Possible manufacture of test allergens in public pharmacies for the diagnosis of type I allergies: Legal aspects.

The availability of high-quality skin test allergens is a prerequisite for the reliable diagnosis of occupational type I allergies. Due to the withdrawal of existing marketing authorizations (MAs) by pharmaceutical companies and the lack of new MAs for commercial test allergens, there is an increasing diagnostic gap in Germany and other EU member states, which makes it necessary to investigate alternative ways of providing in vivo diagnostics. The German Medicinal Products Act (Arzneimittelgesetz = AMG) allows for the possibility of preparing medicinal products in pharmacies without the need for an MA or a manufacturing authorization pursuant to Section 13 (2) No. 1 in conjunction with Section 13 (2a) Sentence 2 No. 3 AMG. This also includes test allergens. In addition to the AMG, the requirements of the German Ordinance on the Operation of Pharmacies (Apothekenbetriebsordnung - ApBetrO) and the European Pharmacopoeia apply in particular. Medicolegal and practical challenges, as well as potentials of manufacturing skin prick test solutions in public pharmacies are presented based on examples of different allergen source materials.

Hair Product Allergy: A Review of Epidemiology and Management.

Allergy to hair products is an increasingly common issue among people given the exposure to these products on a daily basis. Allergic reactions could be in the form of delayed-type contact dermatitis or the form of immediate-type hypersensitivity reactions. Hair products contain many ingredients and chemicals that patients may have allergies to, but common allergens are hair dyes, fragrances, persulfate salts, ammonium thioglycolate, coconut fatty acid derivatives, and acrylates. Allergy to hair dye is the most common followed by other allergens such as fragrances and persulfate salts. We discussed testing for hair dye allergy along with suggestions for alternative hair dyes that patients may use. Allergy to topical scalp medications is also seen in patients using those products. Allergy to topical minoxidil is seen more often due to the increased use of minoxidil sprays and foams among patients to increase hair growth. We will discuss in this review the diagnosis and alternatives for patients with minoxidil allergy. Hairdressers are at higher risk of allergy to hair products compared to the general population due to prolonged exposure to allergens and specific measures should be implemented to minimize the hazards of exposure.

Plant and Arthropod IgE-Binding Papain-like Cysteine Proteases: Multiple Contributions to Allergenicity.

Papain-like cysteine proteases are widespread and can be detected in all domains of life. They share structural and enzymatic properties with the group's namesake member, papain. They show a broad range of protein substrates and are involved in several biological processes. These proteases are widely exploited for food, pharmaceutical, chemical and cosmetic biotechnological applications. However, some of them are known to cause allergic reactions. In this context, the objective of this review is to report an overview of some general properties of papain-like cysteine proteases and to highlight their contributions to allergy reactions observed in humans. For instance, the literature shows that their proteolytic activity can cause an increase in tissue permeability, which favours the crossing of allergens through the skin, intestinal and respiratory barriers. The observation that allergy to PLCPs is mostly detected for inhaled proteins is in line with the reports describing mite homologs, such as Der p 1 and Der f 1, as major allergens showing a frequent correlation between sensitisation and clinical allergic reactions. In contrast, the plant food homologs are often digested in the gastrointestinal tract. Therefore, they only rarely can cause allergic reactions in humans. Accordingly, they are reported mainly as a cause of occupational diseases.

[Climate change and type I allergies at the workplace]. / Klimawandel und Typ-I-Allergien im Beruf.

The consequences of climate change, the increasing frequency, duration and intensity of extreme events such as excessive drought, heat waves, large-scale forest fires, heavy rainfall and associated flooding also affect workers' conditions in the workplace in many ways. Allergic diseases of the respiratory tract and skin due to workplace exposure can also arise or be influenced by direct and indirect consequences of climate change. This affects outdoor workers not only through increased exposure to pollen allergens, but also through climate-related increases in typical workplace allergens. As an indirect effect of climate change, manufacturing processes and exposure at workplaces are changing, which can also cause new sensitization and allergies. Lifestyle changes, which are primarily intended to contribute to climate protection and sustainability, can also lead to new or changed products and thus to changed manufacturing processes and exposures in the workplace, so this should also be considered an indirect effect of climate change on the health of workers. The emergence of new occupational sources of sensitization due to new or changed allergen exposures must be considered in the context of occupational health and safety and requires proactive measures to protect workers.

Animal bite anaphylaxis, rarely diagnosed but underappreciated.

BACKGROUND: Animal allergies are common, with reactions ranging from rhinoconjunctivitis from respiratory exposure to anaphylaxis, usually from animal bites. Since animal bites are also common, this raises the question of how often anaphylaxis occurs following a bite. MATERIALS AND METHODS: A PubMed, Google, and Google Scholar literature review was performed using keywords such as animal bite anaphylaxis. An inquiry was made to the Anaphylaxis Registry ANAPHYLAXIE.net to see if additional cases were contained in the registry. RESULTS: Approximately 40 cases of animal bite anaphylaxis are described in the literature, mostly from rodent bites (mice, rats, hamsters, and guinea pigs). A survey of laboratory animal bite anaphylaxis in the U.S. identified previously unreported cases, suggesting that most cases are not reported. CONCLUSION: Anaphylaxis from animal bites is rarely reported, but occurs more frequently than suggested by case reports and should be considered in a symptomatic patient following a bite.

Frequent Allergic Sensitization to Farmed Edible Insects in Exposed Employees.

BACKGROUND: Exposure to insects used in pet food, scientific research, or live fish bait can cause an occupational allergy. The recent shift toward enhanced insect production for human consumption and animal feed will likely expose more employees. OBJECTIVE: To investigate sensitization and symptoms in employees exposed to edible insects in Flanders. METHODS: Fifteen insect-exposed employees were recruited and sensitization was explored by skin prick test, basophil activation test, and immunoblotting. Lung function, FeNO, histamine provocation, and sputum induction were studied. Airborne dust sampling was performed and proteins were studied by silver stain and immunoblotting. RESULTS: Sixty percent of employees self-reported upper respiratory tract symptoms related to insect exposure. Ten employees (71.4%) had a positive histamine provocation test concentration causing a 20% drop in FEV1 less than 8 mg/mL and four (26.7%) had FeNO levels above 25 ppb. Four employees (30.7%) had a positive skin prick test for at least one insect, and seven (58.3%) had a positive basophil activation test. In eight participants with insect sensitization, four (50%) had co-occurring house dust mite sensitization. Two participants had strong IgE binding to a 50-kDa migratory locust allergen, one to a 25-kDa mealworm allergen, and one to mealworm α-amylase. In one center, facility adjustment resulted in a substantial decrease in the inhalable dust fraction. CONCLUSIONS: Insect exposure leads to high levels of sensitization among employees. Most employees reported symptoms of the upper respiratory system, and two-thirds of employees had bronchial hyperreactivity. Prevention and health surveillance will be important in the developing insect-rearing industry.

Exposure to soluble platinum salts in precious metal refinery workers over a 17-year period.

BACKGROUND: Occupational exposure to soluble chlorinated platinum (Pt) salts, commonly called chloroplatinates, is a known cause of Pt salt sensitisation (PSS) and occupational asthma. We aimed to model inhalable soluble Pt salts exposure levels based on measurements in precious metal refineries for use in a retrospective cohort study on PSS. METHODS: Five platinum refineries located in the United Kingdom (3 sites), United States, and South Africa provided time weighted average inhalable soluble Pt salts exposure data, measured in 2,982 personal air samples over a 17-year period (2000-2016). We used a Bayesian hierarchical model to estimate geometric mean (GM) exposure levels for each refinery and job title over time. RESULTS: The GM of measured exposure levels over all facilities was 92 ng/m3 with a geometric standard deviation (GSD) of 9.07. Facility-specific GMs ranged from 48 ng/m3 (GSD 15.3) to 242 ng/m3 (GSD 5.99). Exposure modelling showed that soluble Pt salts exposure levels declined approximately 10% per year in two of the five facilities, but there were no clear time trends in the other facilities. A priori specified exposure groups captured most of the between-jobs differences, which helps to accurately predict exposures for jobs with no measurement data available. CONCLUSIONS: We applied exposure modelling to estimate time, refinery, and job-specific soluble Pt salts exposures. A significant annual decline in exposure levels was observed in two of the five participating facilities. Modelled exposure levels can be linked to individual workers' job history for exposure-response analysis of PSS in an epidemiological study.

Clinical Characteristics and Sensitization Profile of Patients Allergic to Cow Epithelium.

INTRODUCTION: Cow epithelium allergy (CEA) has been described in workers highly exposed to cattle, such as farmers and veterinarians, being a health problem in this population since it is their main livelihood. This study aimed to characterize the main clinical manifestations and define the sensitization profile of the cow epithelium-allergic population treated in our health area. METHODS: This is a retrospective study including a total of 34 patients with a clinical diagnosis of CEA, confirmed by skin tests, bovine epithelium-specific IgE levels and allergen-specific conjunctival challenge test in some cases. They were distributed by age, sex, profession, clinical symptoms, specific IgE levels to other mammalian epithelia, pollens, mites, and foods. Immunoblotting was performed with extracts from cow dander, cow body fluids (urine and saliva), bull urine, and 17 sera from immunotherapy-untreated CEA patients. RESULTS: The mean age of the patients was 44 years, with a higher incidence in cattle farmers. Rhinoconjunctivitis occurred in 100% of cases, with 35% having monosensitization to cow epithelium. Sera from most patients detected a 20-kDa IgE-binding band in cow dander, cow saliva, cow urine, and bull urine, corresponding to the major allergen Bos d 2 (bovine lipocalin). In 70% of the patients, a 25-kDa band was detected in cow and bull urine extracts, whose identification by mass spectrometry and investigation with protein databases led to the identification of a Bos taurus lipocalin (UniProt protein ID: A0A3Q1LGU7_BOVIN). CONCLUSION: CEA should be considered in patients exposed to cattle and as a cause of occupational disease. The IgE immunodetection revealed sensitization to a protein present in cow and bull urine (odorant-binding protein) not previously described.

Component-Resolved Diagnosis Based on a Recombinant Variant of Mus m 1 Lipocalin Allergen.

Exposure to the Mus m 1 aeroallergen is a significant risk factor for laboratory animal allergy. This allergen, primarily expressed in mouse urine where it is characterized by a marked and dynamic polymorphism, is also present in epithelium and dander. Considering the relevance of sequence/structure assessment in protein antigenic reactivity, we compared the sequence of the variant Mus m 1.0102 to other members of the Mus m 1 allergen, and used Discotope 2.0 to predict conformational epitopes based on its 3D-structure. Conventional diagnosis of mouse allergy is based on serum IgE testing, using an epithelial extract as the antigen source. Given the heterogeneous and variable composition of extracts, we developed an indirect ELISA assay based on the recombinant component Mus m 1.0102. The assay performed with adequate precision and reasonable diagnostic accuracy (AUC = 0.87) compared to a routine clinical diagnostic test that exploits the native allergen. Recombinant Mus m 1.0102 turned out to be a valuable tool to study the fine epitope mapping of specific IgE reactivity to the major allergen responsible for mouse allergy. We believe that advancing in its functional characterization will lead to the standardization of murine lipocalins and to the development of allergen-specific immunotherapy.

A Cross Sectional Study of Respiratory and Allergy Status in Dairy Workers.

INTRODUCTION: Workers on dairy farms face exposures to organic dusts and endotoxin. At the same time, a number of studies of farmers have reported a lower prevalence of asthma in farmworkers compared to persons without farm contact. The "hygiene hypothesis" suggests that early life exposures on farms could be protective against allergic disease and asthma. Such protective relationships are less well studied in adult farm workers. METHODS: A cross-sectional analysis of respiratory function and allergy status was performed in a sample of dairy farm workers (n = 42) and community controls (n = 40). Measures of respiratory status (spirometry, exhaled nitric oxide FeNO, self-reported symptoms) and levels of total and bovine-specific IgE were compared between the groups. RESULTS: Prevalence of self-reported asthma and most respiratory symptoms was similar in the two groups, with the exception of increased report of dyspnea among dairy workers. In the dairy workers, level of lung function was not reduced and FeNO was not increased. In unadjusted and adjusted models, dairy work was not associated with reduced lung function or increased airway inflammation. Mean IgE levels did not differ significantly between workers and controls, but elevated bovine-specific IgE was detected only among dairy workers, with an apparent association between elevated bovine IgE and increased FeNO. CONCLUSION: While dairy workers did not demonstrate increased asthma prevalence compared to controls, sensitization to bovine antigen in several workers appeared to be associated with airway inflammation. Occupational health programs for dairy workers should consider the risk of animal allergy as part of respiratory health protection efforts.

Allergenic Properties and Molecular Characteristics of PR-1 Proteins.

Only a small fraction of proteins in plants and animals are classified as allergens. The allergenic properties are frequently attributed to certain functional characteristics of the proteins, such as a role in the plant defense against biotic and abiotic stress, to achieve the systematic acquired resistance. In line with this, eight members out of 17 functional pathogenesis-related (PR) protein families have been characterized as allergens. The present review summarizes the molecular features and allergenic significance of allergens of the PR-1 family. Not many allergens have been identified as belonging to this protein family, with most of them having a pollen origin, like mugwort or Bermuda grass. Molecular and structural features of allergenic PR-1 proteins are discussed and attributed to their IgE-reactive properties, clinical manifestation, and cross-reactivity among different foods and inhalants.

Hexamerin-2 Protein of Locust as a Novel Allergen in Occupational Allergy.

BACKGROUND: Occupational exposure to locusts induces a high prevalence of allergic sensitization. However, knowledge on occupational locust allergens remains unclear. OBJECTIVE: This study aimed to identify the allergens from locusts causing occupational allergies. METHODS: We conducted a survey of 57 persons exposed to locusts using questionnaires and immunological tests for occupational allergies in long-term locust laboratories. The major allergen was identified by immunoblotting and analysed by mass spectrometry. The allergenicity of the allergen was assessed by sIgE detection, immunoblotting and ELISA inhibition assays. RESULTS: The survey indicated that the frequency of locust occupational allergies was 40.4% among subjects exposed to locust. The symptoms in most males were allergic rhinitis, while females showed higher prevalence of atopic dermatitis. Occupational exposure increased the allergy risk. The recombinant hexamerin-2 protein possesses high allergenicity in the allergic exposure group. Hexamerin-2 protein can inhibit IgE reactivity with locust protein extracts by approximately 60%. The potential for cross-reactivity with cockroaches was indicated by sequence alignment of hexamerin-2 protein and allergens of cockroaches. CONCLUSION: The hexamerin-2 protein of locusts as an important allergen was identified. Therefore, occupational exposure is an important risk factor for locust allergy.

High Prevalence of Sensitization to Mites and Insects in Greenhouses Using Biologic Pest Control.

BACKGROUND: Mites and insects are widely used as biologic pest control in greenhouses. A few studies have reported sensitization to mites among greenhouse workers, but the prevalence of sensitization to pest control insects is not known. OBJECTIVE: We aimed to determine the prevalence of IgE-mediated sensitization to pests and their control organisms in the population of exposed greenhouse workers and the relationship between sensitization and allergic symptoms. METHODS: In a cross-sectional study, we interviewed 117 tomato and cucumber greenhouse workers from eight companies that use biologic pest control. Sensitization to nine organisms was assessed by serum-specific IgE measurement. We also measured fractional exhaled nitric oxide. RESULTS: The prevalence of specific sensitization to pests and pest control organisms was 50%; to mites, 29%; and to insects, 46%. Of the individual species, Macrolophus pygmaeus insect sensitization had the highest prevalence (46%). Asthma symptoms were significantly associated with sensitization to pest and pest control organisms (odds ratio [OR] = 3.9; 95% confidence interval [CI], 1.2-12.5) and with a fractional exhaled nitric oxide level of 25 ppb or greater (OR = 4.8; 95% CI, 1.7-13.8), indicating eosinophilic airway inflammation. Southeast Asian origin was significantly associated with sensitization (OR = 5.1; 95% CI, 2.1-12.1) and rhinitis (OR = 2.8; 95% CI, 1.2-6.3). CONCLUSIONS: Tomato and cucumber greenhouse workers were commonly sensitized to predatory insect M pygmaeus and pest control mites. Our findings stress the importance of surveilling and preventing work-related allergic diseases among greenhouse workers.

[New allergens for occupational dermatology?] / Neue Allergene für die Berufsdermatologie?

BACKGROUND: The environment is continuously subject to change. Exposures in the work environment and therefore the importance of occupational type I and type IV allergens may change. OBJECTIVES: The most important trends concerning occupational allergens, new occupational allergens/allergen exposures, the diagnostic procedure to detect new allergens in practice and regulatory developments are presented. MATERIALS AND METHODS: Building on known relevant allergen exposures in occupational dermatology, published trends from clinical cohorts are evaluated and a systematic literature search (PubMed 2016-2021) for new occupational allergens is also performed RESULTS: Occupations with the highest incidence of occupational allergic contact urticaria and/or protein contact dermatitis include bakers, farmers and farm workers, veterinary technicians, veterinarians, cooks, dairy and livestock workers, gardeners, and hairdressers. The highest risk of developing occupational contact dermatitis is in health care, agriculture, metalworking occupations and machine operators, the food sector, service industries, and construction occupations. The search strategy "new occupational allerg*" yielded 603 hits and "novel occupational allerg*" 158 hits. A total of 25 papers included results relevant to the research question and were processed. New protein-based immediate-type allergens, as well as contact allergens (haptens) relevant for occupational dermatology, are presented. CONCLUSIONS: Current trends on known occupational allergens and new occupational allergens in the period 2016-2021 can be identified. Only a thorough individual workplace history and testing of patients' own materials can identify new allergens in occupational dermatology.

Respiratory sensitization to insect allergens: Species, components and clinical symptoms.

Airborne insect particles have been identified as an important cause of respiratory allergies, including allergic asthma and rhinitis. In the literature, the significance of respiratory exposure to insect particles as a cause of occupational allergy has been well-documented. Indeed, many cases of occupational allergy have been reported including allergy to the larvae of flies and moths in anglers and occupationally exposed workers, to grain pests in bakers or other workers handling grains, and to crickets and/or locusts in researchers and workers in aquaculture companies. Furthermore, the prevalence of sensitization to insect allergens is considerably high among patients with asthma and/or rhinitis who are not occupationally exposed to insects, suggesting the clinical relevance of exposure to insects in indoor and outdoor environmental non-occupational settings. Exposure to cockroaches, a well-studied indoor insect, is associated with cockroach sensitization and the development and exacerbation of asthma. Booklice, another common indoor insect, were recently identified as a significant sensitizer of asthmatic patients in Japan and India, and potentially of asthma patients living in warm and humid climates around the world. Lip b 1 was identified as an allergenic protein contributing to the species-specific sensitization to booklice. Moths are considered a significant seasonal outdoor allergen and their allergens are considered to have the highest sensitization rate among Japanese patients. However, other than cockroaches, allergenic insect proteins contributing to sensitization have not been fully characterized to date.

A case of anaphylactic reaction following oyster mushroom (Pleurotus ostreatus) inhalation.

Oyster mushroom (Pleurotus ostreatus) is one of the most widely consumed mushrooms in the world. Its spores are highly potent allergens, but their main allergen, Pleo, has so far been very rarely reported. In indoor farms, fungal spores are often found to be floating in the air. This study presents a case of a non-atopic, healthy 32-year-old woman who opened an oyster mushroom farm with her husband. During the first harvest, after 30-minute exposure, she experienced dyspnoea. Similar symptoms occurred several more times while on the farm. A month later, during packing and sorting mushrooms, after 10 min, she again felt dyspnea, accompanied by weakness, rapid pulse, and skin itching with urticaria which occurred on her forearms. Immediately after one of the exposures to oyster mushrooms, spirometry was performed. The results showed a reduced airflow obstruction. Standard skin prick tests with an inhalant and food allergens were also performed - all rendering negative results. The diagnosis also included a prick-to-prick test with oyster mushrooms (a wheal size of 12 mm), this time with a positive result. Increased total IgE (78 iu/ml) in the serum was recorded. On the basis of her medical history, reported symptoms and diagnostic tests, the patient could be diagnosed with occupational anaphylaxis and work-related asthma. A constant exposure of indoor mushroom cultivators to Pleurotus ostreatus spores increases the risk of respiratory allergy development. An environmental monitoring of oyster mushroom spores is reasonable in the industry, as it may prove useful in the prevention of the disease. Int J Occup Med Environ Health. 2021;34(4):575-9.

Asthma Phenotypes and Host Risk Factors Associated With Various Asthma-Related Outcomes in Health Workers.

Background: Work-related asthma phenotypes in health workers (HWs) exposed to cleaning agents have not been investigated extensively as other occupational exposures. This study aimed to describe asthma phenotypes and to identify important host risk factors associated with various asthma-related outcomes. Methods: A cross-sectional study of 699 HWs was conducted in two large tertiary hospitals. A total of 697 HWs completed questionnaire interviews. Sera collected from 682 HWs were analyzed for atopy (Phadiatop) and IgE to occupational allergens (NRL-Hev b5, Hev b6.02; chlorhexidine and ortho-phthalaldehyde-OPA). Methacholine (MCT), bronchodilator challenge (BDR) and fractional exhaled nitric oxide (FeNO) were performed. An asthma symptom score (ASS) used five asthma-related symptoms reported in the past 12 months. Current asthma was based on use of asthma medication or an asthma attack or being woken up by an attack of shortness of breath in the past 12 months. Nonspecific bronchial hyperresponsiveness (NSBH) was defined as having either a positive MCT or a significant bronchodilator response. Two continuous indices of NSBH [continuous index of responsiveness (CIR) and dose-response slope (DRS)] were calculated. Results: The prevalence of current asthma was 10%, atopic asthma (6%) and non-atopic asthma (4%). Overall, 2% of subjects had work-related asthma. There was a weak positive association between NSBH and FeNO [CIR: Beta coefficient (ß) = 0.12; CI: 0.03-0.22 and DRS: ß = 0.07; CI: 0.03-0.12]. Combining FeNO ≥ 50 ppb with a BDR [mean ratio (MR) = 5.89; CI: 1.02-34.14] or with NSBH (MR = 4.62; CI: 1.16-18.46) correlated better with ASS than FeNO alone (MR = 2.23; CI: 1.30-3.85). HWs with current asthma were twice as likely to be atopic. FeNO was positively associated with atopy (OR = 3.19; CI: 1.59-6.39) but negatively associated with smoking status (GMR = 0.76; CI: 0.62-0.94). Most HWs sensitized to occupational allergens were atopic. Conclusion: Atopic asthma was more prevalent than non-atopic asthma in HWs. Most asthma-related outcomes were positively associated with allergic predictors suggesting a dominant role for IgE mechanisms for work-related symptoms and asthma associated with sensitization to OPA or chlorhexidine.

Allergic Contact Dermatitis due to Methacrylates in a Dental Technician - a Clinical Case.

INTRODUCTION: Methacrylate-based materials are used daily in dental practice. Specialized publications report these materials as allergens with a high sensitizing potential. AIM: To draw the attention of dental doctors and personnel to risk factors of developing occupational allergies. MATERIALS AND METHODS: History and dermatological status of the patient were taken and he was given an epicutaneous test. RESULTS: The allergy testing revealed a strong positive allergic reaction to methacrylates which persisted and was observed at 72 hours as well as on day 7. A diagnosis of allergic contact dermatitis was made on the basis of the patient's history, the clinical examination and the results of the epicutaneous test. CONCLUSION: The presented clinical case shows that early identification of the specific causative agents allows clinicians to take adequate measures and achieve results without having to use a medicine, and stop the progression of the occupational disease and the development of complications.