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Résumé Les points forts de cette revue sont les suivants : les manifestations cliniques de l’anaphylaxie diffèrent chez les grands enfants (souvent cardiovasculaires) et les plus jeunes (gastro-intestinales et respiratoires), chez lesquels elles doivent faire suspecter une réaction anaphylactique lorsqu’elles surviennent brutalement ; des premiers cas d’anaphylaxie à certains aliments exotiques (crocodile, natto, etc.) ont été publiés et ont probablement un « bel avenir » ; la tendance à faire effectuer des tests de provocation prolongés d’emblée, avant tout testing cutané et biologique, se confirme chez les enfants rapportant des réactions non immédiates peu préoccupantes aux bêtalactamines ; les réactions d’hypersensibilité allergique aux anti-inflammatoires non stéroïdiens seraient plus fréquentes chez l’enfant que chez l’adulte, chez qui prédominent les réactions d’hypersensibilité non allergique ; les réactions locales aux vaccins sont fréquentes et récidivent fréquemment tandis que les réactions généralisées post-vaccinales, plus préoccupantes, sont rares et récidivent rarement, exception faite des réactions anaphylactiques immédiates ; les hémaglutinines des vaccins grippaux et les anatoxines des vaccins pneumococciques conjugués peuvent induire des réactions anaphylactiques ; la mastocytose pourrait représenter un facteur de risque d’anaphylaxie vaccinale ; de même que « l’allergie » aux moustiques, l’allergie aux hyménoptères tend à guérir chez les enfants rapportant des réactions systémiques bénignes à modérées ; chez les enfants rapportant des réactions graves aux piqûres d’hyménoptères, la désensibilisation est vraiment efficace, mais son efficacité tend à diminuer avec le temps et ainsi exposer les patients à des réactions anaphylactiques lors de repiqûres accidentelles. Most interesting findings are as follows: clinical symptoms of anaphylaxis are not similar in older children (cardiovascular) and younger ones (gastro-intestinal and respiratory) in whom sudden occurrence of such symptoms should evoke anaphylaxis; first cases of anaphylaxis to exotic foods (crocodile, natto, etc.) have been published and will probably increase during near future; prolonged provocation tests should precede skin and in vitro tests in children reporting non-immediate and non-severe reactions to beta-lactams; allergic hypersensitivity to non-steroidal anti-inflammatory drugs is probably more frequent in children than in adults, in whom most reactions are non-allergic; local reactions to vaccines are relatively frequent and reccur frequently, but are benign-moderately severe. In contrast, generalized reactions are rare and relapses are infrequent, except for immediate anaphylactic reactions; hemagglutinins of influenza viruses (influenza vaccines) and toxoids in conjugated vaccines (pneumococcal) may induce anaphylactic reactions; mast cell diseases may be a risk of vaccine-induced anaphylaxis; as well as mosquito « allergy », hymenoptera venom allergy resolve spontaneously in children reporting mild to moderately severe generalized reactions to hymenoptera stings; in children reporting severe reactions to hymenoptera stings, specific immunotherapy is efficient, but efficiency decreases with age and patients may have anaphylaxis when restung several years after the end of immunotherapy. [ABSTRACT FROM AUTHOR]

Insects represent an alternative for meat and fish in satisfying the increasing demand for sustainable sources of nutrition. Approximately two billion people globally consume insects. They are particularly popular in Asia, Latin America, and Africa. Most research on insect allergy has focussed on occupational or inhalation allergy. Research on insect food safety, including allergenicity, is therefore of great importance. The objective of this review is to provide an overview of cases reporting allergy following insect ingestion, studies on food allergy to insects, proteins involved in insect allergy including cross-reactive proteins, and the possibility to alter the allergenic potential of insects by food processing and digestion. Food allergy to insects has been described for silkworm, mealworm, caterpillars, Bruchus lentis , sago worm, locust, grasshopper, cicada, bee, Clanis bilineata , and the food additive carmine, which is derived from female Dactylopius coccus insects. For cockroaches, which are also edible insects, only studies on inhalation allergy have been described. Various insect allergens have been identified including tropomyosin and arginine kinase, which are both pan-allergens known for their cross-reactivity with homologous proteins in crustaceans and house dust mite. Cross-reactivity and/or co-sensitization of insect tropomyosin and arginine kinase has been demonstrated in house dust mite and seafood (e.g. prawn, shrimp) allergic patients. In addition, many other (allergenic) species (various non-edible insects, arachnids, mites, seafoods, mammals, nematoda, trematoda, plants, and fungi) have been identified with sequence alignment analysis to show potential cross-reactivity with allergens of edible insects. It was also shown that thermal processing and digestion did not eliminate insect protein allergenicity. Although purified natural allergens are scarce and yields are low, recombinant allergens from cockroach, silkworm, and Indian mealmoth are readily available, giving opportunities for future research on diagnostic allergy tests and vaccine candidates. [ABSTRACT FROM AUTHOR]

Résumé En 2015, la majorité des études confirment, tout en les complétant et précisant, les résultats d’études publiées antérieurement. Toutefois, certains articles ont semblé particulièrement intéressants. C’est ainsi que : (1) même si l’on ignore encore la signification du phénomène, les IgE maternelles traversent le placenta sous forme de complexes immuns IgE-IgG anti-IgE interagissant avec les récepteurs placentaires des IgG ; (2) les écoles devraient disposer de stylos d’adrénaline auto-injectables non nominatifs, autorisant des injections à n’importe quel enfant ou adulte présentant une réaction anaphylactique, notamment inaugurale ; (3) outre l’adrénaline, les corticoïdes diminuent la gravité et le risque de prolongation ou de récidive des réactions anaphylactiques ; (4) le diagnostic d’allergie alimentaire ou de tolérance naturelle ou acquise suite à une éviction ou une désensibilisation pourrait être amélioré par l’établissement du rapport entre les IgE sériques spécifiques et les IgE totales, plus que par le simple dosage des IgE spécifiques et la surveillance de leur évolution ; (5) les tests de provocation orale alimentaires donnent moins de réactions graves lorsque les doses progressivement croissantes d’aliments sont administrées toutes les 30 min que lorsqu’elles sont administrées plus rapidement ; (6) le diagnostic des réactions non immédiates et/ou non préoccupantes aux médicaments repose avant tout sur les tests de provocation/réintroduction, éventuellement prolongés au domicile des enfants, et non sur les tests cutanés et/ou les examens biologiques ; (7) enfin, il faut absolument penser aux additifs et contaminants chez les enfants réagissant à de nombreux aliments et/ou médicaments et substances biologiques. Most studies published in 2015 confirm, but also complete and precise, results of previous studies. However, some interesting news arise from recent publications: (1) although the signification of the phenomenon remains unknown, maternal IgE are transferred transplacentally as IgE-IgG anti-IgE immune complexes interacting with the placental IgG receptor; (2) schools should be allowed to use non nominative self-injectable epinephrine pens to treat anaphylactic reactions occurring in any child or staff patient; (3) corticosteroids administered rapidly after epinephrine significantly reduce the severity and risk of duration/relapse of anaphylactic reactions; (4) diagnosis of food allergy and of food tolerance (natural, acquired based on eviction or specific sublingual/oral immunotherapy) may be improved by establishment of serum specific/total IgE concentrations, rather than on (repeated) dosages of specific IgE; (5) oral food challenges induce less severe reactions when increasing doses are administered at 30 min intervals than when they are administered more rapidly; (6) diagnosis of non-immediate and/or non-severe reactions to drugs is based on challenge tests with the suspected drugs (betalactams especially), including prolonged challenge tests performed at home, and not on skin and/or biological tests; (7) finally, one may perform skin and/or oral challenge tests with additives and contaminants in children reporting allergic-like reactions to numerous foods and/or drugs or biological substances. [ABSTRACT FROM AUTHOR]

Edible insects are currently being evaluated as an alternative and more sustainable protein source for humans. The introduction of new food sources can lead to development of novel allergies. Because in the Western world, insects are unlikely to be consumed raw, it is important to know how processing and in vitro digestion might influence their allergenicity. Three edible mealworm species ( Tenebrio molitor , Zophobas atratus and Alphitobius diaperinus ) subjected to processing and in vitro digestion were analysed for IgE cross-reactivity. Immunoblot and MALDI-MS/MS analyses revealed that IgE from crustaceans or House dust mite (HDM) allergic patients showed cross-reactivity to mealworm tropomyosin or α-amylase, hexamerin 1B precursor and muscle myosin, respectively. Heat processing as well as in vitro digestion did diminish, but not eliminate, HDM or tropomyosin IgE cross-reactivity. Results show that individuals allergic to HDM or crustaceans might be at risk when consuming mealworms, even after heat processing. [ABSTRACT FROM AUTHOR]

The main insects causing allergy reactions to stinging insect in humans are Apidae (bees), Vespidae (wasps, yellow jackets and hornets) and Formicidae (ants). Their venom stings are composed of various biologically active peptides and protein components, some of which can cause toxicity or anaphylaxis in humans. The protein venom demonstrate some common allergenic activity such as for fire ants and vespids, which have two common allergens that are phospholipase A 1 (enzymatic activity) and antigen 5 with unknown biological activity. The common allergens seem to share some degree of immunological cross-reactivity, particularly when the sequence homology is above 70%. Therefore immunotherapeutic approaches targeting more than one specific species are of interest. Recent widespread increases of various ant species in many countries have resulted in higher number of reported about serious allergic reactions to stings. Most insect-allergy related cases have been reported for species from Solenopsis , Myrmecia and Pachycondyla genera, and their stings can often result in human fatalities. In addition, stinging ants can have serious health effects on livestock, agricultural damage adversely affecting the biodiversity of the region. This review discusses the impact of important ant species on human health in the Asia-Pacific region along with the molecular immunological aspects of the identified venoms and current status of diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Résumé Plus les années passent, plus c’est « un peu la même chose ». Le lait maternel transfère des allergènes, qui, au moins chez la souris, induisent une sensibilisation du souriceau dont les conséquences (tolérogènes ou allergisantes) restent à déterminer. Un allaitement au sein prolongé et une diversification incluant des fruits et des légumes frais, et des repas « maison » avec des aliments frais diminueraient le risque d’allergie, alimentaire notamment. Les chances de guérison, spontanée ou induite par la désensibilisation, sont inversement proportionnelles au degré de sensibilisation initiale et à la gravité de l’allergie alimentaire. La désensibilisation aux aliments doit initialement être effectuée en milieu sécurisé, puis entretenue à domicile par des familles bien informées et éduquées, compte tenu de la fréquence élevée des réactions, parfois graves. Lorsque la tolérance est acquise, elle paraît durable, sous réserve de poursuivre une consommation régulière de l’aliment concerné. La majorité des études confirme que seule une faible proportion des enfants consultant pour suspicion d’allergie médicamenteuse est réellement atteinte d’une hypersensibilité allergique ou non allergique aux médicaments. Lorsqu’ils sont validés, les tests cutanés présentent une bonne valeur diagnostique dans les réactions IgE-médiées, alors que le diagnostic des réactions non IgE-médiées repose le plus souvent sur l’histoire clinique (toxidermies potentiellement sévères notamment) ou sur la positivité des tests de provocation/réintroduction. Enfin, la prévalence de l’allergie aux bêta-lactamines chez les enfants atteints de mucoviscidose est, contrairement à la notion classique, extrêmement faible, peut-être parce que les traitements répétés à fortes doses exercent des effets tolérogènes. Years go by but most things seem to remain the same. Breast milk passively transfers aeroallergens and food allergens to the child, and, at least in mice, these allergens can induce sensitization in the offspring; still, the consequences – tolerogenic or allergenic – of the sensitization remain unknown. Breastfeeding for at least 4 months, early introduction of fresh vegetables and fruits, and homemade meals with fresh foods may reduce the risk of subsequent food allergy. Regarding food-allergic children, the probability of tolerance development following avoidance or allergen immunotherapy is correlated inversely with the degree of sensitization and the severity of the child's symptoms. Due to the potentially high incidence of reactions, often severe, specific food immunotherapy should be initiated in a well-equipped medical setting with experienced personnel, initially escalating the dose administered. Maintenance at home can be carried out by parents who have been well prepared and who are well equipped, e.g., for epinephrine injection. When tolerance has developed, it will persist if the child continues regular and frequent consumption of the food involved. It has been reported that only a small fraction of children with suspected drug hypersensitivity are actually allergic to the suspected drug. In children with a history of an immediate-type hypersensitivity reaction to a drug, a positive immediate skin test has good diagnostic value. On the contrary, the diagnosis of delayed-type hypersensitivity reactions to drugs is mainly based on the clinical history; it may be supported by a drug provocation test. To close, the prevalence of beta-lactam allergy in children with cystic fibrosis appears very low. This may be the result of their frequent treatment with high doses of a beta-lactam, which has induced tolerance. [ABSTRACT FROM AUTHOR]

Myrmecia pilosula is an endemic Australian ant whose sting is a frequent cause of insect allergy in southeast Australia, and several deaths due to M. pilosula sting envenomation have been documented. In this review, we discuss the composition and bioactivity of M. pilosula venom. In addition to various enzymes and pharmacologically active constituents, the venom contains four families of highly basic low molecular weight peptides trivially named Pilosulins. These peptides are unique and have low structural homology to other Hymenoptera venom peptides. Moreover, M. pilosula venom is relatively simple in its composition with 5 predominant peptides making up about 90% by weight. These peptides display cytotoxic, hypotensive, histamine-releasing and antimicrobial activities. Within the M. pilosula venom, Pilosulin 3 has been classified as a major allergen and [Ile 5 ]pilosulin 1 and Pilosulin 4.1 are classified as minor allergens. Several uncharacterised higher molecular weight components with allergenic activities have also been identified. The revised naming of M. pilosula venom peptides according to the International Union of Immunological Societies (IUIS) criteria for allergen nomenclature is discussed in this review. [ABSTRACT FROM AUTHOR]

Résumé Le risque d’allergie alimentaire semble accru chez les enfants atteints de reflux gastro-œsophagien et serait majoré par les traitements antisécrétoires. La majorité des enfants rapportant des réactions présumées allergiques aux aliments n’est pas atteinte d’allergie alimentaire. Un bilan est donc impératif pour éviter des angoisses familiales et des régimes d’exclusion préjudiciables. Les consultations régulières chez l’allergologue ont un impact favorable sur la reconnaissance des réactions anaphylactiques et leur prise en charge par l’entourage des enfants. Des « hot-lines » spécialisées, disponibles 24 h/24, et des « écoles de l’allergie alimentaire » dispensées de façon ludique dans le cadre de centres de vacances semblent avoir un impact favorable sur la prise en charge des réactions anaphylactiques d’origine alimentaire par les parents et les enfants eux-mêmes. Enfin, la réactivité au blé varie avec la nature des aliments, la tolérance des biscuits n’excluant pas le risque de réaction à d’autres aliments contenant du blé. Si la prévalence des réactions présumées allergiques aux médicaments est élevée, il se confirme que, exception faite des réactions aux anti-inflammatoires non stéroïdiens, la grande majorité des enfants rapportant des réactions de type allergique aux médicaments n’est pas atteinte d’hypersensibilité médicamenteuse. Il se confirme aussi, encore une fois, que les tests de réintroduction doivent être effectués de façon prolongée, au domicile, chez les enfants rapportant des réactions non immédiates aux médicaments, au risque d’infirmer à tort un diagnostic d’hypersensibilité médicamenteuse. Enfin, la désensibilisation aux venins d’hyménoptères est particulièrement efficace chez l’enfant, son efficacité perdurant pendant au moins 7–8 ans, comme chez l’adulte. Food allergy risk is increased in children with gastroesophageal reflux, and even more increased when these children are treated by anti-acids. Most children with suspected food allergy are not allergic to foods. Thus, a well-conducted allergological work-up is necessary to avoid familial anxiety and food evictions that may be harmful for the children. Frequent consultations at the allergist's office are associated with a better identification of severity and a better emergency treatment of anaphylactic reactions by the parents. Specialized 24 h/24 helplines and educational support provided during activity holidays are associated with a significant benefit on management of food-induced anaphylaxis by the parents and the children themselves. Finally, reactivity to wheat may vary according to the wheat-containing foods administered to the children, and children tolerant to wheat cereal biscuits may react to other wheat-containing foods such as bread or pasta. If many children report suspected allergic reactions to drugs, only a few of these children are truly suffering from drug hypersensitivity, except for children reporting reactions to non-opioid analgesics, antipyretics and non-steroidal anti-inflammatory drugs. Once more, it is shown that drug challenges should be performed at home and prolonged in children reporting non-immediate reactions, at the risk of underdiagnosing drug hypersensitivity. Finally, hymenoptera venom immunotherapy is efficient in children, and its efficacity persists during 7–8 years at least. [ABSTRACT FROM AUTHOR]

Résumé: Des études ayant porté sur de très nombreux enfants confirment que : les aliments sont les principaux pourvoyeurs d’anaphylaxie ; l’anaphylaxie pédiatrique est globalement sous-reconnue et sous-traitée, alors même que la précocité du traitement améliore le pronostic évolutif, même si les décès sont exceptionnels ; la prévalence générale de l’allergie alimentaire continue d’augmenter, notamment chez les (très) jeunes enfants ; même si le risque d’allergie alimentaire et la gravité des réactions augmentent globalement avec le niveau de sensibilisation détectée par les prick-tests et les dosages des IgE spécifiques, le test de provocation par voie orale reste souvent l’examen diagnostique déterminant ; les dosages des IgE spécifiques des allergènes moléculaires présentent un intérêt diagnostique certain et pourraient diminuer les indications des tests de provocation ; la tolérance des aliments cuits (lait et œuf notamment) est un bon facteur prédictif d’évolution vers la tolérance aux aliments crus ; les protocoles d’induction de tolérance par voie orale, en particulier au lait et l’œuf, sont globalement efficaces et plutôt bien tolérés ; seule une faible proportion des enfants, y compris des enfants atteints de mucoviscidose, rapportant des réactions présumées allergiques aux médicaments anti-infectieux est réellement allergique à ces médicaments ; et la vaccination antigrippale est usuellement bien tolérée par les très grands allergiques à l’œuf. Enfin, les allergies persistantes au lait de vache, rapportées chez les nourrissons exclusivement allaités au sein, pourraient résulter d’une importante réactivité croisée entre les protéines du lait maternel et les protéines du lait de vache. [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This review highlights some of the research advances in anaphylaxis; hypersensitivity reactions to foods, drugs, and insects; and allergic skin disease that were reported in the Journal in 2010. Key epidemiologic observations include an apparent increase in peanut allergy, with more than 1% of children affected, and increasing evidence that early food allergen exposure, rather than avoidance, might improve allergy outcomes. Advances in food allergy diagnosis include improved insights into prognosis and estimation of severity through component-resolved diagnostics and characterization of IgE binding to specific epitopes. Regarding treatment, oral and epicutaneous immunotherapy show promise. Studies of drug allergies show insights into pathophysiology, and studies on insect hypersensitivity reveal improved diagnostic methods. Genetic and functional studies have revealed the important role of epidermal differentiation products in the pathogenesis of atopic dermatitis. Cross-talk between the atopic immune response with the innate immune response have also been found to predispose to infection in patients with atopic dermatitis. New therapeutic approaches to control chronic urticaria have also been identified during the past year. [ABSTRACT FROM AUTHOR]

Abstract: Allergens from cockroaches cause major asthma-related health problems worldwide. Among them Per a 3 belongs to the most potent allergens. Although the sequences of some members of the Per a 3-family are known, their biochemical and biophysical properties have not been investigated. Here we present for the first time a thorough structural characterization of these allergens, which have recently been tested to induce an increase of allergy specific indicators in blood of Europeans. We isolated two Per a 3 isoforms, which occur freely dissolved in the hemolymph as hexamers with molecular masses of 465±25kDa (P II) and 512±25kDa (P I). Their sedimentation coefficients (S 20,W) were determined to be 17.4±0.7 S (P II) and 19.0±0.9 S (P I), respectively. Sequence analysis revealed that P II consists of two subunit types known as allergens Per a 3.01 and Per a 3.0201, while PI consists of a new allergenic subunit type designated as Per a 3.03. A 3D model of the hexameric allergen Per a 3 was obtained by homology modelling. Almost all of the recently predicted 11 putative antigenic peptides and reported IgE-epitopes could be located on the surface of the hexamer, thus being freely accessible in the hexameric structure of the native molecules. We propose this might contribute to their allergic potential as well as their extreme stability with respect to temperature. [Copyright &y& Elsevier]

Background: Large local reactions to insect stings cause significant morbidity and impair quality of life. Venom immunotherapy is not recommended because of a low risk for future systemic reaction and unproven efficacy in preventing large local reactions. Objective: To determine the feasibility of performing a controlled trial to examine the efficacy of venom immunotherapy in reducing the size and duration of large local reactions. Methods: Sting challenge in 41 patients with previous large local reactions and positive venom skin tests caused large local reactions 16 cm or larger in 34 patients, and 29 consented to treatment. Venom immunotherapy was initiated in 19, and 10 were untreated controls. Sting challenge was repeated after 7 to 11 weeks (control patients then began venom immunotherapy), and annually for as long as 4 years. Results: After 7 to 11 weeks of treatment, the size and duration of large local reactions decreased 42% and 53%, respectively, in treated patients and 18% in controls (P < .01 for both). The response was similar after 1 year, and improved after 2 to 4 years to 60% and 70%, respectively. Conclusions: Venom immunotherapy significantly reduced the size and duration of the large local reactions, and the efficacy improved over a period of 2 to 4 years of treatment. Further studies are needed to establish the safety and efficacy of venom immunotherapy for large local reactions, the optimal duration of treatment, and the mechanism for the differences in degree and rate of clinical response compared with venom immunotherapy in systemic reactors. [Copyright &y& Elsevier]

This review highlights some of the research advances in anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects and in allergic skin disease that were reported in the Journal in 2008. Key epidemiologic observations include a rise in anaphylaxis in a population-based study and lower rates of peanut allergy in Israel, where infants consume peanut early compared with the United Kingdom, where dietary introduction is generally delayed. Advances in food allergy diagnosis include IgE epitope mapping that discloses the likelihood and severity of allergy; studies correlating likelihood of clinical reactivity on the basis of food-specific IgE to sesame, peanut, milk, and tree nuts; and an observation that a low baseline angiotensin-converting enzyme level may be associated with having pharyngeal edema during a reaction. Molecular, immunologic, and genetic studies are discerning pathways that are key in development of food allergy, identifying new modalities to interrupt mast cell degranulation, and elucidating risks associated with penicillin allergy. Regarding treatment, clinical studies show a majority of children with milk and egg allergy tolerate these proteins in modest amounts when they are extensively heated in baked goods, and studies show promise for oral immunotherapy to treat milk allergy and sublingual immunotherapy for honey bee venom hypersensitivity. The importance of skin barrier dysfunction has continued to be highlighted in the pathophysiology of atopic dermatitis (AD). Research has also continued to identify immunologic defects that contribute to the propensity of patients with AD to develop viral and bacterial infection. New therapeutic approaches to AD, urticaria, and angioedema have been reported including use of probiotics, biologics, vitamin D, and skin barrier creams. [Copyright &y& Elsevier]

Genetic factors involved in susceptibility to insect bite hypersensitivity (IBH) in Belgian Warmblood horses (BWP) were investigated. Data relating to 3409 horses were collected using a questionnaire, administered to owners during sport competitions, BWP breeding days, breeder visits and after phone calls. Horses were classified as IBH-affected or unaffected, based on two ‘disease classifiers’: a lifetime record, based on owner information (life_status) and another based on whether or not the horse was showing clinical signs at the time of questioning (clin_status). IBH prevalence was 10% based on life_status, and 6.2% based on clin_status. The heritabilities estimated using threshold animal models varied from 0.65 to 0.78 on the underlying scale (0.18–0.26 on the observed scale). These research findings indicate that susceptibility to IBH is a heritable trait in BWP. [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. Objective: We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. Methods: We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 μg of venom monthly. The sting challenge was repeated after 6 months. Results: Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm (P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. Conclusion: Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed. [Copyright &y& Elsevier]

Background: Venom immunotherapy (VIT) is a treatment with established efficacy for the prevention of repeated anaphylactic reactions in patients with Hymenoptera allergy, which also allows patients to discontinue carrying an EpiPen. Despite their merits, both treatments can have negative aspects potentially important to patients. Objective: We examined possible negative aspects of the EpiPen in comparison with VIT as perceived by patients. Methods: Positive and negative aspects of both treatments were measured by using a burden of treatment questionnaire together with statements about the EpiPen. Results: One hundred ninety-three patients were included, of whom 94 consented to randomization: 47 received VIT, and 47 received the EpiPen. Of the remaining 99, 75 chose VIT, and 26 chose the EpiPen. Of the patients receiving VIT, 91.5% were (extremely) positive about their treatment, and 85% would choose VIT again. Of the patients receiving the EpiPen, only 48% were positive about their treatment, and even of these patients, 68% preferred to be treated with VIT after 1 year of carrying the EpiPen. Although most patients indicated that it is reassuring to carry an EpiPen and makes them feel safe, many patients also indicated that it is inconvenient and troublesome. Especially patients who were negative about the EpiPen indicated that they would not dare use the EpiPen if necessary and were afraid at possible side effects. Conclusion: In contrast to VIT, the EpiPen is perceived as burdensome by most patients with venom allergy. For most patients, an EpiPen is an unsuitable definitive treatment. Clinical implications: As VIT enables patients with venom allergy to get rid of the EpiPen, patients should be offered VIT. [Copyright &y& Elsevier]

Abstract: The parasitic fungus, Metarhizium anisopliae, is non-pathogenic to humans and licensed for indoor control of cockroach infestation. An important reason for the elimination of this vermin is that sensitisation to cockroaches is associated with asthma. Previously M. anisopliae has been shown to cause allergic- and asthma-like responses in mice and in the present study we have examined the adjuvant activity of M. anisopliae on the allergic response to the model allergen ovalbumin (OVA) in a mouse model. Levels of OVA-specific IgE, IgG1 and IgG2a in serum were measured and the weight and cell number of the excised popliteal lymph node were determined. Mice primed with mycelium+OVA and boosted with OVA had increased anti-OVA IgE and IgG1 levels compared with mice primed with OVA alone or mycelium. Priming with M. anisopliae (as mycelium or MACA) increased weight or cell number of the excised PLNs. These results suggest that M. anisopliae has the ability to increase an allergic response to an allergen and consequently, may worsen allergy in susceptible individuals. [Copyright &y& Elsevier]

Background: Sol i 1, the venom phospholipase of imported fire ant venom is an important allergen and exhibits some cross-reactivity with IgE antibodies from patients sensitized to other Hymenoptera venoms. Objective: To determine the primary structure of Sol i 1 and evaluate the roles of protein and carbohydrate epitopes in its cross-reactivity. Methods: Sol i 1 was purified from venom, proteolytic peptides prepared and amino acid sequences obtained. The cDNA for Sol i 1 was cloned, sequenced, and compared with sequences of other wasp venom phospholipases. The role of carbohydrate epitopes in the cross-reactivity with other Hymenoptera venoms was studied by RAST inhibition. Results: The sequence identified Sol i 1 as a lipase of the GX class, lipoprotein lipase superfamily, pancreatic lipase homologous family and RP2 subgroup phospholipases as are the vespid venom phospholipases. The 148 residues identified by amino acid sequencing represent about 48% of the translated cDNA sequence. Sol i 1 was 31-32% identical to yellow jacket phospholipases. The identical regions of sequence were clustered in the domain which forms the serine hydrolase active site. Mannosylated N-glycans could completely inhibit binding of IgE from honeybee venom sensitized patients to Sol i 1. Inhibition by glycan of IgE binding from yellow jacket venom sensitized patients was low or absent for three of eight sera and substantial, but not complete for five sera. Conclusions: Sol i 1 is related to wasp venom phospholipases. Cross-reactivity with honeybee venom is caused by carbohydrate, whereas cross-reactivity with yellow jacket venom involves reactivity with both carbohydrate determinants of hyaluronidase and high molecular weight proteins and phospholipase protein determinants. [ABSTRACT FROM AUTHOR]

Background: B-Blockers may aggravate anaphylactic reactions and interfere with treatment. There is therefore concern about their use in patients who have a history of anaphylaxis or are on allergen immunotherapy. Immunotherapy is the best available treatment for prevention of life-threatening anaphylaxis to Hymenoptera stings, which is often observed in elderly patients who have cardiovascular disease and therefore are on β-blocker treatment. Objective: To analyze the risk of β-blocker treatment during venom immunotherapy. Methods: We screened all 1682 patients with Hymenoptera venom allergy seen during a period of 34 months for immunotherapy, cardiovascular disease, and treatment with β-blockers. Results: Of the 1389 patients in whom immunotherapy was recommended, 11.2% had cardiovascular disease, and 44 of these were on β-blockers before immunotherapy. In 31 of those, the drug was replaced before starting treatment. In 3 with coronary heart disease and 1 with severe ventricular arrhythmia, the drug was continued throughout immunotherapy. In 9, it was reintroduced after reaching the maintenance dose. In an additional 12 patients, β-blockers were newly started during immunotherapy. Of 25 patients on β-blockers during immunotherapy, 3 (12%) developed allergic side effects, compared with 23 (16.7%) of 117 with cardiovascular disease but without β-blockers. Systemic allergic symptoms after re-exposure by sting challenge or field sting were observed in 1 of 7 (14.3%) with and 4 of 29 (13.8%) without β-blockade. No severe reactions to treatment or sting reexposure were observed in patients with β-blockade. Conclusion: Combination of β-blockers with venom immunotherapy may be indicated in heavily exposed patients with severe cardiovascular disease. [ABSTRACT FROM AUTHOR]

Anaphylaxis often occurs in the community in the absence of a health care professional. Prompt administration of self-injectable epinephrine as first-aid treatment in the context of a personalized emergency action plan is the key to survival. There is little argument that physicians should prescribe self-injectable epinephrine for individuals who have already experienced anaphylaxis involving respiratory distress or shock triggered by allergens that might be encountered in the community. A quandary faced by physicians is that additional individuals with identified allergy who have no recognized prior history of anaphylaxis or who have a history of mild symptoms after exposure to a known trigger might also be at risk for subsequent life-threatening anaphylaxis and might also warrant prescription of self-injectable epinephrine. Prescribing for the latter individuals requires considerable clinical judgment and has led to controversy regarding possible overprescription or underprescription of self-injectable epinephrine. A second quandary for physicians occurs with regard to the advice they should give to at-risk individuals about actual use of their self-injectable epinephrine. It is difficult for health care professionals, let alone persons with no health care training, to predict whether anaphylaxis symptoms will occur in an at-risk individual after exposure to a known trigger. Moreover, at the onset of an acute allergic reaction, it is difficult to predict the symptoms that will ultimately develop. We examine these 2 common quandaries and provide examples of clinical scenarios and potential pitfalls in the management of persons identified as being at risk for anaphylaxis in the community. Additional studies of the recognition and treatment of anaphylaxis in the community are needed to develop comprehensive, evidence-based recommendations for its management in this setting. [ABSTRACT FROM AUTHOR]

Background: Asthma-associated morbidity is rising, especially in inner city children. Objective: We evaluated the allergen sensitivities, allergen exposures, and associated morbidity for participants in the Inner City Asthma Study. We also determined geographic variations of indoor allergen levels. Methods: Nine hundred thirty-seven inner city children 5 to 11 years old with moderate to severe asthma underwent allergen skin testing. Bedroom dust samples were evaluated for Der p 1, Der f 1, Bla g 1, Fel d 1, and Can f 1. Results: Skin test sensitivities to cockroach (69%), dust mites (62%), and molds (50%) predominated, with marked study site–specific differences. Cockroach sensitivity was highest in the Bronx, New York, and Dallas (81.2%, 78.7%, and 78.5%, respectively), and dust mite sensitivity was highest in Dallas and Seattle (83.7% and 78.0%, respectively). A majority of homes in Chicago, New York, and the Bronx had cockroach allergen levels greater than 2 U/g, and a majority of those in Dallas and Seattle had dust mite allergen levels greater than 2 μg/g. Levels of both of these allergens were influenced by housing type. Cockroach allergen levels were highest in high-rise apartments, whereas dust mite allergen levels were highest in detached homes. Children who were both sensitive and exposed to cockroach allergen had significantly more asthma symptom days, more caretaker interrupted sleep, and more school days missed than children who were not sensitive or exposed. Conclusion: Geographic differences in allergen exposure and sensitivity exist among inner city children. Cockroach exposure and sensitivity predominate in the Northeast, whereas dust mite exposure and sensitivity are highest in the South and Northwest. Cockroach allergen appears to have a greater effect on asthma morbidity than dust mite or pet allergen in these children. [ABSTRACT FROM AUTHOR]

Whole-body extracts of Hymenoptera were used for diagnosis and treatment until controlled clinical trials proved them no better than placebo, whereas venom is 85% to 98% effective. Studies of natural history reveal why whole-body extracts were thought to work. The chance of future systemic reactions is low in large local reactors and in most children and varies between 20% and 70% in adults. Venom skin tests are most accurate, but RAST is an important complementary test. The degree of sensitivity on skin tests or RASTs does not reliably predict the severity of a sting reaction. Venom immunotherapy is recommended for patients at high risk for sting reactions. Rapid regimens are as safe as slower regimens. The recommended dose is 100 μg, but some patients require higher doses for full protection. Venom immunotherapy is continued every 4 to 8 weeks for at least 5 years in most cases. Skin test results become negative in only 25% after 5 years of therapy but in 60% to 70% after 7 to 10 years. When treatment is stopped after 5 years or more, there is a 10% chance of systemic reaction to each future sting, but most reactions are mild. Some patients have a higher risk of relapse and should continue treatment for an extended period. [ABSTRACT FROM AUTHOR]

Abstract: This article describes the function of a forum (operating by means of an exchange of correspondence) devoted to difficult cases of insect allergy, essentially to hymenoptera venoms. The principal results of this forum as well as its evolution are presented. We hope that all concerned physicians will benefit from this tool. [Copyright &y& Elsevier]

Abstract: Among the hymenoptera, only the aculeate taxa are able to inflict bites by means of their venomous stingers. The diversity of this group in Europe will be reviewed briefly, focussing on families classically known for their ability to induce allergic reactions (the social insects: apideae, vespidea, formicidea), and a few comments will also be made about members of the several thousand less frequently encountered non-social families that humans come in contact with accidently. It is indeed highly likely that certain atypical reactions or those apparently unrelated to known venoms are caused by solitary hymenoptera encountered by chance during various experiences in the countryside as well as in abundantly inhabited areas. [Copyright &y& Elsevier]

Background: The identification of the disease-causing insect in venom allergy is often difficult. Objective: To establish recombinant allergen-based IgE tests to diagnose bee and yellow jacket wasp allergy. Methods: Sera from patients with bee and/or wasp allergy (n = 43) and patients with pollen allergy with false-positive IgE serology to venom extracts were tested for IgE reactivity in allergen extract-based tests or with purified allergens, including nonglycosylated Escherichia coli–expressed recombinant (r) Api m 1, rApi m 2, rVes v 5, and insect cell–expressed, glycosylated rApi m 2 as well as 2 natural plant glycoproteins (Phl p 4, bromelain). Results: The patients with venom allergy could be diagnosed with a combination of E coli–expressed rApi m 1, rApi m 2, and rVes v 5 whereas patients with pollen allergy remained negative. For a group of 29 patients for whom the sensitizing venom could not be identified with natural allergen extracts, testing with nonglycosylated allergens allowed identification of the sensitizing venom. Recombinant nonglycosylated allergens also allowed definition of the sensitizing venom for those 14 patients who had reacted either with bee or wasp venom extracts. By IgE inhibition studies, it is shown that glycosylated Api m 2 contains carbohydrate epitopes that cross-react with natural Api m 1, Ves v 2, natural Phl p 4, and bromelain, thus identifying cross-reactive structures responsible for serologic false-positive test results or double-positivity to bee and wasp extracts. Conclusion: Nonglycosylated recombinant bee and wasp venom allergens allow the identification of patients with bee and wasp allergy and should facilitate accurate prescription of venom immunotherapy. [Copyright &y& Elsevier]

Background: Carmine is a natural red pigment obtained from dried gravid female cochineal insects (Dactylopius coccus or Coccus cacti). There have been several reports of allergies to carmine, but the major allergens responsible have not been identified. Objective: To identify the major allergenic proteins in cochineal. Methods: Immunoblots of purified cochineal extract were probed with sera from 3 patients with allergy. Partial amino acid sequences were determined for the proteins bound by IgE, and the corresponding cDNA, containing a complete coding region, was cloned by 5′ and 3′ rapid cDNA extension and PCR. The recombinant protein was expressed in yeast and subjected to immunoblotting. Results: We identified a full-length cDNA encoding a protein, which we named CC38K, with 335 amino acids and a molecular mass calculated as 38 kd. This amino acid sequence included all the partial amino acid sequences obtained from the purified proteins identified by IgE from patients with allergy. Recombinant CC38K protein was recognized by patients'' sera, indicating that this is a major allergen present in carmine. The CC38K sequence showed homology to phospholipases. Conclusion: We have, for the first time, identified the major allergen in cochineal extract. This protein may be a phospholipase or related enzyme, both of which are known to be allergens in other insects. [Copyright &y& Elsevier]

Background: Cockroach is an important allergen in inner-city asthma. The diagnosis and treatment of cockroach allergy has been impeded by the lack of standardized cockroach extracts. Objective: We investigated the utility of a mediator release assay based on rat basophil leukemia (RBL) cells for comparing the potency of German cockroach extracts. Methods: RBL cells (line 2H3) transfected with human FcεRI were passively sensitized with sera from subjects with cockroach allergy and stimulated with serial dilutions of 3 commercial cockroach extracts (1:10 weight/volume). In addition, the in-house prepared extract was tested in separate experiments with pooled sera that produced optimal performance in the RBL assay. N-hexosaminidase release (NHR) was used as a marker of RBL cell degranulation and was examined in relation to the intradermal skin test (ID50EAL) and serum cockroach-specific and total IgE levels. Results: The median cockroach-specific IgE concentration in 60 subjects was 0.72 kUA/L (interquartile range, 0.35-2.97 kUA/L); 19 sera (responders) produced a minimum 10% NHR to more than 1 extract. Responders had higher median cockroach-specific IgE (7.4 vs 1.0 kUA/L) and total IgE (429 vs 300 kU/L) levels than nonresponders. Ranking of extract potency was consistent between the mediator release assay and the ID50EAL. For the in-house prepared cockroach extract, the dose-response curves were shifted according to the concentration of the extract. NHR was reproducible between different experiments by using pooled sera. Conclusion: The mediator release assay measures biologic potency and correlates with the ID50EAL. It should be further evaluated to determine whether it could be used to replace intradermal skin test titration for assessing the potency of cockroach extract. [Copyright &y& Elsevier]

Presents announcements related to dermatology as of October 1975. Symposium on insect allergy at the 1975 meeting of the Entomological Society of America; Career help from the Association of Professors of Dermatology and the National Program of the American Academy of Dermatology; Information on a meeting of the Dermatology Club.