Stinging insect allergy: Natural history and modification with venom immunotherapy

The natural history of stinging insect allergy and its modification by venom immunotherapy was investigated by follow-up observations of patients with histories of venom anaphylaxis and detectable venom-specific IgE. The patients were divided into three categories: (1) receiving venom immunotherapy, (2) declined venom immunotherapy, and (3) terminated venom immunotherapy. One hundred twenty-seven patients were evaluated after 6 mo to 9 yr of venom immunotherapy. Most received top venom doses of 50 μg of yellow jacket and/or honeybee venoms every 4 wk. There were 87 restings in 48 patients resulting in two systemic reactions, only one of which could be considered a treatment failure (1%). Fifty-six patients never received venom immunotherapy. In this group there were 40 restings in 28 patients with 14 systemic reactions (35%). In 88 patients who stopped venom immunotherapy, 61 restings in 41 patients led to 11 systemic reactions (17%). Patients with cardiovascular/or respiratory symptoms with initial sting anaphylaxis were at risk for subsequent reactions. With one exception, patients with hives and edema only as the initial reaction either had a similar or no reaction when they were restung. These results confirm the efficacy of venom immunotherapy but also suggest that there are factors other than the presence of venom-specific IgE modulating the occurrence of clinical anaphylaxis.     

Assessment of venom-specific IgG antibody in patients treated for hymenoptera allergy

The IgG antibody (Ab) response achieved with specific venom immunotherapy was explored in 32 patients with Hymenoptera hypersensitivity. Venom-specific IgG Ab was quantitated before and after 1 year of immunotherapy using two solid phase radioimmunoassay (SPRIA) methods. An agarose-based test using 125I-Staphylococcus aureus Protein A (SPRIA) was used to determine specific IgG for five Hymenoptera species: yellow jacket (YJ), honeybee (HB), yellow-faced hornet (YH), white-faced hornet (WFH), and Polistes (POL). A cellulose disk test using 125I-anti-IgG (IgG RAST) was available only for YJ and HB venoms. Acceptable agreement (90% concordance) was observed with IgG anti-HB levels measured in the two assays. For the YJ-IgG, however, 17/69 (25%) of sera positive in the SPRIA were negative in the IgG RAST, whereas the converse was not observed. This result suggests that the IgG RAST is insufficiently sensitive to detect YJ-IgG responses in all patients on maintenance level immunotherapy. Using the Protein A SPRIA, there was excellent agreement between the venom used for immunotherapy and the specificity of the IgG Ab response. In 31 patients treated with a total of 90 venom species, 90/90 venom IgG levels were increased or maintained at high pretreatment levels in response to immunotherapy. In the same patients venom IgG levels obtained for venom species not included in therapy were undetectable or declined in 55/60 cases; in 4 cases treatment with YJ venom stimulated a WFH and/or YH IgG response, the remaining case, YJ venom stimulated a small rise in POL IgG. These apparent discrepancies can be explained by variable cross-reactivity among vespid and POL venoms. Among 32 patients with a combined total of 87 positive venom skin tests, 1 year of specific immunotherapy resulted in greater than 5 micrograms/ml of venom-specific IgG in 61 instances. In 25 instances, the level of venom IgG was detectable but less than 5 micrograms/ml, and in 1 case venom IgG could not be detected. Based on recent analyses by Golden et al., some or all of these latter 26 cases may represent suboptimal therapy despite a standard immunotherapy regimen. We conclude that venom IgG measurements can provide a specific and quantitative assessment of the immunologic response to venom therapy, and that such assessment may be clinically useful in detecting instances of suboptimal immunotherapy.     

Transient bradycardia during vespid venom immunotherapy

A woman developed generalized symptoms of hypersensitivity when she was stung requiring treatment with adrenalin. Intradermal venom skin tests showed immediate hypersensitivity to yellow hornet and white-faced hornet thus fulfilling the criteria to receive appropriate venom immunotherapy. During the course of modified rush immunotherapy with yellow hornet and white-faced hornet venoms, she developed transient but progressive bradycardia necessitating interruption of the venom immunotherapy. Transient bradycardia recurred when venom immunotherapy was resumed but it was possible to reach a maintenance dose of 100 mg protein for each venom. Bradycardia has been reported to be induced in experimental animals by oriental hornet venom as well as other venoms, through a direct cholinergic action. It appears that a similar effect may occur in man in susceptible individuals during venom immunotherapy.     

Immunotherapy with Hymenoptera venoms

Immunotherapy with Hymenoptera venoms is widely used throughout the world and is accepted as an effective treatment for most patients with Hymenoptera venom allergy. There are, however, still some unresolved problems with this form of treatment. At present there is no definite test which makes it possible to identify patients at risk - and thus candidates for immunotherapy - unequivocally. On the basis of prospective studies on the natural history of Hymenoptera allergy, venom immunotherapy is indicated in adults with severe systemic anaphylaxis. It is usually not necessary in patients with large local reactions only. Children with mild systemic reactions, e.g. urticaria, will need immunotherapy only in case of repeated reactions and/or a high risk of re-exposure. The selection of venoms for immunotherapy may lead to some confusion owing to common antigenic determinants shared by venoms of various Hymenoptera species. Many different regimens for immunotherapy have been proposed. At present, the three main are: rush, stepwise or clustered and classical. The maintenance dose of 100 micrograms usually protects from life-threatening reactions. However, in some patients 200 micrograms are necessary for complete protection. The usual interval between maintenance injections is 4 to 6 weeks. In many patients a strong increase of venom specific serum IgG-antibodies usually parallels clinical protection induced by venom immunotherapy, although many exceptions have been reported. Allergic side effects of venom immunotherapy are not rare, especially with honey bee venom and during the initial phase of dose increase. The question of the duration of venom immunotherapy is handled differently: although some authors recommend treatment for life, most suggest treating patients until skin tests and RAST become negative.     

Mastocytosis and Hymenoptera venom allergy

PURPOSE OF REVIEW: Mastocytosis is a rare disease characterized by increased mast cells in skin and/or internal organs. We evaluate the impact of mastocytosis on diagnosis and treatment of Hymenoptera venom allergy. RECENT FINDINGS: Patients with Hymenoptera venom allergy who suffer from mastocytosis develop life-threatening sting reactions more often than those who do not. When patients with Hymenoptera venom allergy were systematically examined for mastocytosis, it was found to be represented to an abnormally high extent. Most patients with mastocytosis tolerate venom immunotherapy with no or only minor systemic symptoms. Venom immunotherapy was found to be marginally less effective in patients with mastocytosis than in those without evidence of mast cell disease (defined as absent cutaneous mastocytosis combined with a serum tryptase concentration of <11.4 microg/l). Several deaths from sting reactions were reported in patients with mastocytosis after venom immunotherapy was stopped. These patients should have venom immunotherapy for the rest of their lives. SUMMARY: Patients suffering from mastocytosis and Hymenoptera venom allergy are at risk from a particularly severe sting anaphylaxis. They need optimal diagnosis and treatment. In patients presenting with Hymenoptera venom allergy, screening tests by measurement of serum tryptase concentration, and a careful skin examination, are highly recommended.     

Late onset reactions following venom immunotherapy and venom skin tests

This report describes patients who had late onset reactions following venom immunotherapy and venom skin tests. Six adult patients had symptoms of fatigue, malaise, fever, headache, and joint ache, starting four to six hours after venom immunotherapy and lasting up to four days. Two of the patients had prolonged reactions at or adjacent to the skin test sites. All of these patients had a history of venom anaphylaxis; four had severe cardiovascular symptoms. All received yellow jacket venom immunotherapy and four honeybee venom immunotherapy. In four patients, the reactions occurred following small venom doses, 0.1 to 2 micrograms. Two patients reacted after maintenance doses of 50 micrograms. There was no relationship to the serum IgE or IgG antibody titers. All but one patient had serum venom-specific IgE but the titers covered a wide range. Serum venom-specific IgG was present in four patients. There was no response in lymphocyte culture to bee venom stimulation in two patients. Two of these patients stopped venom immunotherapy; one had reached the maintenance dose. In three patients, prophylactic parenteral steroids have ameliorated the reactions. After a temporary dose reduction, the sixth patient is now asymptomatic. A seventh patient developed asthma, 12 hours following a maintenance dose of 50 micrograms of yellow jacket venom. Concomitant steroid administration has effectively prevented the reaction. Another patient, a 6-year-old boy, developed fever, edema of the face and lips, erythema of the leg, and a large, tender right inguinal node eight hours following venom skin tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective observations on stopping prolonged venom immunotherapy

After a decade spent establishing the safety, efficacy, and optimal techniques for venom immunotherapy, we have begun a series of studies to determine how long venom immunotherapy must be continued. In retrospective surveys, patients who had stopped venom immunotherapy after 1 to 2 years had a substantial risk (25%) of systemic sting reactions, but this was less than 50% of the risk in untreated patients. In this first prospective study, 30 patients elected to stop venom immunotherapy after at least 5 years of therapy. Skin test sensitivity had decreased significantly during therapy in 18/30 patients but remained clearly positive in 23/30 (seven patients became equivocal or negative). Serum venom-specific IgE antibodies were at the lower limit of detection (1 ng/ml) in 11/30 patients. After stopping treatment, the mean serum venom-specific IgG antibody level declined from 5.5 +/- 0.6 micrograms/ml to 2.4 +/- 0.3 micrograms/ml by 9 months, which is the same as the mean venom IgG in untreated patients. After 12 months without therapy, live sting challenge caused no systemic reaction in 29 patients. The mean venom IgG level 1 month after the sting had risen significantly to 4.1 +/- 0.5 micrograms/ml, but there was no significant increase of venom IgE. These results suggest that prolonged venom immunotherapy leads to isotype-specific suppression of the venom IgE antibody response and may provide persistent clinical protection by mechanisms other than IgG blocking antibodies. The observations are to be interpreted very cautiously. Further investigations are needed to extend these observations in additional patients and for longer periods of time, and to examine possible mechanisms for this apparent loss of clinical reactivity.     

New developments in the diagnosis and treatment of hymenoptera venom allergy

According to most textbooks, diagnostic tests with Hymenoptera venoms are reliable, and immunotherapy with these venoms in Hymenoptera-venom-allergic patients leads in near to 100% to full protection. Careful analysis of the literature shows however that the specificity of diagnostic tests is far from perfect and that both efficacy and tolerance, especially in patients receiving honeybee venom immunotherapy, are still suboptimal. The major allergens of honeybee and vespid venoms are now available in recombinant form. Preliminary trials analyzing diagnostic tests with recombinant allergens in honeybee venom allergy are promising: the specificity is clearly increased in both skin testing and in determining venom-specific IgE antibodies when compared to natural venom allergens. An important recent finding is the frequent association of severe Hymenoptera venom allergy and elevated basal serum levels of the mast-cell-specific enzyme tryptase. Elevated levels are found in up to 30% of the patients with a history of severe shock reactions following Hymenoptera stings. The current findings indicate that basal tryptase levels indicating an increased mast cell load are much more frequent than previously thought and are a risk factor for severe or even fatal sting reactions. Premedication with antihistamines in the initial phase of venom immunotherapy reduced both local and systemic allergic side effects in several controlled studies. In a retrospective analysis of one of these trials it was found that reexposure during immunotherapy resulted in significantly more systemic allergic reactions in patients on placebo than on antihistamine premedication, suggesting that initial antihistamine premedication might increase the efficacy of venom immunotherapy. Different ways of allergen modification for venom immunotherapy have been proposed. While the results with chemical modifications were not convincing, recent studies with T-cell epitope peptides from the major bee venom allergen phospholipase A(2) look promising. Patient-tailored cocktails of recombinant venom allergens or isoforms thereof may be another possibility in the future. A number of prospective studies analyzing the duration of venom immunotherapy required for long-term protection have been published in the last decade. While most patients are still fully protected 1 year after discontinuation of therapy, relapses may occur in up to 20% of patients reexposed many years after treatment. Various risk factors for such relapses have been identified.     

Relevance of basophil histamine release changes during venom immunotherapy

We investigated the effect of rush and long-term venom immunotherapy on histamine release parameters in bee venom allergic patients. Ten patients received rush venom immunotherapy, and histamine release data were obtained immediately before and after treatment. 17 patients were assessed by histamine release 24 to 63 months after termination of long-term venom immunotherapy. A control group of 10 non-allergic subjects was included in this study. Histamine released from whole blood was determined in a sensitive radio-enzymatic assay using a single isotope technique. Bee venom phospholipase A-induced histamine release from whole blood proved to be a test procedure of high specificity and sensitivity. Eight of 10 untreated patients and no control subject showed significant antigen-induced histamine release. Results obtained from patients immediately after successful rush venom immunotherapy showed an important decrease (mean 45.9%) of total histamine content of basophil leukocytes in all patients. Antigen-induced maximum histamine release was found to be increased in one, decreased in two and unchanged in seven patients. In patients who received long-term immunotherapy cell sensitivity to phospholipase A was significantly lower than in a group of untreated patients (P less than or equal to 0.002). These results suggest that even years after discontinuation of immunotherapy, histamine release parameters reflect patients' protection from systemic sting reactions as assessed by sting challenges. Histamine depletion of basophils induced by rush immunotherapy may play an important role in patients' protection immediately after termination of the rush regimen.     

A controlled trial of immunotherapy in insect hypersensitivity.

Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively. Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy (P less than 0.01). The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy; one reacted to a subsequent sting. We conclude that venom immunotherapy is clinically superior to therapy on whole-body extract or placebo.     

Efficacy and safety of rush immunotherapy in patients with Hymenoptera allergy in Japan

In Japan, approximately 40 persons die annually from anaphylaxis caused by Hymenoptera stings. Venom immunotherapy is considered safe and effective for the treatment of allergic systemic reactions caused by Hymenoptera stings in patients with Hymenoptera allergy. We studied the efficacy and safety of rush immunotherapy in patients who had a history of systemic reactions to Hymenoptera stings in Japan. Between 1988 and 2002, 95 patients with a history of systemic reactions to Hymenoptera stings were investigated. The stings originated from honeybees in 5 patients, yellow jackets in 28, wasps in 48, both yellow jackets and wasps in 9, and both yellow jackets and honeybees in 5. All patients had venom-specific IgE antibodies in sera (RAST score > or = 2) and received rush immunotherapy with venom extracts at our hospital. Forty-three patients had 63 field re-stings during immunotherapy. Of these patients, 41 (95.3%) with 59 field re-stings (93.7%) had no systemic reactions. Two patients (4.7%) with four field restings (6.3%) had anaphylactic shock. Although anaphylactic reactions developed in two patients (2.1%) during rush immunotherapy with honeybee venom and one patient (1.1%) during maintenance therapy wasp venom, systemic adverse reactions were mitigated by treatment with antihistamines before venom injection. Our results show that immunotherapy is safe and effective for the prevention of systemic reactions to Hymenoptera re-stings in patients with Hymenoptera allergy. We therefore recommend that patients who are allergic to Hymenoptera venom prophylactically receive immunotherapy.     

Discontinuation of yellow jacket venom immunotherapy: Follow-up of 75 patients by means of deliberate sting challenge

Background: Venom immunotherapy is effective in preventing systemic reactions in patients with a history of an anaphylactic reaction to Hymenoptera stings. It is uncertain how long venom immunotherapy should be continued. Objective: We evaluated whether the duration of venom immunotherapy given to yellow jacket–sensitive patients related to the risk of an anaphylactic reaction to a later sting. Methods: Seventy-five yellow jacket–sensitive patients (29 male and 46 female) received a median number of three in-hospital sting challenges from a live insect in 3 subsequent years after discontinuation of venom immunotherapy. An anaphylactic reaction to one or more of the sting challenges was considered a relapse. We analyzed whether patients with and patients without a relapse differed in terms of gender, age, preimmunotherapy skin test data, preimmunotherapy level of venom-specific IgE, severity of the field-sting reaction that preceded immunotherapy, severity of the reaction to the sting challenge that preceded immunotherapy, adverse reactions to immunotherapy, changes in IgE and IgG₄ levels during immunotherapy, duration of immunotherapy, and presence of venom-specific IgE after cessation of therapy. Results: Venom immunotherapy was given for a median duration of 40 months (range, 7 to 120 months). Relapses were observed in six patients. In two of them, a rather severe anaphylactic reaction was observed after the second sting challenge. No relation was found between duration of venom immunotherapy and relapse risk. The relapse rate was higher among patients with high levels of specific IgE before and after immunotherapy. During therapy, the mean level of specific IgE decreased. This decline persisted in the 3 following years. No relapses of sting reactions were observed among patients without detectable specific IgE. Conclusion: Discontinuation of venom immunotherapy appears safe for patients with pretreatment IgE antibodies if these antibodies can no longer be detected during immunotherapy. For the remaining patients, a treatment period of 3 years may suffice. After discontinuation of immunotherapy, a clinical sting challenge can be considered to estimate the patient's current grade of hypersensitivity. (J Allergy Clin Immunol 1997;100:767-70.)     

Advances in hymenoptera venom immunotherapy

PURPOSE OF REVIEW: Venom immunotherapy is highly effective treatment, capable of improving health-related quality of life. This overview examines advances in various aspects of this treatment. RECENT FINDINGS: New findings on the immunological mechanisms of the early and long-term efficacy of venom immunotherapy have been made. The decision to start and then to stop venom immunotherapy is best made on an individual case basis and should take into account medical and other factors, like the influence on patient quality of life. Venoms for use in immunotherapy should be selected according to the geographical distribution of each species and partial cross-reactivity between certain types of venom. Rapid protocols seem to be as safe as slower ones, though the major incidence of bee venom immunotherapy side-effects remains. Patients suffering from mast cell diseases seem to be at greater risk for an adverse reaction during treatment, without influencing its efficacy that much until the immunotherapy is actually ongoing. A number of new strategies for venom immunotherapy, mostly based on genetic engineering, have been described, and so far only a few have been used in humans. SUMMARY: Although there has been progress in the past few years, much remains to be accomplished.     

Use of beta-blockers during immunotherapy for Hymenoptera venom allergy

BACKGROUND: Beta-blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on beta-blocker treatment. OBJECTIVE: To analyze the risk of beta-blocker treatment during venom immunotherapy. METHODS: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with beta-blockers. RESULTS: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on beta-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and 1 with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, beta-blockers were newly started during immunotherapy. Of 25 patients on beta-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without beta-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without beta-blockade. No severe reactions to treatment or sting reexposure were observed in patients with beta-blockade. CONCLUSION: Combination of beta-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease.     

Prolonged interval maintenance venom immunotherapy

Current guidelines recommend indefinite administration of venom immunotherapy at 4-week intervals. To simplify this therapy, we examined the clinical and immunologic response after extending the interval between maintenance venom injections to 6, 8, and 12 weeks. Twenty-six patients who had had sting anaphylaxis and positive skin tests received maintenance bee or yellow jacket venom immunotherapy at greater or equal to 6-week intervals. This extended interval was started after a prior average 4-week maintenance interval of 2.3 years. Injections were given at 6-week intervals to all 26 patients and extended to 8-week intervals in 10, and 12-week intervals in 3 patients. Following venom injections, there were 14 mild local reactions and no systemic reactions. No adjustment in dosing was necessary. While on prolonged interval maintenance venom immunotherapy, there were 17 re-stings in 12 patients with no systemic reactions. During prolonged interval maintenance venom immunotherapy, either the serum venom-specific IgG increased or the already elevated titers remained the same in 18 patients and decreased in 2. In the others, preexisting titers were low and unchanged. Serum venom-specific IgE tended to slowly decrease. These clinical and immunologic data suggest that a 4-week maintenance interval may be safely extended.     

EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H₁‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.     

Venom immunotherapy: adverse reactions and treatment failure

PURPOSE OF REVIEW: Side effects of venom immunotherapy and lack of efficacy represent significant problems in the treatment of patients allergic to Hymenoptera venom. Among these side effects systemic anaphylactic reactions and large local reactions are the most important. This review aims to discuss new insights in frequency, pathogenesis and handling of these common side effects and of treatment failure during venom immunotherapy. RECENT FINDINGS: Several studies showed that severe side effects due to venom immunotherapy are rare. Recently published studies focus on ultrarush protocols and report good tolerance of an ultrarush venom immunotherapy in which the maintenance dose was reached within several hours or 2 days, respectively. Compared to the use of aqueous extracts (administered according to a rush protocol), frequency of local and also systemic side effects was lower when depot extracts and schedules with a slow conventional dose increase were applied. Concomitant treatment with H1-antihistamines was found to reduce local and mild systemic adverse reactions during venom immunotherapy. Up to 25% of patients are not protected when re-stung while on venom immunotherapy with the usual maintenance dose of 100 microg of venom every 4-8 weeks. These patients can achieve full protection by increasing the maintenance dose. SUMMARY: Conventional dose increase using depot extracts is better tolerated than if aqueous extracts are being administered. Concomitant treatment with H1-antihistamines may be helpful. Increasing the venom dose to 200 microg or even more may be therapeutically effective in patients not protected by a lower maintenance dose. To compare tolerance of different treatment protocols prospective comparative studies are required.     

Rush Hymenoptera venom immunotherapy: a safe and practical protocol for high-risk patients

BACKGROUND: Hymenoptera venom immunotherapy in allergic patients is a well-established treatment modality for the prevention of systemic anaphylactic reactions caused by insect stings. A variety of therapy regimens exists, from conventional to rush and ultrarush modalities that operate on continuous or intermittent schedules. OBJECTIVE: The aim of this study was to report the 8-year experience with our rush venom immunotherapy regimen in predominantly high-risk patients and to compare data on safety and convenience with the results of 26 studies published from 1978 to 2001. METHODS: One hundred one patients allergic to bee, yellow jacket, or hornet venom were treated with rush Hymenoptera venom immunotherapy. Diagnosis and selection of patients for venom immunotherapy were carried out according to the recommendations of the European Academy of Allergology and Clinical Immunology. We used a 4-day regimen, and the incidence and nature of systemic reactions (SRs) were documented. Fifty-two patients were treated with honeybee venom, and 49 were treated with yellow jacket venom. RESULTS: One hundred (99%) patients reached the maintenance dose. We observed 8 injection-related SRs (0.47% of all injections given) in 7 (6.9%) patients. The number of SRs was higher in patients treated with bee venom extract (12%) compared with in patients receiving yellow jacket venom extract (2%). There was no significant difference in the risk of SRs between female and male patients. The incidence of SRs was considerably lower than the average of 17.8% reported in the literature. CONCLUSION: With a rush immunotherapy regimen over a time period of 8 years in predominantly high-risk patients, the incidence of SRs was low, despite the high number of patients with bee venom allergy, who are more likely to have side effects. Epinephrine as rescue medication was never necessary, and the regimen proved to be safe and convenient for both the patients and the medical staff.     

Expression of activation markers on basophils in a controlled model of anaphylaxis

BACKGROUND: Anaphylaxis has variable clinical presentations and lacks reliable biomarkers. Expression of activation markers on basophils has been useful in assessing sensitization in IgE-mediated diseases but has not been examined in vivo in anaphylaxis. OBJECTIVE: The study's goals were to assess the baseline expression of activation markers on basophils in individuals with a sting reaction history, the degree of change in expression of these markers after intentional sting challenge, and the relationship between in vitro and in vivo activation marker expression. METHODS: Patients allergic to insect venom were enrolled and grouped by clinical category defined by a history of a systemic or large local reaction and use of venom immunotherapy. Blood was collected before and after sting challenge. Enriched basophils were analyzed for activation marker expression. In select subjects, basophils were examined after in vitro stimulation with insect venom for activation marker expression and histamine release. RESULTS: Of 35 sting-challenge participants, 21 provided adequate samples for analysis. Pre-sting basophil CD63 expression was significantly higher in systemic reactors on immunotherapy. Following sting challenge, the rise in basophil CD69 expression and CD203c was significantly higher in systemic reactors on immunotherapy. Levels of activation markers on basophils were greater after in vitro venom stimulation than after in vivo challenge. CONCLUSION: Broader shifts in expression of basophil activation markers after in vivo challenge occurred among subjects with a history of in vivo systemic anaphylaxis despite venom immunotherapy. CLINICAL IMPLICATIONS: Basophil activation markers may be potential biomarkers for anaphylaxis.     

Allergy to bumblebee venom

Allergy to bumblebee venom is a rare form of Hymenoptera venom allergy. Because bumblebees are increasingly used for the pollination of greenhouse plants, the prevalence of this Hymenoptera allergy has increased during the past decade. The clinical presentation, diagnosis and therapy of bumblebee venom allergy are similar to other Hymenoptera venom allergies. There is a significant immunological cross-reactivity between bumblebee and honeybee venom. It has been claimed that immunotherapy with honeybee venom can protect patients with bumblebee venom allergy. This concept, however, has been called into question after the finding of bumblebee venom-specific IgE lacking cross-reactivity to honeybee venom, and three cases of bumblebee venom-allergic patients in whom immunotherapy with honeybee venom was unsuccessful. Immunotherapy with pure bumblebee venom has been shown to be effective and safe, and is currently the treatment of choice in individuals who cannot avoid contact with bumblebees. Immunotherapy with honeybee venom, however, should be considered in patients with severe reactions to bumblebee stings and concurrent sensitization to honeybee venom.