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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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Disclosures Dr Petrov has served on the advisory board for Genentech, CSL Behring, and Blueprint Medicines. The other authors have no conflicts of interest to declare., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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

Background: 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., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., Competing Interests: Disclosure The author has no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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

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.

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., Competing Interests: Disclosures The authors have no conflicts of interest to report., (Published by Elsevier Inc.)

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.

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.

In the past decade, there has been a global resurgence of bed bug infestations, especially in developed countries. Proper awareness and identification of bed bug infestations are essential to guide treatment and eradication. The purpose of this article is to familiarize physicians with bed bug bites so that they can effectively diagnose, treat, and address questions about bed bug bites and infestations. Bed bug bites are often painless. Typical reactions include pruritic, erythematous maculopapules occurring in clusters or in a linear or curvilinear distribution in exposed areas of the body. A small red punctum may be visualized at the center of the bite mark. Lesions that appear three in a row and papules on the upper eyelid associated with erythema and edema are highly suggestive of bites from bed bugs. Exaggerated local reactions such as vesicles, urticarial wheals, urticarial perilesional plaques, diffuse urticaria, bullae, and nodules may occur in previously sensitized individuals. Reactions to bed bug bites are self-limited. As such, treatment is mainly symptomatic. Topical pramoxine and oral antihistamines can be used to alleviate pruritus. Topical corticosteroids can be used for significant eruptions to control inflammation and pruritus, and to hasten resolution of the lesions. Integrated pest management, an approach for the eradication of bed bugs, includes monitoring devices (active monitors include the use of heat or carbon dioxide attractants and passive monitors include the use of sticky pads for trapping), and judicious use of nonchemical and chemical treatments known to be effective. Nonchemical interventions include keeping affected areas clean and free of clutter, vacuuming, washing linens with hot water, caulking wall holes and cracks where bugs can hide, proper disposal of highly infested items, and placement of bed bug traps/interceptors at the base of beds and furniture. Chemical interventions involve the use of insecticides such as synthetic pyrethroids, silicates, insect growth disruptors, carbamates, organophosphates, neonicotinoids, diethyl-meta-toluamide, chlorfenapyr, fipronil and plant essential oils. Insecticides should be used with caution to prevent over-exposure and toxicity (in particular, cardiovascular and neurologic toxicity), especially if there are young children around. It is important to note that multiple mechanisms of insecticide resistance exist and as such, chemical treatment should only be undertaken by trained professionals who understand the current literature on resistance. Both nonchemical and chemical technologies should be combined for optimal results. Bed bug infestations may cause diverse dermal reactions, stigmatization, poor self-esteem, emotional stress, anxiety, significant adverse effect on quality of life, and substantial socioeconomic burden to society. As such, their rapid detection and eradication are of paramount importance. Consultation with a professional exterminator is recommended to fully eradicate an infestation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

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.

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.

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., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Summary: Vespa velutina nigrithorax (VVN), commonly known as Asian wasp because endemic in Asia, represents an alien species in Europe. VVN can induce allergic reactions similar to those caused by other Hymenoptera and death after VVN stings, presumably due to fatal allergic reactions, has been reported. In the treatment of Hymenoptera venom hypersensitivity, specific immunotherapy (VIT) is highly effective. Currently, there is no specific available VIT for VVN, so it is relevant to assess if patients stung by VVN and showing allergic reactions could be treated with the Hymenoptera commercially available extracts Vespa crabro (VC) and Vespula spp (Vspp) or if they need the specific VIT with VVN venom extract. Methods. Four patients with a clinical history of systemic reactions after VVN sting were evaluated. Serum specific IgE were assayed quantitatively with an automated fluoro-enzyme immunoassay ImmunoCAP™ Specific IgE by Phadia™ 1000 System (Thermo Fisher Scientific, Uppsala, Sweden) for VC, Vspp and VVN. Cap inhibition assays were performed incubating serum samples with 200 μl of each venom at increasing concentrations and subsequently specific IgE against each of the venoms were determined in the samples by Phadia™ 250 System (Thermo Fisher Scientific, Uppsala, Sweden). Results. Our results suggested that both Vspp and VC venoms were able to inhibit the specific IgE for VVN, although the VC compared to the Vspp venom showed a higher inhibition. Conclusions. Our inhibition studies suggested that VIT with VC venom, nowadays when there is not specific available VIT for VVN, may be more effective than Vspp VIT in patients with VVN sting reactions.

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.

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.)

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., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Imported fire ant (IFA) whole-body extract subcutaneous immunotherapy (IT) is a safe and effective treatment for IFA hypersensitivity, with a recommended length of treatment of 3 to 5 years., Objective: To evaluate long-term IFA IT adherence in patients with IFA allergy living in an endemic area., Methods: During 2007 to 2014, patients with IFA-sting systemic reactions and a recommendation to start IFA IT were prospectively enrolled in this study. Subjects were contacted annually for interval IT adherence. Institutional review board approval was obtained., Results: A total of 87 subjects, ages 2 to 64 years, with a recommendation to initiate IFA IT, were enrolled. Subjects were predominantly adult (76%) and female (55%), and 30% had asthma. Of these patients, 77 (89%) initiated treatment within 1 year of recommendation; 18 (23%) adhered to a 3-year course; and 10 (13%) adhered to a 5-year course. At 3 years, there were no significant differences in adherence between male and female subjects (28% vs 19%, P = .33), children and adults (25% vs 22%, P = .79), or those with or without asthma (30% vs 20%, P = .31). Adherence in subjects with mild initial reactions was lower than in subjects with moderate-to-severe reactions (0% vs 25%, P = .05) at 3 years only. Conventional buildup and concurrent flying Hymenoptera venom immunotherapy were predictive of adherence. Reasons for discontinuation were relocation to a nonendemic area (29%) and inconvenience (27%)., Conclusion: This study showed poor long-term adherence to IFA IT at 3 and 5 years. Initial sting severity, buildup protocol, and concurrent flying Hymenoptera venom immunotherapy were predictors for long-term IT adherence., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 S. Karger AG, Basel.)

Objectives: The aims of this study, for the first time in the literature, are to evaluate the symptoms, clinical course, and treatment management of penile bee stings in children and to discuss whether bee stings can be evaluated within the scope of summer penile syndrome., Methods: Records of all pediatric patients presented to the emergency department of our hospital from June 2020 to October 2021 due to bee sting of penis were reviewed. Only patients with isolated penile bee stings were included in the study. Patients were evaluated in terms of the age at presentation, time of occurrence, symptoms, and treatment modality., Results: There were 10 patients treated for penile bee sting. Patients ranged in age from 3 to 7 years (mean, 4.2 years). The most common complaints of the patients at presentation were pain (100%), swelling (100%), and dysuria (70%). Three of the patients were unable to void. The gauze moistened with warm saline was applied to the penis of these patients who developed glob, and all of these patients urinated after the warm application. Three of the patients had progressive erythema on the penile skin. These patients were admitted to the pediatric surgery department to monitor whether skin necrosis would develop. In all patients, the erythema regressed significantly within 48 hours and regained its completely normal appearance at the end of 72 hours., Conclusions: The probability of the development of serious local reactions and urological problems in penile bee stings is low. Oral nonsteroidal anti-inflammatory drug and warm, wet dressing are usually sufficient to treat local reactions. Penile bee stings may be evaluated within the scope of summer penile syndrome because their symptoms, clinical findings, and treatments are almost similar., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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

Venom immunotherapy (VIT) with Hymenoptera venom extracts is highly effective in preventing large local, systemic allergic, and anaphylactic reactions to insect stings. VIT is not required for patients with cutaneous systemic or large local allergic reactions to stings because it is uncommon for reactions to become more severe. The clinical history, with confirmatory skin or serum tests for venom IgE, can clarify the risk for future anaphylaxis and the need for VIT. For initial treatment, rush regimens are recommended because they have the same or less risk of systemic reactions than slower traditional regimens. VIT is relatively safe with a low incidence of systemic reactions. Injection-site reactions can be bothersome but do not predict systemic reactions to venom injections. Patients who need VIT should be screened for baseline serum tryptase and possible underlying mast cell disorders. VIT can be discontinued after five years in most patients, but those with known high-risk factors should continue VIT indefinitely.

Inducing tolerance in Hymenoptera-allergic patients, bee venom immunotherapy (BVIT) is a widely accepted method to treat severe allergy to bee stings. In order to increase the existing knowledge on the underlying immunological mechanisms and look for possible biomarkers predictive of efficacy, a group of 20 bee-venom-allergic patients (AG) were thoroughly examined during their first year of BVIT. In addition, the results of treated patients with those of an untreated group of 20 tolerant beekeepers (TG) who had previously shown a firm suppressor-regulatory profile were compared. Tolerance in AG patients was invariably associated with a significant regulatory response characterised by the expansion of Helios - subpopulation and increased IL-10, specific IgG4 (sIgG4), and kynurenine levels. Although specific IgE (sIgE) levels increased transiently, surprisingly, the T helper type 2 (Th2) population and IL-4 levels rose significantly after one year of immunotherapy. Thus, the picture of two parallel phenomena emerges: a tolerogenic response and an allergenic one. Comparing these results with those obtained from the TG, different immunological mechanisms appear to govern natural and acquired tolerance to immunotherapy. Of particular interest, the kynurenine levels and T regulatory (Treg) Helios - population could be proposed as new biomarkers of response to BVIT.

Background: Diagnosis of patients with hymenoptera venom hypersensitivity consists of elucidating clinical symptoms suggestive of systemic reaction (SR) and then confirmation of sensitization via intradermal skin testing (IDST) first and serum IgE assays such as ImmunoCAP (ICAP) as a complementary modality of diagnosis., Objective: Determine the concordance between ICAP and IDST in patients with a clinical history suggestive of hymenoptera venom SR. Determine whether venom immunotherapy would change on the basis of IDST versus ICAP results., Methods: A prospective diagnostic study was designed to test the concordance between IDST and ICAP venom testing in the diagnosis of hymenoptera venom hypersensitivity. This study entailed testing both IDST and ICAP for 5 hymenoptera venoms (honey bee, wasp, yellow jacket, yellow hornet, and white-faced hornet) in both a case group with SR to hymenoptera venom (N = 70) and a control group without SR (N = 51)., Results: Significant discordance was observed between positive IDST and ICAP results for any of the 5 hymenoptera venoms (McNemar test, P = .001). In the case group, there was significant discordance for wasp (P < .0001), yellow jacket (P = .002), and white-faced hornet (P = .02). More than 47% of the case patients would have different venom immunotherapy prescriptions if ICAP and IDST had been performed during initial diagnosis versus IDST alone., Conclusions: Our study shows significant discordance between IDST and ICAP; however, they are complementary. On the basis of our data, we propose ICAP testing first followed by IDST for ICAP-negative venoms as an alternative and efficient diagnostic strategy., (Published by Elsevier Inc.)

Objective: The objective of this study was to list the social vespids occurring in Spain, determine their presence in each region, and correlate the data with the vespids responsible for allergic reactions and their progression over time., Methods: Insects distribution data were collected in two phases: from the southern half of Spain (2008-2012), and from the northern half of Spain (2016-2019). Data for the vespids were collected from the prescriptions of Hymenoptera venom immunotherapy (HVIT) at six Spanish hospitals in the years 2009 and 2019., Results: Polistes dominula and Vespula germanica were the most widely distributed species. Vespa velutina was found to be present in a large part of northern Spain. During the 10 year period, the prescriptions of vespid VIT increased by 42.63%. The north of Spain saw a 3.61 fold greater predominance of prescriptions for Vespula (to some extent influenced by Vespa velutina allergy) whereas in central and southern Spain, there was a 3.97 fold greater predominance of prescriptions for Polistes ., Conclusions: It is the first study that compares the vespid distribution maps with VIT prescription. A noteworthy finding is the wide presence of Polistes dominula and Vespula germanica in Spain and the appearance of Vespa velutina allergy in the northern part of the country. Data of HVIT prescriptions reflect inter-regional variability with the predominance of Vespula (due to Vespula and Vespa ) in the north and that of Polistes in the center and south of Spain.

Objective: To describe clinical effects and outcomes of hymenopteran stings and to explore the non-laboratory factors associated with adverse clinical outcomes, a composite outcome including death, respiratory failure requiring intubation, acute kidney injury (AKI) requiring dialysis and hypotension requiring vasopressor use., Methods: A retrospective cross-sectional study was performed at the Ramathibodi Poison Center, a poison centre of a tertiary care hospital in Thailand. All cases of hymenopteran sting consultations from January 2015 to June 2019 were consecutively enrolled, and charts were reviewed. Demographics, initial clinical characteristics and outcomes were collected. Factors associated with adverse clinical outcome were explored., Results: One hundred and fourteen hymenopteran stings cases (wasp 48%, bee 33%, hornet 14% and carpenter bee 8.8%) were included (median age, 36.5 years (interquartile range 9-55); male 63%). The prevalence of adverse clinical outcomes was 12.3% (95%CI 6.88-12.8). At initial presentation, 100% of cases had local skin reactions, 11.4% were clinical anaphylaxis, and 8% had red urine. Adverse clinical outcomes included death ( n  = 10), respiratory failure requiring intubation ( n  = 9), AKI requiring dialysis ( n  = 6) and hypotension requiring vasopressor use ( n  = 2). None of the patients with carpenter bee or hornet stings developed adverse clinical outcomes. In univariable analysis, urticaria, wheezing, red urine, wasp sting and sting number > 10 were significantly associated with adverse clinical outcomes. In multivariable analysis, red urine (adjusted OR 11.1 (95% CI 1.57-216)), wheezing (adjusted OR 16.7 (95% CI 1.43-402)) and a number of stings > 10 (adjusted OR 21.5 (95% CI2.13-2557)) were significant., Conclusions: Adverse clinical outcomes in hymenopteran stings were not uncommon among cases inquiring to a national Thai poison centre. At initial presentation, red urine, wheezing and a number stings >10 were significantly associated with adverse clinical outcomes. Larger epidemiologic studies are required to confirm these associations.

Background/aim: This study mainly aimed to explore the therapeutic effects of 3 renal replacement therapy (RRT) modalities on acute kidney injury (AKI) caused by wasp stings., Methods: A retrospective study from September 2016 to December 2019 was conducted. Thirty-one patients with AKIs caused by wasp sting were selected and divided into 3 groups according to the initial RRT modality received, namely, (1) the intermittent hemodialysis combined with hemoperfusion (IHD + HP) group, (2) the continuous veno-venous hemodiafiltration (CVVHDF) group, and (3) the CVVHDF combined with HP (CVVHDF + HP) group. The laboratory results were measured and analyzed before treatment on the 3rd, 7th, and 14th days of treatment. The renal function outcomes and survival of the patients were investigated at 3 months follow-up., Results: The laboratory results of enzyme measures and inflammatory indicators in wasp sting patients increased significantly in the early stage and 3 RRT modalities were effective in reducing these indicators. In addition, continuous RRT modality (CVVHDF and CVVHDF + HP) showed better clearance of myoglobin than IHD + HP. The serum creatinine levels of patients in the 3 groups did not recover to baseline within 14 days after beginning treatment. Nevertheless, the CVVHDF + HP group was better than the CVVHDF group, and CVVHDF was better than the IHD + HP group on the 3rd day. The interleukin (IL)-6 and IL-10 levels in CVVHDF + HP and IHD + HP groups were obviously lower than those in the CVVHDF group on the 3rd day. In the follow-up study, the recovery rate of renal function in CVVHDF and CVVHDF + HP groups was significantly better than that in the IHD + HP group., Conclusion: Early RRT was effective in the treatment of patients with A KI caused by wasp sting. CVVHDF + HP and CVVHDF modalities were better than the IHD + HP group in venom clearance and renal function recovery., (© 2021 S. Karger AG, Basel.)

Caterpillar envenomation is a worldwide problem, with manifestations ranging from dermatitis to iridocyclitis and a fatal hemorrhagic diathesis. This article focuses on the diagnosis and management of dermatoses related to caterpillars.

Introduction: Hymenoptera stings usually have a multitude of presentations from very subtle to life-threatening conditions. Various cardiac manifestations including Kounis syndrome often get missed due to lack of suspicion. The aim of the study was to describe the clinical profile of the cardiac etiologies associated with hymenoptera stings and review literature with focus on diagnosis and treatment strategies., Methodology: A retrospective chart analysis was performed including all adult patients who had a hymenoptera sting during a two-year window (October 2018 - October 2020). Of these, patients with cardiac features were enrolled. A structured case record form was used to capture information like basic demography, clinical profile, and outcomes., Results: Thirteen cases presented with hymenoptera stings of which six cases had cardiac presentation and were considered. The most common presentations were breathlessness and generalised itching with only one patient complaining of chest pain. All patients(with available data) had ECG changes suggestive of ischemia and associated raised troponin levels with 2D echo changes. The diagnoses considered included Kounis syndrome, hypersensitivity myocarditis, and Takotsubo cardiomyopathy. Patients were managed conservatively with one patient undergoing a coronary angiography. All patients were stable at discharge., Conclusion: Cardiac manifestations with hymenoptera stings although rare may complicate diagnosis and treatment.It should be borne in mind during assessment and standardised guidelines should be developed for ED treatment such as the one recommended in this study., Competing Interests: Declaration of Competing Interest No conflicts to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

As a tribute to Butantan Institute in its 120th anniversary, this review describes some of the scientific research efforts carried out in the study of Lonomia envenoming in Brazil, a country where accidents with caterpillars reach over 42,000 individuals per year (especially in South and Southeast Brazil). Thus, the promising data regarding the studies with Lonomia 's toxins contributed to the creation of new research centers specialized in toxinology based at Butantan Institute, as well as to the production of the antilonomic serum (ALS), actions which are in line with the Butantan Institute mission "to research, develop, manufacture, and provide products and services for the health of the population". In addition, the study of the components of the Lonomia obliqua bristle extract led to the discovery of new molecules with peculiar properties, opening a field of knowledge that could lead to the development and innovation of new drugs aimed at cell regeneration and inflammatory diseases.

Anaphylaxis is a suddenly occurring potentially life-threatening systemic allergic reaction. In childhood, food allergens play a major role but insect stings and drugs are also potential triggers. The symptoms appear in minutes up to few hours on the skin, airways, gastrointestinal tract and/or the cardiovascular system. Intramuscular adrenaline is the drug of first choice due to its rapid effectiveness and its low side effect potential. A detailed patient history and the determination of potential IgE antibodies must be carried out to identify the triggers. The register for anaphylaxis has improved knowledge on epidemiology. An education in anaphylaxis is useful for every patient as well as parents and caregivers. Allergen-specific immunotherapy is currently the only causal treatment option; however, at the present time it is only available for insect bites and peanut allergy., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)