Holger Mosbech

Diagnosis of Hymenoptera venom allergy.

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10–50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross‐reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE‐mediated or non‐IgE‐mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom‐allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health‐related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom‐specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.

Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group position paper

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

Allergen-induced histamine release in intact human skin in vivo assessed by skin microdialysis technique: Characterization of factors influencing histamine releasability☆☆☆★★★

BACKGROUND The purposes of the study were to characterize allergen-induced histamine release in intact human skin in vivo by using a novel microdialysis technique and to study covariates influencing histamine releasability. METHODS Hollow microdialysis fibers were inserted into the upper dermis in 15 timothy-sensitivity subjects. Up to 12 fibers were inserted in each subject. Each fiber was perfused with Krebs-Ringers solution at a rate of 3.0 microliters/min. Three to four serial dilutions of allergen were applied to the skin by intracutaneous injections or skin prick test above individual fibers. Samples were collected in two 2-minute fractions before skin challenge and in 10 consecutive samples for 20 minutes after skin challenge. Histamine was assayed spectrofluorometrically. RESULTS A significant dose-response relationship for histamine release was demonstrated with intracutaneous tests and skin prick tests. The time to reach peak histamine release after an intracutaneous test was 4 to 8 minutes, compared with 12 to 14 minutes for a skin prick test. Histamine release correlated significantly with wheal size. Intrasubject coefficient of variation on histamine release was about 20%. A substantial intersubject variation in histamine releasability was observed. Seventy to seventy-five percent of the variation could be accounted for by a combination of gender, total and allergen-specific IgE, and an in vitro basophil histamine release test. CONCLUSIONS Using a skin microdialysis technique, we have described in detail histamine release in intact human skin by allergen. The microdialysis method proved to be a reproducible technique for monitoring histamine release in allergic skin reactions and for studying histamine releasability of skin mast cells in vivo.

The sting challenge test in Hymenoptera venom allergy Position paper of the subcommittee on Insect Venom Allergy of the European Academy of Allergology and Clinical Immunology

Ruëff F, Przybilla B, Müller U, Mosbech H. The sting challenge test in Hymenoptera venom allergy. Position paper of the Subcommittee on Insect Venom Allergy of the European Academy of Allergology and Clinical Immunology. Allergy 1996: 51: 216–225.

Side-effects of allergen-specific immunotherapy. A prospective multi-centre study

Background and objective The safety of allergen‐specific immunotherapy (SIT) is a parameter of great interest in the overall assessment of the treatment. A clinical database was developed in order to obtain early warnings of changes in the frequency and severity of side‐effects and sufficient data for the evaluation of possible risk factors.

Antihistamine premedication in specific cluster immunotherapy: A double-blind, placebo-controlled study

BACKGROUND Specific immunotherapy treatment in allergic diseases involves a risk of systemic side effects. A double-blind, placebo-controlled study was performed in 45 patients allergic to pollen to determine whether pretreatment with loratadine could reduce the number and severity of systemic reactions during the dose-increase phase of cluster immunotherapy. METHODS The patients received cluster immunotherapy with a standardized birch (Betula verrucosa) or grass (Phleum pratense) pollen extract adsorbed to aluminum hydroxide. The immunotherapy schedule involved seven visits and 14 injections to reach a maintenance dose of 100,000 standardized quality units. Loratadine, 10 mg, or placebo tablets were administered 2 hours before the first injection at each visit. RESULTS A total of 720 injections were given (309 injections in 21 patients receiving loratadine and 411 injections in 24 patients receiving placebo). The median numbers of injections to reach maintenance dose were 15 (range, 14 to 18) in the loratadine group and 16 (range, 14 to 23) in the placebo group (p = 0.037). The numbers of patients with systemic reactions were seven (33%) and 19 (79%) in the loratadine and placebo groups, respectively (p = 0.002). Twenty-five reductions caused by systemic reactions were observed in the placebo group in contrast to nine in the loratadine group (p = 0.047). No life-threatening systemic reactions were observed in either group. Systemic reactions were, however, more severe in the placebo group, mainly because of a significantly higher incidence of urticaria (10 vs 1, p = 0.022). CONCLUSION Pretreatment with loratadine seems to reduce both the number and severity of systemic reactions in specific cluster immunotherapy.

Mucosal symptoms elicited by fragrance products in a population‐based sample in relation to atopy and bronchial hyper‐reactivity

Background Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown.

Allergen cross‐reactivity between house‐dust mites and other invertebrates

Keywords: allergens; Chironomidae; cockroaches; cross-reaction; Crustacea; Dermatophagoides; food hypersensitivity; hypersensitivity; mites; Mollusca

Death caused by wasp and bee stings in Denmark 1960-1980.

During a 21‐year period in Denmark a total of 26 deaths were caused by wasp or bee stings (according to the National Health Service). The deaths might be classified, with some overlapping, as caused by either anaphylactic/anaphylactoid shocks (between 65% and 80%), suffocation after stings in the airways (about 15%) or preexisting diseases, especially arteriselerotic heart disease (approx 20%). Characteristically, in most persons with shock reactions uncosciousness and death occurred very shortly after the sting (within 45 min), while the interval between sting and death was longer (30 min to a couple of hours) when death was caused by suffocation.

Immunotherapy with yellow jacket venom. A comparative study including three different extracts, one adsorbed to aluminium hydroxide and two unmodified.

Thirty‐two patients with previous systemic allergic reaction to yellow jacket stings were randomly allocated to three groups receiving immunotherapy with different preparations of yellow jacket venom: 1) extract adsorbed to aluminium hydroxide (Alutard®‐SQ), 2) Pharmalgen® extract or 3) non‐adsorbed extract from Allergologisk Laboratorium (ALK aq.). Regular examinations showed a decrease in skin prick test size in nearly all patients. Specific IgE‐antibody (RAST and CRIE scores) showed a similar, but not significant tendency to decrease in all three groups. Specific IgG‐antibody increased considerably in the Alutard group only; after 2 years, however, no difference could be detected between the three groups. During dose increase, patients treated with ALK aq. generally had smaller local reactions to injections than those treated with Pharmalgen. Few systemic reactions occurred in all three groups. Nineteen patients treated for 21/2–31/2 years were challenged in‐hospital with stings from yellow jackets. No systemic and only minor local reactions occurred. Consequently, with the dose regimens applied all three extracts seem effective even though no common changes in either specific IgE or IgG could be demonstrated.