA in Hymenoptera venom allergy., Methods: We evaluated data from 500 patients who were referred to our department for the diagnosis of Hymenoptera venom allergy during a period of 11 years to identify risk factors for SA., Results: Six significant risk factors for SA were identified (P < .05): short interval from sting to reaction, absence of urticaria or angioedema (U/A) during anaphylaxis, older age, male sex, elevation of baseline serum tryptase (BST) level, and diagnosis of systemic mastocytosis. Moreover, elevation in BST level was significantly associated with the absence of U/A and older age. No association could be established between SA and comorbidities, concurrent cardiovascular medication, or the severity of the systemic reaction during the initiation of venom immunotherapy., Conclusion: Apart from BST and older age, male sex, short interval from sting to reaction, and absence of U/A are also risk factors for SA. The association between elevated BST level and SA was largely confined to those who had an absence of U/A after field sting, possibly because of the higher risk of concurrent systemic mastocytosis. Patients with an SA after a field sting do not have an elevated risk of systemic reactions during the initiation of venom immunotherapy compared with patients with mild anaphylaxis; therefore, additional preventive measures are not necessary., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Bee venom acupuncture has been used in treating patients with shoulder adhesive capsulitis, yet the effectiveness and safety remains unclear. Therefore, this systematic review will aim to assess the effectiveness and safety of bee venom acupuncture for shoulder adhesive capsulitis., Methods: Electronic databases including EMBASE, PUBMED, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, and Chinese Biomedical Literature Database will be searched for relevant randomized controlled trials from their inception to the search data without language and publication status. Randomized controlled trials involving bee venom acupuncture for treating shoulder adhesive capsulitis will be included. The primary outcome will be pain visual analogue scale, and secondary outcomes include active and passive range of motions, shoulder pain and disability index. Meta-analysis will be conducted using Review Manager software (V.5.3). The results will be presented as risk ratio for dichotomous data, and standardized or weighted mean difference for continuous data., Results: The results will be disseminated through a peer-reviewed journal publication., Conclusion: These systematic review findings will provide an evidence of bee venom acupuncture for shoulder adhesive capsulitis, and help to inform clinical practitioners and policy-makers in the decision-making., Ethics and Dissemination: Ethics approval and patient consent are not required as this study is a systematic review based on published articles.

Hymenoptera stings may cause both local and systemic allergic reactions and even life threatening anaphylaxis. Along with pharmaceutical drugs and foods, hymenoptera venom is one of the most common causes of anaphylaxis in humans. To date, no parameter has been identified that may predict which sensitized people will have a future systemic sting reaction (SSR), however some risk factors, such as mastocytosis and age >40 years are known. Venom immunotherapy (VIT) is the most effective method of treatment for people who had SSR, which is shown to be effective even after discontinuation of the therapy. Development of peripheral tolerance is the main mechanism during immunotherapy. It is mediated by the production of blocking IgG/IgG4 antibodies that may inhibit IgE dependent reactions through both high affinity (FcεRI) and low affinity (FcεRII) IgE receptors on mast cells, basophils and B cells. The generation of antigen specific regulatory T cells produces IL-10 and suppresses Th2 immunity and the immune responses shift toward a Th1-type response. B regulatory cells are also involved in the production of IL-10 and the development of long term immune tolerance. During VIT the number of effector cells in target organs also decreases, such as mast cells, basophils, innate type 2 lymphocytes and eosinophils. Several meta-analyses and randomized controlled studies have proved that VIT is effective for preventing SSR to a sting and improves the quality of life. In this review, the risk of SSR in venom allergy and how VIT changed this risk are discussed.

Objectives: To evaluate purified honey bee ( Apis mellifera ) venom (HBV) biotherapy for the treatment of osteoarthritis (OA) knee pain and physical function. Design and Patients: Five hundred and thirty-eight patients with Kellgren/Lawrence grade 1-3 radiographic knee OA and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score ≥2 were randomized 1:2 to either control ("histamine") or HBV in this double-blind study. Interventions: After a dose escalation period, patients received 12 weekly dermal injections of control ("histamine") or HBV. At each of the 12 weekly visits, a set of 15 dermal injections (each containing 2.75 μg histamine or 100 μg HBV) were administered at prespecified acupuncture points (5 on each knee: knee top, eye-1 medial, eye-2 lateral, ST 34, BL 40 and 5 near the spinous processes: BL 19, 21, 23, 25, and 27). Outcome Measures: Assessments included WOMAC pain and physical function subscales, visual analog scale (VAS), patient global assessment (PGA), and physician global assessment (PhGA). Rescue medication use (acetaminophen) and routine safety parameters were monitored. Results: HBV biotherapy demonstrated a highly significant improvement over control in WOMAC pain score after 12 weeks (1.1 U mean difference; confidence interval [95% CI]: 0.3-2.0; analysis of covariance [ANCOVA] p  = 0.0010 with baseline as covariate) that was also sustained 4 weeks post-treatment. Furthermore, WOMAC physical function was significantly improved over control with HBV (3.1 U mean difference; 95% CI: 0.3-5.9; ANCOVA p  = 0.0046), and sustained 4 weeks post-treatment. VAS scores were significantly improved with HBV versus control, as well as PGA and PhGA evaluations, which showed that patients responded more favorably ("very good/good") to their overall OA condition (82.0% vs. 62.4% [ p  = 0.0001] and 82.1% vs. 54.9% [ p  = 0.0015], respectively). Use of rescue acetaminophen was similar between the groups (77%-78% of patients). HBV was associated with higher incidence of injection site reactions (<5%); however, the overall safety profiles were comparable between the treatment groups. Conclusions: This phase 3 trial demonstrated that HBV biotherapy resulted in significant improvements in knee OA pain and physical function.

Allergic reactions caused by sting of honeybees or wasps are very often and make also very severe anaphylactic reaction, up to 3,5 % of population. Mostly sting reactions are dependent to IgE induced reactions type I.Established are history, skin tests and specific IgE antibodies. Recombinant antibodies complete diagnostics in special cases. Specific immunotherapy is recommended as a very successful therapy in treating allergies due to honeybees and wasps. Many protocols are established, the standard maintenance dose is 100 mg. The hyposensitization is very successful with rates of nearly 100 % success. In most times a dose of 100 mg is sufficient, in some cases the dose must be increased to 200 mg. In most patients immunotherapy can be stopped after 3-5 years. Sting challenge tests should be done for proving the efficiency of immunotherapy. Many patients after immunotherapy have an improved live quality after sting provocations., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Brugada pattern on electrocardiography (ECG) can manifest as type 1 (coved pattern) and type 2 (saddleback pattern). Brugada syndrome represents an ECG with Brugada pattern in a patient with symptoms or clinical factors, including syncope, cardiac arrest, ventricular dysrhythmias, and family history. Brugada syndrome is caused by a genetic channelopathy, but the Brugada pattern may be drug-induced. Epinephrine-induced Brugada pattern has not been reported previously., Case Report: A 63-year-old man developed anaphylaxis secondary to a bee sting, had a transient loss of consciousness, and self-administered intramuscular epinephrine. He subsequently presented to the emergency department and was found to have a type 1 Brugada pattern on ECG that resolved during observation. A historic ECG was reviewed that demonstrated a baseline type 2 Brugada pattern. His anaphylaxis was managed with steroids and antihistamines. He was observed without subsequent dysrhythmic events on telemetry or any further symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The differential diagnosis for syncope includes dysrhythmia, such as Brugada syndrome. Among other possible drugs, epinephrine may induce a type 1 Brugada pattern. Patients with Brugada pattern on ECG should be referred immediately to electrophysiology for consideration of implantation of a cardioverter-defibrillator device, given the association of Brugada pattern with sudden cardiac arrest and ventricular dysrhythmias., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Allergy to bee and wasp venom can lead to life-threatening systemic reactions. The identification of the culprit species is important for allergen-specific immunotherapy., Objectives: To determine a panel of recombinant bee and wasp allergens which is suitable for the identification of bee or wasp as culprit allergen sources and to search for molecular surrogates of clinical severity of sting reactions., Methods: Sera from eighty-seven patients with a detailed documentation of their severity of sting reaction (Mueller grade) and who had been subjected to titrated skin testing with bee and wasp venom were analyzed for bee and wasp-specific IgE levels by ImmunoCAPTM. IgE-reactivity testing was performed using a comprehensive panel of recombinant bee and wasp venom allergens (rApi m 1, 2, 3, 4, 5 and 10; rVes v 1 and 5) by ISAC chip technology, ImmunoCAP and ELISA. IgG4 antibodies to rApi m 1 and rVes v 5 were determined by ELISA and IgE/IgG4 ratios were calculated. Results from skin testing, IgE serology and IgE/IgG4 ratios were compared with severity of sting reactions., Results: The panel of rApi m 1, rApi m 10, rVes v 1 and rVes v 5 allowed identification of the culprit venom in all but two of the 87 patients with good agreement to skin testing. Severities of sting reactions were not associated with results obtained by skin testing, venom-specific IgE levels or molecular diagnosis. Severe sting reactions were observed in patients showing < 1 ISU and < 2kUA/L of IgE to Api m 1 and/or Ves v 5., Conclusion: We identified a minimal panel of recombinant bee and wasp allergens for molecular diagnosis which may permit identification of bee and/or wasp as culprit insect in venom-sensitized subjects. The severity of sting reactions was not associated with parameters obtained by molecular diagnosis., Competing Interests: Rudolf Valenta has received research grants from Biomay AG, Vienna, Austria, and Viravaxx, Vienna, Austria. He is a consultant for Biomay AG, and Viravax. Natalija Novak has received grants from the German Research Council, from GIF, CK Care and ALK Abello, served as a consultant for ALK Abello, HAL Allergy, Leti Pharma and Stallergenes and received lecture fees from ALK, HAL, Sanofi and Leti Pharma. The other authors have no conflict of interest to declare. Thermo Fisher Scientific provided the Api m 3 and Api m 5 ImmunoCAP tests. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Bee venom is a very complex mixture of natural products extracted from honey bee which contains various pharmaceutical properties such as peptides, enzymes, biologically active amines and nonpeptide components. The use of bee venom into the specific points is so called bee venom therapy, which is widely used as a complementary and alternative therapy for 3000 years. A growing number of evidence has demonstrated the anti-inflammation, the anti-apoptosis, the anti-fibrosis and the anti-arthrosclerosis effects of bee venom therapy. With these pharmaceutical characteristics, bee venom therapy has also been used as the therapeutic method in treating rheumatoid arthritis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, liver fibrosis, atherosclerosis, pain and others. Although widely used, several cases still reported that bee venom therapy might cause some adverse effects, such as local itching or swelling. In this review, we summarize its potential mechanisms, therapeutic applications, and discuss its existing problems., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing guidelines for allergen immunotherapy (AIT) for the management of allergic rhinitis, allergic asthma, IgE-mediated food allergy and venom allergy. To inform the development of clinical recommendations, we undertook systematic reviews to critically assess evidence on the effectiveness, safety and cost-effectiveness of AIT for these conditions. This study focusses on synthesizing data and gaps in the evidence on the cost-effectiveness of AIT for these conditions., Methods: We produced summaries of evidence in each domain, and then, synthesized findings on health economic data identified from four recent systematic reviews on allergic rhinitis, asthma, food allergy and venom allergy, respectively. The quality of these studies was independently assessed using the Critical Appraisal Skills Programme tool for health economic evaluations., Results: Twenty-three studies satisfied our inclusion criteria. Of these, 19 studies investigated the cost-effectiveness of AIT in allergic rhinitis, of which seven were based on data from randomized controlled trials with economic evaluations conducted from a health system perspective. This body of evidence suggested that sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) would be considered cost-effective using the (English) National Institute for Health and Clinical Excellence (NICE) cost-effectiveness threshold of £20 000/quality-adjusted life year (QALY). However, the quality of the studies and the general lack of attention to characterizing uncertainty and handling missing data should be taken into account when interpreting these results. For asthma, there were three eligible studies, all of which had significant methodological limitations; these suggested that SLIT, when used in patients with both asthma and allergic rhinitis, may be cost-effective with an incremental cost-effectiveness ratio (ICER) of £10 726 per QALY. We found one economic modelling study for venom allergy which, despite being based largely on expert opinion and plausible assumptions, suggested that AIT for bee and wasp venom allergy is only likely to be cost-effective for very high-risk groups who may be exposed to multiple exposures to venom/year (eg bee keepers). We found no eligible studies investigating the cost-effectiveness of AIT for food allergy., Conclusions: Overall, the evidence to support the cost-effectiveness of AIT is limited and of low methodological quality, but suggests that AIT may be cost-effective for people with allergic rhinitis with or without asthma and in high-risk subgroups for venom allergy. We were unable to draw any conclusions on the cost-effectiveness of AIT for food allergy., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: Bee (Apis mellifera L.) venom (BV) has been used as a cosmetic ingredient owing to its anti-aging, anti-inflammatory, and antibacterial effects. The aim of this study was to assess the skin safety of BV., Methods: For this purpose, skin phototoxicity and sensitization tests were conducted in healthy male Hartley guinea pigs. The animals were divided into three groups (n=5) for the phototoxicity test: G1 (negative control), G2 (BV gel treatment), and G3 (positive control). After specified treatments, the animals were irradiated with ultraviolet A (15 J/cm 2 ). The photosensitivity test was also performed in three groups: G4 (negative control, n=5), G5 (BV gel treatment, n=10), and G6 (positive control, n=5)., Results: Erythema and edema were observed after 24, 48, and 72 hours in the positive control group, but not in the negative control and BV gel groups. Application of BV to the guinea pig skin had no toxic effects on any clinical signs, body weight, or mortality. In addition, it did not evoke a skin reaction in both either the skin phototoxicity and skin photosensitization tests., Conclusion: Therefore, it can be concluded that BV has the potential to be developed as a drug ingredient for topical uses., (© 2017 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)

Background: Acupuncture is one of the most popular modalities used to treat various diseases in traditional Korean and Oriental medicine. However, its risk of adverse events can be easily overlooked., Objective: We investigated dermatological adverse events associated with acupuncture to draw attention to the risk of such adverse events., Methods: We evaluated the types of acupuncture, clinicopathologic diagnoses, treatments, and prognoses in patients with a causal relationship between acupuncture and dermatoses., Results: The study population comprised 25 patients (mean age, 52 years) with a history of acupuncture. Bee venom acupuncture was performed the most frequently (13 of 25 patients), and most patients received acupuncture to control pain (19 of 25 patients). The most common adverse event was infectious skin disease such as atypical mycobacterial infection or pyoderma/abscess, followed by hypersensitivity reactions, localized lipoatrophy, and hypertrophic scar. Acupuncture-related dermatoses required a relatively long treatment period (average, 8.6 weeks)., Conclusion: Various dermatoses may occur following acupuncture. To minimize the risk of these dermatoses, proper training and medical knowledge in acupuncture practice are necessary for medical personnel. Dermatologists, oriental medical practitioners, and patients should pay attention to the potential adverse events of acupuncture., (© 2015 The International Society of Dermatology.)

We investigated the range and frequency of significant adverse events (AEs) in use of pharmacopuncture and acupuncture using large-scale, single-center safety data as evidence supporting safety of acupuncture with pharmacopuncture, used extensively in Asia, is scarce. Status reports (nurse records in ambulatory and inpatient care units, and administrative event records) as a part of an internal audit at a Korean Medicine hospital specializing in the treatment of musculoskeletal disorders, patient complaints filed through the hospital website, and medical records of patients visiting from December, 2010 (inception of internal audit) to October, 2014 were retrospectively reviewed. A total 80,523 patients (5966 inpatients and 74,557 outpatients) visited during this period. Inpatients received an average 31.9 ± 20.7 acupuncture, 23.0 ± 15.6 pharmacopuncture, and 15.4 ± 11.3 bee venom pharmacopuncture sessions, and outpatients were administered 8.2 ± 12.2 acupuncture, 7.8 ± 11.5 pharmacopuncture, and 10.0 ± 12.3 bee venom sessions, respectively. AEs associated with acupuncture/pharmacopuncture were forgotten needle (n = 47), hypersensitivity to bee venom (n = 37), presyncopic episode (n = 4), pneumothorax (n = 4), and infection (n = 2). Most cases were mild requiring little or no additional intervention and leaving no sequelae. Although serious AEs including infection (n = 2) and anaphylaxis associated with bee venom treatment (n = 3) were also reported, incidence was rare at 0.002% in infection and 0.019% in anaphylaxis. Incidence of AEs associated with acupuncture/pharmacopuncture treatment was low, and most cases were not serious. Still, however rare, avoidable AEs can and should be prevented through education and corrective action. Further prospective studies on the effect of error reduction strategies on incidence of adverse effects are warranted.

Background: Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back pain. On the other hand there have been a number of reported complications of BVT use such as ITP. We present a case report on ITP after BVT., Case Presentation: A 61 year old lady presented with gum bleeding and ecchymosis and found to have isolated thrombocytopenia (platelet count of 9 × 10(9)/L) after receiving four direct bee sting sessions. There was no evidence of any other risk factors of ITP., Conclusion: Bee venom components and toxicity may be associated with thrombocytopenia as a complication. Further research is needed to postulate guidelines and protocol for BVT. In the meantime, monitoring of the practice of BVT should be made, with an emphasis on patient education regarding the safety profile and associated risks compared to the gained benefits.

Venom immunotherapy is the only curative intervention for subjects with Hymenoptera venom allergy who suffering systemic reactions upon bee or wasp stings. Venom immunotherapy can restore normal immunity against venom allergens, as well as providing to allergic subjects a lifetime tolerance against venoms. Nevertheless, it is necessary using safety assays to monitoring the development of tolerance in the VIT protocols to avoid fatal anaphylactic reactions. The purpose of this study was to assess the modifications in several markers of tolerance induction in subjects with Hymenoptera venom allergy undergoing immunotherapy. The studies were performed at baseline time and after six month of VIT. Intradermal skin tests, basophil activation tests, specific IgE levels; and the T-cell markers (IL-4 and IFN-γ producing cells; and expression of the surface activation markers CD40L and CTLA-4) were assayed. At six month of immunotherapy all parameters studied had significant alterations. All decreased, except the IFN-γ producing cells. In addition, modifications in intradermal skin test showed a significant correlation with both, CD40L expression on CD4 T lymphocytes (p=0.043) and IL-4 producing T lymphocytes (p=0.012). Neither basophil activation test nor serum levels of sIgE demonstrated any correlation with the immunological parameters studied nor among them. These results suggest that both IL-4 production and CD40L expression could be two good indicators of the beneficial effects of venom immunotherapy which translate into skin tests., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: The ultrarush protocol is an attractive approach in the buildup phase of venom immunotherapy (VIT-UR). However, the degree of risk of VIT-UR in children remains unknown. The objective of this study was to compare the safety of VIT-UR in children and adults., Methods: We performed a study based on prospectively gathered medical records of children and adults with hymenoptera venom allergy treated with VIT-UR in 3 allergy centers in Poland., Results: The study population comprised 134 children (mean [SD] age, 12.6 [3.7] years; males, 70.1%) and 207 adults (mean age, 42.4 [14.0] years; males, 47.8%). The number of children in the subgroups of bee venom (BV) allergy and wasp venom (WV) allergy were comparable, although sensitization to WV was more predominant in the adult group (70.1%). Skin reactivity to both venoms was more common in children than in adults (P < .001); however, children had higher concentrations of total IgE and specific IgE to BV (both P < .001). Systemic allergic reactions (VIT-SARs) occurred in 6.2% of the patients (3.7% in children and 7.7% in adults; nonsignificant). In adults, SARs occurred more frequently in patients treated with BV than WV extracts (21.4% vs 2.6%; P < .001). The same pattern was observed in children (7.2% vs 0%; P = .058). However, VIT-SARs to BV were less frequent in children than in adults (P = .034). Similarly, no significant relationship was noted between children and adults receiving WV VIT (2.6% vs 0%; nonsignificant). The severity of VIT-SAR did not differ between children and adults., Conclusions: VIT-UR is safer in children. Age below 18 is not a risk factor for VIT-SARs.

The role of CD1a-reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a-reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom-responsive CD1a-reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a-transfected K562 cells in the presence of wasp or bee venom. T-cell response was evaluated based on IFNγ, GM-CSF, and IL-13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN-γ, GM-CSF, and IL-13 producing CD1a-reactive T cells responsive to venom and venom-derived phospholipase than healthy individuals. Venom-responsive CD1a-reactive T cells were cross-responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a-reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein-specific T cell and antibody responses. Here, we show that lipid antigens and CD1a-reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy., (© 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bee venom is a complex substance which acts in different ways; local or systemic anaphylaxis associated with IgE and direct toxic effects of the large volume of injected venom. We report a 10- year-old boy who was the vulnerable of 5989 honey bee attacks. To the best of our knowledge, this case had the ultimate number of honey bee stings in the literature, until now. He was admitted to pediatric intensive care unit after 3 hours of incident. Plasmapheresis was started to remove circulating venom that can cause many systemic side effects. Unfortunately, multiorgan failure developed on the 2nd day of admission due to severe hemolysis and rabdomyolysis. Additional therapies modalities, mechanical ventilation, hemodialysis, and antihypertensive drugs were added to the treatment during the disease process. Despite all of the treatments, the patient was failed on 12th day of hospitalization.

Background: Adverse systemic reactions (SRs) are more common in honeybee venom immunotherapy (VIT) than in wasp VIT. Factors that might be associated with SRs during the honeybee VIT are poorly understood., Objective: Our aim was to evaluate risk factors for SRs during the build-up phase of honeybee venom immunotherapy., Methods: We included 93 patients who underwent ultra-rush honeybee VIT. The adverse SRs and their severity was compared to various immunological (sIgE, tIgE, basophil CD63 response, baseline tryptase, and skin tests), patient-specific (age, sex, cardiovascular conditions and medications, and other allergic diseases), and sting-specific factors (anaphylaxis severity, time interval to onset of symptoms, and absence of cutaneous symptoms)., Results: Twenty-three patients (24.7%) experienced mild SRs and 13 patients (14%) severe SRs. In five patients with severe SRs, the build-up was stopped. High basophil allergen sensitivity, evaluated as dose-response curve metrics of EC15, EC50, CD-sens, AUC, or the response to submaximal 0.01 μg/mL of venom concentration, was the most significant risk factor and only independent predictor of severe SRs and/or build-up stop. Time interval of <5 min after sting to onset of symptoms and lower specific IgEs to rApi m1 was also associated with severe SRs. There was no difference in other immunological, patient-specific, or sting-specific factors, including the baseline tryptase. None of the studied factors was associated with mild SRs., Conclusion and Clinical Relevance: High basophil allergen CD63 sensitivity phenotype was a major indicator of severe adverse SRs during the build-up phase of honeybee VIT. Possibly role was also showed for short latency to filed sting reaction and low sIgE to rApi m1. Before honeybee VIT, measurement of basophil allergen sensitivity should be used to identify patients with a high risk for severe side-effects., (© 2015 John Wiley & Sons Ltd.)

Unlabelled: Few data exists about re-sting reactions and their prognosis in children with moderate to severe venom hypersensitivity. The reasons behind not consenting to or prematurely ending venom immunotherapy (VIT) and the preparedness of children who refused or quit VIT for future moderate-severe systemic reaction (SR) to re-stings have not been studied. Data on children with moderate to severe SR after Hymenoptera stings was collected for a 17-year period using our database. A standardized questionnaire was administered to patients who accepted to be interviewed at the clinic. These patients were evaluated in terms of their preparedness for future moderate-severe SR to re-stings. A total of 55 children, 75 % of whom commenced on VIT, were included in the analysis. Different reasons exist for not consenting to VIT; the most common of which is living at a distance from the allergy center. There were no differences in terms of the number of re-stung patients (27.7 and 27.2 %, respectively) and moderate-severe SR (60 and 16.6 %, respectively) between children who prematurely ended or who did not consent to VIT and children who completed VIT. Sixty-four percent of the children who refused or discontinued VIT were not prepared for future moderate-severe SR to re-stings., Conclusion: Long-term prognosis for re-sting reactions is good in children with moderate to severe SR to venoms. Some of the reasons behind refusing or discontinuing VIT may be related to quality of life issues. Preparedness of children who refused or discontinue VIT in emergencies is very low.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

Bee venom acupuncture has been widely used in Oriental medicine with limited evidence of effectiveness. Most of the complications due to bee venom acupuncture are local or systemic allergic reactions. However, serious medical and neurological complications have also been reported. We herein describe the treatment of a 68-year-old woman who developed progressive quadriplegia 10 days after receiving multiple honeybee venom sting acupuncture treatments. The electrophysiological findings were consistent with Guillain-Barré syndrome (GBS). The temporal relationship between the development of GBS and honeybee venom sting acupuncture is suggestive of a cause-and-effect relationship, although the precise pathophysiology and causative components in honeybee venom need to be verified.