Venom Sensitization Research Articles

Venom Component Allergen IgE Measurement in the Diagnosis and Management of Insect Sting Allergy

Accurate identification of the allergy-eliciting stinging insect(s) is essential to insuring effective management of Hymenoptera venom-allergic individuals with venom-specific immunotherapy (VIT). Diagnostic testing using whole venom extracts with skin tests and serological-based analyses remains the first level of discrimination for honeybee versus vespid venom sensitization in clinical history-positive patients. As a second-level evaluation, serological testing using molecular venom allergens can further discriminate genuine sensitization (honeybee venom: Api m 1, 3, 4, and 10 versus yellow jacket venom/Polistes dominula venom Ves v 1/Pol d 1 and Ves v 5/Pol d 5) from inter-species cross-reactivity [hyaluronidases (Api m 2, Ves v 2, Pol d 2) and dipeptidyl peptidases IV (Api m 5, Ves v 3, Pol d 3)]. Clinical laboratories use a number of singleplex, oligoplex, and multiplex immunoassays that employ both extracted whole venom and molecular venom allergens (highlighted above) for confirmation of allergic venom sensitization. Established quantitative singleplex autoanalyzers have general governmental regulatory clearance worldwide for venom allergic patient testing with maximally achievable analytical sensitivity (0.1 kUA/L) and confirmed reproducibility (inter-assay CVs<10%). Emerging oligo- and multiplex (fixed panel) assays conserve on serum and are more cost-effective, but they need regulatory clearance in some countries and are prone to higher rates of detecting asymptomatic sensitization. Ultimately, the patient’s clinical history, combined with the proof of sensitization, is the final arbiter in the diagnosis of Hymenoptera venom allergy.

Leech-bite induced anaphylaxis with or without Hymenoptera venom sensitization

Leech-bite induced anaphylaxis with or without Hymenoptera venom sensitization

Skin prick tests are not useful for the qualification for venom immunotherapy in children

BackgroundThe basis for qualification for venom immunotherapy (VIT) is the fulfilment of both the clinical and immunological criteria. Diagnostic tests that confirm the immunological criterion of an IgE-mediated sensitization include skin prick tests (SPT), intradermal tests (IDT), and serum specific IgE (sIgE) for the culprit venom. ObjectiveThis study aimed to assess the usefulness of SPT as the immunological marker in the diagnosis of insect venom sensitization in children with history of systemic reaction (SR) to insect sting evaluated by means of I-IV-grades Mueller's scale. There are no such studies in children. MethodsThis cross-sectional study sample consisted of 416 children aged 3–18 years (mean age 10.6 ± 3.8), 76% males, all with the history of a systemic reaction (SR) after a Hymenoptera sting (48% of grade III/IV according to Mueller scale), diagnosed between 1999 and 2019 in the tertiary referral centre. The standard diagnostic tests were used. Specificity, sensitivity, and positive and negative predictive values were computed to assess the diagnostic properties of the clinical tests to distinguish between mild and severe SR. To assess the relative value of an individual test in predicting the qualification to VIT we incorporated the Shapley value (SV). ResultsPositive SPT results were found in up to no more than 3% of children; among them less than 1% had only positive SPT and were negative for sIgE and IDT. Approximately 85% of the children had detectable venom sIgE, followed by positive IDT (75%). Almost 70% of children had positive both sIgE and IDT results. In children with grade III/IV reaction, about 80% of children had positive results of both of these tests. sIgE and IDT had sensitivity >0.80, whereas SPT had high specificity (>0.97) in differentiating between mild and severe SR. Relative value of diagnostic tests in predicting qualification to VIT varied between venoms. Bee venom IDT had higher SV (0.052) than sIgE (0.041). In contrast, wasp venom sIgE had higher SV (0.075) than IDT (0.035). ConclusionSPTs are not an useful immunological marker of venom sensitization in children, and eliminating SPT does not result in a loss of diagnostic accuracy. Limiting diagnostics to venom sIgE and IDT would shorten the procedure and reduce costs. Future studies are needed to determine if venom sIgE as the first line diagnostic test, with IDT added only if the venom sIgE is undetectable, is an optimal diagnostic process.

Local and Systemic Reactions due to Subcutaneous Allergen Immunotherapy: Our Single-Center 5-Year Experience

Aim: Subcutaneous allergen immunotherapy (SCIT) currently represents the only disease-modifying therapeutic option for the treatment of allergic rhinitis/conjunctivitis, asthma, and venom sensitization. Although SCIT represents a fairly safe therapeutic option in the hands of experienced physicians and centers, it may also be associated with certain adverse effects. In this study, we describe the local and systemic adverse effects in our adult patients undergoing immunotherapy over a 5-year period in an effort to define the causative factors. Materials and Methods: A total of 4413 injections administered to 119 patients (58 female, 61 male) were analyzed. Results: A total of 119 patients with a mean age of 33.7 ± 12 years were included (Female: 58, 48%; Male: 61, 51.3%). In the total population of 119 patients, 6 (5%) developed local reactions, 21 (17.7%) developed large local reactions, and 9 (7.6%) had systemic reactions. Of all injections administered throughout the study period, 0.14% were associated with local reactions, 0.48% with large local reactions, and 0.20% with systemic reactions. Four patients with systemic reactions (44.4%) required epinephrine injection. Patients who did or did not develop adverse effects were significantly different with regard to IgE levels and eosinophil counts (p=0.001 and p=0.002). There was a significant difference between the rates of total adverse reactions developing during the build-up or maintenance phase (p=0.025). Conclusion: Clinicians’ awareness regarding the local, large local, and systemic reactions associated with SCIT should be improved, and clinicians should be more careful during the immunotherapy, especially in the build-up phase, for adverse events.

Cross-reactivity between tick and wasp venom can contribute to frequent wasp sensitization in patients with the α-Gal syndrome.

Backgroundα‐Gal syndrome (AGS) is a food allergy with severe delayed allergic reactions, mediated by IgE‐reactivity to galactose‐α1,3‐galactose (α‐Gal). AGS is strongly associated with tick bites. An increased incidence of venom sensitization has been found in AGS patients. Here, we evaluated the frequency of wasp sensitization in Swedish AGS patients and the possible cross‐reactivity between wasp venom and tick proteins.MethodsSera from 136 Swedish AGS patients and 29 wasp‐positive non‐AGS control sera were analyzed for IgE‐reactivity against wasp venom (Vespula spp.), the European tick Ixodes ricinus (Streptavidin ImmunoCAP), α‐Gal and total IgE by ImmunoCAP. The presence of α‐Gal on wasp venom proteins (Vespula vulgaris) was investigated by western blot (WB), and possible cross‐reactivity between wasp venom and tick proteins by enzyme‐linked immunosorbent assay and WB. Involvement of cross‐reactive carbohydrate domains (CCDs) was also assessed.ResultsWasp sensitization was present in 54% of AGS patients, although the IgE levels were low. Wasp sensitized patients had higher IgE levels to α‐Gal and total IgE levels compared to non‐wasp sensitized AGS patients. α‐Gal was not detected in wasp venom, but cross‐reactivity between wasp and tick proteins was demonstrated which was not dependent on CCDs. The same cross‐reactivity was also observed in the control sera. Furthermore, 17 putative cross‐reactive peptides were identified using an in silico approach.ConclusionsFor the first time, cross‐reactivity between wasp venom and tick proteins has been described. This may be a reason why the majority of Swedish AGS patients, who have all been tick bitten, are also sensitized against wasp.

Composition des venins d’hyménoptères et de la salive des arthropodes hématophages

Hymenoptera venoms contain many substances with toxic properties causing inflammation at sting location. Biogenic amines, enzymes and mast cell degranulating peptides are identified in Apidae and Vespidae venoms. In Formicidae, alkaloids are involved. These substances have also hemolytic, cytolytic and for some of them neurotoxic properties. Numerous allergens are identified especially in bee venom. Phospholipase A 2 (Api m 1) and hyaluronidase (Api m 2) are major allergens. Other allergens playing a major role in bee venom sensitization are mellitin (Api m 4), dipeptidylpeptidase (Api m 5) and the more recently described icarapin (Api m 10). In total, twelve bee venom allergens are registered in the international nomenclature. In Vespidae, major allergens are phospholipase A 1, hyaluronidase and the antigens 5. These allergens are more or less shared between Vespula, Polistes and Vespa species, which makes accurate diagnosis by means of serology particularly difficult. Ant venoms are less studied: essentially a phospholipase (Sol i 1) is described in the venom of Solenopsis species. The saliva of blood-sucking arthropods contains also many less well known components, except for mosquito where nine salivary allergens have been identified. All these allergens are often common to different species, explaining the high frequency of cross reactions observed in studies, as well in vivo as in vitro. These allergenic similarities may also explain cases of co-sensitization between hymenoptera and diptera..

Proteomic features characterization of Hymenoptera venom allergy

BackgroundHymenoptera venom allergy is one of the most frequent causes of anaphylaxis. In its most severe form, the reaction to wasp and honey bee stings may be life-threatening. Therefore, immediate and proper diagnosis of venom allergy and implementation of suitable therapy are extremely important. Broadening the knowledge on the mechanism of the allergic reaction may contribute to the improvement of both diagnostic and treatment methods. Thus, this study aimed to discover changes in protein expression in serum of patients allergic to Hymenoptera (wasp and honeybee) venom and to point out proteins and peptides involved in the allergic inflammation.MethodsSerum proteomic patterns typical to allergic patients and healthy volunteers were obtained with MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) mass spectrometer. The spectra were processed, analyzed and compared using advanced bioinformatics tools. The discriminative peaks were subjected to identification with liquid chromatography coupled with tandem mass spectrometry.ResultsThis methodology allowed for the identification of four features differentiating between allergy and control groups. They were: fibrinogen alpha chain, coagulation factor XIII chain A, complement C4-A, and inter-alpha-trypsin inhibitor heavy chain H4. All of these proteins are involved in allergic inflammatory response.ConclusionsExtending the knowledge of the Hymenoptera venom sensitization will contribute to the development of novel, sensitive and specific methods for quick and unambiguous allergy diagnosis. Understanding the basis of the allergy at the proteomic level will support the improvement of preventive and therapeutic measures.

Prevalence of Hymenoptera venom allergy and sensitization in the population-representative German KORA cohort

Allergic reactions to Hymenoptera venoms represent potentially life-threatening conditions. However, studies on their prevalence in Germany and their relation to specific IgE sensitization are rare. The aim of this study was to evaluate the prevalence of Hymenoptera venom allergy as well as the frequency of venom-specific IgE sensitization in a large population-based adult German cohort. Questionnaire data were collected from the participants of the German population-based KORA (Cooperative Health Research in the Region of Augsburg) S4 baseline study population (n = 4,261) and the follow-up F4 study population (n = 3,074), which was conducted seven years later. Moreover, sIgE antibodies to honeybee (HBV) and yellow jacket venom (HJV) as well as to common aeroallergens were measured in the S4 study population. The prevalence of systemic sting reactions ranged between 2.3 % and 2.6 %. sIgE sensitization (≥ 0.35 kUA/L) to HBV and YJV was demonstrated in 23.1 % and 31.7 % of the population, respectively (41.6 % to HBV and/or YJV). Double-sensitization to both venoms occurred in 13.2 % of the individuals. Approximately 53 % and 77 % of the individuals who reported shock symptoms after honeybee and yellow jacket stings, respectively, exhibited sIgE ≥ 0.35 kUA/L to the culprit venom. In contrast, only 2.8 % of the venom-sensitized individuals reported symptoms exceeding local reactions. Local reactions were reported by 4.4 to 4.8 % of the population. Self-reported Hymenoptera sting reactions and venom sensitization are frequent in the general German population. In many cases, sensitization and clinically relevant allergy are not observed in the same individual, indicating that comprehensive diagnostic approaches are a prerequisite for the identification of patients at risk for severe reactions.

Allergy and sensitization to Hymenoptera venoms in unreferred adults with a high risk of sting exposure

BackgroundHymenoptera venom sensitization in highly exposed individuals frequently requires risk assessment for future severe sting reactions. In this study, we determined the prevalence of Hymenoptera venom sensitization in individuals who hunt and fish and analyzed possible correlations between the severity of sting reactions and the IgE sensitization profile. MethodsIn this cross-sectional study, paper-based, self-filled questionnaires about previous insect stings and sting reactions were obtained from individuals who hunt and fish in Bavaria, Germany. Blood samples were taken and analyzed for the levels of tryptase, total IgE and IgE to honey bee (i1) and wasp (13) venom, the recombinant allergens rApi m 1, rApi m 2, rApi m 3, rApi m 5, rApi m 10, rVes v 1, rVes v 5, and the CCD marker molecule MUXF3. Odd ratios (ORs) for sensitization and anaphylaxis and Pearson's correlations for the different allergens were calculated. ResultsOf 257 participants, 50.2% showed a sensitization to honey bee venom (i1), and 58.4% showed sensitization to wasp venom (i3). A total of 98.4% of participants claimed to have been stung at least once. Anaphylaxis was reported in 18.7%, and a local sting reaction was reported in 18.3%. The highest sensitization rates were found for whole venom extracts, sensitization to any of the available recombinant allergens exceeded sIgE levels to honeybee venom (i1) in 28.5% and to wasp venom (i3) in 52.9% of participants. Participants with a history of more than 5 stings showed a higher risk for anaphylaxis. ConclusionsSensitization to Hymenoptera venom and their recombinant allergens are present in the majority of individuals who hunt and fish. Sensitization to distinct recombinant allergens does not necessarily affect the severity of sting reactions including anaphylaxis. A meticulous medical history of the number of previous stings as well as systemic reactions remains essential.

Component-resolved diagnosis in selecting patients for yellowjacket venom immunotherapy

BackgroundVenom immunotherapy is effective in preventing systemic allergic reactions (SARs), but the diagnosis of venom allergy is problematic. ObjectiveTo compare the performance of component-resolved diagnosis and conventional tests in patients referred for venom immunotherapy. MethodsWe measured serum-specific immunoglobulin E to yellowjacket and honeybee venoms (Ves v 1 and Ves v 5 and Api m 1), cross-reactive carbohydrate determinants, serum basal tryptase (ImmunoCAP, ThermoFisher Scientific, Uppsala, Sweden), and skin prick test reactions in 84 patients referred to receive venom immunotherapy. History of SAR and its severity were evaluated. ResultsOf the 78 patients with suspected yellowjacket venom (YJV) allergy, a history of SAR was confirmed in 47 (60%) and 31 (40%) had a non-SAR reaction. The most accurate tests to confirm venom allergy after a SAR were serum-specific immunoglobulin E to yellowjacket whole-venom extract spiked with Ves v 5 (area under the curve 0.87, 95% confidence interval 0.77–0.97, P < .001) and Ves v 5 (area under the curve 0.86, 95% confidence interval 0.76–0.96, P < .001). Sensitization to Ves v 1 was infrequent and its area under the curve was low (0.62, 95% confidence interval 0.47–0.76, P = .106). Sensitivity of the YJV skin prick test was 86%, but its specificity was low at 54%. Double sensitization to yellowjacket and honeybee occurred frequently in skin prick tests. Of the patients without a SAR, 26% showed a positive reaction to YJV in any serum test and 46% showed a positive reaction in skin tests. ConclusionSpecific immunoglobulin E to the YJV spiked with Ves v 5 confirmed the allergy after a SAR. A history of SAR should be confirmed before testing, because venom sensitization is frequent in other types of reactions.

Tricky cases in in-vitro diagnostics of hymenoptera venom allergy

Hymenoptera stings give rise to anaphylactic reactions in 1.2-3.5 % of the population. The risk of repeat anaphylaxis following subsequent stings is greatly reduced through immunotherapy with the culprit venom. A prerequisite for allergen-specific immunotherapy is a precise diagnostic work-up. We review the efficacy of currently available in-vitro diagnostic tests for hymenoptera venom allergy in different clinical scenarios. A targeted literature review in PubMed and a review of the current guideline on hymenoptera venom allergy were performed. For illustrative purposes, a series of clinical cases from our allergy department are presented. The correct diagnosis in hymenoptera venom allergy is influenced by a number of factors including patients' ability to identify the insect and time lapsed to diagnostic tests. The high rate of clinically irrelevant sensitizations, cross-reactivity and suboptimal sensitivity of the currently available diagnostic tests further complicate the picture. In the case of multiple sensitizations, molecular allergy diagnostics has improved the detection of clinically relevant sensitizations allowing the cost and risks of unnecessary double immunotherapy to be avoided. This is true in particular with regard to wasp venom allergy. For bee venom allergy, improvements in molecular allergy diagnostics have shown promising results and their implementation in clinical practice is planned. In patients with no sensitization in skin or serological tests but with a convincing history of insect sting anaphylaxis, the increased sensitivity of a basophil activation test may deliver crucial evidence of venom sensitization. The value of the basophil activation test may be further improved using specific marker allergens. The diagnosis of allergy to paper wasps (Polistinae) and white-faced hornets (Dolichovespula) remains problematic as they show partial cross-reactivity to wasp venom and specific marker allergens particular to these, still have to be identified.

Impact of Hymenoptera venom allergy and the effects of specific venom immunotherapy on mast cell metabolites in sensitized children.

Mast cells (MC) are effector cells during severe systemic reactions (SR) to Hymenoptera stings. Venom specific immunotherapy (VIT) is the treatment of choice for prevention of SR to stings. Tryptase and prostaglandin D₂ metabolites (PGD₂) are the markers of MC activation. The study design was to 1. compare baseline values of serum tryptase concentration (BST) and PGD₂ metabolites in children with/without venom sensitization, 2. to evaluate an influence of rush VIT on MC markers in treated children. Sensitized group: 25 children with SR to Hymenoptera sting. 19 healthy children. Active treatment: 5-day-rush-VIT. BST was evaluated by ImmunoCAP, PGD₂ metabolites in blood and urine by GC-NICI-MS. The baseline blood levels of MC markers were significantly higher, while urinary concentration of 9α,11β-PGF₂ was significantly lower in the whole group of venom-sensitized children compared to controls. Severity of SR showed negative correlation with urinary PGD₂ metabolites, while positive with plasma 9α,11β-PGF₂ and BST concentration The highest sensitivity was obtained for plasma 9α,11β-PGF₂ whereas the highest specificity for urinary PGD-M. In children with IgE-mediated SR to Hymenoptera stings, elevation of baseline values of PGD₂ metabolites in blood is accompanied by decreased excretion of its urinary metabolites. Assessment of stable PGD₂ metabolites might serve as an independent MC marker to identify allergic children. There is an association between urinary PGD₂ metabolites and severity of the SR to Hymenoptera stings.

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

Basophil Activation Test for the Diagnosis of Hymenoptera Venom Allergy in Childhood: a Pilot Study

Cellular in vitro tests such as the CD63-based basophil activation test (BAT) have been successfully used to diagnose hymenoptera venom sensitization in adult patients while this has not been investigated in children so far. 15 children (9 male, 6 female; 12.7±3.5 years) with suspected allergy to vespula (VE) or honey bee (HB) venom entered this study. Besides serum tryptase (ST) levels, sensitisation against VE and HB was assessed by titrated skin testing and determination of venom-specific serum IgE (sIgE) in all patients. After stimulation with 50 ng of insect venom, CD63-expression of activated basophils was measured by flow cytometry. Skin testing permitted identification of the culprit insect in 7 patients, 3 cases were diagnosed by additional sIgE measurements. In addition, BAT identified mono-sensitization in 3 further patients with double sensitization upon skin and sIgE testing. Test sensitivity was lower for the BAT (67-75%) than for skin testing (89-100%) and sIgE determination (100%). Neither basophil activation nor sIgE serum levels were identified as reliable predictors of sting reaction severity. In all patients, ST measurements yielded values below the upper reference value. The current pilot study suggests a possible clinical benefit of BAT analysis in the diagnostic workup of pediatric insect venom allergy. However, further large-scale trials are required to investigate whether the BAT reliably contributes to the correct identification of the culprit insect venom. Due to its comparatively low sensitivity, the BAT should currently not be used in isolation from, but only in combination with established diagnostic instruments.

Predictors of Bothrops jararaca venom allergy in snake handlers and snake venom handlers

Since allergic sensitization to snake venom has been reported, anaphylactic reactions to snake venom might be an underestimated factor contributing to fatal snakebites, independently from the toxicity of the venom itself. However, little information is available on the determinants of such reaction. Hence, we studied a group of workers exposed to Bothrops jararaca venom (BJV), in order to clarify the factors related with snake venom allergy. The aim of this work was to investigate the prevalence and predictors of venom allergy among workers exposed to BJV and to confirm the involvement of IgE-mediated mechanisms in this condition. Workers exposed to BJV were assessed for venom allergy using questionnaires and immunological tests. The presence of BJV sensitization was determined through quantification of specific IgE. Allergens were studied using the Western blots and inhibition assays. Of the 67 workers evaluated, 7 (10.4%) presented specific IgE antibodies to BJV. Of those, 6 presented typical symptoms of an IgE-mediated allergic reaction when exposed to BJV. Venom sensitization was associated with length of employment ( P=0.042), high levels of total IgE ( P=0.034), atopy ( P=0.051), and specific tasks, primarily the handling of dried venom ( P=0.014). Our observations suggest that exposure to BJV can result in allergic sensitization in snake handlers through IgE-mediated mechanisms. The prevalence rate of this condition appears to be high among these workers, and the handling of dried venom, total IgE level above 100 kU/L, length of employment, and probably history of atopy were predictors of its occurrence.

Pattern of sensitization to honeybee venom in beekeepers: A 5-year prospective study

Beekeepers are at increased risk for honeybee (Hb) venom allergy and they represent a unique population for Hymenoptera venom studies. The aim of this was to prospectively examine the pattern of Hb venom sensitization over a 5-year period in new beekeepers and define possible predisposing factors. Thirty-five beekeepers were tested every 6 months for 5 years with in vivo and in vitro methods to detect the possible development of sensitization to Hb and common wasp (Cw) venom. Inclusion criteria included the lack of previous beekeeping activity and absence of sensitization or reported reaction to Hymenoptera stings. Subjects with both in vivo and in vitro tests that were definitely positive or with one definitely positive and the other doubtful were considered sensitized. Ten of 35 new beekeepers (28.6%) and 3 of 36 controls (8.3%) developed sensitivity to Hb venom during the 5-year period. The risk ratio in incidence studies was calculated at 3.43 (SE of log risk ratio = 0.61; 95% CI of risk ratio = 1.03-11.42). All sensitized beekeepers were detected within the first 18 months of occupational exposure; 8 of 10 (80%) beekeepers were detected during the initial 12 months and the 2 remaining beekeepers were detected between 12 and 18 months. One of 35 (2.9%) beekeepers and 1 of 36 controls (2.8%) were sensitized to Cw venom. The number of stings per year and atopy had no effect on sensitization rate. Although predisposing factors to sensitization or anaphylaxis could not be identified, beekeepers developed sensitization to bee venom in <18 months.

Prevention of allergy by a recombinant multi-allergen vaccine with reduced IgE binding and preserved T cell epitopes

Novel approaches for the prevention of allergy are required, because of the inevitably increasing prevalence of allergic diseases during the last 30 years. Here, a recombinant chimeric protein, which comprises the whole amino acid sequences of three bee venom major allergens has been engineered and used in prevention of bee venom sensitization in mice. Phospholipase A2 (Api m 1), hyaluronidase (Api m 2) and melittin (Api m 3) fragments with overlapping amino acids were assembled in a different order in the Api m (1/2/3) chimeric protein, which preserved entire T cell epitopes, whereas B cell epitopes of all three allergens were abrogated. Accordingly, IgE cross-linking leading to mast cell and basophil mediator release was profoundly reduced in humans. Supporting these findings, the Api m (1/2/3) induced 100 to 1000 times less type-1 skin test reactivity in allergic patients. Treatment of mice with Api m (1/2/3) led to a significant reduction of specific IgE development towards native allergen, representing a protective vaccine effect in vivo. These results demonstrate a novel prototype of a preventive allergy vaccine, which preserves the entire T cell epitope repertoire, but bypasses induction of IgE against native allergen, and side effects related to mast cell/basophil IgE FcepsilonRI cross-linking in sensitized individuals.

Hymenoptera Venom Allergy: Time Course of Specific IgE Concentrations during the First Weeks after a Sting

Detection of IgE antibodies specific to honeybee or Vespula venoms is an important criterium firstly for the diagnosis of sensitization and secondly for the indication for a specific immunotherapy. Some authors recommend to postpone blood analysis after an insect sting for a certain time because circulating IgE antibodies might be consumed by the allergic reaction, which would result in a false–negative test outcome. We investigated IgE concentrations during the first weeks after an insect sting in 31 patients with an unequivocal history of an anaphylactic reaction after a honeybee (n = 13) or Vespula (n = 18) sting. Blood samples for analysis of specific IgE concentrations (CAP system, Pharmacia Diagnostics, Sweden) were collected within 2 weeks and 5±2 weeks after the insect sting. 12/13 patients with honeybee venom and 14/18 patients with Vespula venom sensitization had CAP classes 1 or higher within the first 2 weeks. Those 5 patients with CAP class 0 within the first 2 weeks had detectable IgE concentrations a few weeks later. We conclude that testing for specific IgE to hymenoptera venoms is in most cases useful even during the first 2 weeks after the hymenoptera sting. This allows early decisions on further diagnostic procedures and the therapeutic way to choose. Patients with no detectable IgE should, however, be retested after a few weeks.

Epidemiological study of the prevalence of allergic reactions to Hymenoptera in a rural population in the Mediterranean area.

Systemic allergic reactions to Hymenoptera venom occur in a percentage that varies from 0.4 to 3.3%. Epidemiological studies indicate that from 15 to 25% of the general population can be sensitized to different Hymenoptera venom as well as the fact that the degree of exposure may be related to the prevalence found in those studies. The objective of this study was to evaluate the prevalence of insect sting allergy and the venom sensitization in a rural population to three Hymenoptera previously found in the area: Polistes dominulus (Pd), Vespula germanica (Vg) and honey bee (Hb). A rural community located in the south-east of Spain, close to the Mediterranean Sea, was selected since the stinging Hymenoptera having been previously identified. A random sample of 310 subjects from the village census was studied. A questionnaire and a serum sample were obtained from every patient. The evaluation was conducted by a family doctor, who focused on the reactions to Hymenoptera sting, age, sex, occupation, atopia, previous Hymenoptera sting, stinging insect, interval to last sting and average stings per year. RAST to Hymenoptera venoms were also determined. The prevalence of systemic reactions was 2.3% (57.6% of them had a positive RAST). Large local reactions were found in 26.4% (only 28.5% of them had a positive RAST). Asymptomatic sensitization (positive RAST) was observed in 16.4% of subjects without reaction. Only a weak correlation between subjects with less than 3 years' interval to last sting exposure and positive RAST results was noted, whether they presented with a clinical reaction or not (P < 0.05). The prevalence of systemic sting reactions in our rural community is higher than other general populations in the same Mediterranean area, and similar to other rural populations studied. The degree of exposure influences not only the prevalence found but also the detection of specific serum IgE.

Natural history of Hymenoptera venom sensitivity in adults

Background: Epidemiologic studies of Hymenoptera venom allergy in adults show a prevalence of positive venom skin test results, RASTs of 15% to 25%, or both, but most such individuals have had no systemic reactions to stings. The clinical significance and natural history of this apparently common sensitivity is uncertain. Objective: We sought to determine the natural history of venom sensitization by observing the rate of decrease or increase in sensitivity in normal adults over 5 to 10 years. The clinical significance of these findings is related to the frequency of systemic reactions to stings during the period of observation. Methods: Serial observations were planned in 520 volunteers and randomly selected subjects. Two follow-up visits were attempted, once after 2 to 3 years and again after 5 to 9 years, to perform repeat venom skin tests and RASTs and to review any history of interim stings and their outcomes. Results: Follow-up visits were conducted with 398 subjects (375 early visits and 205 late visits). Overall, in the 398 subjects with one or more visits after a mean of 4 years, skin test responses changed from positive to negative in 44 of 98 (45%) and from negative to positive in 27 of 309 (8.7%) of the subjects. Skin test responses changed from positive to negative in 29 of 87 (33%) subjects after 2.5 years and in 43 of 54 (80%) after 6.8 years. Even when the skin test response became negative, venom-specific IgE remained positive in 11 of 29 (38%) subjects after 2.5 years and in 13 of 43 (30%) after 6.8 years. The rate of loss of sensitivity was 12% per year, similar to retrospective estimates. Skin test sensitivity to venoms disappears more rapidly in these subjects without symptoms (half-life, 4 years) than in patients receiving venom immunotherapy (half-life, 7 years). Skin test responses changed from negative to positive in 23 of 288 (8%) subjects after 2.5 years and in 9 of 151 (6%) after 6.8 years. Insect stings caused no reaction in 120 subjects with a negative skin test response, but 17% (11 of 65) of subjects with a positive skin test response (but with a negative history) had systemic reactions when stung. There was no difference between the early and late visits in the frequency of systemic reactions reported. The risk may be higher than 17% for the specific individuals (67% after 2.5 years and 20% after 6.8 years) whose positive skin test responses persist for years. This risk is lower than that of patients with a positive history (50%) but higher than that of “normal” adults or venom-treated patients (<2%). It is still not clear whether any subset of adults with a positive skin test response but a negative history can be identified, in whom the risk of systemic sting reaction would justify venom immunotherapy even before any reaction occurs. Conclusion: Asymptomatic venom sensitization in adults is common but transient, disappearing at the rate of 12% per year. However, the risk of a systemic reaction to a subsequent sting is significant in adults without symptoms but with positive venom skin test responses (17%) and may be higher when skin test sensitivity does persist for years. (J Allergy Clin Immunol 1997;100:760-6.)