Unraveling wasp sensitization in a patient with systemic mastocytosis by CAP-inhibition assay.

Systemic mastocytosis (SM) is a clonal mast cell disorder that can lead to potentially severe anaphylactic reactions. Hymenoptera sting is one of the most frequent triggers of anaphylaxis in these patients, and diagnosis of indolent SM (ISM) without skin involvement (ISMs) is not rare. In this subgroup of patients, venom immunotherapy (VIT) is an effective treatment decreasing subsequent systemic reactions, and lifelong administration is recommended. An individualized diagnosis is necessary to offer the most adequate VIT, and molecular diagnosis (MD) may be useful to discriminate between primary sensitization and cross-reactivity. Nevertheless, other techniques such as ImmunoCAP inhibition assays may be necessary to identify the genuine sensitization to offer the most suitable VIT. We present a male patient with an anaphylactic reaction following several wasp stings. The patient was diagnosed with ISM, and allergy to both Polistes dominula and Vespula sp venom was confirmed. In this scenario, MD did not discriminate between a genuine double sensitization and venom cross-reactivity between both vespids. Thus, CAP-inhibition assay was performed. This case indicated the importance of an accurate diagnosis of hymenoptera venom allergy (HVA). It also highlights the usefulness of CAP-inhibition assays when MD fails to distinguish between genuine double Polistes-Vespula sensitization and cross-reactivity.

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.

Mucocutaneous Leishmaniasis Rhinology Complications: A Rare Presentation.

OBJECTIVE: This case report presents a unique manifestation of Mucocutaneous Leishmaniasis (MCL) in a 56-year-old woman with chronic nasal symptoms. Initially diagnosed with chronic sinusitis and septal perforation, the patient's history of a childhood sandfly bite and subsequent episodes of Leishmaniasis, revealed after nasal surgery, provided crucial information for accurate diagnosis. METHODS: A retrospective review was conducted on this patient's electronic medical record. RESULTS: The patient's life-long struggle with nasal obstruction, congestion, and a septal perforation initially masked the underlying MCL. Sinus surgery and persistent symptoms further complicated the diagnostic process. Only after postoperative complications, including grainy skin texture extending into the nasal passages, did the patient recall the sandfly bite, prompting reevaluation and diagnosis of MCL. The case highlights the challenges of diagnosing MCL due to its varied presentation and potential mimicry of other chronic nasal conditions. It emphasizes the importance of thorough patient history-taking, especially when symptoms are atypical or persistent. Additionally, the report underscores the potential for unexpected postoperative complications in MCL patients and the need for vigilance in recognizing and assessing them. CONCLUSION: This case contributes to the understanding of MCL's diverse clinical presentation and the importance of early diagnosis and multidisciplinary management for prompt intervention and improved outcomes.

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.

[Intradermal and serologic testing for insect bite hypersensitivity in a Dahomey-Ox]. / Intradermaler und serologischer Allergietest zur Abklärung einer Insektenstich-Hypersensitivität bei einem Dahomey-Ochsen.

This case report describes an eosinophilic dermatitis on the prepuce of a Dahomey-Ox caused by an insect bite hypersensitivity against Culicoides spp. To the best of the authors' knowledge, this is the first report describing intradermal allergy and serological testing in cattle.

[Insect venom allergies-What will change in times of global change?] / Insektengiftallergien ­ Was wird sich ändern in Zeiten des globalen Wandels?

BACKGROUND: In Germany, honeybees (Apis mellifera) and various Vespula species (wasps) are primarily relevant for hypersensitivity reactions to stings. Hornets (Vespa crabro), bumblebees, paper wasps (Polistes) and yellowjackets (Dolichovespula) less frequently cause sting reactions. OBJECTIVE: What effects do intensive agricultural utilization and climate change have on the living conditions and occurrence of Hymenoptera and what consequences do they have for the diagnostics and treatment of hypersensitivity reactions to Hymenoptera stings. MATERIAL AND METHODS: A literature search was carried out. RESULTS: Honeybees and wild bees are endangered due to introduced diseases, invasive species and pesticides. The aim of widespread beekeeping activity is to protect honeybees, which is why no reduction in stings is to be expected despite increased bee mortality. In Germany, there is evidence of the spread of thermophilic Polistes species (paper wasps) from south to north and the immigration of Vespa velutina nigrithorax (Asian hornet). It is unlikely that these species will lead to a significant increase in sting reactions. Nests of the red fire ant (Solenopsis invicta), which was originally common in South America, were first detected in Sicily in 2022. Red fire ants are aggressive insects with a high potential for adverse sting reactions. CONCLUSION: Invasive insects must be considered as a trigger in the anamnesis and diagnostics. Diagnostics are only available for the detection of Polistes sensitization. Therapeutic allergens can be obtained from other European countries for venom immunotherapy of a Polistes allergy. Due to cross-reactivity, diagnostic and therapeutic allergens from Vespula spp. are used for the diagnosis and treatment of suspected allergies to the Asian hornet.

Alterações oculares decorrentes de picada de abelha na córnea / Ocular changes due to corneal bee sting

RESUMO O propósito deste estudo foi reportar as alterações oculares observadas após picada de abelha com ferrão retido na córnea. Destacamos o tratamento e o desfecho de uma lesão de córnea incomum e sua patogênese. Trata-se de relato de caso e revisão da literatura de lesões oculares por picada de abelha. Paciente do sexo feminino, 63 anos, procurou atendimento oftalmológico de urgência devido à picada de abelha na córnea do olho direito há 6 dias. Queixava-se de embaçamento visual, dor e hiperemia ocular. Apresentou acuidade visual de vultos no olho afetado. Ao exame, notaram-se hiperemia moderada de conjuntiva bulbar, edema corneano com dobras de Descemet e presença do ferrão alojado na região temporal, no estroma profundo da córnea. A paciente foi internada para ser abordada no centro cirúrgico sob anestesia geral. Durante a cirurgia, o ferrão teve que ser retirado via câmara anterior, mediante a realização de uma paracentese e uma lavagem da câmara anterior, com dupla via e solução salina balanceada. Ainda não existe na literatura um tratamento padrão na abordagem de pacientes com lesões oculares por picada de abelha, sendo importantes a identificação e o reconhecimento precoce de possíveis complicações que ameacem a visão.

ABSTRACT The purpose of this study was to report the ocular changes observed after a bee sting with a stinger retained in the cornea. We show the treatment and outcome of an unusual corneal injury and its pathogenesis. This is a case report and literature review of ocular injuries caused by bee stings. A 63-year-old female patient sought emergency ophthalmic care because of a bee sting on the cornea of her right eye six days before. She complained of blurred vision, pain, and ocular hyperemia. She had glare sensitivity on visual acuity in the affected eye. Examination revealed moderate hyperemia of the bulbar conjunctiva, corneal edema with Descemet's folds and a stinger lodged in the temporal region, in the deep stroma of the cornea. The patient was admitted to the operating room under general anesthesia. During surgery, the stinger had to be removed via the anterior chamber, by performing a paracentesis and washing the anterior chamber with a double flushing and balanced saline solution. There is still no standard treatment in the literature for patients with eye injuries caused by bee stings, and early identification and recognition of possible sight-threatening complications is important.

Sensitivity of a Hymenoptera serological immunoglobulin (Ig)E assay for the diagnosis of venom hypersensitivity in dogs.

BACKGROUND: Hymenoptera envenomation with honey bee (Apis mellifera) and paper wasp (Polistes spp.) may cause life-threatening anaphylaxis in dogs. In human patients, clinical history, intradermal testing (IDT) and measurement of allergen-specific serological immunoglobulin (Ig)E (sIgE) are used to support a diagnosis of Hymenoptera venom hypersensitivity. The utility of venom allergen-specific sIgE has not yet been evaluated for this purpose in dogs. OBJECTIVES: The objective of the study was to investigate the sensitivity (sn), specificity (sp) and positive predictive value (PPV) of honey bee and paper wasp serological titres using a commercially available sIgE assay [VARL (Veterinary Allergen Reference Laboratory) Liquid Gold] against clinical history for a diagnosis of Hymenoptera hypersensitivity in dogs. MATERIALS AND METHODS: Honeybee and paper wasp IgE serum titres were measured in 15 client-owned dogs with a diagnosis of Hymenoptera venom hypersensitivity based on a history of anaphylaxis, owner observation of Hymenoptera, and positive IDT to bee and/or wasp; and in 10 client-owned dogs with no known history of anaphylaxis or Hymenoptera exposure and a negative IDT to bee and wasp. RESULTS: Analysis of receiver operating characteristic (ROC) curves demonstrate that a VARL score cut-off of one of six for honeybee yields Sn, Sp and PPV of 40%, 60% and 60%, respectively, and two of six for wasp yields Sn, Sp and PPV of 25%, 78% and 60%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Owing to the poor sensitivity and PPV of sIgE assays for both bee and wasp hypersensitivity in dogs with known envenomation and anaphylaxis, the use of sIgE cannot be recommended as a tool for venom identification.

Basophil Activation Test in Double-Sensitized Patients With Hymenoptera Venom Allergy: Additional Benefit of Component-Resolved Diagnostics.

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.

Efficacy of Concentrated Heat for Treatment of Insect Bites: A Real-world Study.

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.

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

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.

Diagnostic and disease severity determination criteria for hydroa vacciniforme lymphoproliferative disorders and severe mosquito bite allergy.

Hydroa vacciniforme lymphoproliferative disorder (HV-LPD) and severe mosquito bite allergy (SMBA) are both cutaneous forms of Epstein-Barr virus (EBV)-associated T/natural killer (NK) cell LPDs and are closely related to chronic active EBV disease (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). HV-LPD is further divided into classic HV, a benign subtype mediated by EBV-positive γδT cells, and systemic HV, another life-threatening subtype mainly associated with EBV-positive αßT or γδT cells. The vast majority of patients with SMBA have increased numbers of EBV-infected NK cells in the blood. Clinical symptoms of HV-LPD and SMBA often overlap in the same patient and may progress to more serious disease conditions equivalent to the systemic form of CAEBV. To define the disease spectrum of HV-LPD and SMBA, we propose the diagnostic criteria and the determination criteria for disease severity. The proposed diagnostic criteria are consistent with those for CAEBV and EBV-HLH in the guidelines for the management for CAEBV and related disorders 2023.

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.

Venom Anaphylaxis: Decision Points for a More Aggressive Workup.

Diagnostic testing of patients who present for evaluation of insect venom allergy can involve many levels of investigation. A detailed initial history is critical for diagnosis and prognosis. The severity of previous sting reactions and the presence or absence of urticaria or hypotension predict severe future sting reactions and underlying mast cell disorders. Venom skin tests and specific IgE measurement can confirm the diagnosis but have limited positive predictive value for the frequency and severity of future sting reactions. Testing for serum IgE to recombinant venom component allergens can distinguish true allergy from cross-reactivity to honey bee and yellowjacket venoms. Basophil activation tests can improve the detection of venom allergy and predict the severity of reactions and the efficacy of venom immunotherapy but are limited in availability. An elevated basal serum tryptase level is an important marker for severe sting anaphylaxis and underlying mast cell disorders (eg, hereditary α-tryptasemia and clonal mast cell disease). When there is high suspicion (eg, using the Red Espanola de Mastocytosis score), bone marrow biopsy is the definitive tool to characterize mast cell disorders that are associated with the most severe outcomes in patients with insect sting allergy.

Hymenoptera venom skin testing: Adopting an accelerated test protocol.

BACKGROUND: The standard method of Hymenoptera venom intradermal skin test is performed at a starting concentration of 0.001 to 0.01 µg/mL and increased by 10-fold concentrations until positive or a maximum concentration of 1 µg/mL. Accelerated methods that start at higher concentrations have been reported as safe; however, many institutions have not adopted this approach. OBJECTIVE: To compare the outcome and safety of standard and accelerated venom skin test protocols. METHODS: This was a retrospective chart review of patients with suspected venom allergy who underwent skin testing at 4 allergy clinics within a single health care system from 2012 to 2022. Demographic data, test protocol (standard vs accelerated), test results, and adverse reactions were reviewed. RESULTS: Of 134 patients who underwent standard venom skin test, 2 (1.5%) experienced an adverse reaction, whereas none of the 77 patients who underwent accelerated venom skin test experienced an adverse reaction. One patient, with a history of chronic urticaria, experienced urticaria. The other experienced anaphylaxis requiring an epinephrine although had tested negative to all venom concentrations. Within the standard testing protocol, more than 75% of the positive results occurred at concentrations of 0.1 or 1 µg/mL. Within the accelerated testing protocol, more than 60% of the positive results occurred at 1 µg/mL. CONCLUSION: The study underscores the overall safety of venom intradermal skin test. Most of the positive results occurred at 0.1 or 1 µg/mL. Adopting an accelerated approach would reduce time and cost associated with testing.