Sting Allergy Research Articles

Case series of 23 deaths from Hymenoptera stings among United States Air Force populations

Medical conditions arising from hymenopteran sting allergy or mass envenomation are a serious health concern, particularly in austere environments. Both practicing allergists and entomological pest control personnel should consider the relevance of stinging insects when responding to problems with Hymenoptera. Recent occupational reviews of civilian deaths from insect bites and stings prompted our review of the US Air Force Mortality Registry to determine the relevance of insect stings and bites as a cause of death in the US Air Force. After reviewing over 40 years of death records we identified 23 death records, among US Air Force Active duty, guard, or retirees that arose directly from hymenopteran stings.

Insect sting allergy in adults: key messages for clinicians.

During their lifetime, 94.5% of people are stung by wasps, honeybees, hornets, or bumblebees (order Hymenoptera). After a sting, most people show typical local symptoms, 5% to 15% develop local allergic reactions, and 3% to 8.9%--systemic allergic reactions (SARs), which may be potentially life-threatening in about 10% of them. In mild forms of Hymenoptera-venom allergy (HVA), the leading symptoms are urticaria and edema (grades I and II, respectively, according to the Mueller classification). Severe SARs are classified as grade III (respiratory symptoms) and IV (cardiovascular symptoms). Rare manifestations of HVA are Kounis syndrome and takotsubo cardiomyopathy. All patients after an SAR require standard (skin test, IgE, tryptase) or comprehensive (component diagnosis, basophil activation test) allergy testing. All patients with severe systemic symptoms (hypertension, disturbances in consciousness) should be tested for mastocytosis. Additionally, a relationship was found between the severity of HVA symptoms and intake of angiotensin-converting enzyme inhibitors (ACEIs). There is a similar concern, although less well-documented, about the use of β-blockers. Patients with HVA who have experienced a SAR are potential candidates for venom immunotherapy (VIT), which is effective in 80% to 100% of individuals treated for 3 to 5 years. An increased risk of a VIT failure has been reported in patients with systemic mastocytosis and those treated with ACEIs. In certain groups (beekeepers, patients who develop a SAR to stings during a VIT with a standard dose, as well as those with a SAR to maintenance doses of VIT), a twice higher maintenance dose is recommended. Indications, contraindications, treatment protocols, and vaccine doses are regulated by the international guidelines of allergy societies.

Stinging insect allergy: current perspectives on venom immunotherapy.

Systemic allergic reactions to insect stings affect up to 5% of the population during their lifetime, and up to 32% of beekeepers. Such reactions can be fatal, albeit very rarely, and fear of a further systemic reaction (SR) can lead to significant anxiety and quality of life impairment. A recent Cochrane systematic review confirmed that venom immunotherapy (VIT) is an effective treatment for people who have had a systemic allergic reaction to an insect sting. VIT reduces risk of a further SR (relative risk 0.10, 95% confidence interval 0.03–0.28), but VIT also reduces risk of a future large local reaction, and significantly improves disease-specific quality of life. However, health economic analysis showed that VIT is generally not cost effective for preventing future SRs; most people are stung infrequently, most SRs resolve without long-term consequences, and a fatal outcome is extremely rare. VIT only becomes cost effective if one is stung frequently (eg, beekeepers) or if quality of life improvement is considered. Thus, for most people with insect sting allergy, anxiety and quality of life impairment should be the overriding consideration when making treatment decisions, highlighting the importance of a patient-centered approach. Areas which need to be explored in future research include efforts to improve the safety and convenience of VIT such as the use of sublingual immunotherapy; quality of life effects of venom allergy in children and adolescents as well as their parents; and the optimal duration of treatment.

CME Exam: When Can Immunotherapy of Insect Sting Allergy Be Stopped?

CME Exam: When Can Immunotherapy of Insect Sting Allergy Be Stopped?

When Can Immunotherapy for Insect Sting Allergy Be Stopped?

Stings by Hymenoptera (honey bees, vespids, ants) can cause systemic allergic reactions (SARs). Venom immunotherapy (VIT) is highly effective and reduces an allergic patient's risk of a recurrent SAR to less than 5-20%. The risk of a recurrent SAR to a re-sting decreases the longer VIT is continued. The recommended duration of VIT is at least 3 to 5 years. Risk factors for recurrent SARs to a sting after stopping VIT have been identified and discussed: Recommendations concerning stopping VIT: For patients without any of the identified risk factors, VIT should be continued for 5 rather than 3 years. In patients with definite risk factors, a longer duration of VIT has to be discussed before stopping it. In mast cell disorders, VIT for life is recommended. Because of the residual risk of SARs after VIT, all patients are advised to carry an epinephrine autoinjector indefinitely and to continue to take measures to avoid Hymenoptera stings.

New directions in diagnostic evaluation of insect allergy.

Diagnosis of insect sting allergy and prediction of risk of sting anaphylaxis are often difficult because tests for venom-specific IgE antibodies have a limited positive predictive value and do not reliably predict the severity of sting reactions. Component-resolved diagnosis using recombinant venom allergens has shown promise in improving the specificity of diagnostic testing for insect sting allergy. Basophil activation tests have been explored as more sensitive assays for identification of patients with insect allergy and for prediction of clinical outcomes. Measurement of mast cell mediators reflects the underlying risk for more severe reactions and limited clinical response to treatment. Measurement of IgE to recombinant venom allergens can distinguish cross-sensitization from dual sensitization to honeybee and vespid venoms, thus helping to limit venom immunotherapy to a single venom instead of multiple venoms in many patients. Basophil activation tests can detect venom allergy in patients who show no detectable venom-specific IgE in standard diagnostic tests and can predict increased risk of systemic reactions to venom immunotherapy, and to stings during and after stopping venom immunotherapy. The risk of severe or fatal anaphylaxis to stings can also be predicted by measurement of baseline serum tryptase or other mast cell mediators.

The relationship between insect sting allergy treatment and patient anxiety and depression.

Quality of life is affected by history of bee sting allergy. In addition, worry about being stung and also the need to use self-injection of medicine can create or increase anxiety, which can further compromise a patient's ability to enjoy the outdoors and participate in activities. We sought to determine the depression and anxiety in three groups of individuals. We assessed patients with bee sting allergy without epinephrine, bee sting allergy with epinephrine, and bee sting allergy receiving immunotherapy (venom immunotherapy [VIT]). We use two standardized surveys after having Intuitional Review Board approval to determine depression and anxiety in the three cohorts noted previously. We compared the three groups using Wilcoxon rank sum test and statistical significance was considered present for a value of p = 0.05. Overall, the epinephrine group had higher mean anxiety and depression scores compared with the other treatment groups. The VIT group had the lowest mean and median scores for both anxiety and depression. It appears that VIT not only decreases the risk of anaphylaxis and death, but also improves quality of life by reduction of anxiety and depression, especially in female subjects. We found that VIT patients, when compared with nontreated and treated only with epinephrine, had lower anxiety and depression scores.

Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper.

Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis.

Risk factors for eczema in infants born in Cuba: a population-based cross-sectional study

BackgroundThere is a concern that allergic disease in childhood is higher than expected in Cuba. The aim of this study was to determine the risk factors for eczema of infants aged 12–15 months living in Havana.MethodsWe used a cross-sectional epidemiological study design. Data on eczema symptoms and a wide range of lifestyle factors were collected by researcher administered questionnaires.ResultsData were collected on 1956 children (96% response rate), of whom 672 (34%) were reported as having had eczema. Independent risk factors for eczema included young maternal age (adjusted odds ratio (OR) 0.98 per additional year of age; 95% confidence interval (CI) 0.97-0.99), child’s weight (OR 1.13 per additional kg; 95% CI: 1.03-1.25), insect sting allergy (OR 2.11; 95% CI: 1.33-3.35), rodents in the home (OR 1.39; 95% CI: 1.10-1.76), attendance at childcare facilities (OR 1.34: 95% CI: 1.05-1.70) and self-reported mould in the home (OR 1.23; 95% CI: 1.07-1.41). Infant exposure to paracetamol was associated with an increased risk of eczema even after adjustment for wheeze (OR 1.22; 95% CI: 1.03-1.46).ConclusionDespite a very different culture and environment, the consistency of these findings with those from more economically developed countries suggests potential causal associations. The association with paracetamol, even after adjustment for wheeze, suggests that intervention studies are required in young infants, to ascertain if this commonly used anti-pyretic medication increases allergic disease.

Angioedema in the emergency department: clinical presentation and outcomes

was significantly longer in patients with urticaria (p<0.001), but the presence of urticaria did not predict admission. A probable cause was identified in 48.8% of visits. Periorbital angioedema was associated with environmental, contact, and insect sting allergy (p<0.001). 58.3% of patients with angioedema due to drug allergy had lip angioedema (p=0.032). C1 esterase inhibitor deficiency was most frequently associated with a history of previous episodes. Several factors were found to predict admission, including NSAID-induced angioedema (OR=15.3), epinephrine treatment (OR=8.34), hypotension (OR=15.7), multiple site angioedema (OR=4.25), pharyngeal angioedema (OR=1.23), and tongue angioedema (OR=4.62). Conclusions This large cohort retrospective review confirms causeclinical associations in angioedema and demonstrates novel predictors of morbidity, with implications in clinical practice.

Food allergy and anaphylaxis – 2038. Insect and sting allergy

This article was originally published online on 23 April 2013 Insect and sting allergy in immunocompetent populations. A comparison. Observation made in diferent subsets of population who had insect and sting allergy (bees, wasps, scorpions, mosquitos parasites etc). 1) Immunocompetent population in the developing world engaged in farming and related activities regularly exposed to all gradient of allergens like dust molds, dander, pets, etc and when they are exposed to insect and mosquito bites, bees and wasps stings even scorpion bites they suffer to a lesser extent. 2) Immunocompromised population in the developed world far away from natural gradient of exposure of nearly all the allergens and when they are exposed to scorpion bite or bees and wasp stings there are reports of fatal reactions and even mosquito and insect bites causes serious wheal and flare reaction, this observation was made specially on the second generation of children from parents of Indian origin now living in USA and other affluent countries, where there is minimal exposure to all the allergens. Based on the observation made on nearly 2 lakh patients it was observed that there is a direct relationship of levels of exposure to all the natural allergens and the immunotolerance achieved by this natural exposure or natural immunotherapy. After above mentioned observations we reached to the conclusion that exposure to natural gradient of allergens, insect bites mosquito bites is troublesome for the immunocompromised populations who follow avoidance of exposure to allergens as a rule and this is a disaster for them there are many deaths reported due to the above mantioned exposure, at the same time the immunotolerant population which is exposed to all sorts of allergens insect bites mosquito bites bees and wasps stings suffers to a lesser extent.

Basal tryptase linked to severe reactions in children with sting allergy

Basal tryptase linked to severe reactions in children with sting allergy

Venom Immunotherapy: Pitfalls and Open Questions

Depending on the climate, 56.6–94.5% of the general adult population have been stung by a hymenoptera species at least once in their lives [1]. The rate of self-reported systemic sting reactions (SSRs) in European epidemiological studies ranges from 0.3 to 8.9% while large local reactions (LLRs) range from 2.4–26.4% [1]. There is, however, to date no existing parameter that enables clinicians to predict who will have a future reaction and whether it will be a LLR or SSR. Recently, Bilo and Bonifazi reviewed in Immunotherapy that insect sting allergy and venom immunotherapy (VIT) remains an excellent model for the study of anaphylaxis and immune tolerance, and that VIT is the most effective form of specific immunotherapy [2]. Indications as well as contraindications, the natural history and risk factors, selection of venoms, treatment protocols, side effects, monitoring and duration of VIT, are well characterized by studies, with the daily practice of VIT following unequivocal guidelines [3] and practive parameter recommendations [4].

Safety of hymenoptera venom immunotherapy: a systematic review

Introduction:The efficacy of venom immunotherapy (VIT) in patients with insect sting allergy is not questioned. However, its safety, especially when honeybee is used, is a matter of concern.Areas covered:A systematic review of the literature on VIT was done, with both aqueous and depot extracts, to compare the frequency of systemic reactions to honeybee and vespid venoms. A Medline search was performed using the keywords ‘venom immunotherapy’, ‘safety’ and ‘tolerability’. The articles obtained were analyzed regarding the total number of patients treated with either honeybee or vespid VIT, the number and severity of systemic reactions during therapy, the type of extract used (aqueous or depot) and the administration regimen.Expert opinion:The incidence of systemic reactions to VIT was 25.1% for honeybee venom and 5.8% for vespid venom (p < 0.0001), while it was similar with aqueous and depot extracts in the whole population of patients. This confirms that during VIT systemic reactions are significantly more frequent with honeybee venom compared with vespid venom, while there are no significant overall differences in systemic reactions between aqueous and depot extracts.

European Academy of Allergy and Clinical Immunology task force report on ‘dose-response relationship in allergen-specific immunotherapy’

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

Detection of IgE to recombinant Api m 1 and rVes v 5 is valuable but not sufficient to distinguish bee from wasp venom allergy

Detection of IgE to recombinant Api m 1 and rVes v 5 is valuable but not sufficient to distinguish bee from wasp venom allergy

Purification and characterization of two new allergens from the salivary glands of the horsefly, Tabanusyao

Horsefly bite can cause allergic reactions in humans. There is no information about allergenic horsefly proteins. The current work aims to purify and characterize IgE-binding proteins from horsefly salivary glands. Two IgE-binding proteins, Tab a 1 and Tab a 2 with molecular weight of 26 and 35 kd, respectively, were purified and characterized from 60,000 pairs of horsefly salivary glands of Tabanus yao, respectively. Their primary sequences were determined by Edman degradation and cDNA cloning. Their allergenicity was examined using enzyme-linked immunosorbent assay (ELISA), ELISA inhibition tests, and immunoblots. Immunoblotting demonstrated IgE binding by 32 and 34 of 37 (86.5% and 91.8%) subjects' sera to Tab a 1 and Tab a 2, respectively. They were identified as an antigen 5-related (Ag 5) protein and hyaluronidase, respectively. ELISA inhibitions of serum IgE reactivity to the horsefly salivary gland extract (SGE) using purified Tab a 1 and Tab a 2 were significant (about 45%). In addition, these proteins showed some IgE-binding capacity to sera of subjects with wasp sting allergy. We have first identified and characterized two IgE-binding proteins, Tab a 1, an Ag 5-like protein and Tab a 2, a hyaluronidase, from the horsefly salivary glands. They appear to be of importance for the allergic reactions induced by horsefly bite. These allergens are thus not only found in stinging but also found in hematophagous insects. These results also provided support for the presence of the so-called wasp-horsefly syndrome (WHS).

Guidelines for clinical practice: hymenoptera sting allergy in children

Guidelines for clinical practice: hymenoptera sting allergy in children

Basophil responsiveness in patients with insect sting allergies and negative venom‐specific immunoglobulin E and skin prick test results

Current guidelines do not adequately address the question of how best to manage patients with a convincing history of insect allergy, but negative venom-specific IgE and skin test results. Forty-seven patients out of a total of 1219 (4%), with a positive history of sting allergy, were recruited over a period of 4.5 years. All recruited patients had a convincing history of a severe or a life-threatening anaphylactic reaction of Mueller grade II-IV (median grade III) after Hymenoptera sting, but negative venom-specific IgE and skin prick test results. Diagnostic work-up was prospectively followed by the CD63 basophil activation test and by intradermal skin testing. A control group of 25 subjects was also assessed. Thirty-five out of 47 (75%) patients demonstrated a positive basophil CD63 response after stimulation with bee and/or wasp venom. Intradermal venom skin tests were performed for 37 patients, 17 (46%) of whom showed positive results. Out of 20 patients who demonstrated negative intradermal test results, 12 patients showed a positive CD63 response (60%). In contrast, out of 9 patients who showed a negative CD63 response, only one was detected by intradermal testing (11%). In the control group, only two out of 25 (4%) subjects displayed a positive basophil response and/or intradermal test. Here we show that, in complex cases with inconclusive diagnostic results, the CD63 activation test could be particularly useful and more sensitive than intradermal skin testing.

The natural history and epidemiology of insect venom allergy: clinical implications

Hymenoptera stings can cause severe systemic allergic reactions and occasionally fatal anaphylaxis, which contribute significantly to morbidity and deterioration in health-related quality of life. The latest epidemiological data confirm the importance of insect sting allergy as a cause of anaphylaxis. Despite the high prevalence of asymptomatic sensitization, the prevalence of sting-induced systemic reactions (SRs) is low. However, to date, no parameter has been identified that can predict who will have a future reaction and whether it will be a large local reaction or anaphylactic. The combination of several concomitant factors, which include environmental, genetics and individual factors, may account for the occurrence of a system reaction in individual patients. Several not completely known factors may be associated with the severity of systemic re-stings. As about 50% of subjects with fatal sting reactions had no documented history of a previous SR, greater insight of the natural history and risk factors is required, especially in asymptomatic sensitized subjects. For patients with SRs, prevention of future severe allergic reactions starts with referral to an emergency department, correct administration of epinephrine by medical staff, referral to an allergist and coaching for the self-administration of epinephrine. However, most insect sting victims failed to seek medical advice and hospital attendance does not always correlate with the severity of the allergic reaction. Moreover, only about one-third of patients received a prescription for self-injectable epinephrine and were officially referred to an allergist after being discharged, causing the non- or delayed prescription of specific immunotherapy. Significantly, this means that at least half of the sting fatalities in patients with a positive history could have been avoided through the timely administration of specific immunotherapy. These findings indicate the urgent need to educate the general population and doctors on the management of venom-allergic patients.