Sensitization to Hymenoptera venoms is common, but systemic sting reactions are rare.

BACKGROUND: Sensitization to Hymenoptera venom without systemic sting reactions (SSRs) is commonly observed in the general population. Clinical relevance for a future sting has not yet been investigated. OBJECTIVE: We aimed to evaluate the effect of these debatable sensitizations with deliberate sting challenges and to monitor serologic changes for up to 2 years. METHODS: One hundred thirty-one challenges with bees and wasps were performed in 94 subjects with a hitherto irrelevant sensitization. The clinical outcome was recorded, and results of specific IgE (sIgE) determinations, skin tests, and basophil activation tests were correlated to the sting reaction. sIgE levels were monitored in reactors and nonreactors after 3 hours, 1 week, 4 weeks, and 1 year. RESULTS: Only 5 (5.3%) patients had SSRs, but 41 (43.6%) had large local reactions (LLRs) after the sting. Compared with the general population, there was a 9.5-fold higher risk for LLRs but not for SSRs. Three hours after the sting, sIgE levels slightly decreased, but none of the 94 subjects' results turned negative. After 1 week, sIgE levels already increased, increasing up to 3.5-fold (range, 0.2- to 34.0-fold) baseline levels after 4 weeks. To assess the clinical relevance of this increase, we randomly selected 18 patients for a re-sting. Again, 50% had an LLR, but none had an SSR. CONCLUSION: Although sensitization to Hymenoptera venoms was common, the risk of SSRs in sensitized subjects was low in our study. The sIgE level increase after the sting was not an indicator for conversion into symptomatic sensitization. Currently available tests were not able to distinguish between asymptomatic sensitization, LLRs, and SSRs.

Asymptomatic sensitization to hymenoptera venom is related to total immunoglobulin E levels.

BACKGROUND: The detection of specific serum immunoglobulin E (sIgE) to Hymenoptera venoms is an established diagnostic tool to diagnose insect venom hypersensitivity. However, the specificity of sIgE detection is a debated issue. METHODS: In 145 subjects, total IgE (tIgE) and sIgE to Hymenoptera venoms as well as sIgE to rapeseed as a marker of cross-reactive carbohydrate determinants were measured. In addition, an atopy score was determined for each patient. We looked for a possible association between tIgE and the presence of sIgE in subjects with a negative history of large local or systemic reactions to insect stings. RESULTS: Fifteen of 65 subjects (23.1%) with low levels of tIgE (<50 kU/l) had sIgE for bee or wasp venom, and 23 of 47 subjects (48.9%) with a tIgE from 50 to 250 kU/l showed sIgE. The highest rate of asymptomatic sensitization (22 of 33; 66.7%) was found in patients with tIgE levels higher than 250 kU/l. Median sIgE was approximately 4.8 times higher in subjects with tIgE levels above 250 kU/l than in those with tIgE levels <50 kU/l. Interestingly, a significant difference in median tIgE was recorded between individuals with and without sIgE to rapeseed [776.5 kU/l (25, 75% percentiles: 252.5, 2,000.0) vs. 50.5 kU/l (20.1, 172.0), respectively; p < 0001]. CONCLUSION: Specific antibodies are frequently seen in individuals with high tIgE, but appear to be largely irrelevant in clinical terms. This might lead to misdiagnosis in persons with an inconclusive sting history.

Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study.

BACKGROUND: Three botulinum neurotoxin type A preparations (incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA) are widely approved in Europe and in the US for the treatment of glabellar frown lines. The purpose of this study was to determine and compare the time to onset and duration of treatment effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA for the treatment of glabellar frown lines. SUBJECTS AND METHODS: Subjects aged 20-60 years with moderate to severe glabellar frown lines received one treatment of either 21 units (U) incobotulinumtoxinA, 21 U onabotulinumtoxinA, or 63 U abobotulinumtoxinA. Assessments were made over a period of 180 days. Onset of treatment effect was defined as the day that the observer noted a decrease in glabellar muscle activity compared with baseline photographs and videos. Duration of treatment effect was defined as the time until glabellar muscle action returned to the baseline level. Analyses were performed using a Weibull log(T) regression model. RESULTS: The study enrolled 180 subjects; 60 per group. For all three products, onset of treatment effect occurred earlier in female subjects compared to male subjects. For both sexes, a significantly earlier time to onset of treatment effect was seen for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; in female subjects these times were 3.02 days, 5.29 days, and 5.32 days, respectively. The duration of treatment effect was longer for incobotulinumtoxinA compared to onabotulinumtoxinA and abobotulinumtoxinA; for all products, treatment effect duration was longer in females than in males. Time to onset was not a predictor of treatment duration. CONCLUSION: IncobotulinumtoxinA demonstrated a more rapid onset and a longer duration of treatment effect than onabotulinumtoxinA (1:1 dose ratio) and abobotulinumtoxinA (1:3 dose ratio). Onset of effect was faster and duration of effect was longer in female subjects compared to male subjects.

Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: a randomised, double-blind, placebo-controlled cross-over study.

OBJECTIVES: The term histamine intolerance stands for a range of symptoms involving various effector organs after the consumption of histamine-rich food. Our intention was to objectify and quantify histamine-associated symptoms and to analyse whether oral administration of the histamine-degrading enzyme diamine oxidase (DAO) caused a reduction of symptoms. PATIENTS AND METHODS: Four Austrian centres participated. Patients suspected to be histamine intolerant were recruited. The first step consisted in the open oral provocation of these patients with 75 mg of liquid histamine. Patients who developed symptoms were tested in a randomised double blind crossover provocation protocol using histamine-containing and histamine-free tea in combination with DAO capsules or placebo. Main and secondary symptoms (strongest and weaker symptoms based on a ten-point scale) were defined, the grand total of all symptoms of the individual provocation steps was determined and changes in symptoms after administration of DAO were measured. RESULTS: Thirty nine patients reacted to the open histamine provocation and were enrolled in the blinded part. Here, both the main and secondary symptoms were not reproducible. Subjects reacted sometimes unexpectedly and randomly. Regarding the total symptom scores, the differences between the three treatment groups were statistically significant. The intake of DAO demonstrated a statistically significant reduction of histamine-associated symptoms compared to placebo (P = 0.014). CONCLUSIONS: Oral provocation with 75 mg of liquid histamine failed to reproduce histamine-associated single symptoms in many patients. One may suggest that histamine-intolerant subjects reacted with different organs on different occasions. As a consequence, reproducibility of single symptoms alone may not be appropriate to diagnose histamine-intolerance whereas a global symptom score could be more appropriate. The fact, that the intake of DAO capsules compared to placebo led to a statistically significant reduction of total symptom scores, may indirectly point in the same direction.

Inconsistent results of diagnostic tools hamper the differentiation between bee and vespid venom allergy.

BACKGROUND: Double sensitization (DS) to bee and vespid venom is frequently observed in the diagnosis of hymenoptera venom allergy, but clinically relevant DS is rare. Therefore it is sophisticated to choose the relevant venom for specific immunotherapy and overtreatment with both venoms may occur. We aimed to compare currently available routine diagnostic tests as well as experimental tests to identify the most accurate diagnostic tool. METHODS: 117 patients with a history of a bee or vespid allergy were included in the study. Initially, IgE determination by the ImmunoCAP, by the Immulite, and by the ADVIA Centaur, as well as the intradermal test (IDT) and the basophil activation test (BAT) were performed. In 72 CAP double positive patients, individual IgE patterns were determined by western blot inhibition and component resolved diagnosis (CRD) with rApi m 1, nVes v 1, and nVes v 5. RESULTS: Among 117 patients, DS was observed in 63.7% by the Immulite, in 61.5% by the CAP, in 47.9% by the IDT, in 20.5% by the ADVIA, and in 17.1% by the BAT. In CAP double positive patients, western blot inhibition revealed CCD-based DS in 50.8%, and the CRD showed 41.7% of patients with true DS. Generally, agreement between the tests was only fair and inconsistent results were common. CONCLUSION: BAT, CRD, and ADVIA showed a low rate of DS. However, the rate of DS is higher than expected by personal history, indicating that the matter of clinical relevance is still not solved even by novel tests. Furthermore, the lack of agreement between these tests makes it difficult to distinguish between bee and vespid venom allergy. At present, no routinely employed test can be regarded as gold standard to find the clinically relevant sensitization.

CD203c-based basophil activation test in allergy diagnosis: characteristics and differences to CD63 upregulation.

BACKGROUND: The basophil activation test (BAT) based on CD203c upregulation has been validated as a reliable tool for the diagnosis of IgE-mediated allergies. Nevertheless, CD203c-based BAT is hardly comparable with that of CD63-based tests, as the mechanisms of CD203c versus CD63 induction differ considerably. The aim of the present study was to identify potent influencing factors of the CD203c-based BAT and to emphasize differences between CD63 and CD203c detection. METHODS: CD203c-based BAT was determined in 82 healthy controls and in 79 allergic patients. The effects of interleukin (IL)-3 and degranulation enhancing substances were investigated and compared with CD63 upregulation. Furthermore, the influence of different storage conditions and incubation times was evaluated and the impact of antiallergic drugs on the test results was assessed. RESULTS: CD203c and CD63 expression was rapidly upregulated reaching a maximum after 20-30 min. Basophil CD203c upregulation assayed after storage times up to 48 h declined already after 4 h. IL-3 treatment increased CD203c and CD63 baseline levels and decreased basophil CD203c responses in a dose-dependent manner. In contrast, cytochalasin B and latrunculin B did not affect CD203c responses but decreased CD63-based BAT. Finally, therapeutic concentrations of dimetindene and desloratadine did not affect CD203c upregulation. CONCLUSION: CD203c-based basophil activation test should be performed preferentially within 4 h after taking the blood samples. Priming and degranulation-enhancing factors are not required for CD203c-based BAT. In contrast to skin testing, CD203c-based BAT can be performed in patients undergoing antiallergic treatment. © 2010 International Clinical Cytometry Society.