Search Results (46)

Hymenoptera venom allergy is a cause of anaphylaxis, which significantly affects patients’ daily lives due to the constant fear of accidental stings. Venom immunotherapy (VIT) is the only treatment capable of preventing severe systemic reactions (SSRs). Limited long-term real-life data are available, integrating both clinical and immunological outcomes. A five-year prospective observational study was conducted on 35 patients with a history of SSR who underwent VIT at a tertiary allergy center in Southern Italy; two of them had a diagnosis of systemic mastocytosis. Most patients were sensitized to Vespula, but others to Apis, Polistes dominula and Vespa crabro, reflecting the exposure pattern characteristic of Mediterranean regions. Clinical outcomes following accidental re-stings and serological trends, including total IgE, venom-specific IgE, and baseline serum tryptase, were assessed at treatment initiation and after five years of maintenance therapy. During the entire follow-up, all patients tolerated VIT. No SSRs occurred after accidental stings in 17/35 patients, confirming clinical protection achieved with VIT. Vespula serum-specific IgE presented a highly significant decrease; total IgE, tryptase and specific IgE for Apis, Polistes dominula and Vespa crabro showed a statistically significant decrease. Our findings reinforce the role of VIT as a well-tolerated, effective and disease-modifying treatment in a real-world setting. Full article

With the global increase in population aging, allergic diseases in older adults are becoming an increasingly relevant clinical and public health challenge. Age-related molecular and cellular alterations significantly affect the pathophysiology, clinical manifestations, diagnosis, and management of major allergic diseases in the elderly. This review focuses on immunosenescence in major allergic conditions, including asthma, chronic urticaria and angioedema, dermatitis, food and drug allergies, and hymenoptera venom hypersensitivity. Particular emphasis is placed on molecular mechanisms underlying immune aging, such as inflammaging, dysregulation of innate and adaptive immune responses, epithelial barrier dysfunction, microbiota alterations, neuro-immune interactions, and age-related comorbidities. Sex-related differences in immune responses are also addressed, together with current diagnostic and therapeutic strategies, including the opportunities and limitations of biologic therapies in aging populations. Despite growing interest in this field, a major limitation remains the paucity of studies specifically targeting geriatric populations, underscoring the need for age- and sex-specific research and dedicated clinical trials. A personalized approach integrating frailty assessment and immune profiling is essential to optimize the management of allergic diseases in older adults. Full article

Background/Objectives: Evidence-based recommendations are vital in healthcare to standardize care, reduce variability, and improve patient outcomes. In children, anaphylaxis, allergy to antibiotics, and hymenoptera venom allergy are among the commonest reasons for allergological evaluation. This work was intended to optimize the prescriptions for allergological evaluation and for the related diagnostic tests with the aim of improving the management of children with allergic diseases and promoting resource efficiency. Methods: A systematic literature review of the literature was performed to formulate recommendations on the diagnostic management of children with anaphylaxis, drug allergy, and hymenoptera venom allergy. Results: Effective management of anaphylaxis involves rapid assessment and specialist follow-up to identify triggers, prevent recurrence, and ensure patients and caregivers are educated and equipped with an adrenaline auto-injector. Integrating skin testing, specific serological assays, and oral provocation tests into the diagnostic process for children with suspected beta-lactam allergy enhances diagnostic accuracy and minimizes unnecessary avoidance of first-line antibiotics. Children and adolescents with systemic reactions to hymenopteran stings should be referred to an allergy specialist for diagnosis, risk assessment, management education, and adrenaline prescription. Conclusions: These recommendations may enhance care quality, minimize inappropriate prescriptions, and support standardized methods of diagnosis of allergological diseases in children. Full article

Specific venom immunotherapy (VIT) in patients with hymenoptera venom allergy (HVA) represents a well-studied approach to reduce the severity of a possible anaphylactic reaction. Currently, data on mechanisms of tolerance induction at the cellular level within the first hours of therapy are lacking. To address this, total and unoccupied high-affinity IgE receptor (FcεRI) numbers per basophil, soluble FcεRI (sFcεRI) and serum tryptase levels were measured before and after the first day of VIT induction in HVA patients. Additionally, basophil activation tests (BATs) were performed at those time points. In the early phase of VIT induction, no significant change in total FcεRI receptor density on basophils was observed, but a significant increase in unoccupied FcεRI was noticeable, predominantly in patients with high total IgE and low baseline unoccupied FcεRI density. No meaningful difference in serum tryptase levels or sFcεRI levels was observed after VIT induction. BATs showed heterogeneous results, often unchanged before and after VIT (in 47% of the cases), sometimes increased (in 40%) and only rarely decreased EC₅₀ sensitivity (in 13%). Changes in the BAT EC₅₀ correlated with FcεRI receptor density changes in basophils. In summary, VIT induction led to an increased ratio of unoccupied-to-total FcεRI without notable tryptase or sFcεRI serum elevation, pointing towards subthreshold cell activation with receptor internalization and recycling. However, the mostly unchanged or even increased basophil sensitivity in EC₅₀ calls for further research to clarify the clinical relevance of these rapid receptor modulations. Full article

The efficacy of Hymenoptera venom immunotherapy is contingent upon the accurate identification of the insect responsible for the allergic reaction. The techniques used to detect specific IgE suffer from difficulties due to the cross-reactivity between Hymenoptera venoms (false positives), diagnostic ability, and the limited availability of allergenic components (false negatives). In this study, we analyzed the discrepancies in the results obtained with Euroline^® DPA-Dx and ImmunoCAP^® in the diagnosis of allergic reactions due to Hymenoptera stings in 151 patients. The results (positive/negative) of ImmunoCAP^® and Euroline^® agreed in 77/151 (50.99%) cases; with 15/151 (9.93%) cases positive for the same insect, and 61/151 (40.4%) cases positive for multiple insects. When the results were used to decide which venom to use for immunotherapy, there was a statistically significant discrepancy for Polistes dominula (21.8% of cases with ImmunoCAP^® compared to only 8.4% with Euroline^®). The presence of Polistes venom phospholipase (Pol d 1) in Euroline^® did not increase its ability to differentiate double sensitization to wasps. ImmunoCAP^® and Euroline^® exhibited comparable diagnostic performance in bee venom allergy. For vespid venom allergy—particularly involving Polistes species—ImmunoCAP^® appeared to show a slight diagnostic advantage, although this finding should be interpreted with caution. Full article

Reliable assessment of protection in venom immunotherapy (VIT) patients remains a clinical challenge, especially due to the limitations of conventional sting challenge tests (SCTs), which require complex insect handling and may compromise test accuracy. This study introduces StingReady, a novel, user-friendly device designed to streamline the SCT process by enabling safe, efficient, and minimally manipulative exposure to hymenopteran stings. For the first time, StingReady was applied to conduct SCTs with Vespa velutina, an invasive hornet species of increasing clinical relevance. The device was tested in a real-world setting at Belvís Park in Santiago de Compostela, Spain, where hornets were successfully captured and transported to the hospital without anesthesia or limb removal. The design features adjustable mesh sizes, allowing compatibility with various hymenopteran taxa. Using StingReady, nine patients underwent SCTs with no need for direct insect handling during the hospital procedure. The process improved patient safety and comfort while preserving the insect’s natural stinging behavior, thereby enhancing test reliability. This study demonstrates that StingReady significantly improves SCT methodology, offering a practical, reproducible, and ethically sound alternative for evaluating VIT efficacy across diverse hymenopteran species. Full article

Background and Clinical Significance: Upper gastrointestinal (GI) bleeding is a common emergency, typically requiring prompt intervention. This case report presents a unique situation where apparent GI bleeding was ultimately identified as anaphylaxis triggered by accidental wasp ingestion. Such cases are rare, underscoring the need for a broad differential diagnosis in atypical presentations. Case Presentation: A 53-year-old male with a history of heavy alcohol use presented with presumed acute hematemesis, hypotension, and tachycardia. An initial examination revealed mild anemia and elevated liver enzymes. An urgent upper GI endoscopy showed severe esophagitis with no signs of active or stigmata of recent bleeding; instead, two dead wasps were found in the gastric antrum. Further inquiry revealed that the patient had recently consumed a home-brewed alcoholic beverage, likely contaminated with the wasps. The patient’s symptoms were then attributed to anaphylaxis from venom exposure rather than hemorrhagic shock. The patient’s condition improved with antihistaminic therapy, and he was discharged with follow-up recommendations. Conclusions: This case highlights the importance of considering rare but critical diagnoses, such as insect-induced anaphylaxis, in patients presenting with presumed GI bleeding. It reinforces the value of thorough history taking, prompt endoscopy, and systematic management in assessing and treating atypical emergency presentations. Full article

Hymenoptera venom allergy (HVA) is a potentially life-threatening condition, making accurate diagnosis crucial for identifying significant IgE sensitizations and enabling effective venom immunotherapy. In this review, we provide a detailed overview of biomarkers for the molecular diagnosis of IgE-mediated hypersensitivity to Hymenoptera insect venoms in clinical practice, and we present, in a structured manner, their importance in differentiating genuine sensitizations versus cross-sensitizations using different diagnostic procedures. Updated algorithms are provided, along with the advantages and limitations of molecular diagnosis approaches. Geographical variations and rare species may pose further challenges in diagnosing and treating HVA, adding complexity to HVA management. This review informs readers about performing tailored diagnostics based on molecular allergen biomarkers and subsequent treatment strategies. Full article

Hymenoptera venom allergy (HVA) is an IgE-mediated hypersensitivity reaction caused by Hymenoptera species stings (honeybee, vespid, or ant). The only effective treatment is Hymenoptera venom immunotherapy (VIT). Our study aimed to evaluate whether humoral and cellular biomarkers measured before, during, and after honeybee VIT are associated with the success of VIT, which was assessed by the response to a sting challenge one year after finishing VIT. In this prospective study, blood biomarkers of 25 patients undergoing honeybee VIT at the referral center in Slovenia were evaluated. A controlled honeybee sting challenge confirmed successful VIT in 20 of 25 (80%) patients. Honeybee venom (HBV) recombinant allergen profiles, evaluated before the treatment, were comparable between responders and non-responders. Longitudinal follow-up, up to 1 year after finishing VIT, showed that the immune responses do not differ significantly between patients with successful VIT and treatment failure. Those responses were characterized by decreased sIgE, tIgE, and BST, whereas sIgG4 levels increased. The basophil sensitivity also significantly decreases after VIT in both groups of patients. The analyzed biomarker which correlated considerably with treatment failure was higher basophil sensitivity to allergen stimulation before VIT. Similarly, systemic adverse events (SAEs) during the build-up phase of VIT correlated with treatment failure. Our study demonstrated similar sensitization profiles, and humoral and basophil immune responses to immunotherapy, in two different well-characterized groups of patients, one with successful VIT and the other with treatment failure. Notably, only high basophil sensitivity measured before VIT and SAEs during VIT were significantly associated with VIT failure, and both have the potential to be predictors of VIT failure. Full article

Sensitization to cross-reactive allergens complicates identifying the culprit insect in Hymenoptera venom allergy via diagnostic tests. This study evaluates sensitization to hyaluronidases (Api m 2 from honey bee (Apis mellifera) venom, HBV; Pol d 2 from European paper wasp (Polistes dominula) venom, PDV; and Ves v 2.0101 and Ves v 2.0201 from yellow jacket (Vespula vulgaris) venom, YJV) and their cross-reactivity in allergic patients from Italy, Spain, and Germany using ImmunoCAPs, ELISA, and basophil activation tests. Sensitization rates were 45% for Api m 2 in HBV-allergic subjects, 25% for Pol d 2 in PDV-allergic individuals, and 20% and 10% for Ves v 2.0201 and Ves v 2.0101 in YJV-allergic patients, respectively. Patients primarily sensitized to Api m 2 showed minimal cross-reactivity to vespid hyaluronidases, whereas those primarily sensitized to Pol d 2 or Ves v 2.0201 exhibited IgE reactivity to Api m 2. Neither Pol d 2 nor Ves v 2.0201 triggered basophil activation. Cross-reactivity of Api m 2, Pol d 2, and Ves v 2.0201 depends on the primary sensitizing venom. Sensitization to Pol d 2 and Ves v 2.0201 remains below 25%, yet these patients may exhibit cross-reactivity to Api m 2. Conversely, HBV-allergic patients sensitized to Api m 2 show minimal reactivity to Pol d 2 or Ves v 2.0201. Full article

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

Detecting IgE sensitizations in the serum of allergic dogs is commonly performed using allergen extracts, but these are difficult to standardize. This article details the development and validation of the Pet Allergy Xplorer (PAX; Nextmune, Stockholm, Sweden), the first multiplex macroarray for the detection of IgE sensitization in dogs using allergen extracts and molecular components; the PAX is derived from the Allergy Xplorer (ALEX²; MacroArray Diagnostics, Vienna, Austria). The selection of allergens, cartridge processing, strategy for identifying and blocking IgE directed against cross-reactive carbohydrate determinants (CCDs), and the method used for determining the positivity threshold are described. The validation of the PAX included evaluations of the specificity of its anti-IgE monoclonal antibody, specificity of IgE binding to target allergens, assay precision, and internal consistency. Additionally, the influence of possible confounding factors, such as sample type, the influence of hemolysis, lipemia, bilirubinemia, and elevated CCD-IgE, was tested. Finally, the sensitization rates of 23,858 European dogs to 145 environmental and Hymenoptera venom allergens were summarized. The PAX is accurate and reproducible and has a unique CCD-detection and blocking strategy; its molecular allergens offer a unique window on allergen cross-reactivity. Full article

Insect venom is one of the most common triggers of anaphylaxis in the elderly population. Venom immunotherapy (VIT) remains the only treatment for Hymenoptera venom allergy (HVA). However, little is known about the differences in indication for VIT in the group of patients aged 60 years and older. The objective of this study was to assess the clinical and diagnostic differences of HVA in elderly patients. The study compared data from patients aged ≥ 60 (N = 132) to data from patients aged from 11 to 60 years (N = 750) in terms of HVA severity, comorbidities, and immunological parameters, namely, intradermal testing (IDT), specific IgE (sIgE) levels against extracts and major allergenic molecules, and serum tryptase level (sBT). The severity of systemic HVA (I–IV Müller scale) did not differ between adults and seniors. However, the severity of cardiovascular reactions (IV) increased with age, while the frequency of respiratory reactions (III) decreased. No differences were found in the immunological parameters of sensitization IDT, venom-specific IgE concentrations, or sIgE against Api m 1, 2, 4, 5, and 10 between patients below and above 60 or 65 years of age. Differences were noted for sIgE against Ves v1 and Ves v5; they were higher and lower, respectively, in seniors. In the seniors group, sBT levels were higher. Elevated tryptase levels, along with the aging process, can represent a risk factor within this age category. Nevertheless, advanced age does not influence the immunological parameters of immediate HVA reactions, nor does it impact the diagnosis of HVA. Full article

This study aimed to investigate the venom sac extracts (VSEs) of the European hornet (EH) Vespa crabro (Linnaeus, 1758) (Hymenoptera: Vespidae), focusing on the differences between stinging females, gynes (G), and workers (W), at the protein level. Using a quantitative “Sequential Window Acquisition of all Theoretical Fragment Ion Mass Spectra” (SWATH-MS) analysis, we identified and quantified a total of 240 proteins. Notably, within the group, 45.8% (n = 110) showed significant differential expression between VSE-G and VSE-W. In this set, 57.3% (n = 63) were upregulated and 42.7% (n = 47) downregulated in the G. Additionally, the two-hundred quantified proteins from the class Insecta belong to sixteen different species, six of them to the Hymenoptera/Apidae lineage, comprising seven proteins with known potential allergenicity. Thus, phospholipase A1 (Vesp v 1), phospholipase A1 verutoxin 2b (VT-2b), hyaluronidase A (Vesp v 2A), hyaluronidase B (Vesp v 2B), and venom allergen 5 (Vesp v 5) were significantly downregulated in the G, and vitellogenin (Vesp v 6) was upregulated. Overall, 46% of the VSE proteins showed differential expression, with a majority being upregulated in G. Data are available via ProteomeXchange with identifier PXD047955. These findings shed light on the proteomic differences in VSE between EH castes, potentially contributing to our understanding of their behavior and offering insights for allergy research. Full article

Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers. Full article