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Hymenoptera stings mostly cause acute urticaria but we describe a case of CU after wasp stings which remitted during venom immunotherapy. IgE‐mechanisms have not been fully clarified in CU, except for isolated circumstances. In our case immunotherapy has played a positive role reducing immune cells reactivity and improving urticaria symptoms.

SummaryBackground An omalizumab treatment and a high maintenance venom dose may both help to prevent recurrent systemic allergic reactions (SAR) to venom immunotherapy (VIT). The effectiveness of this combination therapy, however, is unclear. Objective We wanted to explore the possibility whether a temporary treatment with the anti-IgE antibody omalizumab combined with a VIT using an elevated maintenance dose of >100 μg venom may establish a permanent tolerance of maintenance VIT. Methods For this retrospective case series, we scoured our institutional data base for patients who had had an insect venom allergy, and in whom it had not been possible to continue VIT because of repeated unstoppable SAR during maintenance VIT. Patients were divided into those who had received the combination therapy (omalizumab group) and those who had not received omalizumab because its costs could not be covered (controls). Guided by the total IgE level and by body weight, omalizumab had been given subcutaneously 5, 3 and 1 weeks before VIT had been restarted. Three to 6 months after an elevated maintenance dose (200-300 μg venom) had been reached, omalizumab had been stopped. Results Between 2006 and 2011, 15 patients had qualified for an off-label use of omalizumab: 10 patients had received the combination therapy, and 5 patients had remained without such a therapy. The combination therapy leads to a durable tolerance of VIT in all patients even after omalizumab had been discontinued (median of follow-up time 5.8 years, IQR 2.7-8.6 years). Sting challenge tests were tolerated by all of the re-stung omalizumab patients (n = 8). In all controls, VIT had to be stopped permanently due to repeated SARs (P

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors, of which the relative importance is unknown.Our aim was to evaluate the association of baseline serum tryptase concentration (BTC), mastocytosis in the skin (MIS) and of other parameters with the frequency of objective systemic reactions during in-hospital sting challenge (SC).In this observational retrospective study, we enrolled 1532 patients (1609 cases due to double SC) with established honeybee or vespid venom allergy who had undergone VIT and a subsequent SC. Data were collected on various putative risk factors. Adult-onset MIS and/or a BTC 20.0 μg/L was defined as clinical indicators of systemic mastocytosis. Relative rates were calculated with logistic regression models.Ninety-eight patients (6.4%) presented with MIS and/or BTC 20.0 μg/L. 104 cases (6.5%) developed objective generalized symptoms during SC. In the absence of MIS, a BTC ≤ 20 μg/L did not increase the risk for VIT failure. The most important factors associated with a worse outcome were ACE inhibitor medication (OR 5.24, 95% CI 1.83-13.00, P 0.001), honeybee venom allergy (OR 5.09, 95% CI 3.17-8.15, P 0.001), systemic allergic reaction during VIT (OR 3.07, 95% CI 1.79-5.14, P 0.001), and a substantial likelihood to suffer from SM (OR 2.74, 95% CI 1.37-5.22, P = 0.003), whereas a double VIT (OR 0.51, 95% CI 0.27-0.90, P = 0.027) and a longer duration of therapy (OR 0.68 per treatment month, 95% CI 0.50-0.93, P = 0.017) reduced the failure rate.The magnitude of therapeutic success correlates with type of venom, duration of therapy, and venom dose. Adult-onset MIS and/or a BTC 20 μg/L is a significant, albeit not the strongest determinant for VIT failure. According to its odds ratio, ACE inhibitor therapy appears to be associated with the highest risk for VIT failure.

Background Allergen-specific immunotherapy (SIT) has been used since 1911, yet its mechanism of action remains to be elucidated. There is evidence indicating that CD4+FOXP3+ regulatory T cells (Treg cells) are induced during SIT in allergic patients. However, the contribution of these cells to SIT has not been evaluated in vivo. Objective To evaluate the in vivo contribution of (i) CD4+ CD25+ T cells during SIT and of (ii) SIT-generated inducible FOXP3+ Treg cells during allergen exposure to SIT-mediated suppression of asthmatic manifestations. Methods We used a mouse model of SIT based on the classical OVA-driven experimental asthma. Treg cells were quantified by flow cytometry 24 and 96h post SIT treatment. We depleted CD4+CD25+ T cells prior to SIT, and CD4+FOXP3+ T cells prior to allergen challenges to study their contribution to the suppression of allergic manifestations by SIT treatment. Results Our data show that depletion of CD4+CD25+ T cells at the time of SIT treatment reverses the suppression of airway hyperresponsiveness (AHR), but not of airway eosinophilia and specific IgE levels in serum. Interestingly, the number of CD4+CD25+FOXP3+ T cells is transiently increased after SIT in the spleen and blood, suggesting the generation of inducible and presumably allergen-specific Treg cells during treatment. Depletion of CD4+FOXP3+ Treg cells after SIT treatment partially reverses the SIT-induced suppression of airway eosinophilia, but not of AHR and serum levels of specific IgE. Conclusion and clinical relevance We conclude that SIT-mediated tolerance induction towards AHR requires CD4+CD25+ T cells at the time of allergen injections. In addition, SIT generates CD4+CD25+FOXP3+ T cells that contribute to the suppression of airway eosinophilia upon allergen challenges. Therefore, enhancing Treg cell number or their activity during and after SIT could be of clinical relevance to improve the therapeutic effects of SIT.

The most important causative factor for anaphylaxis in mastocytosis are insect stings. The purpose of this review is to analyse the available data concerning prevalence, diagnosis, safety and effectiveness of venom immunotherapy (VIT) in mastocytosis patients. If data were unclear, authors were contacted personally for further information. Quality of evidence (A: high, B: moderate, C: low and D: very low) and strength of recommendation (strong 1 and weak 2) concerning VIT in mastocytosis patients are assessed according to the Grading of Recommendations Assessment, Development and Evaluation and are marked in square brackets. Results of VIT were described in 117 patients to date. The mean rate of side-effects during treatment in studies published so far is 23.9% (7.6% requiring adrenaline) with an overall protection rate of 72%. Based on the review we conclude that (1) mastocytosis patients have a high risk of severe sting reactions in particular to yellow jacket, (2) VIT could be suggested [2] in mastocytosis, (3) probably should be done life long [2], (4) VIT in mastocytosis is accompanied by a higher frequency of side-effects, so (5) special precautions should be taken into account notably during the built up phase of the therapy [2], (6) VIT is able to reduce systemic reactions, but to a lesser extent compared to the general insect venom allergic population [2], so (7) patients should be warned that the efficacy of VIT might be less than optimal and they should continue carrying two adrenaline auto injectors [2].

BACKGROUND Venom immunotherapy (VIT) is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, controversies exist relating to diagnosis, indications for treatment and treatment schedules. We audited current practice of VIT in the United Kingdom to evaluate adherence to international guidelines. METHODS An online questionnaire was sent to all clinicians practising immunotherapy identified on the British Society of Allergy and Clinical Immunology website. Eighty-six questionnaires were sent and 53 responses (61.6%) were received. Of these, 48 (85%) carried out VIT at their centre. RESULTS Skin prick tests (SPT) and serum venom-specific IgE (SSIgE) were equally preferred as first-line investigation. Fifty percent of the respondents perform intradermal tests if both SPT and SSIgE are negative. While 8% of respondents commence VIT in patients with negative SSIgE and a history of severe reaction, 57% prefer to repeat the tests in 6-12 months if serum tryptase is elevated. If the insect responsible is uncertain and SSIgE is detected against bee and wasp venoms, 22% of the respondents will desensitize to both while 32% initiate treatment against the venom with the higher SSIgE. A protocol of weekly up-dosing for 12 weeks is preferred for induction and only 25% of respondents have ever used rush or ultra-rush protocols. Three years is thought to be optimum duration of VIT by most (56%). Eleven percent perform sting challenges at the end of treatment. Although 47% measure SSIgE at the end of treatment, only 3% use these results as a basis for discontinuing VIT. CONCLUSION Currently there is considerable variation in the diagnosis and management of hymenoptera venom allergy in the United Kingdom. This audit has demonstrated that the current international guidelines for the diagnosis and management of hymenoptera venom allergy are not being followed by UK allergy practitioners.

Summary Background: Hymenoptera venom anaphylaxis is a frightening event that affects physical and psychical functioning. Patients and Methods: Retrospective survey of 182 Hymenoptera venom allergic patients living in a rural area using a questionnaire targeting on patients' satisfaction during therapy, fear of anaphylactic recurrences and changes in lifestyle before and after venom immunotherapy (VIT). Additionally, patients' self-assessment of quality of life, daily outdoor time and re-sting rate were recorded. Results: 146 patients returned the questionnaire (58.9% male, 41.1% female, 25.3% honey bee allergic, 67.8% wasp allergic, 41.1% re-sting rate, mean follow-up time 6.5 years).Measurement of the parameters fear,satisfaction and changes in lifestyle revealed a significant improvement after VIT.This correlated with the patients'self-assessment of quality of life,when 89.7% declared an improvement after VIT.Although the improvement was higher in patients with re-stings, also patients without re-stings clearly benefited from VIT. Interestingly,females were significantly more affected by Hymenoptera venom allergy than males,whereas both genders showed a similar improvement after VIT. Conclusions: Patients with Hymenoptera venom sting allergy significantly benefit from VIT in regard to both biological and psychological outcome. VIT should still be provided to all Hymenoptera venom allergic patients as standard of care.

Journal compilation © 2007 Blackwell Publishing Ltd, Clinical and Experimental Allergy © 2007 The Authors

Summary Serum venom-specific IgE and IgG were monitored in twenty-three patients receiving venom immunotherapy for more than 3 years. Two response patterns of IgE antibody were found. Following initiation of therapy, seven patients had a rise in serum venom-specific IgE, peaking at one year, then decreasing. Sixteen patients had a persistent fall in IgE antibody titres following initiation of therapy. At the end of 3 years, levels of serum venom-specific IgE in both groups were comparable. The presence of atopy may have influenced the rising IgE antibody response. Serum venom-specific IgG either rose or remained elevated if the pretreatment titres were high. After several years of therapy, there was generally a decrease in serum venom-specific IgG.

Summary Clinical and immunological studies were conducted in fifty insect-sensitive patients receiving bee and yellow jacket venom immunotherapy. All patients had had anaphylactic reactions and had elevated serum levels of venom-specific IgE (RAST) prior to therapy. Venom injections were given weekly starting at a dose of about 0.001 μg and aiming for a maximum of 50 μg or greater. Maintenance injections were administered monthly. In the majority of patients, venom-specific IgG was produced by immunizing doses above 1 μg. Highest titres were related to higher doses. Almost all patients receiving doses of 50 μg of venom had an IgG antibody response. Sequential measurements of venom-specific IgE were done in thirty-seven patients. Twenty-two had a declining titre, ten had a persistently elevated titre and five patients had a rise in antibody titre. There was no relationship between IgE and IgG antibody titres except for four patients who had a marked rise of both antibodies following venom therapy. Ten of the fifty patients received subsequent stings with no reactions. At the time of the subsequent uneventful sting, all but one had detectable serum IgG antibodies. These studies suggest: (1) venom immunotherapy appears effective for immunization of insect-sensitive individuals; and (2) considerable variability in individual immunological response to therapy and thus the probable need to individualize the degree and extent of venom therapy.

In a series of 102 patients consulting for allergic reactions following hymenoptera sting, fifty-two of them, who had experienced one or more severe systemic adverse reactions were selected for rush immunotherapy. The method employed made it possible to attain the maintenance dose of 100 micrograms of venom in 3 days. Patient tolerance was excellent, no serious side-effect was observed; immunotherapy never had to be stopped. Clinical effectiveness seems to be very satisfactory, since no abnormal reaction was reported in seven patients who later were spontaneously stung, and in fourteen patients who received an induced insect sting. The level of IgG antivenom antibodies rose regularly from the first month onwards to remain at a stable level. Because of its safety and effectiveness, it appears that this method should be recommended for immunotherapy in patients who are allergic to hymenoptera stings.