Christoph Bucher

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.

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.

Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations.

Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition to low C4 levels, the most important laboratory parameter for correct diagnosis of HAE or angioedema due to acquired C1-Inh deficiency is reduced C1-Inh function (fC1-Inh). No direct recommendations about the assays for fC1-Inh or sample handling conditions are available, although this would prove especially useful when a laboratory first starts to offer assays on fC1-Inh for HAE diagnosis. In the present study we evaluated the performance of fC1-Inh assays in the 15 different laboratories that are specialised in HAE diagnostics and assessed inter-laboratory variation with each laboratory using their own assays and standards. A double-blind survey was conducted using plasma/serum samples from healthy donors and HAE patients and the uniformity of HAE diagnosis was evaluated. It can be concluded that the diagnosis of fC1-Inh deficiency was made correctly in most cases in this survey. We can recommend the chromogenic assay for the determination of fC1-Inh, while the complex ELISA needs further investigation.

Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema.

Background:  Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks in patients with hereditary angioedema (HAE). The present study aimed to reinvestigate the relationship between H. pylori infection and the attack rate in the framework of an international collaborative study.

Clinical Expression of Nickel Contact Dermatitis Primed by Diagnostic Patch Test

Introduction: Persistence of allergen and immunocompetent cells at sites of healed contact dermatitis has been reported. Flare-up reactions triggered by patch testing and after systemic provocation with allergen are well-known phenomena. To our knowledge, we report the first flare-up of a previous patch test site following casual cutaneous application of nickel in an individual with hitherto latent nickel sensitization. Case Report: Patch testing in a 23-year-old female patient was performed for dermatitis following application of various gels and adhesive bandages: positive delayed-type hypersensitivity reactions were noted for nickel sulfate and potassium dichromate. The patient had never noticed skin reactions to nickel-containing items before. Three weeks following these patch tests, the patient wore earrings which in the past had been well tolerated. She subsequently developed dermatitis of both earlobes within hours and dermatitis at the site of nickel patch testing within a day. Conclusions: Nickel exposure for 48 h in a patch test is sufficient to induce overt delayed-type hypersensitivity on re-exposure with a previously tolerated antigen in a previously clinically unresponsive individual. Antigen and/or antigen-specific effector cells at the site of previous positive patch testing can be recruited into a delayed-type hypersensitivity reaction for a prolonged period of time.

Bone Mineral Content in Patients with Anaphylactic Reactions, Signs of Mastocytosis and Elevated Basal Serum Tryptase Levels~!2009-08-20~!2009-12-01~!2010-02-12~!

Introduction: To examine the relationship between elevated basal serum tryptase levels (BST), a marker of total mast cell mass, and bone mineral density (BMD) in patients with anaphylactic reactions and signs of mastocytosis. Methods: Retrospective evaluation of patient charts at an allergy unit. Patients with BST levels above 20 ng/ml were eligible if clinical and follow-up data and results of dual X-ray absorptiometry (DXA) were available. Patients with previous use of anti-osteoporotic medications and with osteoporosis not caused by mastocytosis were excluded. Spearman’s rank correlation, Mann-Whitney test and receiver operating characteristic curve (ROC) was used for analysis. Results: 24 patients were included. The main presenting symptom (17 of 24 patients) was anaphylactic reactions to insect stings. BST levels ranged between 21 and 158 ng/ml (median 48 ng/ml). Study participants with Z-score values below 1.0 had a median BST level of 46 ng/ml, the patients with Z-score values above or equal to -1.0 had a median BST level of 27 ng/ml. ROC analysis of the patient group with BST values between 30 and 100 ng/ml revealed a best cut-off value of BST to detect a low BMD when BST level would be at least 27 ng/ml resulting in a sensitivity of 92% and a specificity of 70%. Conclusion: Patients with moderately elevated BST levels seem to be at increased risk for low BMD.

Newsletter No. 6/2009

1. Local Organizing Committee: Commencing Full Operation Despite the hard work some key local Organizing Committee members have been engaged in to prepare for the 22nd WCD, many local members have, until recently, been thinking that the congress is a long way off . However, the program committee meeting in Berlin in February brought about a general realization that the Congress is really only two years away. To further spread this anticipation to each individual, a local Organizing Committee Meeting was held on March 17, 2009 at COEX, Seoul – the venue for the 22nd WCD. About 60 Korean Organizing Committee members gathered together and reaffi rmed their commitment to the success of the 22nd World Congress of Dermatology. 2. First Announcement: Distribution Actively Supported by Many ILDS Member Societies As of mid-April 2009, we have received positive confi rmation from 42 societies across 38 countries of their willingness to cooperate to promote the 22nd World Congress of Dermatology by distributing the fi rst announcement to their members. The fi rst announcement has already been delivered to these member societies, except to those societies that have off ered to contribute by directly sending us their member databases. In addition, the ILDS has formally asked each member society to distribute the announcement electronically. Those member societies who have not yet distributed the announcements are asked to make a request to the local Organizing Committee (wcd2011@koconex.com).