Clinical complications in envenoming by Apis honeybee stings: insights into mechanisms, diagnosis, and pharmacological interventions.

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.

A lifesaving improvised peritoneal dialysis on a toddler with acute kidney injury following a swarm of bees' sting at Iringa Regional Referral Hospital, Southern Highland-Tanzania: a case report.

BACKGROUND: Peritoneal dialysis as one of the nephrology services in children with acute kidney injury is a safe and cost-effective modality of treatment in low and lower-middle income countries. Despite evidence of its effectiveness in limited resource settings, the service is still provided only in tertiary level healthcare facilities in Tanzania. CASE PRESENTATION: In this case report, we narrate the survival of a 22-month-old male patient of African descent with an acute kidney injury following a swarm of bees' stings at home. A lifesaving, although low-quality and high-risk, peritoneal dialysis was performed for 5 days at Iringa Regional Referral Hospital, a secondary level health facility in rural Tanzania with lack of standard and recommended expertise, laboratory investigations, and equipment. CONCLUSION: Lower- and middle-income countries in collaboration with stake holders should ensure that this service is available, accessible, and safe in the lower-level health facilities, given that access to the tertiary-level facilities is inadequate and time limited, hence serving a larger population.

Hymenoptera venom allergy in children and adolescents.

PURPOSE OF REVIEW: This review will identify and summarize the published existing data pertaining specifically to Hymenoptera venom allergy in children and adolescents, highlighting the major studies currently available on venom immunotherapy (VIT) and its prognosis in children. RECENT FINDINGS: The current review covers the incidence and prevalence of Hymenoptera venom allergy (HVA) in children, factors influencing occurrence and severity of reactions (age, sex, comorbidities, etc.), indications to perform diagnostic tests and start VIT in children, different existing VIT protocols and their safety and efficacy. SUMMARY: Hymenoptera venom allergy is the second most common cause of anaphylaxis in children and it considerably affects quality of life. Cutaneous reactions are the most prevalent clinical presentation in children who usually have a more favourable prognosis than adult patients. However, studies on HVA in children and adolescents are still limited. Currently VIT is the only treatment able to modify the natural history of HVA in adults as well as in children, and to protect patients from systemic reactions after subsequent stings.

A retrospective study of a novel 3-session rush venom immunotherapy protocol.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment for life-threatening stinging-insect hypersensitivity. Rush VIT protocols allow patients to reach maintenance dosing faster, thus conferring protection sooner. The published protocols vary in dosing regimens, monitoring parameters, and safety profiles. OBJECTIVE: To describe a novel 3-session outpatient rush VIT protocol with full therapeutic dosing achieved at the end of session 3. METHODS: We conducted a retrospective chart review of adult patients treated with rush VIT in an outpatient university allergy/immunology clinic. Demographic and clinical data, including the type of sting reaction, the number of venom allergens, and any systemic reactions (SRs) during VIT, were analyzed. RESULTS: Over a 14-year period, 55 patients (28 females and 27 males) with a median age of 47 years underwent our VIT protocol. A total of 46 patients (84%) tolerated the procedure without SR, and 53 (96%) attained full maintenance dosing. All reactions during rush were Brown anaphylaxis criteria grade 1 or 2. Although the most common venom allergy was yellow jacket, most patients had multiple venom allergies and received therapy with more than 1 venom. Furthermore, 10 patients were re-stung while on maintenance with only 1 patient having a mild SR. CONCLUSION: Our 3-session outpatient rush VIT protocol is effective and safe. Most patients had no SR and attained maintenance dosing. Compared with other 3-session rush protocols, our protocol requires non-invasive monitoring, and patients achieved monthly maintenance dosing immediately on completion.

Evidence-based data support strategies for the prevention of Hymenoptera venom anaphylaxis.

PURPOSE OF REVIEW: This review aims to identify phenotypes at-risk of Hymenoptera venom-induced anaphylaxis (HVA), focusing on different perspectives (epidemiological, clinical, and therapeutic) in order to adapt future preventive strategies. RECENT FINDINGS: HVA remains one of the leading causes of anaphylaxis, with a broad pattern of symptoms. Although most cases occur outside healthcare settings, data indicate a high emergency admission rate due to insect stings. Mortality is often underestimated because of the lack of witnesses and difficulties in recognizing the signs and the culprit. Targeting risk factors could be a clue to improve these statistics and the prognosis of the disease.Potential risk factors for severe HVA in the European population are basal serum tryptase (BST) above 8 µg, mast cell disorders, the absence of skin symptoms, and cardiovascular conditions requiring the use of beta blockers and ACE inhibitors. Identifying these criteria, mainly based on clinical patterns, helps to develop personalized strategies for management and prevention. SUMMARY: With a personalized medicine approach, phenotypes must be characterized to adapt to the management of patients suffering from Hymenoptera venom anaphylaxis (HVA), including venom immunotherapy (VIT). In this systematic review, all articles mentioned systemic reactions with heterogeneous severity degrees. Half of those reported grade III-IV systemic reactions (Ring and Messmer). HVA clinical patterns could be worsened by one Hymenoptera sting, a patient's history with mast cell disorders, or cardiovascular diseases. VIT failure was attributed to bee venom extract and monotherapy in two-thirds of publications. Findings stress the difficulty of having uniform epidemiological data on HVA and the lack of financial support in some world regions to support appropriate management of these conditions. Although observing a heterogeneity of data, we were able to identify potential risk factors, in particular for the severe cases. We believe our work will support allergists and health professionals to implement improved personalized management of patients suffering from severe HVA.

Clinical features, severity, and immunological changes during venom immunotherapy in children and adults.

Background: Hymenoptera venom allergy (HVA) is among the most common causes of severe allergic reactions worldwide. Objective: To investigate clinical features and factors that affect the severity of HVA and to determine the alterations in immunologic biomarkers after venom immunotherapy (VIT). Methods: Seventy-six adults and 36 children were prospectively investigated. We analyzed specific immunoglobulin E (sIgE) and sIgG4 levels of venom extracts and components (rApi m1, rApi m10, rVes v1, rVes v5, rPol d5) before and after the first year of VIT. Results: Although cardiovascular symptoms were more common in adults (p < 0.001), the skin was the most affected organ in children (p = 0.009). Serum basal tryptase (sBT) levels were higher in the adults than the children (p < 0.001). The absence of urticaria (odds ratio [OR] 4.208 [95% confidence interval {CI}, 1.395-12.688]; p = 0.011) and sBT ≥ 5.2 ng/mL (OR 11.941 [95% CI, 5.220-39.733]; p < 0.001) were found as the risk factors for grade IV reactions. During VIT, changes in sIgE levels were variable. In the Apis VIT group, we observed remarkable increases in sIgG4 levels in Apis extract and rApi m1 but not in Api m10. Vespula extract, rVes v1, and rVes v5 sIgG4 levels were significantly increased in Vespula VIT group, we also detected significant increases in the Polistes extract and rPol d5 sIgG4 levels, which were not observed in the Apis VIT group. In the patients who received both Apis and Vespula VIT, increases in sIgG4 levels were observed for both venoms. Conclusion: Adults and children can have different clinical patterns. After 1 year, VIT induced a strong IgG4 response. Although Apis immunotherapy (IT) induced Apis sIgG4, excluding Api m10, Vespula IT induced both Vespula and Polistes sIgG4.

Efficacy and safety of hymenoptera venom immunotherapy.

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 ß-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.

Pruritic Horse: Approach to Allergic Skin Diseases in Horses.

Allergy to insects is the most common skin allergy in horses. Pruritus in affected patients can be extreme. Face, ears, mane, and tail area are commonly affected areas. Diagnosis of insect bite hypersensitivity (IBH) is clinical and is based on history, clinical signs, and response to repellents. Allergy tests are not to be used for diagnostic purposes. Currently, there is no specific treatment for IBH other than insect avoidance, treatment of secondary infections, and symptomatic relief of pruritus. Many allergic horses become also sensitized to pollens. For these patients, allergen specific immunotherapy is beneficial.

Hymenoptera venom immunotherapy: Safety and efficacy of an accelerated induction regimen with depot aluminum adsorbed extracts.

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.

High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy.

BACKGROUND: In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. METHODS: 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. RESULTS: 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3-4 vs. 11% [n = 78 of 709] with Grade 1-2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3-4 vs. 0.001% [n = 78] in Grade 1-2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). CONCLUSIONS: By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.

Evaluation of the Cytokine Response Induced by Specific Allergen Immunotherapy in Patients with Vespa velutina Anaphylaxis.

INTRODUCTION: Changes in the cytokine profile from type 2 to type 1 together with the induction of regulatory cells are expected during hymenoptera venom immunotherapy (VIT). The present study was aimed to investigate the changes in type 1, type 2, and regulatory cytokines induced by a Vespula spp. VIT in patients with anaphylaxis to Vespa velutina. METHODS: Twenty consecutive patients with anaphylaxis due to Vespa velutina were treated with Vespula spp. VIT. Serum cytokines (IL-4, IL-5, IL-10, IL-13, and IFN-É£) were measured at baseline, 6, and 12 months after starting VIT. RESULTS: A significant increase in serum IFN-y was detected after 6 and 12 months of VIT. An increase in serum IL-10 and a decrease in IL-5 were observed after 12 months. IL-4 was undetectable all along the study, and an unexpected increase of IL-13 was present at 12 months of treatment. CONCLUSION: Vespula spp. VIT seems to be able to induce a shift to type 1 cytokine production measured through IFN-y levels and IL-10 production after, at least, 6 and 12 months of VIT, respectively.

Imported fire ant immunotherapy.

Imported fire ants (IFAs) permeate many areas of the United States. The IFA allergy is a significant health problem for children and adults. Stings from IFAs cause pustules, localized reactions, and anaphylaxis. There have been at least 32 deaths attributed to IFA stings. Because of the difficulty with the extraction of venom from the fire ants, whole body extracts are the only commercially available serum for immunotherapy. Fortunately, whole body extract immunotherapy given conventionally or through the rush method has proven to be efficacious and safe. It is recommended for the treatment of IFA hypersensitivity. Maintenance immunotherapy is typically given at 4-week intervals. However, more recent research has revealed that these intervals can gradually be extended up to 12 weeks similar to flying Hymenoptera venom immunotherapy. Long-term adherence to IFA immunotherapy remains an obstacle for many patients despite its potential as a life-saving treatment.

Bee venom: apitherapy and more.

Honeybees are becoming increasingly familiar to the general population due to the growing popularity of backyard and amateur beekeeping. Although bee venom produces reactions ranging from mild local irritation to life-threatening anaphylaxis, it is also used for life-saving desensitization immunotherapy in those with severe reactions to bee stings. The use of honeybee venom for immunotherapy has increased due to an enhanced interest in natural therapeutics. Recently, honeybee venom has been administered as a successful, safe, and cost-effective treatment for rheumatoid arthritis, back pain, and skin diseases. During the past two decades, studies have tested honeybee venom's efficacy for treating various skin disorders, including atopic dermatitis, wound healing, and psoriasis. We will review bee venom from multiple perspectives, including its medical applications and mechanisms for dermatological pathologies.

Presentation and management of insect bites in out-of-hours primary care: a descriptive study.

OBJECTIVES: To describe the population presenting to out-of-hours primary care with insect bites, establish their clinical management and the factors associated with antibiotic prescribing. DESIGN: An observational study using routinely collected data from a large out-of-hours database (BORD, Birmingham Out-of-hours general practice Research Database). SETTING: A large out-of-hour primary care provider in the Midlands region of England. PARTICIPANTS: All patients presenting with insect bites between July 2013 and February 2020 were included comprising 5774 encounters. OUTCOME MEASURES: This cohort was described, and a random subcohort was created for more detailed analysis which established the clinical features of the presenting insect bites. Logistic regression was used to model variables associated with antibiotic prescribing. RESULTS: Of the 5641 encounters solely due to insect bites, 67.1% (95% CI 65.8% to 68.3%) were prescribed antibiotics. General practitioners were less likely to prescribe antibiotics than advanced nurse practitioners (60.5% vs 71.1%, p<0.001) and there was a decreasing trend in antibiotic prescribing as patient deprivation increased. Pain (OR 2.13, 95% CI 1.18 to 3.86), swelling (OR 2.88, 95% CI 1.52 to 5.46) and signs of spreading (OR 3.45, 95% CI 1.54 to 7.70) were associated with an increased frequency of antibiotic prescribing. Extrapolation of the findings give an estimated incidence of insect bite consultations in England of 1.5 million annually. CONCLUSION: Two-thirds of the patients presenting to out-of-hours primary care with insect bites receive antibiotics. While some predictors of prescribing have been found, more research is required to understand the optimal use of antibiotics for this common presentation.

Modified rush venom immunotherapy in dogs with Hymenoptera hypersensitivity.

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.

Basophil Activation Test in Double-Sensitized Patients With Hymenoptera Venom Allergy: Additional Benefit of Component-Resolved Diagnostics.

BACKGROUND: In Hymenoptera venom allergy serologically double-sensitized patients, it is often difficult to identify the culprit insect for venom immunotherapy (VIT). OBJECTIVES: To evaluate if basophil activation tests (BATs) performed not only with venom extracts but additionally with single component-resolved diagnostics could differentiate between sensitized and allergic individuals and how the test results influenced the physicians' decision regarding VIT. METHODS: BATs were performed with bee and wasp venom extracts and with single components (Api m 1, Api m 10, Ves v 1, and Ves v 5) in 31 serologically double-sensitized patients. RESULTS: In 28 finally included individuals, 9 BATs were positive and 4 negative for both venoms. Fourteen of 28 BATs showed positive results for wasp venom alone. Two of 10 BATs positive for bee venom were only positive to Api m 1 and 1 of 28 BATs only to Api m 10, but not for whole bee venom extract. Five of 23 BATs positive for wasp venom were only positive for Ves v 5 but negative for wasp venom extract and Ves v 1. Finally, VIT with both insect venoms was recommended in 4 of 28 individuals, with wasp venom alone in 21 of 28 patients and with bee venom alone in 1 of 28. In 2 cases no VIT was recommended. CONCLUSIONS: BATs with Ves v 5, followed by Api m 1 and Api m 10, were helpful for the decision for VIT with the clinically relevant insect in 8 of 28 (28.6%) patients. A BAT with components should therefore be additionally carried out in cases with equivocal results.

Efficacy of Concentrated Heat for Treatment of Insect Bites: A Real-world Study.

Insect bites that cause itch, pain and swelling are very common. The use of concentrated heat for relief of these symptoms may be a promising approach; however, the scientific evidence for efficacy of hyperthermia treatment is sparse. We report here the results of a large real-world study using a randomized control group to assess the efficacy of hyperthermia on insect bites in real-world conditions, specifically considering mosquito bites as the most common type. The study was conducted in a decentralized manner via a smartphone-controlled medical device, heat it®, for treatment of insect bites and stings through application of heat. The application that controls the device was accompanied by additional questionnaires, that collected data related to insect bites, such as itch and pain intensity. Analysis of data from over 12,000 collected treated insect bites, generated by approximately 1,750 participants (42% female, 39 ± 13 years) showed significant inhibition of itch and pain for all investigated insect species (mosquitoes, horseflies, bees and wasps). Mosquito bite-induced itch was reduced by 57% within the first minute and by 81% 5-10 min after treatment, and the overall reduction in itch and pain was more pronounced than in the control group. In conclusion, the results indicate that local application of heat relieves symptoms of insect bites.