Receiving Venom Immunotherapy Research Articles

Component-Resolved Evaluation of the Risk and Success of Immunotherapy in Bee Venom Allergic Patients.

Venom immunotherapy (VIT) is the only efficient therapy for the Hymenoptera insect venom allergy. Immunotherapy with bee venom is encumbered with a higher risk of systemic side effects and/or therapeutic failures. The objective of the study was to assess if specific profiles of molecular IgE (Immunoglobulin E) responses are associated with an increased risk of systemic side effects and/or the treatment’s inefficacy. The study group numbered 64 bee venom allergic patients (BVA) who received venom immunotherapy modo ultra-rush (VIT-UR), (f/m: 32/32, mean age 43.4 ± 17.2). In total, 54.84% of them manifested allergic reactions of grades I-III (acc. to Mueller’s scale), while 48.66% manifested reactions of grade IV. In all the patients, IgE against bee venom extract, rApi m 1 and tryptase (sBT) were assessed. In 46 patients, assessments of IgE against rApi m 2, 3, 5, 10 were also performed. BVA patients manifesting cardiovascular symptoms (SYS IV0) showed higher levels of both sIgE-rApi m 5 (p = 0.03) and tryptase (p = 0.07) than patients with SYS I–III. Systemic adverse events during VIT with bee venom were more frequent in the induction phase than in the maintenance phase: 15.22% vs. 8.7%. In BVA patients who experienced systemic adverse events during VIT, higher concentrations of sIgE-rApi m 5 (p < 0.05), rApi m 1 (p = 0.009), and sBT (p = 0.019) were demonstrated. We conclude that higher levels of sIgE against rApi m 1, rApi m 5, and tryptase many constitute a potential marker of the severity of allergic reactions and therapeutic complications that can occur during VIT with bee venom.

M034 A CASE OF ISOLATED VOMITING AFTER MULTIPLE INSECT STINGS IN A 3-YEAR-OLD MALE

Accurate diagnosis of venom allergy is essential in identifying patients to receive venom immunotherapy and reduce risk of anaphylaxis. How do you classify a child with multiple stings and isolated vomiting?

Reasons for Declining Venom Immunotherapy.

Hymenoptera venom allergy is associated with significant morbidity and deterioration in health-related quality of life, andrisk of fatal systemic reactions. Although venom immunotherapy is safe and the only effective treatment in allergic individuals, somepatients prefer not to pursue this treatment. Since 2011, when the 50% reimbursement was stopped, patients must fully support the costof immunotherapy. This study aimed to ascertain the reasons why patients decline immunotherapy. A medical records review of all patients proposed to receive venom immunotherapy at an Allergy and ClinicalImmunology Department in Porto, Portugal, between 2006 and 2015, followed by a phone interview to patients refusing treatment. A total of 83 subjects were enrolled, with a mean (± SD) age of 44.4 (14.7) years and 55 (66%) males; 27 refused venomimmunotherapy between 2006 and 2015. Nineteen were interviewed and 14 of those stated price as the main reason for decliningtreatment. The only identified risk factor associated with immunotherapy refusal was being proposed after 2011 (OR: 3.29; 95% CI:1.12 - 9.68; p = 0.03). The number of patients refusing venom immunotherapy doubled since reimbursement was withdrawn. Price was identifiedas the major obstacle to treatment completion. Immunotherapy proposal after reimbursement was stopped was associated with a 3-foldincrease in the risk of refusing treatment. These findings show how economic decisions may have a detrimental effect on patient care, as immunotherapy refusalleft them exposed to an avoidable life-threatening risk.

Hymenoptera Venom Anaphylaxis

Systemic reactions to insect sting can be life-threatening. Life-threatening systemic reactions to insect sting are estimated to occur in 0.4% to 0.8 % of children and in 3 % of adults. Hymenoptera stings that includes Apoidea (bees), Vespoidea (wasps, hornets, and yellow jackets), and Formicidae (ants) cause more deaths than other insects all over the world. Hymenoptera venom include mixtures of numerous relevant allergens .The diagnosis of venom allergy is based on both of clinical history and positive skin test response, and/or specific immunoglobulin E antibodies. Allergic reactions may develop after stinging by hymenoptera venom. It is ranging from local up to severe systemic reactions and even fatal anaphylaxis. The treatment of large local reactions is oral antihistamines and corticosteroid therapy. Patients with any signs or symptoms of anaphylaxis should immediately receive epinephrine intramuscularly, emergency medical attention and treatment. After acute treatment of a sting reaction, patients should be given a prescription for an epinephrine autoinjector. Patients with experiences of systemic reactions after hymenoptera venom sting with positive specific IgE should receive venom immunotherapy. Venom immunotherapy is the only causal treatment to prevent further systemic sting reactions. The protective rate of venom immunotherapy is reported 98% in patients with had venom anaphylaxis history.

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.

Are ACE Inhibitors and Beta-blockers Dangerous in Patients at Risk for Anaphylaxis?

The objective of this article is to review the available studies regarding angiotensin converting enzyme (ACE) inhibitors and beta-blockers and their effect on patients at risk for anaphylaxis. A literature search was conducted in PUBMED to identify peer-reviewed articles using the following keywords: anaphylaxis, ACE inhibitor, beta-blocker, food allergy, radiocontrast media, venom allergy, skin testing, and immunotherapy. Some studies show an increased risk of anaphylaxis in patients who are taking ACE inhibitors and beta-blockers, whereas others studies do not show an increased risk. For venom immunotherapy, there are more data supporting the concomitant use of beta-blockers and ACE inhibitors in the build-up and maintenance phases. Most of the medical literature is limited to case reports and retrospective data. Prospective controlled trials are needed on this important topic. For those patients at risk of anaphylaxis who lack cardiovascular disease, it is recommended to avoid beta-blockers and possibly ACE inhibitors. However, for those patients with cardiovascular disease, beta-blockers and ACE inhibitors have been shown to increase life expectancy. Consideration should be given for the concomitant use of these medications while patients are receiving venom immunotherapy.

It is time to beelieve the CD1a hype!

Conventional T cells have historically been linked to exacerbating allergy. By efficiently generating primarily TH 2 cells, allergens skew the immune response to produce IL-4, IL-13, and IgE. Previously, CD1a-responsive T cells were shown to functionally respond to bee and wasp venom allergens. In this issue of the European Journal of Immunology, Subramaniam et al. [Eur. J. Immunol. 2016. 46: 242-252] show that more functionally active CD1a-restricted cells are present in bee venom-allergic patients than in healthy patients. Additionally, the authors show that these cells are not as frequently found in individuals receiving venom immunotherapy. Consequently, this study implicates CD1a-reactive cells as the primary responders to venom allergy, which considerably regulate the downstream immune response.

Evaluation of the quality of life in subjects with a history of severe anaphylactic reaction to the Hymenoptera venom.

Sensitization to the Hymenoptera venom is one of the main causes of anaphylaxis in Poland. Venom immunotherapy is the only effective treatment in such cases. Comprehensive patient care includes also education. The aim of our study was to assess the state of knowledge and to evaluate the quality of life and the anxiety level in patients allergic to the Hymenoptera venom after anaphylactic reaction. The survey was carried out in the period of the insects flight in 61 adult subjects (35 wasp and 26 bee allergic), using a validated Vespid Allergy Quality of Life Questionnaire (VQLQ), Hospital Anxiety and Depression Scale, and subjective assessment of anxiety level. The majority of respondents received venom immunotherapy. Sensitized to the wasp venom had significantly impaired quality of life (VQLQ score) as compared to the bee venom allergic (p = 0.014). The intensity of anxiety decreased with the duration of immunotherapy (p = 0.01). The majority of subjects knew how to recognize and treat anaphylaxis, but only 8% employed an identification card and about 50% implemented rules of the pre-exposition prophylaxis. History of a severe anaphylaxis to the Hymenoptera venom affected the quality of life. Venom immunotherapy reduced anxiety. We hope that presented surveys and their results might be useful in qualifying for immunotherapy in clinically uncertain cases.

The prevalence of Hymenoptera venom allergy in adults: The results of a very crowded city in Euroasia

BackgroundThere are scarce data about the prevalence of Hymenoptera venom allergy in the general population. The aim of this study was to determine the prevalence of Hymenoptera venom allergy in the general adult population of Istanbul. MethodsA total of 17,064 randomly selected telephone numbers were contacted and 11,816 (69.25%) individuals who agreed to participate completed a questionnaire. Those who disclosed hypersensitivity reactions due to Hymenoptera stings in this initial survey were called again and given another questionnaire. Those who were suspected of experiencing hypersensitivity reactions to Hymenoptera stings were invited for a clinical investigation with in vivo and in vitro diagnostic tests. ResultsAccording to the first questionnaire, a total of 1171 (9.9%; 95% CI: 9.38–10.47%) were suspected of having a hypersensitivity to Hymenoptera stings. 51.75% (n: 606) answered the second questionnaire and 21% (n: 128) of these were still suspected of having a hypersensitivity to Hymenoptera stings (1.1%; 95% CI: 0.9–1.29%). The confirmed prevalence of hypersensitivity to Hymenoptera stings according to skin tests and in vitro sIgE levels was 0.2% (95% CI: 0.14–0.30%). Nearly all of the participants with systemic reactions were admitted to the emergency department, although only one tenth of them received adrenaline in the emergency room. 2.3% carried an adrenaline injector, whereas none of the patients received venom immunotherapy. ConclusionsThe prevalence of Hymenoptera sting reactions in our geographical region is comparable with other European studies. There is a need to increase the awareness of adrenaline in the emergency management of insect sting anaphylaxis and venom immunotherapy in the prophylaxis.

Clinical Features and the Diagnostic Value of Component Allergen-Specific IgE in Hymenoptera Venom Allergy

PurposeAlthough patient history is vital for the diagnosis of hymenoptera venom allergy, specific IgE detection is also important to identify the culprit insect and monitor the effect of immunotherapy. We evaluated the diagnostic value of serum-specific IgE detection of hymenoptera venom component allergens and documented changes in allergen-specific IgE after immunotherapy.MethodsFifty-six hymenoptera venom allergy patients receiving venom immunotherapy were recruited from Ajou University Hospital, Korea. The clinical manifestations of the patients were noted, and serum-specific IgE detection was performed, using conventional venom extracts as well as component allergens. Data were analyzed retrospectively.ResultsA total of 35 (62.5%) patients were male, and 33 (73.3%) patients were atopic. The mean patient age was 44.9±13.8 years. Localized reactions occurred in 23.2% of patients, and systemic reactions occurred in 76.8%. The most common clinical manifestations included skin involvement, such as urticaria and angioedema, and respiratory involvement. Yellow jackets were the most frequent culprit insect, followed by yellow hornets, white-faced hornets, honeybees, and paper wasps, as determined at the time of diagnosis. Double sensitization to both Apidae and Vespidae species was detected in 70.9% of patients. The positive predictive values (PPV) of rVes v 5-specific and rPol d 5-specific IgE detection were 85.7% and 87.5%, respectively, which correlated well with conventional venom extract-specific IgE detection (r=0.762 and r=0.757, respectively). In contrast, the PPV of rApi m 1-specific IgE detection at the time of diagnosis was 34.8%. Three years of venom immunotherapy resulted in decreased venom-specific IgE, particularly IgE specific for Vespidae venom components.ConclusionsStings by yellow jackets and male sex may be risk factors for hymenoptera venom allergy in Korea. Vespidae component-specific IgE, but not Apidae component-specific IgE, had diagnostic and monitoring value in hymenoptera venom allergy comparable to that of conventional hymenoptera venom extract-specific IgE.

Debilitating beliefs and emotional distress in patients given immunotherapy for insect sting allergy: A prospective study

Patients who receive venom immunotherapy (VIT) for systemic reactions (SRs) to insect stings are advised that once they reach the maintenance dose they are almost 100% protected against future SRs. However, initial evidence indicates that some patients continue to perceive themselves as highly debilitated by the allergy and are preoccupied with the allergic event. These factors have significant impact on their emotional well-being and allergy-related quality of life (ARQOL). We aimed to explore prospectively whether patients would experience these adverse psychological outcomes after receiving VIT coupled with professional explanation and reassurance of protection. Thirty-four patients who received VIT for systemic insect allergy and were under close medical surveillance were included. Before and 1 year after initiation of treatment, patients completed a questionnaire that measured debilitating beliefs, preoccupation with the SR event, emotional distress ARQOL, and QOL in general. Physician-graded severity of the reaction was recorded as well. VIT had a beneficial effect on all allergy-related variables. Self-imposed debilitating beliefs, preoccupation with the anaphylactic event, and ARQOL significantly but modestly improved over time. No association was found between ARQOL and QOL in general. The later variable as well as emotional distress remained unchanged after the VIT. This study shows that patients with sting allergy guided by trained personnel and treated with VIT show a reduction in dysfunctional beliefs and an improvement in ARQOL. Disputing medically unfounded beliefs that persist in some patients might improve their ARQOL.

The local and systemic side-effects of venom and inhaled-allergen subcutaneous immunotherapy

Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 microg (range 2-100 microg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

Safety of angiotensin-converting enzyme inhibitors while receiving venom immunotherapy

Case reports have raised concern about concurrent use of angiotensin-converting enzyme inhibitors (ACE-Is) in patients receiving venom immunotherapy (VIT). No surveys have been performed on the number of venom allergic patients who take ACE-Is and their outcomes. To survey the use of ACE-Is and systemic reaction (SR) characteristics in patients receiving VIT. A retrospective medical record review was performed on all patients evaluated for Hymenoptera venom allergy at a single center from 2000 to 2005. Patient records were evaluated for presenting symptoms, specific IgE testing, VIT treatment course, ACE-I use during VIT, and the presence of any SRs to field stings or VIT. Of 288 patients evaluated from 2000 to 2005 for Hymenoptera venom allergy, 157 were found to have venom specific IgE. Of these 157 patients, 79 (50%) of those with Hymenoptera venom allergy underwent VIT. Seventeen of these 79 patients (21%) were taking an ACE-I during VIT. The mean overlap of a patient taking an ACE-I with the time they were receiving VIT was 30.9 months (range, 3-114 months). Patients taking ACE-Is were older (mean age, 56.2 vs 36.4 years; P < .001) and received VIT for a longer period (mean, 72.3 vs 29.9 months; P < .04). Thirteen of 62 patients not taking an ACE-I (21%) experienced an SR during their VIT. No patients taking an ACE-I experienced an SR to VIT while taking an ACE-I (P = .03). This study suggests that there is not an association between ACE-I use and increased frequency of SRs to venom immunotherapy.

Insect allergy in children

Some aspects of insect sting allergy are unique in children. This review will identify and update the published data that exist pertaining specifically to insect allergy in children. Children have a different pattern of insect sting allergy than adults. Honeybee allergy is more common in children. Severe systemic reactions are less common than in adults but the risk of recurrence can persist for decades. Systemic reactions are limited to mild 'cutaneous' reactions in over 60% of children (but only 15% of adults). Children with mild systemic reactions rarely get worse. Children with moderate or severe systemic reactions still had a 30% chance of a similar reaction even 20 years later. The long-term immune tolerance induced by venom immunotherapy is greater in children than adults. Children who had received venom immunotherapy for 3-5 years were still immune 10-20 years later. Children with insect sting allergy are tested and treated in much the same way as adults. Children with mild systemic reactions do not require testing or immunotherapy. Children with moderate to severe systemic reactions are at risk for decades and should receive venom immunotherapy, which gives very long-lasting protection.

Beta Blockers, Ace Inhibitors, and Angiotensin Receptor Blockers in Hymenoptera Allergy: A 5 Year Chart Review

RATIONALE: Patients taking beta blockers (BBs) or ace inhibitors (ACEIs) may have severe or refractory systemic reactions (SRs) when receiving venom immunotherapy (VIT). It is not currently known if angiotensin receptor blockers (ARBs) play a similar role. We examined the role of BBs, ACEIs, and ARBs in the evaluation and treatment of suspected hymenoptera allergy.

Outcomes of Allergy to Insect Stings in Children, With and Without Venom Immunotherapy

Golden DB, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. N Engl J Med . 2004;351:668–674 To determine if children outgrow their allergy to insect stings and to determine the long-term efficacy of venom immunotherapy. Subjects included were patients who had a reaction after an insect sting as a child. Reactions varied in severity and included large local reaction, mild (cutaneous) systemic reaction, and moderate-to-severe systemic reactions. Patients in the study either received venom immunotherapy or did not receive venom immunotherapy after their initial reaction. Between 1978 and 1985, allergic reactions to insect stings were diagnosed in 1033 children, of whom 356 …

Outcomes of allergy to insect stings in children, with and without venom immunotherapy.

Children are thought to "outgrow" the allergy to insect stings, but there are no reports documenting the natural history of this reaction. We studied the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated. Between 1978 and 1985, we diagnosed allergic reaction to insect stings in 1033 children, of whom 356 received venom immunotherapy. We conducted a survey of these patients by telephone and mail between January 1997 and January 2000, to determine the outcome of stings that occurred in the period from 1987 through 1999. Of the 1033 patients, 512 patients (50 percent) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and an incidence of stings of 43 percent. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients, or 3 percent) than in untreated patients (19 of 111 patients, or 17 percent; P=0.007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients, or 32 percent) than if they had received venom immunotherapy (2 of 43 patients, or 5 percent; P=0.007). In patients who had been treated and who had a history of mild (cutaneous) systemic reaction (i.e., one with only cutaneous manifestations), none of the 21 subjects who received stings had a systemic reaction. A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults.

Bee-Sting Allergies in Children: 20-Year Follow-Up Study

The natural history of bee-sting allergies is important for therapeutic and prognostic purposes. Investigators from Baltimore followed 512 patients in whom insect-sting allergy had been diagnosed 10 to 20 years earlier (median age at diagnosis, 8). Among children with systemic reactions, 163 had received venom immunotherapy, and …

Effects of CD80 and CD86 on cytokine production in patients with wasp-venom allergy who receive venom immunotherapy.

Several studies have provided evidence that activation of antigen-specific T cells requires interactions between CD28 on T cells and its ligands, CD80 and CD86, on antigen-presenting cells (APCs). However, the effects of CD80 and CD86 on cytokine production in patients with Hymenoptera venom allergy who receive venom immunotherapy remain unclear. We examined the effects of CD80 and CD86 on Th1- and Th2-cytokine production before and after venom immunotherapy in patients with wasp-venom allergy. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with wasp-venom allergy before and after three months of venom immunotherapy. CD4+ T cells and monocytes were isolated as APCs from PBMCs and were cocultured with wasp venom in the presence of anti-CD80 or -CD86 blocking antibodies. Interleukin (IL)-4, IL-10, and interferon (IFN)-gamma were measured by enzyme-linked immunosorbent assay. The expression of CD80 and CD86 on CD14+ PBMCs was detected by fluorescence-activated cell-sorter analysis. The expression of CD86, but not that of CD80, on CD14+ PBMCs cocultured with venom increased after three months of venom immunotherapy, but not before venom immunotherapy. Blockade of CD86 reduced IL-10 production after three months of venom immunotherapy. IL-10 production promoted by CD86 costimulation may be involved in the mechanism of venom immunotherapy in patients with venom allergy.

Evaluation of the risk of anaphylactic reactions by wasp venom-extract challenges in children.

Diagnostic sting challenges have been shown to provide information on the risk of further anaphylactic reactions to bee stings. We present a follow-up study in wasp venom-hypersensitive children after diagnostic venom extract challenges to analyze their risk of further anaphylactic reactions. Responses were obtained from 104 patients with wasp venom hypersensitivity out of 115 former patients. Only one of the 104 patients showed more than a severe local reaction to the sting challenge irrespective of the performance of a single or sequential challenge; therefore, only one patient received venom immunotherapy. The performance of a diagnostic sting challenge with wasp venom extract in children had a high negative predictive value of 94.6% for the risk of further systemic reactions. This was shown by analysis of later field stings, since 37 children experienced further field stings and only two of these children(5.4%) developed a mild systemic reaction (urticaria) equal to or less severe than the index sting. The value of the venom extract challenge can be interpreted in two ways: either it is less sensitive than a native sting challenge since the rate of systemic reactions to the challenge was very low, or the prognosis of wasp venom hypersensitivity in children is extremely favorable. Since the latter hypothesis is supported by the low incidence of systemic field sting reactions, we postulate that venom immunotherapy is necessary only in a minority of children with wasp venom hypersensitivity with an index sting reaction of Mueller grade I or II. However, the value of venom extract challenges as a general diagnostic instrument in children with Mueller I and II reactions due to wasp venom hypersensitivity may be questioned. It may have a place as a safe procedure in demonstrating to parents and physicians the often self-limiting natural course in most of these children.