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.

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.

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy.

Skin Tests versus Serology: Specific IgE May Suffice for Diagnosis of Vespid Venom Allergy and Follow-Up of Allergen Immunotherapy.

INTRODUCTION: In adults, allergic reactions to insect stings are among the most frequent causes of anaphylaxis, a potentially life-threatening condition. Recurrent anaphylaxis following vespid stings may be prevented by allergen immunotherapy (AIT). The aim of this study was to evaluate the benefit of measuring venom-induced wheal area in intracutaneous skin tests (ICT), in comparison to various serological and clinical parameters, for the diagnosis of severe vespid venom allergy and during follow-up of AIT. METHODS: We conducted a monocentric, retrospective evaluation of 170 patients undergoing AIT against vespid venoms. We scanned ICT wheals at baseline and at three time points after AIT initiation and measured wheal area using objective data analysis software. RESULTS: We found that ICT histamine-induced and venom-induced wheal areas did not correlate. In addition, the venom-induced wheal area was independent from the minimal venom concentration required to elicit a wheal in an ICT and all other parameters. No correlation was found between wheal area and the severity of anaphylaxis. Wheal area standardized to the application of 0.1 µg/mL venom inversely correlated with anaphylaxis severity and positively correlated with venom-specific IgE levels. During AIT, mean areas of venom-induced wheals did not change. In contrast, venom-specific IgG and IgG4 levels, and the minimal venom concentration required to induce a positive ICT result increased, while the venom wheal area standardized to 0.1 µg/mL venom application and specific IgE levels decreased over time. CONCLUSION: Wheal area evaluation did not provide additional information over specific IgE analysis. We therefore recommend that ICTs are used only as a secondary measure for confirming serological test results.

Venom Hypersensitivity.

Stinging insects are a frequent cause of local and systemic hypersensitivity reactions, including anaphylaxis. For those with a history of life-threatening anaphylaxis, venom immunotherapy is effective, safe, and can be life-saving. Arachnids are a much less common source of envenomation through bites or stings and are less likely to cause a hypersensitivity reaction. However, recognizing the clinical manifestations when they do present is important for accurate diagnosis and treatment, and, when indicated, consideration of other diagnoses.

Wings and stings: Hymenoptera on vacation.

Traveling to different regions, one might encounter a species to which they have a known allergy, or other related and unrelated species. A first-time systemic reaction can occur while on vacation, even in those with previous asymptomatic stings. Three main groups of Hymenoptera are responsible for most sting reactions. Honey bee species are virtually identical around the world. Among social wasps (family Vespidae), the yellowjacket (genus Vespula and Dolichovespula) and hornet (genus Vespa) venoms have almost complete cross-reactivity, whereas paper wasp (genus Polistes) venoms show only partial cross-reactivity with other vespid venoms. Venom immunotherapy (VIT) confers 80% to 95% protection against related insects, though isolated species of paper wasps and yellowjackets exist in every country that may be distinct from the ones at home. Those allergic to imported fire ants (genus Solenopsis) in the United States should not react to other ant species around the world. Stinging ants belong to several unrelated subfamilies in different geographic regions, which do not have cross-reactive venom. The chances of encountering specific species of Hymenoptera at a traveler's destination vary by location, planned activities, and season. In this article, we discuss special considerations for traveling, including distribution of stinging insects around the world, risk factors for more severe reactions, ways to prepare for a trip, and when allergist examination or treatment may be helpful before travel.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Extracorporeal membrane oxygenation support in refractory anaphylactic shock after bee stings: A case report.

An allergy to insect stings is one of the most frequent causes of anaphylactic reactions. Such reactions can be fatal, even on the first reaction, although it very rarely happens. The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) in refractory anaphylactic shock was previously described. We report a case of a 31-year-old female who presented with refractory anaphylactic shock after bee stings without the presence of cutaneous manifestations other than the rashes in her neck. The toxic component of bee venom and systemic allergic response plays a vital role in pathophysiology. She did not respond to conventional advanced life support, but following urgent VA ECMO, she survived neurologically intact. Despite an uncommon indication for anaphylaxis, ECMO support may be possible and effective in patients with refractory shock.