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Simple Summary: Hymenoptera venom allergy (HVA) is a potentially life-threatening systemic hypersensitivity reaction. In this study, data from 178 dogs with insect sting allergic reactions were analyzed and several risk factors for severe systemic reactions to Hymenoptera stings were identified. Furthermore, a significant number of dogs suffered subsequent systemic reactions to Hymenoptera stings, indicating that venom immunotherapy may be a valuable intervention to prevent future reactions. This study should raise the awareness of dog owners that Hymenoptera stings are associated with HVA and its possible consequences. Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA. [ABSTRACT FROM AUTHOR]

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Nina Hein,1 Conner Callaway,2 Devin Ford,2 John C Carlson1 1Ochsner Health System, Department of Allergy and Clinical Immunology, New Orleans, LA, USA; 2Tulane University, School of Medicine, New Orleans, LA, USACorrespondence: John C Carlson, Department of Pediatrics, Ochsner Health System, 1315 Jefferson Hwy, New Orleans, LA, 20121, USA, Tel +1-504-842-3900, Fax +1-504-842-5848, Email john.carlson@ochsner.org

Background: Allergen immunotherapy (AIT) is a well-established and efficient method of causative treatment for allergic rhinitis, asthma and insect venom allergy. Traditionally, a recent history of malignant neoplasm is regarded as a contraindication to AIT due to concerns that AIT might stimulate tumor growth. However, there are no data confirming that the silencing of the Th2 response affects prognosis in cancer. Objectives: The aim of this study was to investigate frequency of malignant tumors in patients undergoing AIT and the association between AIT and cancer-related mortality. Patients and Methods: A group of 2577 patients with insect venom allergy undergoing AIT in 10 Polish allergology centers was screened in the Polish National Cancer Registry. Data on cancer type, diagnosis time and patients' survival were collected and compared with the general population. Results: In the study group, 86 cases of malignancies were found in 85 patients (3.3% of the group). The most common were breast (19 cases), lung (9 cases), skin (8 cases), colon and prostate cancers (5 cases each). There were 21 cases diagnosed before AIT, 38 during and 27 after completing AIT. Laplace's crude incidence rate was 159.5/100,000/year (general population rate: 260/100,000/year). During follow-up, 13 deaths related to cancer were revealed (15% of patients with cancer). Laplace's cancer mortality rate was 37.3/100,000/year (general population rate: 136.8/100,000/year). Conclusions: Malignancy was found in patients undergoing immunotherapy less often than in the general population. Patients with cancer diagnosed during or after AIT did not show a lower survival rate, which suggests that AIT does not affect the prognosis. [ABSTRACT FROM AUTHOR]

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-ɣ) 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. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy remains a widely recognized and widely used method for the treatment of selected allergic diseases. Currently, according to the European Academy Of Allergy and Clinical Immunology (EAACI) guidelines, venom immunotherapy (VIT) may be considered for patients over 60. Nevertheless, no separate studies have confirmed the efficacy and safety of this therapy. This study aimed to evaluate the short-term effectiveness of VIT against wasp allergens in an ultra-rush protocol for older patients compared to young patients. Methods: Among the 113 patients included in this study, 51 were older than 60 years (Group A), and 62 formed the control "young group" (age range: 18–35 years). All patients were desensitized to wasp venom using the ultra-rush protocol according to Muller and aqueous solutions of vaccines containing wasp venom. A basophil activation test (Basotest, Orpegen Pharma, Germany) and intracutaneous tests with dilutions of wasp allergen and specific IgE to extract wasp venom were performed at the start and after six months of VIT. The safety of VIT was assessed on the basis of the international Mueller scale. Results: One hundred and eleven patients with confirmed wasp allergies completed six months of VIT: 51 participants over 60 years of age (Group A) and 60 young people (Group B). No systemic adverse reactions were observed during the VIT induction phase. However, large local reactions were noted in 17% of older patients and 20% of young patients at a similar level (p > 0.05). During maintenance VIT, two mild grade I systemic reactions were confirmed in young patients. These symptoms resolved spontaneously. There were no such reactions in older patients. The effectiveness of VIT was tested using BAT. There was a statistically significant reduction in CD63 reactivity in 86% of patients in Group A, and a comparable and substantial decrease in 84% of young patients in Group B. According to the BAT test, the mean reductions in the area under the curve (AUC) after six months of VIT were significant (p < 0.05) and comparable between Groups A and B: −6.52 vs. 7.21. Conclusions: VIT against wasp venom is safe and effective in short-term observation, and is comparable to that used for young patients. [ABSTRACT FROM AUTHOR]

Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA.

Introduction: Venom immunotherapy (VIT) and adrenaline autoinjector (AAI) are important therapies in venom anaphylaxis. Adherence to VIT and AAI in patients with venom allergy has been evaluated in a few studies; however, solid data are lacking. This study aimed to evaluate VIT and AAI retrieval rates in patients with venom allergy with a special focus on adherence to treatment. Adherence was compared to subcutaneous immunotherapy (SCIT) with inhalant allergens. Methods: This was a retrospective study among patients registered for allergen immunotherapy at the Allergy Center, Odense University Hospital, Denmark, from January 1, 2010, to December 31, 2014. Data on purchased immunotherapy and AAI were obtained from the Danish National Health Service Prescription Database. Multivariable logistic regression was used to analyze if allergen, age, sex, mastocytosis, and treatment site affected adherence. Results: The 3-year adherence to VIT was 92.4% (244/264) compared to 87.4% (215/246) in SCIT with inhalant allergens, and the 5-year adherence to VIT was 84.1% (222/264) compared to 74.8% (184/246) in SCIT with inhalant allergens (p = 0.045). Females treated with VIT were more adherent than males (p = 0.45 [3-year], p = 0.008 [5-year]), whereas allergen, age, mastocytosis, or treatment site did not significantly affect adherence. Only 28.6% of patients (12/42) purchased an AAI after premature termination of VIT. Conclusion: In this register-based study, we found that the 3- and 5-year adherences to VIT and SCIT with inhalant allergens are at the upper end of the spectrum hitherto reported. Patients' 5-year adherence to VIT was higher than patients' 5-year adherence to SCIT with inhalant allergens. If VIT was prematurely terminated, less than 1/3 would have purchased an AAI. [ABSTRACT FROM AUTHOR]

Introduction: Hymenoptera venom allergy is second most common cause of anaphylaxis in childhood. Currenty, the only causal therapy that can induce tolerance is venom immunotherapy (VIT). Aim: In our work, we focused on the analysis of selected clinical and laboratory characteristics in a group of pediatric patients with hymenoptera venom allergy treated with VIT. Material and methods: We created a prospective study in which we gradually included 20 pediatric patients (13 boys, 7 girls), which fulfilled indication criteria for VIT. Data were collected from 2015 to 2022. We defined the basic characteristics of the set, we focused on the overall tolerance of treatment in pediatric patients and the occurance of adverse effects during VIT administration, we also performed blood sampling to determine the dynamics of immunological laboratory parameters in precisely determined time intervals. Results: The mean age was 11 ± 4,37 years, with the mean age of firts systemic reactions after the hymenoptera sting 9,15 ± 3,58 years. Of the 20 enrolled patients, 14 were allergic to bee venom and 6 to waps venom. VIT was started at an average age of 10 ± 3,86 years, of which 2 patients started before the fifth year of life. The most frequently represented clinical manifestations of systemic reaction in our group were facial angioedema (70 %), dyspnea (65 %), urticaria (55%) and whole body pruritus (45 %). We observed the occurence of the adverse effects most often during the initial phase of administration in terms of local reactions, whereas no patient developed a systemic reaction. Spontaneus re-exposure during VIT occured in 25% of patients, whereas no patient developed a systemic reaction. During VIT we also noted dynamic changes in individual evaluated laboratory parameters with a gradual decrease of specific IgE against the extract and allergen component of hymenoptera venom and increase of specific IgG4 against the allergen extract. Conclusion: Allergy to hymenoptera venom is classified as a serious to life-threating condition, while the only possible therapy nowadays that can prevent systemic reaction and improve the patient´s quality of life is VIT. A higher effectiveness of VIT and also a lower risk of treatment failure are described in pediatric patients. Our experencie clearly proves the effectiveness and safety of VIT in childhood and at the same time confirms positive changes in laboratory parameters indicating the induction of immune tolerance. [ABSTRACT FROM AUTHOR]

Hymenoptera venom–triggered anaphylaxis (HVA) affects up to 8.9% of the general population and is the most frequent cause of anaphylaxis in adults, accounting for approximately 20% of all fatal anaphylaxis cases. Quite often, a fatal reaction is a victim's first manifestation of HVA. Mastocytosis represents one of the most important risk factors for severe HVA. We analyzed patients with documented fatal HVA for the presence of underlying clonal mast cell disorder (cMCD). Here, we report three cases of fatal HVA, with undiagnosed underlying cMCD identified by the presence of the peripheral blood and/or bone marrow KIT p.D816V missense variant postmortem. In the first case, anaphylaxis was the initial episode and was fatal. In the other two cases, both patients were treated with specific venom immunotherapy (VIT), nevertheless, one died of HVA after VIT discontinuation, and the other during VIT; both patients had cardiovascular comorbidities and were taking beta-blockers and/or ACE inhibitors. Our results point to the importance of screening all high-risk individuals for underlying cMCD using highly sensitive molecular methods for peripheral blood KIT p.D816V variant detection, including severe HVA and possibly beekeepers, for proper management and the need for lifelong VIT to prevent unnecessary deaths. Patients at the highest risk of fatal HVA, with concomitant cardiovascular and cMCD comorbidities, might not be protected from field stings even during regular VIT. Therefore, two adrenaline autoinjectors and lifelong VIT, and possibly cotreatment with omalizumab, should be considered for high-risk patients to prevent fatal HVA episodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Insect venom allergy is a potentially life-threatening allergic reaction following a bee, wasp, or ant sting. The only treatment to prevent further systemic sting reactions is venom immunotherapy (VIT), with an efficacy of up to 98% in humans. Prospective clinical data on VIT efficacy in dogs are currently lacking. In this investigation, 10 dogs with severe allergic reactions to either bee or wasp stings were treated with VIT. All dogs tolerated the therapy without adverse effects and the dogs which were re-stung tolerated the sting. This means that VIT is not only safe, but also efficacious in these patients. Furthermore, it was also shown that in addition to skin testing, two serum allergen-specific IgE tests were reliable to identify the underlying patients' insect sensitization pattern. Hymenoptera allergens are the main triggers for anaphylaxis in susceptible dogs and humans. Hymenoptera venom specific immunotherapy (VIT), the only disease-modifying treatment, has the potential to prevent future life-threatening reactions in human patients. Prospective clinical data on VIT efficacy in dogs are currently lacking. Therefore, the aim of this study was to show that VIT is not only safe but also efficacious in preventing anaphylaxis in dogs allergic to Hymenoptera. This uncontrolled prospective clinical trial included 10 client-owned dogs with a history of anaphylaxis following repeated Hymenoptera stings. The sensitization to bee and wasp allergens was demonstrated by intradermal testing (IDT) and allergen-specific IgE serology. For VIT induction (induction phase), dogs received a shortened rush immunotherapy protocol with aqueous allergens, which was then followed by monthly injections of 100 µg of alum-precipitated allergen (maintenance phase). VIT efficacy was determined by observing patients' clinical reactions to re-stings. No systemic adverse events were seen during the induction and maintenance phases. From the seven re-stung dogs, only one developed a mild angioedema at the site of the sting; the remaining dogs were asymptomatic. These results show that VIT represents a safe and effective treatment option for Hymenoptera-allergic dogs. [ABSTRACT FROM AUTHOR]

Introduction: IgE-mediated bee venom allergy can be treated with allergen-specific immunotherapy (AIT). Subcutaneous immunotherapy (SCIT) is time and cost intensive due to the repeated consultations, but the costs are justified by the high risk of potentially life-threatening allergic reactions, including anaphylaxis. However, intralymphatic immunotherapy (ILIT) offers potential to reduce treatment costs due to a significant reduction in injections and a shorter duration of therapy. Therefore, we calculated the cost savings that arise when switching from SCIT to ILIT. Methods: Treatment protocols for ILIT were based on previous ILIT studies. Treatment protocols for SCIT were based on routine treatment at the University Hospital Zurich (USZ). The treatment costs were calculated based on the internal hospital information system (KISIM). Results: The calculations revealed a potential two-fold reduction in treatment costs if ILIT is used instead of SCIT in patients with bee venom allergy. The costs could be reduced from EUR 11,612.59 with SCIT to EUR 5,942.15 with ILIT over 5 years. Conclusions: This study shows that bee venom ILIT has a cost-benefit potential for health insurances and patients, which should encourage further ILIT studies and which should be taken into account when considering future implementation of ILIT in the standard care of venom allergy. [ABSTRACT FROM AUTHOR]

Background: Allergen immunotherapy remains a widely recognized and widely used method for the treatment of selected allergic diseases. Currently, according to the European Academy Of Allergy and Clinical Immunology (EAACI) guidelines, venom immunotherapy (VIT) may be considered for patients over 60. Nevertheless, no separate studies have confirmed the efficacy and safety of this therapy. This study aimed to evaluate the short-term effectiveness of VIT against wasp allergens in an ultra-rush protocol for older patients compared to young patients. Methods: Among the 113 patients included in this study, 51 were older than 60 years (Group A), and 62 formed the control “young group” (age range: 18–35 years). All patients were desensitized to wasp venom using the ultra-rush protocol according to Muller and aqueous solutions of vaccines containing wasp venom. A basophil activation test (Basotest, Orpegen Pharma, Germany) and intracutaneous tests with dilutions of wasp allergen and specific IgE to extract wasp venom were performed at the start and after six months of VIT. The safety of VIT was assessed on the basis of the international Mueller scale. Results: One hundred and eleven patients with confirmed wasp allergies completed six months of VIT: 51 participants over 60 years of age (Group A) and 60 young people (Group B). No systemic adverse reactions were observed during the VIT induction phase. However, large local reactions were noted in 17% of older patients and 20% of young patients at a similar level (p > 0.05). During maintenance VIT, two mild grade I systemic reactions were confirmed in young patients. These symptoms resolved spontaneously. There were no such reactions in older patients. The effectiveness of VIT was tested using BAT. There was a statistically significant reduction in CD63 reactivity in 86% of patients in Group A, and a comparable and substantial decrease in 84% of young patients in Group B. According to the BAT test, the mean reductions in the area under the curve (AUC) after six months of VIT were significant (p < 0.05) and comparable between Groups A and B: −6.52 vs. 7.21. Conclusions: VIT against wasp venom is safe and effective in short-term observation, and is comparable to that used for young patients.

Jack Jumper ant venom allergy is a uniquely Australian medical issue. The stinging ant is a leading cause of insect venom allergy in south‐eastern Australia. An effective venom immunotherapy‐based treatment was successfully developed by the Tasmanian Jack Jumper Allergy Research group. This paper provides a synopsis of our 25 years' research journey in developing this evidence‐based treatment modality. [ABSTRACT FROM AUTHOR]

Neurological complications after a single Hymenoptera insect sting are very rare. The authors of this paper describe two instances of cerebral ischemic stroke that occurred immediately after a wasp sting. Two distinct pathomechanisms involved in the cases are put forward. When diagnosing such cases, it is vital to rule out the possibility of an immunoglobulin E (IgE)-dependent reaction of hypersensitivity. However, if sIgE antibodies against wasp venom extract and/or its allergenic components are detected, after hospitalization the patient should be qualified for venom immunotherapy, which is the only efficient method of protection from severe allergic reactions caused by an insect sting. Although the incidence of ischemic stroke in patients stung by insects is very low, it is important to be aware of this complication. This will allow rapid implementation of appropriate diagnostics and treatment. The optimal stroke treatment (thrombolysis or mechanical thrombectomy) in these rare cases has not yet been established.

Background: The basis for qualification for venom immunotherapy (VIT) is the fulfilment of both the clinical and immunological criteria. Diagnostic tests that confirm the immunological criterion of an IgE-mediated sensitization include skin prick tests (SPT), intradermal tests (IDT), and serum specific IgE (sIgE) for the culprit venom. Objective: This study aimed to assess the usefulness of SPT as the immunological marker in the diagnosis of insect venom sensitization in children with history of systemic reaction (SR) to insect sting evaluated by means of I-IV-grades Mueller's scale. There are no such studies in children. Methods: This cross-sectional study sample consisted of 416 children aged 3–18 years (mean age 10.6 ± 3.8), 76% males, all with the history of a systemic reaction (SR) after a Hymenoptera sting (48% of grade III/IV according to Mueller scale), diagnosed between 1999 and 2019 in the tertiary referral centre. The standard diagnostic tests were used. Specificity, sensitivity, and positive and negative predictive values were computed to assess the diagnostic properties of the clinical tests to distinguish between mild and severe SR. To assess the relative value of an individual test in predicting the qualification to VIT we incorporated the Shapley value (SV). Results: Positive SPT results were found in up to no more than 3% of children; among them less than 1% had only positive SPT and were negative for sIgE and IDT. Approximately 85% of the children had detectable venom sIgE, followed by positive IDT (75%). Almost 70% of children had positive both sIgE and IDT results. In children with grade III/IV reaction, about 80% of children had positive results of both of these tests. sIgE and IDT had sensitivity >0.80, whereas SPT had high specificity (>0.97) in differentiating between mild and severe SR. Relative value of diagnostic tests in predicting qualification to VIT varied between venoms. Bee venom IDT had higher SV (0.052) than sIgE (0.041). In contrast, wasp venom sIgE had higher SV (0.075) than IDT (0.035). Conclusion: SPTs are not an useful immunological marker of venom sensitization in children, and eliminating SPT does not result in a loss of diagnostic accuracy. Limiting diagnostics to venom sIgE and IDT would shorten the procedure and reduce costs. Future studies are needed to determine if venom sIgE as the first line diagnostic test, with IDT added only if the venom sIgE is undetectable, is an optimal diagnostic process.

Venom immunotherapy (VIT) is one of the most effective treatment methods for allergic diseases. Neurological symptoms are infrequent among systemic reactions. In this case report, the clinical and radiological features of a patient who developed acute brainstem ischemia two hours after a VIT up-dosing phase were evaluated. A 48-year-old male patient developed dyspnea, angioedema, and syncope after a honeybee sting and was diagnosed with anaphylaxis. VIT was started with the conventional schedule (depot extract). The patient went to the emergency department due to numbness in his right arm and impaired speech two hours after VIT was started during an up-dosing phase. In the neurological examination, the patient was conscious and fully cooperative. The pupillary light response, eye movements, and visual field were normal. The right nasolabial groove was faint and consistent with central facial paralysis. Brain diffusion-weight magnetic resonance imaging (MRI) detected diffusion restriction consistent with acute lacunar infarct in the pons. The patient was started on clopidogrel (75 mg/day), atorvastatin (10 mg/day), and levetiracetam (1000 mg/day) treatment. When re-evaluated 30 days later, his muscle strength deficit and speech had improved. VIT is a life-saving treatment option applied in cases of anaphylaxis as a result of bee stings. Although systemic reactions are sometimes observed during the applications, it is rare to see neurological symptoms after VIT. In patients undergoing VIT, one should be vigilant regarding ischemia development, especially during an up-dosing phase. [ABSTRACT FROM AUTHOR]

Background: Assessment of health-related quality of life (HRQoL) in patients with allergy to the venom of the Jack Jumper Ant (JJA), Myrmecia pilosula - a Hymenoptera order species native and endemic to the South-Eastern quarter of Australia. This has not previously been studied, despite an estimated population prevalence of generalised allergic symptoms as high as 3% in some areas., Objective: To validate the VQLQ HRQoL instrument - previously validated in wasp and bee venom allergic patients - for use in this specific ant venom-allergic population., Methods: The 14-item VQLQ survey instrument was administered to patients with clinical allergy to JJA venom presenting at the state treatment centre for venom-immunotherapy. Surveys were performed at different time points of the progression through visits for venom immunotherapy treatment. Cross-sectional and longitudinal validation was performed against 'expectation of outcome'(EO) questionnaire by determining correlation and agreement., Results: 271 individuals contributed survey data, comprising a median age of 52 years (3-85) with a bimodal distribution, with 25% being < 18 years of age. Internal consistency was excellent, with a Cronbach of 0.95. Cross-sectional validity was demonstrated with a positive correlation VQLQ to EO of 0.44 (p < 0.001). Performance was nearly identical when stratified into adults and children(<18 yo). Longitudinal Validity was suggested as both VQLQ and EO improved over time in both adults and children, but this only had paired correlation at two time points in adults. Bland-Altman analysis demonstrated an acceptable agreement between VQLQ and EO and no evidence of systematic bias., Conclusion: The VQLQ appears to offer similar performance of HRQoL measurement in patients suffering from JJA venom allergy, as has previously been demonstrated in other Hymenoptera species. In addition, this is the first study to demonstrate cross-sectional validity specifically in a paediatric population 3-18 years of age., (Copyright © 2024. Published by Elsevier Inc.)

Hymenoptera allergens are the main triggers for anaphylaxis in susceptible dogs and humans. Hymenoptera venom specific immunotherapy (VIT), the only disease-modifying treatment, has the potential to prevent future life-threatening reactions in human patients. Prospective clinical data on VIT efficacy in dogs are currently lacking. Therefore, the aim of this study was to show that VIT is not only safe but also efficacious in preventing anaphylaxis in dogs allergic to Hymenoptera. This uncontrolled prospective clinical trial included 10 client-owned dogs with a history of anaphylaxis following repeated Hymenoptera stings. The sensitization to bee and wasp allergens was demonstrated by intradermal testing (IDT) and allergen-specific IgE serology. For VIT induction (induction phase), dogs received a shortened rush immunotherapy protocol with aqueous allergens, which was then followed by monthly injections of 100 µg of alum-precipitated allergen (maintenance phase). VIT efficacy was determined by observing patients’ clinical reactions to re-stings. No systemic adverse events were seen during the induction and maintenance phases. From the seven re-stung dogs, only one developed a mild angioedema at the site of the sting; the remaining dogs were asymptomatic. These results show that VIT represents a safe and effective treatment option for Hymenoptera-allergic dogs.

Background/aim: Venom immunotherapy (VIT) is the most effective treatment method to prevent recurrent systemic reactions to Hymenoptera stings. In this study, the demographic characteristics of VIT patients, the success rates of VIT, the difficulties we encountered during VIT, and solutions for these difficulties in our clinic were presented. Materials and methods: We retrospectively analyzed patients with venom allergy who applied venom immunotherapy between 20132020. Data on age, gender, Hymenoptera species with the first reaction, grade of the reaction, beekeeping history, skin prick and specific IgE and component results, double sensitization, blood groups, and reactions with VIT and/or sting during built-up and maintenance periods were recorded. Results: A total of 73 patients were enrolled in the study. The median time from the first sting reaction to the application to the allergy outpatient clinic was 12 (0.5-24) months. The first sting reaction of 38 (52.1%) of the patients was with honey bees, and 24 (32.9%) were with wasps. Double positivity was present in 29 (40%) of the patients in prick results and 26 (36%) serologically. There was no correlation between the severity of first reactions and Apis Mellifera or Vespula prick diameters (p = 0.643; r = -0.056; p = 0.462; r = 0.089, respectively). High-dose VIT was administered to 4 patients. Omalizumab has been used as an alternative agent to achieve the maintenance dose in 2 patients with frequent systemic reactions during VIT. Conclusion: Most patients were able to tolerate VIT. Double positivity is one of the most common difficulties before VIT. In patients who develop systemic reactions in the VIT maintenance phase, a maintenance dose increase should be considered in the maintenance phase. Adding omalizumab does not seem to be a permanent solution in patients who develop a severe systemic reaction. [ABSTRACT FROM AUTHOR]

Neurological complications after a single Hymenoptera insect sting are very rare. The authors of this paper describe two instances of cerebral ischemic stroke that occurred immediately after a wasp sting. Two distinct pathomechanisms involved in the cases are put forward. When diagnosing such cases, it is vital to rule out the possibility of an immunoglobulin E (IgE)-dependent reaction of hypersensitivity. However, if sIgE antibodies against wasp venom extract and/or its allergenic components are detected, after hospitalization the patient should be qualified for venom immunotherapy, which is the only efficient method of protection from severe allergic reactions caused by an insect sting. Although the incidence of ischemic stroke in patients stung by insects is very low, it is important to be aware of this complication. This will allow rapid implementation of appropriate diagnostics and treatment. The optimal stroke treatment (thrombolysis or mechanical thrombectomy) in these rare cases has not yet been established. [ABSTRACT FROM AUTHOR]

Allergy to Polistes dominula (European paper wasp) venom is of particular relevance in Southern Europe, potentially becoming a threat in other regions in the near future, and can be effectively cured by venom immunotherapy (VIT). As allergen content in extracts may vary and have an impact on diagnostic and therapeutic approaches, the aim was to compare five therapeutic preparations for VIT of P. dominula venom allergy available in Spain. Products from five different suppliers were analyzed by SDS-PAGE and LC-MS/MS and compared with a reference venom sample. Three products with P. dominula venom and one product with a venom mixture of American Polistes species showed a comparable band pattern in SDS-PAGE as the reference sample and the bands of the major allergens phospholipase A1 and antigen 5 were assignable. The other product, which consists of a mixture of American Polistes species, exhibited the typical band pattern in one, but not in another sample from a second batch. All annotated P. dominula allergens were detected at comparable levels in LC-MS/MS analysis of products containing P. dominula venom. Due to a lack of genomic information on the American Polistes species, the remaining products were not analyzed by this method. The major Polistes allergens were present in comparable amounts in the majority, but not in all investigated samples of venom preparations for VIT of P. dominula venom allergy. [ABSTRACT FROM AUTHOR]

Hymenoptera venom hypersensitivity reaction affects about 3% of the general population and a higher percentage (14%–43%) in beekeepers. Bee venom immunotherapy (bVIT) is effective in reducing subsequent severe systemic reactions and has a significant beneficial effect on disease-specific quality of life in both children and adults. In patients with a history of recurrent systemic anaphylactic reaction with bee venom, successful bVIT is difficult to achieve and can often lead to withdrawal of treatment. The combination of bVIT and omalizumab is a good option for these patients. Omalizumab is a humanized nonanaphylactogenic monoclonal anti-immunoglobulin (Ig) E antibody against the Cε3 domain of IgE to reduce the allergenicity, if combined with bVIT. We describe a successful treatment with combined omalizumab and bVIT in a case of recurrent anaphylaxis by honey bee sting hypersensitivity. Herein, subcutaneous omalizumab 150 mg was started 15 days before the initiation of bVIT and subsequently once a month for 30 months along with cluster doses of bVIT till the cumulative dose of 100 μg was achieved successfully.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment's inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR), (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller's scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV0) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I–III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom. [ABSTRACT FROM AUTHOR]

Objectives Venom immunotherapy (VIT) is an effective treatment method and is addressed to patients with a history of an anaphylactic reaction to Hymenoptera stings. However, the immunological mechanisms of protection have not been explained yet. The objective of this study was to analyze neutrophils, interleukin 8 (IL-8) and interleukin 17 (IL-17) before and after the initial phase of the immunotherapy. Material and Methods Overall, 40 individuals, including 20 wasp venom sensitized and 20 bee venom sensitized patients, were included in the study. The patients had had a history of severe allergic reactions type III and IV according to Mueller’s classification. An ultra-rush VIT protocol was used in this study. The concentration of serum IL-8 and IL-17A was determined using the ELISA enzymatic method. Results The authors demonstrated a significant rise in the IL-8 level after the immunotherapy, compared to baseline (14.9 vs. 24.7, p < 0.05). The rise in the neutrophils level was also noticeable but proved to be barely out of the range of statistical significance (4.3 vs. 5.0, p = 0.06). The shift in IL-17A was negligent and not statistically significant in the paired samples t-test (1.6 vs. 1.5, p = 0.34) Conclusions Venom immunotherapy induces neutrophils and IL-8 activity after 2 days. After the desensitization, the level of IL-17A did not change. Int J Occup Med Environ Health. 2020;33(6):811–7

Allergen immunotherapy (AIT) and venom immunotherapy (VIT) are meant to work on the causes of allergies, respectively, to respiratory allergens and Hymenoptera venom, inducing tolerance to the allergens and modifying the natural history of allergy. Both types of immunotherapies have evidence of efficacy, but actually they present wide differences in both effectiveness and safety. Indeed, as far as the effectiveness of VIT is concerned, if the protection against fatal reactions to stings is considered as the primary objective, more than 40 years of clinical practice demonstrate complete success. The clinical success of AIT is measurable on the basis of reduction or disappearance of allergic symptoms. The difference between the two treatments is even higher as regards safety: AIT has been concerned in the past by a series of fatal reactions caused, which underwent a progressive decrease when it was understood that they were related to the presence of uncontrolled asthma. However, fatal reactions related to failure to recognize the presence of risk factors or administration errors are still reported. Similarly to what has been observed for efficacy, VIT has never been affected by fatal reactions to the administration of venom, and the most important risk of anaphylaxis, which is the concomitance of mastocytosis, is now identified by measuring its marker serum tryptase. To date, mechanisms of hypersensitivity reactions that differentiate respiratory allergy from Hymenoptera venom allergy have not been successfully demonstrated. We have examined the past and present literature in order to propose reasonable hypotheses about the mechanisms actually involved.

Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity., Competing Interests: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this article.

This review summarizes new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters 2023 Anaphylaxis practice parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision-making are essential to support patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services after home epinephrine administration may not be required in all cases, and patients should be engaged in shared decision-making to determine when home management may be appropriate., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Understanding the risk factors leading to severe systemic sting reactions (SSRs) is crucial for initiating venom immunotherapy (VIT) and for educating affected individuals and their families. Some of these risk factors are well established, some are no longer considered risk factors, and some remain controversial. Well-established risk factors for severe SSRs include clonal mast cell disease, high baseline serum tryptase, and advanced age. The absence of skin symptoms and the rapid onset of symptoms are indicators of severe SSRs. Recent publications indicate that antihypertensive treatment and stings in the head and neck area are not risk factors for severe SSRs. VIT is the only available treatment that can potentially prevent further anaphylactic reactions. Although rare and generally manageable, individuals undergoing VIT may experience systemic adverse events (sAEs). More sAEs are expected in patients undergoing bee VIT compared with vespid VIT. The role of elevated baseline serum tryptase as a risk factor for sAEs remains debated, but if it is a factor, the risk is increased by only about 1.5-fold. Rapid updosing protocols, depending on the specific regimen, can also be associated with more sAEs. Severe initial SSRs, antihypertensive medication, high skin test reactivity, and high specific IgE levels are not risk factors for sAEs., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Before starting venom-specific immunotherapy (VIT), systemic sting reactions to Hymenoptera venoms require allergological workup in order to prove an IgE-mediated reaction and to identify the culprit insect venom. In addition to skin tests and the determination of specific IgE antibodies, the basophil activation test (BAT) using flow cytometry has emerged as a powerful tool and sensitive marker for this purpose in recent years. BAT seems to have a better informative value in terms of clinical relevance compared to the other tests. In Hymenoptera venom allergies, BAT is particularly useful for the diagnosis of cases with unclear or contradictory history and sensitization profile. Its results are associated with adverse reactions during VIT and efficacy of VIT and therefore have a certain predictive value for side effects and treatment failure of VIT. In research, it is mainly used to characterize the allergenic components of Hymenoptera venoms. This review article focuses on these topics., Competing Interests: BE reports non-financial support from Bühlmann Laboratories outside the submitted work. KB received lecture fees from ALK, Bencard and ThermoFisher and reports non-financial support from Bühlmann Laboratories outside the submitted work. SB reports grants and personal fees from Bencard, Thermo Fisher Scientific and Allergy Therapeutics, grants from Leti Pharma, and non-financial support from Siemens Healthineers, outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest. Table 1. Overview of possible current applications of basophil activation test for Hymenoptera venom allergy. Field of applicationGroup of patientsAllergens to be used in the BATDiagnosis of Hymenoptera venom allergyPatients with negative results in routine testingWhole venom extracts, allergen componentsPatients with double sensitizationWhole venom extracts, allergen components Efficacy and tolerance of VITPatients with adverse events during VITSubmaximal concentrations of whole venom extracts in the course of VITPatients with systemic reactions after a field sting or sting challenge during VITSubmaximal concentrations of whole venom extracts in the course of VIT Characterization of allergen componentsPatients with a history or sensitization profile relevant to the scientific issueAllergen components BAT = basophil activation test; VIT = venom-specific immunotherapy., (© Dustri-Verlag Dr. K. Feistle.)

Mastocytosis or an elevated basal serum tryptase (bST) level are known risk factors for patients with insect venom allergy. We report on 3 patients with a history of severe anaphylactic insect sting reactions who underwent a detailed workup for insect venom allergy before starting venom immunotherapy. In addition to insect venom sensitization, an elevated concentration of bST (15.5, 20.8, and 23.2 µg/L) was found in all cases. There was no evidence of mastocytosis in the skin (MIS). Further testing revealed hereditary α-hypertryptasemia (HαT) in 2 patients and a D816V mutation by liquid biopsy in 1 patient, which is a minor diagnostic criterion for indolent systemic mastocytosis. Even without iliac crest puncture, causes of elevated bST can be narrowed down with minimally invasive diagnostic measures. As this has practical implications, patients with elevated bST should always undergo further work-up to determine the cause of this abnormal finding., Competing Interests: FR has participated in advisory boards for ALK-Abelló Arzneimittel GmbH, Blueprint medicines (Germany), and received payments for lectures from ALK-Abelló Arzneimittel GmbH Novartis, and ThermoFisher. MW received payments for lectures from ALK-Abelló Arzneimittel GmbH. The other authors declare that there are no conflicts of interest in connection with this case report. Table 1.Characterization of the patients. Patient123Age at time of first presentation and biological sex47 yrs, male46 yrs, female34 yrs, femaleSting history: Type of insect, severity of sting reaction (Ring and Messmer)Wasp, repeated SAR (grade III) Wasp, SAR grade III Bee, SAR grade IIIInsect venom-specific IgE concentration at first presentation kUA/L (CAP class)Bee0.91 (2)0.15 (0)6.22 (3)Vespula0.55 (1)9.81 (3)0.05 (0)Lowest venom concentration resulting in a positive skin prick testBeeNegative up to 100 µg/mLNegative up to 300 µg/mLn.d.VespulaNegative up to 100 µg/mLNegative up to 300 µg/mLn.d.Intradermal test 1 μg/mLBeeNegativen.d.n.d.VespulaPositiven.d.n.d.bST (µg/L)20.8 23.215.5 Venom dose for initial treatment200 µg bee venom and 100 µg Vespula venom100 µg Vespula venom200 µg bee venomSymptoms during VITNo SARNo SARRepeated SAR (grade II) good tolerance of dosing-up while receiving omalizumab (for 5 months) Reactions after sting provocation/field sting n.d.SAR grade II following a field sting No SAR following VIT dose increase No SARbST (µg/L) during VIT20.2 17.216.3 TPSAB1 gene mutationGermline duplication Germline triplicationAbsentKIT mutation (D816V)AbsentAbsentPresentBone densitometry findingsNormalMild osteopenian.d.SAR = systemic allergic reaction; n.d. = not done; bST = basal serum tryptase; VIT = venom immunotherapy. Table 2.Criteria for the diagnosis of systemic mastocytosis [6]. Major criterionMultifocal dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organsMinor criteria≥ 25% of all mast cells in sections of bone marrow or other extracutaneous organs are atypical, e.g., spindle-shapedKIT-activating KIT point mutation at codon 816 in the bone marrow or another extracutaneous organCD2 and/or CD25 and/or CD30 expression on mast cellsBasal tryptase in serum > 20 µg/LIf at least 1 major and 1 minor criterion or 3 minor criteria are met, the diagnosis of a systemic mastocytosis is confirmed., (© Dustri-Verlag Dr. K. Feistle.)

Summary: Background. In diagnosing insect venom allergy and making immunotherapy decisions, clinical history, skin tests, and specific serum IgE levels are commonly utilized. This study aims to emphasize the clinical significance of using the basophil activation test in accurately identifying sensitivities in individuals with insect venom allergy and to compare its effectiveness with other testing methods. Methods. This study included a total of 43 patients, who experienced at least one systemic allergic reaction following insect stings and were deemed suitable for immunotherapy.Basophil activation test, specific serum IgE levels, and skin prick test results utilized in making immunotherapy treatment decisions were recorded. Results. Our study determined that the overall clinical sensitivities of the basophil activation test (BAT), specific serum IgE (spIgE), and skin prick test (SPT) for apis mellifera were 95.5%, 95.7%, and 48.4% respectively, while for vespula vulgaris, they were 83.3%, 100%, and 33.3%. Based on these results, the prediction of systemic reactions to bee stings is ordered as spIgE > BAT > SPT. Additionally, early-stage skin prick tests showed a sensitivity of 67% and specificity of 50% at a cut-off value of 1.5 mm, and 33% sensitivity and 83% specificity at 2.5 mm. Conclusions. This study demonstrates that the basophil activation test (BAT) can provide a high positive predictive value in immunotherapy treatment decisions and offer significant insights in clinical practices.

Stinging ants represent a wide range of over 200 different species across the world, of which Solenopsis, Myrmecia, Pogonomyrmex, and Brachyponera genera account for a substantial economic and healthcare burden. S. invicta (red imported fire ant [IFA]) and M. pilosula (jack jumper ant [JJA]) are 2 species of high clinical importance, known to cause anaphylaxis in humans, with numerous reported fatalities. Diagnostic testing should be performed in patients with a history of a systemic reaction with skin testing and/or in vitro specific immunoglobulin E (IgE) testing. In vitro testing is commercially available for IFA through whole-body extract specific IgE and JJA venom-specific IgE, but not widely available for other stinging ant species. Commercial venom component testing for IFA and JJA is currently not available. Patients with a clinical history and positive specific IgE testing should undergo treatment with specific immunotherapy, which is currently available for IFA and JJA. Buildup may be performed using conventional, semi-rush, rush, or ultra-rush schedules with similar risk profiles for IFA. Optimal duration for whole=body extract immunotherapy for IFA and specific JJA venom immunotherapy is not well studied, but generally recommended for at least 3 to 5 years. Sting challenges are used in research settings, primarily to assess treatment efficacy of immunotherapy., (Published by Elsevier Inc.)

Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLRs based on the relatively low risk of anaphylaxis, but this is debated in this review. On the pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLRs; and VIT is generally safe and highly effective. On the con side: LLRs are benign, stings occur infrequently, VIT has significant cost, systemic reactions occur more often to VIT than to stings in patients with LLRs, and Food and Drug Administration approval and published guidelines do not recommend VIT for LLRs. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mastocytosis is a risk factor for Hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in patients with HVA and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derive from European single-center studies, and the prevalence of HVA with and without mastocytosis in the United States is unknown. We sought to determine the prevalence of HVA and mastocytosis in the United States using an insurance claims database and evaluate the impact of mastocytosis on VIT in patients with HVA in a US cohort. The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Furthermore, a retrospective study of 161 patients undergoing VIT between 2015 and 2018 at the University of Michigan was conducted. In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among patients with HVA versus the general population. In the U-M cohort, 2.6% of patients with VIT had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions. We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US patients with HVA, though at lower rates than previously reported. In patients with VIT there was no correlation between tryptase level and reaction severity. [ABSTRACT FROM AUTHOR]

Hymenoptera stings are generally well-tolerated and usually cause limited local reactions, characterized by self-resolving erythema and edema associated with pain. However, Hymenoptera stings can induce immediate and delayed hypersensitivity reactions. In addition to these manifestations, unusual reactions to Hymenoptera stings have been reported. The latter are defined as unusual because of their atypical characteristics. They may differ from classical hypersensitivity reactions due to the stings' particular localization and the unusual involvement of one or more specific organs. Although unusual reactions to Hymenoptera stings are infrequent, it is essential for clinicians to know the possible related clinical manifestations. Here, we review the available literature and propose a diagnostic and management algorithm. At present, there are no defined guidelines for most of the unusual reactions to Hymenoptera stings, which should be managed in a tailored way according to the specifical clinical manifestations presented by the patients. Further studies are needed to better define these conditions and the underlying pathogenetic mechanisms to improve the diagnostic and therapeutic approach.

Hymenoptera venom hypersensitivity reaction affects about 3% of the general population and a higher percentage (14%-43%) in beekeepers. Bee venom immunotherapy (bVIT) is effective in reducing subsequent severe systemic reactions and has a significant beneficial effect on disease-specific quality of life in both children and adults. In patients with a history of recurrent systemic anaphylactic reaction with bee venom, successful bVIT is difficult to achieve and can often lead to withdrawal of treatment. The combination of bVIT and omalizumab is a good option for these patients. Omalizumab is a humanized nonanaphylactogenic monoclonal anti-immunoglobulin (Ig) E antibody against the Cε3 domain of IgE to reduce the allergenicity, if combined with bVIT. We describe a successful treatment with combined omalizumab and bVIT in a case of recurrent anaphylaxis by honey bee sting hypersensitivity. Herein, subcutaneous omalizumab 150 mg was started 15 days before the initiation of bVIT and subsequently once a month for 30 months along with cluster doses of bVIT till the cumulative dose of 100 μg was achieved successfully. [ABSTRACT FROM AUTHOR]

Background: There is controversy whether taking β‐blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β‐blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β‐blockers, 11.9% ACEI, 5.0% β‐blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p = 0.25). The severity of the initial sting reaction was not affected by the intake of β‐blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p = 0.29). In total, 210 (17.7%) patients were re‐stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β‐blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β‐blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629). [ABSTRACT FROM AUTHOR]

Abstract Hymenoptera stings mostly cause acute urticaria but we describe a case of CU after wasp stings which remitted during venom immunotherapy. IgE‐mechanisms have not been fully clarified in CU, except for isolated circumstances. In our case immunotherapy has played a positive role reducing immune cells reactivity and improving urticaria symptoms.

Hymenoptera stings mostly cause acute urticaria but we describe a case of CU after wasp stings which remitted during venom immunotherapy. IgE‐mechanisms have not been fully clarified in CU, except for isolated circumstances. In our case immunotherapy has played a positive role reducing immune cells reactivity and improving urticaria symptoms. [ABSTRACT FROM AUTHOR]