Hymenoptera Venom Research Articles

The Lights and the Shadows of Controlled Sting Challenge With Hymenoptera.

Hymenoptera venom immunotherapy (VIT) is effective for protecting individuals with systemic allergic reactions caused by Hymenoptera stings. The need for a tool that shows the degree of protection afforded by VIT and the lack of useful biomarkers have made the sting challenge test (SCT) the gold standard for this disorder, although its use has both lights and shadows. SCT with Hymenoptera involves causing a real sting in a patient diagnosed with allergy to the venom of the stinging insect and who is undergoing treatment with specific immunotherapy. In Spain, SCT is included in the list of services offered by some hospitals and forms part of their daily clinical practice. This review aims to analyze the strengths and weaknesses of this test and to describe the standardized procedure and necessary resources, based on the experience of a group of Spanish experts and a review of the literature.

Long-term adherence to imported fire ant subcutaneous immunotherapy

BackgroundImported 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. ObjectiveTo evaluate long-term IFA IT adherence in patients with IFA allergy living in an endemic area. MethodsDuring 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. ResultsA 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%). ConclusionThis 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.

Adverse reactions in venom immunotherapy protocols: conventional versus ultra-rush

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

Diagnosis of Hymenoptera Venom Allergy: State of the Art, Challenges, and Perspectives.

Hymenoptera venom allergy is the most common cause of anaphylaxis in adults and the second-most frequent in children. The proper diagnosis of this life-threatening allergy remains a challenge. This review focuses on the current knowledge regarding diagnostics of Hymenoptera venom allergy. The paper includes a brief description of the representatives of Hymenoptera order and the composition of their venoms. Then, diagnostic tests for allergy to Hymenoptera venom are described. Common diagnostic problems, especially double positivity in tests for IgE antibodies specific to honeybee and wasp venom, are also discussed. Special attention is paid to the search for new diagnostic capabilities using modern methodologies. Multidimensional molecular analysis offers an opportunity to characterize changes in body fluids associated with Hymenoptera venom allergy and yields a unique insight into the cell status. Despite recent developments in the diagnostics of Hymenoptera venom allergy, new testing methodologies are still needed to answer questions and doubts we have.

Multisite evaluation of fire ant venom immunotherapy safety and efficacy.

Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings. Our aims were to determine the baseline rates of IFA sensitization in subjects, describe IFA VIT prescribing patterns across the military health system (MHS), and retrospectively evaluate the safety and efficacy of IFA VIT. We prospectively compared IFA sensitization in participants with and without an SR to flying Hymenoptera venom. Separately, IFA VIT prescription records were extracted from a centralized repository, and rates were described across the MHS. Additionally, we retrospectively reviewed the clinical course of patients being treated with IFA VIT at 11 military treatment facilities. The invitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%. Sensitization rates did not differ statistically between the subjects with or without an SR to flying Hymenoptera venom. We found that 60.9% of all MHS IFA VIT prescriptions (491 of 806) were from the 11 facilities in this study. We retrospectively identified 137 subjects actively undergoing IFA VIT. Among the subjects actively undergoing IFA VIT, 28 reported an SR to IFA venom and repeat stings by IFAs after reaching VIT maintenance, and 85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT. This study's results align with those of prior IFA sensitization reports. Asubstantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events.

Incidence of Fatal Anaphylaxis: A Systematic Review of Observational Studies.

Fatal anaphylaxis is very rare, with an incidence ranging from 0.5 to 1 deaths per million person-years. Based on a systematic review, we aimed to explain differences in the reported incidence of fatal anaphylaxis based on the methodological and demographic factors addressed in the various studies. We searched PubMed/MEDLINE, EMBASE, and the Web of Science for relevant retrospective and prospective cohort studies and registry studies that had assessed the anaphylaxis mortality rate for the population of a country or for an administrative region. The research strategy was based on combining the term "anaphylaxis" with "death", "study design", and "main outcomes" (incidence). A total of 46 studies met the study criteria and included 16,541 deaths. The range of the anaphylaxis mortality rate for all causes of anaphylaxis was 0.002-2.51 deaths per million person-years. Fatal anaphylaxis due to food (range 0.002-0.29) was rarer than deaths due to drugs (range 0.004-0.56) or Hymenoptera venom (range 0.02-0.61). The frequency of deaths due to anaphylaxis by drugs increased during the study period (IRR per year, 1.02; 95%CI, 1.00-1.04). We detected considerable heterogeneity in almost all of the meta-analyses carried out. The incidence of fatal anaphylaxis is very low and differs according to the various subgroups analyzed. The studies were very heterogeneous. Fatal anaphylaxis due to food seems to be less common than fatal anaphylaxis due to drugs or Hymenoptera venom.

Standardized allergen extracts for allergen immunotherapy.

Nineteen U.S. allergen extracts were standardized by the U.S. Food and Drug Administration (FDA) between 1987 and 1998, including of two house-dust mites, short ragweed, cat hair and cat pelt, seven temperate and one southern grass, and six Hymenoptera venom preparations. Relevant literature was reviewed. For each allergen, a "representative" extract was established; the potency of each representative extract was determined by measurement of the total protein content (Hymenoptera venom), radial diffusion measurement of the dominant allergen (short ragweed and cat), or, if there was no dominant allergen, then by quantitative skin testing by using the ID50EAL (intradermal dilution for 50 mm sum of erythema determines the bioequivalent allergy units) method. In vitro tests were developed to allow the manufacturer to demonstrate that each lot of its extract was statistically identical, within defined limits, to the FDA reference extract. These tests included radial immunodiffusion, competitive enzyme-linked immunosorbent assay, and isoelectric focusing. The standardized extracts offer the advantage of consistent potency from lot to lot for each manufacturer and also from manufacturer to manufacturer, and assure the presence of recognized significant allergens within the extract. Therefore, standardized extracts offer improved safety and efficacy over their nonstandardized predecessors.

Intracutaneous Skin Tests and Serum IgE Levels Cannot Predict the Grade of Anaphylaxis in Patients with Insect Venom Allergies.

BackgroundAllergies against Hymenoptera venoms are a major cause of severe anaphylaxis. Risk assessment for subjects with suspected allergy is difficult because there are currently no biomarkers that predict the likelihood of high-grade anaphylaxis other than several associated comorbidities.ObjectiveWe investigated the relationship between the severity of anaphylaxis and the results of intracutaneous skin tests (ICTs) together with serum levels of tryptase, total IgE, and venom-specific IgE, IgG, and IgG4.MethodsWe performed a retrospective evaluation of 194 patients who presented to a single medical center with allergies to bee venoms (Apis mellifera, Bombus spp.; n=24, 12.4%), vespid venoms (Vespula spp., Vespa spp., Polistes spp.; n=169, 87.1%), or both (n=1, 0.5%).ResultsIndex bee stings occurred earlier in the year than vespid stings, although the latter were reported more frequently overall. On average, subjects who previously experienced grade IV anaphylaxis required higher dosages of venom to yield positive ICTs than those who exhibited lower grade responses. Patients diagnosed with grade IV anaphylaxis exhibited significantly lower levels of venom-specific IgE and IgG and trended toward elevated levels of tryptase. No significant differences in average levels of venom-specific IgG4 and total IgE were observed.ConclusionOur findings reveal that intracutaneous skin testing and levels of venom-specific IgE do not predict the degree of anaphylaxis that develops in patients with venom allergy. Furthermore, the month of the index sting is not a reliable means to differentiate bee from vespid stings in patients presenting with an uncertain history.

Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide: a protocol for a systematic review of observational studies

IntroductionSystemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for...

Venom allergen immunotherapy.

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.

Long-term efficacy of the sublingual and subcutaneous routes in allergen immunotherapy.

Allergen immunotherapy is highly effective in selected patients with allergic rhinitis, allergic asthma, and Hymenoptera venom allergy. Unlike anti-allergic drugs, both subcutaneous and sublingual immunotherapies have been shown to modify the underlying cause of the disease, with proved long-term clinical benefits after treatment cessation. In this review, we analyzed 10 randomized, double-blind, placebo controlled clinical trials of allergen immunotherapy that included blinded follow-up for at least 1 year after treatment withdrawal. Three studies of pollen subcutaneous immunotherapy provided evidence that a sustained, tolerogenic effect of subcutaneous immunotherapy can be achieved after 3 years of treatment. Six trials of sublingual immunotherapy provided robust evidence for long-term clinical benefit and persistent immunologic changes after grass pollen, house-dust mite, or Japanese cedar immunotherapy, whereas a clinical trial of both sublingual and subcutaneous grass pollen immunotherapies showed that 2 years of immunotherapy were efficacious but insufficient to induce long-term tolerance. These studies strongly supported international guidelines that recommend at least 3 years of allergen immunotherapy of proven value to achieve disease modification and sustained clinical and immunologic tolerance.

Natural and Induced Tolerance to Hymenoptera Venom: A Single Mechanism?

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.

Basophil activation test as alternative method to CAP-inhibition in patients with double sensitization to vespid venoms

Most patients with Hymenoptera venom allergy (HVA) to vespid venoms present double sensitization by specific IgE (sIgE)-mediated cross-reactivity. Thus, it is mandatory could discriminate between a true double and primary sensitization to implement an accurate venom-specific immunotherapy (VIT). To date, CAP-inhibition is the reference method in the diagnosis of cross-reactivity in double sensitized patients to vespid venoms, being the results obtained with the component resolved diagnostics (CRD) conflicting. For this, we have studied in a cohort of double sensitized patients to Vespula vulgaris (VV) and Polistes dominulus (PD) venoms (n = 40) the diagnostic accuracy of CRD using the CAP-inhibition as reference method, as well as to investigate whether basophil activation test (BAT) is an alternative method for inconclusive results obtained by CAP-inhibition. CAP-inhibition showed a sensitivity of 59.46 % in view of the indeterminate results; most patients had true double sensitization (54.5 %), followed by single sensitization to PD (27.27 %) and VV (18.18 %) venoms. CRD based on rVes v 5/rPol d 5 (or vice versa) ratio as well as whole extracts I3/I77 (or vice versa) ratio (specific IgE-I3 to VV/specific IgE-I77 to PD) showed a low diagnostic accuracy (AUC = 0.504, p = 0.974; AUC = 0.35, p = 0.235; respectively). BAT was determined in parallel with CAP-inhibition in 12 patients, presented higher sensitivity than CAP-inhibition (p = 0.021) and a positive agreement of 71.43 %. Likewise it was able to identify 100% of inconclusive results, showing a specificity of 83.3 %. Therefore, CRD is not a suitable method to distinguish monosensitization and BAT appears to be an appropriate method resolving indeterminate results from the gold standard method.

La désensibilisation allergénique au secours de la récidive

Allergy is a frequent and often disabling condition for the patients. In the context of allergic rhinitis and asthma or anaphylactic shock to hymenoptera venom, allergenic desensitization can be proposed to limit the symptoms or recurrence of major reactions. Access to this treatment is made difficult by a lack of allergists, alack of products or, more recently, by the Covid-19 crisis.

Time-dependent effect of desensitization with wasp venom on selected parameters of the immune system

The emergence of tolerance during Hymenoptera venom immunotherapy (VIT) is a complex process. The main goal of VIT is to induce a change from proinflammatory Th2 response to the Th1 response. However, the immune mechanism of acquiring rapid tolerance during VIT has not yet been fully understood. Therefore, we have analyzed (in 4-time points: 0, 2, 6, and 24 weeks after the initiation phase of VIT) the concentration of complement C3, C4, and C5 components, lymphocyte subpopulations (flow cytometry), as well as histamine and tryptase serum concentrations of 43 patients with wasp venom allergy (III and IV Müller grade) classified to ultra-rush treatment and 18 volunteers as the control group (CG). We observed that VIT affected the immune system by inducing changes in the complement system (decreased C3 and C4 compartment protein concentrations) and "normalized" the percentage of lymphocytes and neutrophils in the peripheral blood. Moreover, a significant increase in the percentage of nTreg in the blood of patients treated with VIT was observed. On the other hand, there were no changes in histamine or tryptase concentrations in the blood. Increased percentage of nTreg cells is a well-known mechanism by which VIT affects the immune system. Finally, VIT also modulated the concentrations of the complement components, which may be a previously unknown VIT mechanism of action.

Single-cell profiling reveals novel cellular heterogeneity of monocytes during Hymenoptera venom allergy.

BackgroundHymenoptera stings can induce dysregulated inflammation and immediate hypersensitivity reactions including anaphylaxis. However, the molecular mechanisms underlying peripheral immune responses during Hymenoptera venom allergy (HVA) remain elusive.MethodsHere we determined the single‐cell transcriptomic profiling from highly heterogeneous peripheral blood cells in patients with HVA through unbiased single‐cell RNA sequencing and multiple models of computational analyses.ResultsThrough clustering analysis by uniform manifold approximation and projection, we revealed an increased number of monocytes in the acute phase and identified innate immune responses, leukocyte activation, and cellular detoxification as the main involved biological processes. We used filter analysis to identify that CLU that encodes clusterin was highly expressed in monocytes, and the co‐expressed genes of CLU further supported the key role of monocyte. We further used pseudo‐temporal ordering of cells and scRNA velocity analysis to delineate disease‐associated monocyte lineages and states in patients with HVA.ConclusionsOur comprehensive molecular profiling of blood samples from patients with HVA revealed previously unknown molecular changes, providing important insights into the mechanism of venom allergy and potential therapeutic targets.

Clinical impact and proposed application of molecular markers, genetic variants, and cytogenetic analysis in mast cell neoplasms: Status 2022

Mast cell neoplasms are an emerging challenge in the fields of internal medicine, allergy, immunology, dermatology, laboratory medicine, and pathology. In this review, we discuss the current standards for the diagnosis and prognostication of mast cell neoplasms with special reference to clinically relevant germline and somatic gene variants. In patients with cutaneous mastocytosis or with indolent systemic mastocytosis (SM), various KIT-activating mutations act as key molecular drivers of the disease. In adults, KIT p.D816V is by far the most prevalent driver, whereas other KIT mutants are detected in nearly 40% of children. In advanced SM, including aggressive SM, SM with an associated hematological neoplasm, and mast cell leukemia, additional somatic mutations in other genes, such as SRSF2, JAK2, RUNX1, ASXL1, or RAS, may be detected. These drivers are more frequently detected in SM with an associated hematological neoplasm, particularly in male patients. Recently, hereditary alpha-tryptasemia has been identified as a genetic trait more prevalent in SM compared with healthy controls. Moreover, hereditary alpha-tryptasemia is more frequent in patients with SM with Hymenoptera venom allergy and severe mediator-related symptoms than in patients with SM without symptoms. On the basis of this knowledge, we propose a diagnostic algorithm in which genetic markers are applied together with clinical and histopathologic criteria to establish the diagnosis and prognosis in SM.

Natural History of the Hymenoptera Venom Sensitivity Reactions in Adults: Study Design.

Background: Allergic reactions to Hymenoptera stings can have varying levels of severity, according to the Müller grading system. Methods: By an epidemiological concept, this is a retrospective cohort study. The observed cohort was represented by patients referred to the University Clinic Golnik due to Hymenoptera allergic reaction in the period from 1997 to 2015. From the immunological database of the University Clinic Golnik, we obtained laboratory data (sIgE, skin tests and basophil activation test). The clinical characteristics of patients were obtained from BIRPIS. With the help of a questionnaire, which was sent to each patient in the period from May 2019 to April 2021, we obtained epidemiological data. For the assessment of the association between the severity of allergic reaction for the observed outcome, the severity of the first allergic reaction after Hymenoptera sting was used. Other variables were grouped according to risk factors. Discussion: We will identify the risk factors that could play an important role in a severe systemic reaction: the aetiology of the Hymenoptera sting, sex, age, history and severity of previous systemic reactions, being re-stung in an interval of two months, the frequency of re-stings, atopy, genetic predisposition, preventive medication use, other medication use, beekeeping or living next to beehives and why immunotherapy was not taken. Laboratory data will also be analysed to determine if there is any association with laboratory tests and the severity of the allergic reactions after Hymenoptera stings. Conclusions: Several new approaches are introduced in the study design. The most important is that the protocol covers epidemiological data gained from the questionnaire, as well as clinical data gained from the Immunological database and BIRPIS database. We expect to obtain significant results that will explain the risk factors for the natural history of Hymenoptera sting allergic reactions and will help allergologists, as well as general doctors, when facing those patients allergic to Hymenoptera venom without immunotherapy.

Mastocytosis presenting with mast cell-mediator release-associated symptoms elicited by cyclo oxygenase inhibitors: prevalence, clinical, and laboratory features.

BackgroundNonsteroidal anti‐inflammatory drugs (NSAIDs) are frequently avoided in mastocytosis, because of a potential increased risk for drug hypersensitivity reactions (DHRs) due to inhibition of cyclo‐oxygenase (COX), subsequent depletion of prostaglandin E 2 and release of leukotrienes.ObjectivesHere, we aimed at determining the prevalence of mast cell (MC) mediator release symptoms triggered by NSAIDs in mastocytosis patients and the associated clinical and laboratory features of the disease.MethodsMedical records from 418 adults to 223 pediatric mastocytosis patients were retrospectively reviewed. Patients were classified according to tolerance patterns to NSAIDs and other COX inhibitors (COXi) and compared for epidemiological, clinical and laboratory findings.ResultsOverall, 87% of adults and 91% of pediatric patients tolerated NSAIDs and other COXi. Among adult and pediatric patients presenting DHRs, 5% and 0% reacted to multiple NSAIDs, 4% and 0.7% were single reactors, and 3% and 8% were single reactors with known tolerance to paracetamol but unknown tolerance to other COXi, respectively. Among adults, hypersensitivity to ≥2 drugs was more frequent among females (p = 0.009), patients with prior history of anaphylaxis to triggers other than NSAIDs or other COXi and Hymenoptera venom (p = 0.009), presence of baseline flushing (p = 0.02), baseline serum tryptase ≥48 ng/ml (p = 0.005) and multilineage KIT mutation (p = 0.02). In contrast, tolerance to NSAIDs and other COXi was more frequent among males (p = 0.02), in patients with anaphylaxis caused by Hymenoptera venom (p = 0.02), among individuals who had skin lesions due to mastocytosis (p = 0.01), and in cases that had no baseline pruritus (p = 0.006). Based on these parameters, a score model was designed to stratify mastocytosis patients who have never received NSAIDs or other COXi apart from paracetamol, according to their risk of DHR.ConclusionsOur results suggest that despite the frequency of MC mediator related symptoms elicited by NSAIDs and other COXi apart from paracetamol is increased among mastocytosis patients versus the general population, it is lower than previously estimated and associated with unique disease features. Patients that tolerated NSAIDs and other COXi following disease onset should keep using them. In turn, adults with unknown tolerance to such drugs and a positive score should be challenged with a preferential/selective COX‐2 inhibitor, while the remaining may be challenged with ibuprofen.

Social wasps in Spain: the who and where.

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. 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. 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. 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.