J. Birnbaum

Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: Importance of baseline serum tryptase—a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity

BACKGROUND Severe anaphylaxis to honeybee or vespid stings is associated with a variety of risk factors, which are poorly defined. OBJECTIVE Our aim was to evaluate the association of baseline serum tryptase concentrations and other variables routinely recorded during patient evaluation with the frequency of past severe anaphylaxis after a field sting. METHODS In this observational multicenter study, we enrolled 962 patients with established bee or vespid venom allergy who had a systemic reaction after a field sting. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, and the number of preceding minor systemic reactions before the index field sting. A severe reaction was defined as anaphylactic shock, loss of consciousness, or cardiopulmonary arrest. The index sting was defined as the hitherto first, most severe systemic field-sting reaction. Relative rates were calculated with generalized additive models. RESULTS Two hundred six (21.4%) patients had a severe anaphylactic reaction after a field sting. The frequency of this event increased significantly with higher tryptase concentrations (nonlinear association). Other factors significantly associated with severe reactions after a field sting were vespid venom allergy, older age, male sex, angiotensin-converting enzyme inhibitor medication, and 1 or more preceding field stings with a less severe systemic reaction. CONCLUSION In patients with honeybee or vespid venom allergy, baseline serum tryptase concentrations are associated with the risk for severe anaphylactic reactions. Preventive measures should include substitution of angiotensin-converting enzyme inhibitors.

Rapid Hymenoptera venom immunotherapy: comparative safety of three protocols

We compared 284 sting‐allergic patients treated with either a 4 day (group 1), 6 hr (group 2) or 210 min (group 3) rapid venom immunotherapy (RVIT) protocol using honey bee (HB) or yellow jacket (YJ) venom at cumulative doses of 527.6 μg, 226.6 μg and 101.1 μg respectively. The 4 day protocol involved four times as many injections as the 210 min protocol and twice as many as the 6 hr protocol. Desensitization was conducted in a hospital providing full emergency resuscitation facilities. In group 1, 1 × 100 μg boosters were given on days 7,10,15 and 45 and, in groups 2 and 3, 2 × 50 μg boosters were given on day 15 and 1 × 100 μg on day 45. The patients in the three groups were comparable with regard to clinical characteristics and immunological reactivity determined by skin tests. All patients had large local reactions. Systemic reactions (SR) occurred in 28.2% of patients in group 1, 28.6% in group 2 and 6.9% in group 3. The mean total cumulative venom dose (s.e.m.) for occurrence of SR was 123.75 (± 24.2) in group 1,183.27 (± 28.5) in group 2, and 36.43 (±9.3) in group 3. HB led to more systemic reactions than YJ venom. The rate of SR decreased when the cumulative venom dose was reduced during RVIT. The median dose was 137.6 μg in group 1, 226.6 μg in group 2, and 21.1 μg in group 3. No systemic reactions were observed after the booster injections. The results of this study suggest that short RVIT protocols with low cumulative doses carry a lesser risk of SR.

Predictors of side effects during the buildup phase of venom immunotherapy for Hymenoptera venom allergy: the importance of baseline serum tryptase.

BACKGROUND Severe side effects during venom immunotherapy (VIT) are associated with a variety of risk factors. OBJECTIVE Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters, which are routinely recorded during patient evaluation, with the frequency of severe reactions requiring an emergency intervention during the buildup phase of VIT. METHODS In this observational prospective multicenter study, we enrolled 680 patients with established honeybee or vespid venom allergy who underwent VIT. Data were collected on tryptase concentration, age, sex, culprit insect, cardiovascular medication, degree of preceding sting reaction, preventive antiallergic medication before therapy, time between last preceding sting reaction and VIT, venom specific IgE concentration, and type of buildup procedure. Relative rates were calculated with generalized additive models. RESULTS Fifty-seven patients (8.4%) required an emergency intervention during buildup because of a severe systemic reaction. The frequency of interventions increased significantly with higher BTC (log-linear association; adjusted odds ratio, 1.56; 95% CI, 1.15-2.11; P < .005). The predictive power of BTC was markedly greater when VIT was performed for vespid venom allergy than for bee venom (for bee VIT, no significant association; for vespid VIT, log-linear association; adjusted odds ratio, 2.33; 95% CI, 1.28-4.26; P = .005). The most important other factor significantly associated with severe reactions during the buildup phase of VIT was bee venom allergy. CONCLUSION Before vespid VIT, measurement of baseline serum tryptase concentration should be used to identify patients with a high risk for side effects. Patients with bee venom allergy require a particularly high degree of surveillance during VIT.

Hymenoptera ultra-rush venom immunotherapy (210 min): a safety study and risk factors.

Background In this study, which summarizes our last 5 years of experience, we evaluated the side‐effects of ultra‐rush venom immunotherapy and the possibility to define some risk factors for side‐effects as age, Hymenoptera venom used for treatment, treatment phase, severity of prior insect sting reaction, concentration of skin test positivity, and level of specific IgE.

Prevalence of allergy to hymenoptera stings in different samples of the general population

To get figures of prevalence of systemic reactions (SRs) to hymenoptera sting in adults between the ages of 18 to 65 years, we performed three different surveys using the same questionnaire from 1984 to 1988. The first one was a door-to-door survey in Southeast France, which included 8271 adults and used a questionnaire. The second one, which included 2067 adults, was performed in a health care center and comprised the same questionnaire and venom skin tests in subjects reporting a history of SRs. The third survey was a national poll performed through a home-based national computer network. The percentage of SRs ranged from 0.66% in the second survey including skin tests to 3.3% in the poll survey. The higher prevalence figure in this latter survey may be related to a false-positive history. There was no urban-rural difference in prevalence of SR.

Ultra-rush venom immunotherapy induces differential T cell activation and regulatory patterns according to the severity of allergy.

Background Venom immunotherapy (VIT) induces immune tolerance to hymenoptera venom antigens in allergic patients and is therefore a helpful model for studying modulation of allergic immune response. The objectives were to assess the early effects of ultra‐rush VIT on T lymphocyte activation and regulatory profile induction, in all subjects combined and according to the four severity grades of the Mueller classification.

Prevalence of latex sensitization in subjects attending health screening: implications for a perioperative screening

Background Because latex is a common allergen, the rate of latex sensitization may be high in the general population. A major issue would then be to detennine whether a systematic preoperative screening in the general population should be recommended.

Housing and house‐dust mites

Because the mite‐allergen content in homes is highly variable even in the same geographic area, we tried to determine which variables influence mite infestation. We evaluated mite‐allergen content in bedding relative to housing conditions and living habits. This cross‐sectional study included 108 homes. Housing conditions were assessed by an architect and living habits by a researcher specialized in social and family economics. Group I allergen level was measured on the mattress dust with monoclonal antibodies, and relative humidity (RH) was monitored in the bedroom during a 2‐week period. Homes with low RH did have low mite‐allergen content. In contrast, homes with intermediate RH levels had very variable mite‐allergen content. Using analysis of variance and a logistic regression analysis, we were unable to identify any variable predictive of mite‐allergen content. Thus, factors other than relative humidity seem to influence mite infestation. Moreover, the absence of association between mite infestation and ventilation rate might be accounted for by the gentle climate in our area with notable outdoor RH.

Allergy during anaesthesia

The use of anaesthetic agents, drugs and chemicals during anaesthesia induce a certain number of anaphylactoid reactions. The incidence of anaphylaxis to intravenous agents used during general anaesthesia is about I : 6000. Despite appropriate treatment mortality is about 6%. Different mechanisms are involved. There are multiple risk factors. The main agents used for induction of anaesthesia are neuromuscular blocking agents (muscle relaxants: MR), hypnotics, morphinomimetics, neuroiepties and benzodiazepines. However, other drugs may be used including plasma substitutes such as fluid gelatins or dextrans, latex, ethylene oxide, protamine. each MR used in each country: vecuronium is being increasingly used in France, whereas alcuronium and gallamine are no longer administered.

Sex difference in Fel d 1 allergen production

BACKGROUND Previous experiments have shown that in vivo Fel d 1 production is under hormonal control. It strongly decreased 1 month after castration of male cats and increased after testosterone injection. OBJECTIVE These results led us to put forward the hypothesis that Fel d 1 production could be more important in male that in female cats. Five adult male and five adult female cats were studied. METHODS On day 0 three separate sites of each cats trunk were shaved, and a 5.72 cm2 area in each site was washed twice (D0a and D0b) with 5 ml of distilled water. Then a collar was attached to the neck to prevent contamination from saliva. Twenty-four hours later on day 1, all areas were washed again once (D1a). Skin washes and fur extracts from the shaved areas were evaluated for Fel d 1 content. The same procedures (apart from collection of fur) were repeated 5 months later. RESULTS The Fel d 1 level was higher in the first skin wash of male cats compared with that of female cats on each separate site of the trunk in both experiments, initially and 5 months later. Results were significant in the first experiment (median Fel d 1 per milliliter: 69.4 and 28.9 mU, respectively, for the combined three sites; p < 0.05). Fel d 1 production over a 24-hour period was higher in male cats, but the difference did not reach statistical significance. Furthermore, correlation between Fel d 1 levels in washes D0a and in fur was highly significant (p < 0.01). CONCLUSION These results confirm that Fel d 1 originates from skin. Furthermore, they suggest that Fel d 1 production is higher in male than in female cats.