Content uploaded by Brunello Wüthrich
Author content
All content in this area was uploaded by Brunello Wüthrich on Oct 08, 2014
Content may be subject to copyright.
The "egg-egg" syndrome: Occupational respiratory allergy to airborne egg proteins with consecutive ingestive egg allergy in the bakery and confectionery industry
Abstract
Allergies to various inhalative allergens are a serious problem in the bakery and confectionery industry. Sensitization to wheat flour and enzymes such as alpha-amylase are a frequent cause of occupational asthma. Airborne egg allergens have been reported as another cause of respiratory allergy. We examined bakery and confectionery workers with respiratory symptoms due to egg aerosols. Skin tests (SPT), scratch tests (ST), nasal provocation tests (NPT) and serological examinations (IgE) were performed. Lung function was assessed by spirometry, and continuous registration of aerosols and particulates as well as gravimetric sampling was done at the workplace. Four bakery and two confectionery workers intensively exposed to airborne egg proteins suffered from conjunctivitis and rhinitis, four also from asthma. Subsequently, three of these four workers reported symptoms after ingestion of food that contained egg. SPT with commercial egg white and egg yolk extracts were negative in four cases. Only two employees had clearly positive SPT to commercial egg allergens and reacted also to wheat flour extracts. Scratch tests with native egg proteins were positive in four employees. Specific IgE to egg white and egg yolk were positive (CAP > or = 2) in three and in four cases, respectively, whereas they were negative in two cases. Elevated levels of specific IgE to lysozyme were detected in four employees. Two workers were sensitized to lysozyme but not to other egg proteins. The clinical relevance of egg sensitization was confirmed by continuous air sampling and by correlating the onset of the respiratory symptoms which were reflected by a significant decline (> or = 30%) of the forced one second capacity (FEV1) in two workers. Sieving of egg white powder and an inadequate spray station for liquid eggs were identified as sources of excessive allergen exposure. Bakery and confectionery workers exposed to airborne egg proteins are at risk of developing occupational asthma and subsequent nutritive egg allergy. To our knowledge, these are the first cases of inhalative egg allergy and subsequent nutritive egg allergy reported in the literature, which we refer to as the "egg-egg syndrome" in analogy to the already known "bird-egg" and "egg-bird" syndromes.
... a-livetin has also been identified as the major inhalant allergen in bird-toegg syndrome (14,15), which links respiratory hypersensitivity to bird antigens to egg allergy (16). Exposure to pet birds, poultry, etc. can lead to respiratory allergies, including asthma, by sensitizing people to airborne avian allergens (17)(18)(19)(20)(21). Blood, feathers and droppings can be sources of these aeroallergens (22,23), including serum albumin a-livetin. ...
... The combination of multiple protein allergens with lipid adjuvants in egg is likely to be important in the pathogenesis of food allergy to hen´s egg. In addition to mimicking the clinically relevant sensitization of humans with whole egg, rather than a single egg protein, our airway sensitization scheme has the advantage of mimicking a natural route of sensitization of humans to eggs, as established for patients who have developed the bird-to-egg syndrome (49,50) or have inhaled powdered egg during its manufacture (17)(18)(19)(20). ...
Food allergies are common, costly and potentially life-threatening disorders. They are driven by Th2, but inhibited by Th1 reactions. There is also evidence indicating that IL-2 agonist treatment inhibits allergic sensitization through expansion of regulatory T cells. Here, we tested the impact of an IL-2 agonist in a novel model for food allergy to hen´s egg in mice sensitized without artificial adjuvants. Prophylactic IL-2 agonist treatment expanded Treg populations and inhibited allergen-specific sensitization. However, IL-2 agonist treatment of already sensitized mice increased mast cell responses and allergic anaphylaxis upon allergen re-challenge. These effects depended on allergen-specific IgE and were mediated through IFN-γ, as shown by IgE transfer and blockade of IFN-γ with monoclonal antibodies. These results suggest that although shifting the allergic reaction toward a Treg/Th1 response inhibits allergic sensitization, the prototypic Th1 cytokine IFN-γ promotes mast cell activation and allergen-induced anaphylaxis in individuals that are already IgE-sensitized. Hence, while a Th1 response can prevent the development of food allergy, IFN-γ has the ability to exacerbate already established food allergy.
... Egg allergies in adults are rare and most are carryover from childhood. New-onset egg allergy in adults is unusual and usually develops as the "bird-egg syndrome" caused by cross-reactivity between serum albumins present in bird feathers and yolk (3) or as the "egg-egg syndrome" caused by occupational sensitization in workers in the bakery and confectionary industries (4). Since there are few reports of new-onset adult egg allergy due to causes other than these entities, its pathogenesis is not well understood. ...
Most adult cases of hen's egg allergy are carried over from childhood, and new-onset adult cases are rare. Such cases may result from cross-reactivity or sensitization by inhalation. Here we present a rare case of adult-onset egg allergy due to monosensitization to ovalbumin (Gal d 2) with an unclear sensitization pathway. A 27-year-old woman developed recurrent gastrointestinal symptoms after ingestion of raw and under-cooked eggs. She had never suffered from atopic dermatitis or food allergies. She had never kept birds as pets and had no history of exposure to egg allergens. Prick to prick testing was positive only with raw egg white. Specific IgE testing revealed monosensitization to Gal d 2. She was advised to avoid raw and undercooked eggs and her symptoms resolved. In the management of adult-onset egg allergy, evaluation of allergen components will lead to appropriate elimination guidelines, and investigation of sensitization pathways may help identify the cause of this disease.
... More rarely, food protein-induced enterocolitis, enteropathy, or eosinophilic gastroenteritis syndromes are caused by hen's egg. Exposure to aerosolized dried egg powder is also a cause of occupational asthma in adults and has even been associated with the subsequent development of food allergy upon ingestion in some cases of longstanding aerosolized egg exposure in such individuals (Leser et al., 2001;Escudero et al., 2003). ...
Cover design molecule: Model of the major peanut allergen, Ara h 1, produced with the MPACK suite. (C. H. Schein and coworkers, 2006.) Address editorial correspondence to ASM
... Case reports have implicated many foods including fish, shellfish, seeds, soy, grains, eggs, and milk in causing allergic reactions due to inhalation of a food allergen. Examples of specific proteins implicated in inhalation based allergic reactions include shrimp tropomyosin [271] as well as hen's egg lysozyme [272]. ...
Technological advancement and globalization have led to the spread of foods to countries where the food does not yet have a documented history of consumption, in other words, novel foods. Novel foods also encompass truly novel foods, foods that have been processed in a novel manner, and novel means of exposure. With novel foods comes the potential of food allergens that pose an uncharacterized risk to those with food allergies. Food allergies are an increasingly important facet of public health. Therefore, a deeper understanding of novel foods as well as methods to evaluate consumers’ potential risk is necessary. Literature reviews and experimental evaluations leveraging liquid chromatography-electrospray ionization-mass spectrometry were used to explore the risks posed by novel sources of food allergens. Subject sources of allergens included Acheta domesticus, the house cricket, Tenebrio molitor, the yellow mealworm; extensively thermally processed walnut hulls and peanuts, as well as smoke from the wood of tree nut trees, and vapor from E-cigarette liquids. Novel methodologies to interpret complex mass spectrometry data were developed, allowing resultant information to be used in the assessment of allergenic risk. The methodologies developed in this research expand upon the utility of mass spectrometry to evaluate potentially allergenic proteins from poorly characterized sources. Broader characterization of the hazards and risks posed by food allergens permits stakeholders to be more adequately informed regarding the risks they wish to undertake. Advisor: Philip E. Johnson
Food allergies have increased at an alarming rate over the past two decades, indicating environmental factors are driving disease progression. It has been postulated that sensitization to foods, in particular peanut, occurs through impaired skin. Peanut allergens have been quantified in household dust and may be the culprit source. Indeed, Th2-skewing innate cytokines can be driven by application of food antigens on both intact and impaired skin of mice, resulting in antigen-specific IgE production, and anaphylaxis on allergen exposure. However, allergy induction through the skin can be prevented by oral tolerance induction prior to skin exposure. These observations led to the dual allergen exposure hypothesis, wherein oral exposure to food antigens leads to tolerance, and antigen exposure on impaired skin leads to allergy. Here, we propose the airway as an alternative route of sensitization in the dual allergen exposure hypothesis that leads to food allergy. Specifically, we will provide evidence from mouse models and human cell-based studies that together implicate the airway as a plausible route of sensitization.
A 26-year-old man employed in a company which manufactured hen egg white derived lysozyme for use in the pharmaceutical industry was evaluated for occupational asthma. The worker began to experience immediate-onset asthmatic symptoms two months after starting to work with egg lysozyme powder. The work process involved the production of approximately 1,000 kg of purified dried lysozyme powder per week. Prick skin testing was positive to egg lysozyme (50 mg/ml) and other egg protein components, but negative to whole egg white and egg yolk reagents. Serum specific IgE to egg lysozyme was documented. Decrements in serial peak expiratory flow rates were associated with lysozyme exposure at work. A specific bronchoprovocation challenge to lysozyme powder was positive demonstrating an isolated immediate asthmatic response (48 percent decrease from baseline FEV1). This is the first reported case of lysozyme-induced asthma specifically caused by inhalational exposure to egg lysozyme.
We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.
Blanco Carmona JG, Juste Picón S, Garcés Sotillos M, Rodriguez Gaston P. Occupational asthma in the confectionary industry caused by sensitivity to egg.
We report on a patient with asthma induced by occupational exposure to egg used to spray cakes before baking. A type I hypersensitivity to egg white was demonstrated by means of skin test, immunoassay for specific IgE, and immediate bronchial provocation test response to an egg white extract.
We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.
The use of a spray system to coat meat rolls with egg solution resulted in the development of asthmatic type symptoms in eight of thirteen workers exposed to the spray. Symptoms were severe in five workers, less severe in two, and one worker experienced vague symptoms. Even though precipitins were present in nine of the workers there were no pyrexial episodes nor influenza-like symptoms occurring some hours after inhaling the egg material to suggest extrinsic allergic alveolitis.
All sera with precipitins reacted against an antigen in egg yolk, two sera only to this antigen but no precipitins to ovalbumin were detected. Lung function, X-ray and haematology provided no evidence that the inhalation of egg had lasting detrimental effects.
There was no correlation between clinical response, skin testing, IgE levels and precipitins, hence, for each individual none of these parameters is predictive. However, collectively the results show sensitization and this has been confirmed by lack of symptoms when a different method of coating the pastry was adopted.
The commercially available alpha-amylase from Aspergillus oryzae which is widely used as a baking additive was compared with a highly purified enzyme preparation. We used enzyme allergosorbent test (EAST), EAST inhibition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focussing, immunoblotting, and N-terminal amino acid sequencing to characterize the causative allergen. Our screening comprised 89 partially selected bakers. Forty-three (48%) of them had work-related respiratory symptoms; 14 (32%) of whom were sensitized to the baking additive. Significant immunological differences could not be found between crude and purified sample with the exception that the latter one produced nearly twice as high antibody values. Iodine starch staining demonstrated that the component which was exclusively or predominantly bound by IgE antibodies of symptomatic bakers represents the active alpha-amylase. According to the International Union of Immunological Societies (IUIS) nomenclature, the term Asp o II is suggested for this important occupational allergen.
Thirty-one patients with clinical history of egg allergy, bird allergy, or bird and egg allergy were investigated with the use of the immunoblot technique to compare IgE-binding components in bird feather and egg yolk and white extracts. Patients were classified into three groups according to clinical history, skin prick test results, and RAST results. Patients in group I were sensitized to bird feathers and egg yolk, patients in group II to egg white, and patients in group III to bird feather but not to eggs. Patients with bird-egg syndrome were mainly female adults, whereas egg white allergy was mainly observed in children without any obvious sex predisposition. IgE from patients with bird-egg syndrome recognized a 70 kd protein in egg yolk (chicken serum albumin = alpha-livetin) and some major allergens in bird feather extract (70, 95, and 200 kd). Preincubation of pooled sera from patients with bird-egg syndrome with budgerigar or hen feather extract and egg yolk extract, respectively, led to complete blocking of IgE binding to allergens in egg yolk and bird feather extract. On the other hand, IgE from patients with egg white allergy did not react with allergens in egg yolk and bird feather extract, despite strong IgE binding to egg white allergens. Patients in group III displayed no reactivity to bird feather or egg allergens. Our results demonstrate common epitopes of budgerigar and hen feather and egg yolk alpha-livetin. Therefore we assume that alpha-livetin (chicken serum albumin) leads to a cross-sensitization and consequently to the "bird-egg syndrome."
Serratial peptidase and lysozyme are often used as anti-inflammatory agents. There have been very few documented cases of occupational allergy caused by these substances. We report a case of a pharmaceutical industry worker who developed occupational asthma and rhinitis caused by both serratial peptidase and lysozyme chloride.
It is important to alert physicians to the possibility of occupational asthma when dealing with workers in the pharmaceutical industry.
The patient had strong positive responses to peptidase and lysozyme extracts on skin-prick tests. Bronchoprovocation tests showed a dual asthmatic response to peptidase and an early asthmatic response to lysozyme. Serum specific IgE antibodies to peptidase and lysozyme were detected by enzyme-linked immunosorbent assay (ELISA). In order to further characterize the allergenic component of these extracts, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting studies were also performed. More than ten components ranging form 7.3 to 83.1 kD were found in peptidase extracts, and two IgE binding components (67, 10.9 kD) were detected within the lysozyme extracts.
These findings suggest that inhalation of peptidase and lysozyme can induce IgE-mediated bronchoconstrictions in an exposed worker.