Hymenoptera venom allergy in children and adolescents.

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

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

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

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

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

Efficacy and safety of hymenoptera venom immunotherapy.

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

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

Introduction: Hymenoptera venom immunotherapy (VIT) is the only therapy that protects patients with Hymenoptera venom allergy by preventing systemic reactions after a new sting. Various extracts for VIT are available and used. VIT administration consists of an induction phase and a maintenance phase. Depot preparations of Hymenoptera VIT extracts are typically used for cluster and conventional protocols, and the maintenance phase. Many patients with Hymenoptera allergy need to achieve tolerance quickly because of the high risk of re-sting and possible anaphylaxis. Objective: Our study aimed to show the safety and efficacy of an accelerated regimen with depot preparations on aluminum hydroxide by using relatively high starting doses in a heterogeneous group of patients. Methods: The research focused on a group of patients with a history of severe systemic reactions to Hymenoptera stings, with the necessity of swift immunization due to high occupational risks. Aluminum hydroxide depot extracts either of Vepula species or Apis mellifera extracts were used. Results: The induction protocol was started with the highest concentration of depot venom extract of 100,000 standard quality unit and was well tolerated by 19 of 20 patients. Onne patient presented with a mild systemic reaction during the accelerated induction schedule, which was promptly treated with intravenous steroids and intramuscular H1 antihistamine; when switched to a conventional induction protocol, he had a similar reaction but finally reached maintenance with an H1-antagonist premedication. Conclusion: If validated, the accelerated induction protocol by using depot aluminum adsorbed extracts with the highest concentration of venom from the beginning could offer a streamlined and accessible treatment modality for patients diagnosed with anaphylaxis from bee and wasp venoms in need of rapid desensitization.

Venom Hypersensitivity.

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

Basophil activation in insect venom allergy: comparison of an established test using liquid reagents with a test using 5-color tubes with dried antibody reagents.

BACKGROUND: Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagents while a new development involves the use of tubes with dried antibody reagents. The aim of this pilot study was to compare these two techniques in patients with insect venom allergy. METHODS: Seventeen patients with an insect venom allergy were included in the study. The established "BAT 1" utilizes conventional antibody solutions of anti-CCR3 for basophil identification and anti-CD63 to assess basophil activation, whereas "BAT 2" uses dried anti-CD45, anti-CD3, anti-CRTH2, anti-203c and anti-CD63 for identification and activation measurement of basophils. Negative and positive controls as well as incubations with honey bee venom and yellow jacket venom at three concentrations were performed. RESULTS: Seven patients had to be excluded due to low basophil counts, high values in negative controls or negative positive controls. For the remaining 10 patients the overall mean (± SD) difference in activated basophils between the two tests was 0.2 (± 12.2) %P. In a Bland-Altman plot, the limit of agreement (LoA) ranged from 24.0 to -23.7. In the qualitative evaluation (value below/above cut-off) Cohen's kappa was 0.77 indicating substantial agreement. BAT 2 took longer to perform than BAT 1 and was more expensive. CONCLUSION: The BAT 2 technique represents an interesting innovation, however, it was found to be less suitable compared to an established BAT for the routine diagnosis of insect venom allergies.

Evaluating Hymenoptera Venom Allergy Severity: A Data-Centric Comparison of Grading Instruments.

INTRODUCTION: While a consensus seems to have been reached with regard to the definition of anaphylaxis, there is no universal instrument for scoring allergic reaction severity despite more than 30 having been proposed by the time of writing. This severely hampers comparison of data between studies. While scales have been compared with regard to their utility in grading food-related reactions, no such comparisons have been made for Hymenoptera venom-associated reactions. METHODS: The study conducted a retrospective analysis to compare the severity of Hymenoptera venom allergy reactions in 104 participants with suspected Hymenoptera venom allergy. The study applied six grading instruments to each reaction, also evaluating them against the NIAID/FAAN anaphylaxis criteria. Sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) for identifying anaphylaxis were calculated. Severity scales were simplified into "mild," "moderate," and "severe" categories. The most common severity grade across the five scales was determined using a custom function to establish a consensus severity grade. RESULTS: The most common culprit insects were honeybees (49.0%). Among the 88 participants with generalized reactions, the highest proportion had involvement of four organ systems. The scales showed high specificity for detecting anaphylaxis, especially when using higher grades of the Mueller, WAO, and Dribin scales. The diagnostic yields (AUC) varied, with the WAO scale having the highest AUC (0.94) for grades 3, 4, and 5. Spearman correlation analysis showed the strongest correlations seen between the Brown and Dribin, Ring and Messmer and Dribin, and Ring and Messmer and Reisman scales. The lowest correlations were observed with the Mueller scale when paired with the WAO, Reisman, and Dribin scales. An inter-rater reliability analysis showed substantial agreement between scales with the same number of grading levels. The agreement was highest for the Brown and Dribin scales, indicating a strong consistency in reaction severity classification across different instruments. CONCLUSION: While all instruments were effective in stratifying reactions, they showed limitations in differentiating milder phenotypes. The Brown and Dribin scales stood out for their high agreement with the consensus score and sensitivity in identifying anaphylaxis. Our findings suggest that adopting either of these scales could significantly unify the reporting of allergic reactions. We believe the format of an instrument should be tailored to its intended purpose, with clinical decision aids being simpler and research tools being more detailed.

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

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

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.

Immunomic Investigation of Holocyclotoxins to Produce the First Protective Anti-Venom Vaccine Against the Australian Paralysis Tick, Ixodes holocyclus.

Venom producing animals are ubiquitously disseminated among vertebrates and invertebrates such as fish, snakes, scorpions, spiders, and ticks. Of the ~890 tick species worldwide, 27 have been confirmed to cause paralysis in mammalian hosts. The Australian paralysis tick (Ixodes holocyclus) is the most potent paralyzing tick species known. It is an indigenous three host tick species that secretes potent neurotoxins known as holocyclotoxins (HTs). Holocyclotoxins cause a severe and harmful toxicosis leading to a rapid flaccid paralysis which can result in death of susceptible hosts such as dogs. Antivenins are generally polyclonal antibody treatments developed in sheep, horses or camels to administer following bites from venomous creatures. Currently, the methods to prevent or treat tick paralysis relies upon chemical acaricide preventative treatments or prompt removal of all ticks attached to the host followed by the administration of a commercial tick-antiserum (TAS) respectively. However, these methods have several drawbacks such as poor efficacies, non-standardized dosages, adverse effects and are expensive to administer. Recently the I. holocyclus tick transcriptome from salivary glands and viscera reported a large family of 19 holocyclotoxins at 38-99% peptide sequence identities. A pilot trial demonstrated that correct folding of holocyclotoxins is needed to induce protection from paralysis. The immunogenicity of the holocyclotoxins were measured using commercial tick antiserum selecting HT2, HT4, HT8 and HT11 for inclusion into the novel cocktail vaccine. A further 4 HTs (HT1, HT12, HT14 and HT17) were added to the cocktail vaccine to ensure that the sequence variation among the HT protein family was encompassed in the formulation. A second trial comparing the cocktail of 8 HTs to a placebo group demonstrated complete protection from tick challenge. Here we report the first successful anti-venom vaccine protecting dogs from tick paralysis.

The Diagnostic Importance of Recombinant Allergen IgE Testing in Patients with Hymenoptera Venom Allergy: Comparison of Two Methods.

Adults with systemic anaphylactic reactions (SAR) to insect sting show often multiple-positivity of serum-specific IgE (sIgE) to Hymenoptera venoms. Unnecessary long-lasting venom-specific immunotherapies (VIT) in false-positive patients increase the risk of recurrent SAR. This report aims to analyze the diagnostic importance of recombinant allergen IgE testing in patients with SAR to Hymenoptera sting. In 82 patients we measured sIgE to honeybee venom (HBV), wasp venom (WV) and hornet venom (HV) extracts, recombinant phospholipase A2 from HBV (sIgE-rApi m1), recombinant antigen 5 from WV (sIgE-rVes v5), and cross-reactive carbohydrate determinants-CCD-bromelain by ImmunoCAP. We analyzed the correlation of ImmunoCAP and Immunoblot for HBV and WV extracts, rApi m1, and rVes v5 in 39/82 patients. According to the history of the culprit insect, we compared sensitivity and specificity between the two methods. The severity of the SAR does not depend on the sIgE level to venom extracts and recombinant allergens. Fifty-one percent of the patients had a multiple-positivity to HBV/WV or HBV/WV/HV extracts. Severe SAR and CCD-sIgE were more frequent in multiple-positive than single-positive patients. CCD-sIgE were more frequent in HBV allergic patients than WV and HV allergic patients. There was a significant correlation between levels of sIgE to venom extracts and recombinant allergens measured by ImmunoCAP and Immunoblot. ImmunoCAP has higher sensitivity and specificity than Immunoblot for diagnosis of SAR to Hymenoptera venoms. IgE testing to recombinant CCD-free allergens is necessary for the adequate selection of long-lasting VIT, especially in patients with multiple sensitivities to venom extracts.

Characterization of New Allergens from the Venom of the European Paper Wasp Polistes dominula.

Discriminating Polistes dominula and Vespula spp. venom allergy is of growing importance worldwide, as systemic reactions to either species' sting can lead to severe outcomes. Administering the correct allergen-specific immunotherapy is therefore a prerequisite to ensure the safety and health of venom-allergic patients. Component-resolved diagnostics of Hymenoptera venom allergy might be improved by adding additional allergens to the diagnostic allergen panel. Therefore, three potential new allergens from P. dominula venom-immune responsive protein 30 (IRP30), vascular endothelial growth factor C (VEGF C) and phospholipase A2 (PLA2)-were cloned, recombinantly produced and biochemically characterized. Sera sIgE titers of Hymenoptera venom-allergic patients were measured in vitro to assess the allergenicity and potential cross-reactivity of the venom proteins. IRP30 and VEGF C were classified as minor allergens, as sensitization rates lay around 20-40%. About 50% of P. dominula venom-allergic patients had measurable sIgE titers directed against PLA2 from P. dominula venom. Interestingly, PLA2 was unable to activate basophils of allergic patients, questioning its role in the context of clinically relevant sensitization. Although the obtained results hint to a questionable benefit of the characterized P. dominula venom proteins for improved diagnosis of venom-allergic patients, they can contribute to a deeper understanding of the molecular mechanisms of Hymenoptera venoms and to the identification of factors that determine the allergenic potential of proteins.

Hymenoptera Venom Immunotherapy: Immune Mechanisms of Induced Protection and Tolerance.

Hymenoptera venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after Hymenoptera venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure long-term tolerance post-therapy.

Prevalence of mastocytosis and Hymenoptera venom allergy in the United States.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Precision Medicine in Hymenoptera Venom Allergy: Diagnostics, Biomarkers, and Therapy of Different Endotypes and Phenotypes.

Allergic reactions to stings of Hymenoptera species may be severe and are potentially fatal deviations of the immunological response observed in healthy individuals. However, venom-specific immunotherapy (VIT) is an immunomodulatory approach able to cure venom allergy in the majority of affected patients. An appropriate therapeutic intervention and the efficacy of VIT not only depend on a conclusive diagnosis, but might also be influenced by the patient-specific manifestation of the disease. As with other diseases, it should be borne in mind that there are different endotypes and phenotypes of venom allergy, each of which require a patient-tailored disease management and treatment scheme. Reviewed here are different endotypes of sting reactions such as IgE-mediated allergy, asymptomatic sensitization or a simultaneous presence of venom allergy and mast cell disorders including particular considerations for diagnosis and therapy. Additionally, phenotypical manifestations of venom allergy, as e.g. differences in age of onset and disease severity, multiple sensitization or patients unsusceptible to therapy, are described. Moreover, biomarkers and diagnostic strategies that might reflect the immunological status of the patient and their value for therapeutic guidance are discussed. Taken together, the increasing knowledge of different disease manifestations in venom hypersensitivity and the growing availability of diagnostic tools open new options for the classification of venom allergy and, hence, for personalized medical approaches and precision medicine in Hymenoptera venom allergy.

The effect of hymenoptera venom immunotherapy on neutrophils, interleukin 8 (IL-8) and interleukin 17 (IL-17).

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.

Hymenoptera allergy and anaphylaxis: are warmer temperatures changing the impact?

PURPOSE OF REVIEW: Climate change has brought about many changes in our ecosystem. Prolongation of pollen seasons has been reported, related to earlier frost off in the spring and later onset of frost on in the fall. This review considers recent global evidence that stinging insects are redistributing toward the poles, thereby potentially increasing human exposure and risk of sting events. RECENT FINDINGS: With changing climate, particularly climate warming, range expansion of insects is occurring in both the Northern and Southern Hemispheres. Likewise, stinging insects, such as Hymenoptera and Lepidoptera, are also expanding range. Though there is scant data on associated increase of insect-related anaphylaxis, increased insect-human interaction is certain. SUMMARY: It is likely that climate change will continue to alter the distribution and population of Hymenoptera and other insects. As temperatures warm and regions become suitable for nesting and establishment of colonies, many insects will expand their territory. As already reported in Alaska, one would anticipate expansion of range, especially toward the poles, thereby increasing the probability of human encounters and likewise anaphylaxis.

Natural history and long-term follow-up of Hymenoptera allergy.

PURPOSE OF REVIEW: Information on the natural history of hypersensitivity reactions is helpful for deciding which patient urgently needs a venom immunotherapy (VIT). RECENT FINDINGS: The frequency of self-reported systemic allergic reactions (SAR) to Hymenoptera stings is approximately 3-7% in the Northern Hemisphere. About 25% of SAR are severe (anaphylactic shock). Fatal sting reactions are very rare. The most important risk factor for severe insect sting anaphylaxis is mast cell disease. Other risk factors are higher age, vespid venom allergy (in contrast to honeybee venom allergy), repeated stings, male sex, and treatment with ACE inhibitors. Preceding large local reactions seem not to play a risk factor for subsequent SAR. SUMMARY: The majority of risk factors for severe anaphylaxis are not modifiable. For patients presenting with well defined risk factors for a very severe or even fatal anaphylaxis, VIT is of utmost importance, and they should be performed for the rest of their life. Sting challenge tests are required to identify patients in whom treatment was ineffective. Those patients, who did not receive VIT although presenting with a firm indication, or in whom VIT was stopped, require yearly monitoring to teach preventive measures and to renew the emergency kit.