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.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1398-9995.2005.00963.x

Diagnosis of Hymenoptera venom allergy.

Among food allergens, crustaceans, such as shrimp, crab, crawfish and lobster, are a frequent cause of adverse food reactions in allergic individuals. The major allergen has been identified as the muscle protein tropomyosin. This molecule belongs to a family of highly conserved proteins with multiple isoforms found in both muscle and nonmuscle cells of all species of vertebrates and invertebrates. Its native structure consists of two parallel alpha-helical tropomyosin molecules that are wound around each other forming a coiled-coil dimer. Allergenic tropomyosins are found in invertebrates such as crustaceans (shrimp, lobster, crab, crawfish), arachnids (house dust mites), insects (cockroaches), and mollusks (e.g. squid), whereas vertebrate tropomyosins are nonallergenic. Studies of cross-reactivities among crustaceans and the high degree of sequence identity among them suggest that tropomyosin is probably the common major allergen in crustaceans. Furthermore, immunological relationships between crustaceans, cockroaches and housedust mites have been established and may suggest tropomyosin as an important cross-sensitizing pan allergen.

Tropomyosin: An Invertebrate Pan–Allergen

As a consequence of the general increase in allergic sensitization, the prevalence of hypersensitivity reactions to multiple foods that share homologous proteins has become a significant clinical problem. A variety of these allergens conserved among plants (eg, profilin and lipid transfer proteins) and animals (eg, tropomyosin and caseins) have been characterized. Although studies with molecular biologic techniques have elucidated the nature of these ubiquitous allergens, clinical studies have lagged behind. The physician is called on to determine the risk of reaction to related foods among legumes, tree nuts, fish, shellfish, cereal grains, mammalian and avian food products, and a variety of other plant-derived foods that may share proteins with pollens, latex, and each other. Clinical evaluations require a careful history, laboratory evaluation, and in some cases oral food challenges. The pitfalls in the evaluation of food allergy‐unreliable histories and limitations in laboratory assessment primarily caused by false-positive skin prick test responses/RAST results are magnified when dealing with cross-reactive proteins. This review focuses on the clinical data regarding cross-reacting food allergens with the goal of providing a background for improved risk assessment and a framework on which to approach these difficult clinical questions. (J Allergy Clin Immunol 2001;108:881-90.)

https://www.jacionline.org/article/S0091-6749(01)63295-0/pdf

Clinical implications of cross-reactive food allergens.

The house dust mite (HDM) is a major perennial allergen source and a significant cause of allergic rhinitis and allergic asthma. However, awareness of the condition remains generally low. This review assesses the links between exposure to HDM, development of the allergic response, and pathologic consequences in patients with respiratory allergic diseases. We investigate the epidemiology of HDM allergy to explore the interaction between mites and human subjects at the population, individual, and molecular levels. Core and recent publications were identified by using "house dust mite" as a key search term to evaluate the current knowledge of HDM epidemiology and pathophysiology. Prevalence data for HDM allergen sensitization vary from 65 to 130 million persons in the general population worldwide to as many as 50% among asthmatic patients. Heterogeneity of populations, terminology, and end points in the literature confound estimates, indicating the need for greater standardization in epidemiologic research. Exposure to allergens depends on multiple ecological strata, including climate and mite microhabitats within the domestic environment, with the latter providing opportunity for intervention measures to reduce allergen load. Inhaled mite aeroallergens are unusually virulent: they are able to activate both the adaptive and innate immune responses, potentially offering new avenues for intervention. The role of HDM allergens is crucial in the development of allergic rhinitis and asthma, but the translation of silent sensitization into symptomatic disease is still incompletely understood. Improved understanding of HDMs, their allergens, and their microhabitats will enable development of more effective outcomes for patients with HDM allergy.

https://www.jacionline.org/article/S0091-6749(14)01482-1/pdf

Respiratory allergy caused by house dust mites: What do we really know?

The examination of house dust mite extracts has indicated that over 30 different proteins can induce IgE antibody in patients allergic to the house dust mite. There are however dominant specificities especially the group 1 and 2 allergens which can account for much of the allergenicity of extracts. Of the 19 denominated allergens, the major IgE binding has been reported for the group 1, 2, 3, 9, 11, 14 and 15 allergens. The high-molecular-weight group 11, 14 and 15 allergens have only recently been described and although high IgE binding has been anticipated from immunoblotting, there is a need for considerable corroboration. Similarly, the study of the group 3 and 9 serine protease allergens has been incomplete. The group 4, 5, 7 and 8 allergens have shown intermediate IgE binding and the group 10 tropomyosins are of interest because of their potential cross-reactivity with allergen from disparate species. Although the progress with the production of recombinant group 1 allergens has been recent, many of the allergens can be produced as high IgE-binding polypeptides. The tertiary structure of the group 2 allergens has been determined from recombinant proteins and they are an excellent model for the investigation of modified allergens. An unexpected property of the group 1, 2 and 3 allergens has been the high degree of polymorphism found by cDNA analysis. It has however been possible to identify sequences to represent the variation in the natural allergens. The group 7 and 14 allergens show secondary modifications which vary in different extracts creating batch variation. While some estimate of the importance of allergens can be obtained from IgE binding, few analyses of T-cell responses have been made and these regulate both the development of, and the protection from sensitization.

Characterization and immunobiology of house dust mite allergens.

Sera of 17 patients receiving immunotherapy for house-dust mite allergy were tested for IgE antibodies against snail and shrimp. Serum samples were taken at the start of immunotherapy and 14-20 months later. While the average IgE response to mite, Der p 1, and Der p 2 did not alter significantly, the average response to snail showed a significant increase. This included two conversions from negative to strongly positive. These novel IgE antibodies against snail were shown to be cross-reactive with mite. Three patients had a positive RAST for shrimp. For one of them, a strong increase of IgE against shrimp (and snail) was observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the cross-reactive allergen tropomyosin from mite, snail, and shrimp were demonstrated. A clear IgE response to snail (> 10% binding in a snail RAST) was confirmed by a positive skin prick test (SPT) for 6/10 patients. The two patients with antitropomyosin IgE also had a positive SPT for shrimp, and demonstrated the oral allergy syndrome (OAS) after eating shrimp. The observations in this study indicate that house-dust mite immunotherapy is accompanied by the induction of IgE against foods, including tropomyosin-reactive IgE. Food allergy (OAS) was observed in patients that had IgE antibodies against this cross-reactive allergen. In conclusion, induction of IgE during mite immunotherapy might occasionally cause allergy to foods of invertebrate animal origin.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1398-9995.1996.tb04566.x

Possible induction of food allergy during mite immunotherapy

A group of 28 patients from Italy was studied who had asthma after consumption of snail. All patients also had asthma and/or rhinitis caused by house-dust mite. RAST analyses confirmed the combined sensitization to snail and mite. In a few sera, IgE antibodies reactive with other foods of invertebrate origin (mussel and shrimp) were detected. RAST inhibition showed that most IgE antibodies against snail were cross-reactive with house-dust mite. In contrast, the mite RAST was not significantly inhibited by snail. This indicates that house-dust mite was the sensitizing agent. Immunoblot analyses revealed multiple bands in snail extract recognized by IgE. In contrast to what has been described for cross-reactivity between shrimp and mite, tropomyosin played only a minor role as a cross-reactive allergen in these patients. The observations in this study indicate that snail consumption can cause severe asthmatic symptoms in house-dust-mite-allergic patients. It might, therefore, be advisable to screen mite-allergic asthma patients for allergy to snail and other invertebrate animal foods.

Asthma after consumption of snails in house‐dust‐mite‐allergic patients: a case of IgE cross‐reactivity

The aim of the study was to determine whether a short interval (< 2 months) between two consecutive stings influences the development of Hymenoptera venom allergy. The study compared the sting-interval distribution in 120 allergic patients who experienced a first-time systemic reaction to a Hymenoptera sting, and in 100 healthy controls. A significant difference in sting-interval distribution between the two groups was found (P = 0.0001). In 71 of 120 allergic patients, the sting that provoked the systemic reaction had been preceded by another, completely tolerated sting not more than 2 months before. However, in the control group only four subjects out of 100 had received two consecutive stings within less than 2 months. In conclusion, a short interval between two consecutive stings seems to be a risk factor for the onset of Hymenoptera venom allergy.

Shortness of interval between two stings as risk factor for developing Hymenoptera venom allergy.

Rhinitis is defined as nasal congestion, sneezing, itching and rhinorrhoea, recently classified as allergic, infective, structural or "other". The increasing employment of flexible rhynolaringoscopy may represent one of the most useful diagnostic tools in the complex differential diagnosis between allergic and nonallergic rhinitis. Furthermore, chronic allergic rhinitis, with secondary impairment of mucociliary clearance and the plethora of frequent anatomical variations, especially in the ostiomeatal complex, appear to predispose the patient to recurrent rhinosinusitis. In the last two decades, a better understanding of mucociliary clearance of nasal cavity and paranasal sinuses has shifted the attention from the maxillary sinuses to the area of the antherior ethmoid sinuses. Plain film radiographic examination, the historical standard, due to its inability to individualize ethmoid and sphenoid disease, is being rapidly supplanted by computed tomography and magnetic resonance imaging in the diagnosis of rhinosinusitis. In allergic and non-allergic rhinitis the diagnostic role of magnetic resonance imaging and computed tomography is still under debate. Computed tomography and magnetic resonance imaging are more efficient in demonstrating the bone wall, mucosal layer and sinus content than classical and computerized radiology; they have a higher diagnostic performance index in spite of a higher cost and, for computed tomography, a higher radiation dose.

F. Bonifazi

Papers

Possible induction of food allergy during mite immunotherapy

Asthma after consumption of snails in house‐dust‐mite‐allergic patients: a case of IgE cross‐reactivity

Shortness of interval between two stings as risk factor for developing Hymenoptera venom allergy.

Rhinopharyngoscopy, computed tomography and magnetic resonance imaging