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Background: Anaphylaxis is a systemic allergic reaction that is potentially life-threatening. Occupational anaphylaxis is an anaphylaxis that occurs in an occupational context. In this position paper, we propose diagnostic criteria for occupational anaphylaxis and provide an overview of the current state of knowledge in terms of prevalence, triggers, prevention, and management., Results: The most common triggers of occupational anaphylaxis include Hymenoptera venoms, followed by food and drugs. Chemicals, bites or contact with animals (mammals/snakes/insects) and natural rubber latex are far less common. Occupations at risk for occupational anaphylaxis are therefore beekeepers, outdoor workers, or those who handle food as well as healthcare workers. The route of contact, intensity, and frequency of exposure, type of allergen, and the simultaneous occurrence of co-factors determine the clinical manifestation. A detailed medical history is required to confirm the diagnosis of anaphylaxis and to identify the trigger. Both skin tests and the determination of specific IgE are recommended, but only very few commercially available and quality-tested allergens are available that can be examined using both test methods. Preventive measures are based on avoiding further exposure or, if necessary, replacing a working substance. A written emergency plan and the prescription of an adrenaline autoinjector as well as instructions for its use are mandatory. Allergen immunotherapy is recommended for systemic Hymenoptera venom allergy. Depending on the national healthcare systems, patients with occupational anaphylaxis must be reported to the accident insurance., Conclusion: Occupational anaphylaxis is very rare. We recommend educational measures and generally standardized recording of occupational anaphylaxis for occupations with an increased risk of anaphylaxis., Competing Interests: RT received research support from Sanofi-Genzyme and the Hautnetz Leipzig/Westsachsen e.V. as well as fees for lectures and consultations from AbbVie, Allmirall, ALK-Abello, LeoPharma, Novartis, Pfizer, Sanofi-Genzyme, Viatris and support for congress visit from CSL-Behring; all outside this paper. She is head of working group “Anaphylaxis” of the German Society for Allergy and Clinical Immunology (DGAKI). MW reports support for consultancies, lectures, and other scientific activities from ALK-Abelló Arzneimittel GmbH, Abbvie, Eli Lilly, Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Stallergenes GmbH. AB reports support for lectures, consultancies, and project funding by Abbvie, Almirall, Amgen, AstraZeneca, Biofrontera, Blueberry Therapeutics, Celldex, Centogene, Escient, Galderma, Genentec, Incyte, Jasper, Leo, Lilly, Phavaris, L’Oreal, Novartis, Regeneron, Sanofi, Shire, Takeda. HD reports support for consultancies, lectures, and other scientific activities from LEO Pharma GmbH, Novartis Pharma GmbH, and Stallergenes GmbH, not concerning the contents of the manuscript. GH reports personal fees for consultancies or lectures from Abbvie, Allergopharma, ALK-Abelló, Biotest, Eli Lilly, Leti, Novartis, Sanofi, all outside of this work. UJ has received hotel accommodation and meals for a lecture and for leading a workshop organized by ALK Abello. The fee went to the organization, the RCB. In addition, another hotel night and dinner were recently provided by ALK Abello. Her research on molecular allergology is funded by the Federal Ministry of Education and Science, the Federal Ministry of Food and Agriculture (BMEL), the German Research Foundation, and the Kanert Foundation, all outside the topic of this article. The Federal Ministry of Technology, Economics and Technology has funded their research on assays for the detection of anti-drug antibodies via the AiF-ZIM program. LK reports grants and/or personal fees from Allergopharma, MEDA / Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk, and Cassela med outside the submitted work; and memberships: AeDA, DGHNO, German Academy of Allergology and Clinical Immunology, HNO-BV, GPA, EAACI. MR received fees for lectures from Alk-Abelló Arzneimittel GmbH, Berufsverband Deutscher Baubiologen VDB e.V, Haus der Technik, LetiPharma, ThermoFisher Scientific (Phadia). With regard to the content of this article, there are no conflicts of interest that could arise from an employment relationship, benefits for lectures, or other activities. BW reports support for one-day advisory boards and/or lectures and/or other scientific acitivities by ALK-Scherax, Bencard, Biocryst, CSL Behring, Kalvista, Novartis, Sanofi, Takeda, all outside the submitted work. OP reports grants and/or personal fees from ALK-Abelló, Almirall S.A., Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, GlaxoSmithKline, ROXALL Medizin, Novartis, Sanofi-Aventis and Sanofi-Genzyme, Med Update Europe GmbH, streamedup! GmbH, Pohl-Boskamp, Inmunotek S.L., John Wiley and Sons, AS, Paul-Martini-Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, Wort&Bild Verlag, Verlag ME, Procter&Gamble, ALTAMIRA, Meinhardt Congress GmbH, Deutsche Forschungsgemeinschaft, Thieme, Deutsche AllergieLiga e.V., AeDA, Alfried-Krupp Krankenhaus, Red Maple Trials Inc., Königlich Dänisches Generalkonsulat, Medizinische Hochschule Hannover, ECM Expro&Conference Management, Technische Universität Dresden, Lilly, Paul Ehrlich Institut (PEI), Japanese Society of Allergy, Forum für Medizinische Fortbildung, Dustri Verlag, all outside the submitted work and within the last 36 months; and he is Vice President of EAACI and member of EAACI Excom, member of external board of directors DGAKI; coordinator, main or co-author of different position papers and guidelines in rhinology, allergology, and allergen-immunotherapy and Associate Editor of the journal(s) Allergy and Clinical Translational Allergy (CTA). JR has received honoraria for consulting and lectures from Sanofi, Viatris, Allergika, AbbVie, Pfizer. SS reports support for consultancy and lectures from Mylan Germany, DBV Technologies S.A., Aimmune Therapeutics, all outside this paper. TW reports support for consultancy, lectures, and other scientific activities from AbbVie, ALK Abello, Almirall, Astellas, Bencard, Galderma, Janssen/JNJ, Leo Pharma, Leti, Lilly, Novartis, Pfizer, Regeneron/Sanofi, Stallergenes. TZ reports support for consultations, lectures and other scientific activities by AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Henkel, Kryolan, Leti, Lofarma, L’Oreal, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Sanoflore, Stallergenes, Takeda, Teva, UCB as well as responsible participation in the following organizations: Committee member, WHO initiative ‘Allergic Rhinitis and its Impact on Asthma’ (ARIA), Member of the Board, German Society for Allergy and Clinical Immunology (DGAKI), Head, European Centre for Allergy Research Foundation (ECARF), Secretary General, Global Allergy and Asthma European Network (GA2LEN), Member, Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). KB reports support for consultancies, lectures, and other scientific activities from ALK-Abelló Arzneimittel GmbH, Bencard Allergie GmbH, Novartis AG, HAL Allergie GmbH, DBV Technologies S.A, ThermoFisher, all outside of this paper. DW, WF, TJ, FR, GW, JZ have no conflict of interest. Table 1.Criteria for the diagnosis of anaphylaxis according to Sampson et al. [4]. Anaphylaxis is highly likely when any one of three criteria are fulfilled:1.Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus, or flushing, swollen lips-tongue-uvula)and at least one of the following   a.Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow (PEF), hypoxemia)   b.Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction (e.g., hypotension (collapse), syncope, incontinence)2.Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to several hours):   a.Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula)   b.Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia)   c.Reduced BP or associated symptoms (e.g., hypotension (collapse), syncope, incontinence)   d.Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)3.Reduced BP after exposure to known allergen for that patient (minutes to several hours):   a.Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP*   b.Adults: systolic BP of less than 90 mmHg or greater than 30% decrease from that person’s baseline*Low systolic blood pressure for children is defined as less than 70 mmHg from 1 month to 1 year, less than (70 mmHg + [2 × age]) from 1 to 10 years, and less than 90 mmHg from 11 to 17 years. Table 2.Diagnostic criteria for classification of occupational anaphylaxis. Sensitization at workplace probableAnaphylaxis at workplaceClassification as occupational anaphylaxisExampleYesYesYesInsect allergy in beekeepers Food allergy in cooks or in workers in food service sector and in food industryYesNoYesDrug allergy in healthcare workers (e.g., reaction when receiving antibiotic)No/unknownYesYes, if allergen source belongs to typical work materialFood allergy in cooks or in workers in food service sector and in food industryNo/unknownYesYes, if sensitization at workplace is probable even if allergen source does not belong to typical work materialInsect allergy in forest workersNo/unknownYesNo, if allergen contact is attributable to private activitiesFood consumption at work during break time Table 3.Selected workplaces with possible elicitors of occupational anaphylaxis. Workplace/OccupationPossible elicitorsHealthcare workerDrugs, natural rubber latex, chemicalsBeekeeper, gardener, green house worker, sales assistant in bakeries and confectioneriesInsect venomFood production and processingAnimal and vegetable food (inhalation, ingestion/skin contact)Hunter, rangerAlpha-GAL in meat, insect venomLaboratory workerChemicals, animal bites/contact Table 4.Important aspects for history taking in occupational allergy [10, 11]. Allergen exposureExposure at the workplace or outsideRoute of exposureFrequency of exposureType of allergenPotential cofactorsPhysical activity, exerciseAlcoholStressAcute infectionsConcurrent medications (i.e., beta-blocker, angiotensin-converting enzyme inhibitors)Predisposing individual risk factorsOlder ageIncreased levels of basal tryptase, mastocytosisUncontrolled AsthmaCardiovascular diseaseSex Table 5.Animal- and plant-derived elicitors of occupational anaphylaxis. AllergenOccupation/WorkplaceReferenceAnimal-derived food allergens   SushiCook Truck driver[24, 25]   SeafoodCook[22]   AnisakisFish monger, supermarket#[26]   Cow’s milkDairy industry[27]   Donkey’s milkFood laboratory[28]   Quail eggPoultry worker[29]   OysterOyster mushroom farmer[30]   Red meat/alpha-GALForest service employee, hunter§, cattle worker, cook[18, 20, 31]Plant-derived food allergens   Avocado, banana, chestnut, manioc, and othersHealthcare worker with sensitization to natural rubber latex as cross reaction[21, 32]   BuckwheatCook[33]   BroccoliCook[24]   ChicoryCook[34]   CorianderSpice grinder[35, 36]   PaprikaSpice and condiment seller[37]   SunflowerSunflower processing worker[38]   TamarilloCarpenter with sensitization to obeche wood as cross reaction[39]Wheat flourCook #[24] #Generalized urticaria; §no clinical reactions given in detail) [20]. Table 6.Drugs as elicitors in occupational anaphylaxis. Group of allergen/elicitorAllergenOccupation/workplaceReferenceAntibioticsPencillin Cefotiam Piperacillin-tazobactam Isoniazid RifapentinHealthcare workers[40, 41, 42, 43, 44, 45, 46, 47, 48, 49]DisinfectantsChlorhexidine Povidone Iodine Polyhexanide Chloramine Chlorocresol/chloroxylenolHealthcare workers Butchery Carer[52, 53, 54, 55, 56, 57, 58, 72]LaxativePsylliumHealthcare workers[59]Allergen immunotherapeuticTimothy grassHealthcare worker[60]Coronavirus vaccinesIn question; direct complement activation?Healthcare workers[63, 64, 66]Narcotic agentsSuccinylcholine Neuromuscular blocking agents (several)Healthcare worker Hair dresser Cleaner[61, 62] Table 7.Chemicals as elicitors of occupational anaphylaxis. Elicitor/AllergenApplicationWorkplace/occupationReferenceChlorothalonilFungicideGreenhouse[74]Iridium chlorideChemicalElectrochemistry[75]Cobalt chloridePaintCeramic decorator[76]Polyethylene glycolsExcipients, solventsPainter[79]Chromium vaporChemicalWelder[80]BenzonitrileIntermediate for chemicalsChemical industry[81]HexafluorophosphatesCoupling reagentsLaboratory worker[82]Methyl methacrylateAdhesiveHealthcare worker[84]PerfumesCosmeticsHealthcare worker[85, 86]PersulfatesBleachingsHair dresser[87, 88, 89]Hair/textile dyes (2,4-toluylenediamine/Lanasol Yellow 4G)ColoringsHair dresser, textile industry[90, 91] Table 8.Animals (bites/contact) as elicitors of occupational anaphylaxis. Elicitor/allergenContactWorkplace/occupationReferenceRodents   RatBiteLaboratory[106]   MouseBiteLaboratory[107]   Rat, mouseBites (N = 2)Laboratory[108]   RabbitNeedle injury after contact to rabbit tissueResearch physician[109]Snakes   Different snake venomsBites (n = 3)Outdoor worker[110]   ViperBiteResearch laboratory[111]     Atractaspis corpulentaDeath after bite, anaphylaxis suspected (reaction to antivenom was not ruled out)Mechanical foreman[112]     Bothrops spp.BiteHerpetologist1[113]     Bothrops moojeniBiteViper farm[114]Insects     Rhiphicephalus spp.Tick biteGoatherd[115]     Bruchus pisorumInhalation of dust of peas infested by B. pisorumFarmer[116]     Thaumetopoea pityocampa2Skin contactPine/oak or resin collectors/ woodcutters Farmers/Stockbreeders Farmers/stockbreeders[117]     Thaumetopoea pityocampa2Skin contactPine-resin worker[118]     Thaumetopoea pityocampa2Skin contactForest[119]     Glossina morsitans3BiteLaboratory[120] 1Experts working with amphibians and reptiles; 2processionary caterpillar; 3tsetse fly. Table 9.Summarized recommendations for management of occupational anaphylaxis 1.Improved diagnostic criteria for classification of occupational anaphylaxis have to consider that   a.sensitization may take place at the workplace or outside the workplace (e.g., Hymenoptera allergy)   b.clinical reaction may not only manifest at the workplace but also outside the workplace (e.g., drug allergy in healthcare workers).2.The acute management of an anaphylactic reaction at the workplace should follow general guidelines on anaphylaxis.3.In Germany, urgent medical suspicion of occupational anaphylaxis must be reported to the Social accident insurance in Germany (Unfallversicherungsträger).4.Prevention measures in patients with a history of occupational anaphylaxis should include training in allergen avoidance and eliminating the allergen as completely as possible.5.Every measure to prevent further exposure should be carried out, this includes (according to STOP principle): Substitution of elicitors, Technical measures, Organizational measures for elicitor avoidance, and Personal safety precautions.6.Patients with history of occupational anaphylaxis should be equipped with emergency medications including adrenaline autoinjectors and a written emergency management plan. They should receive safety education and training.7.In any occupational setting where there is an employee with a history of previous anaphylaxis, the availability of adrenaline and a person trained in its administration are mandatory.8.In patients with venom anaphylaxis, an occupational factor should always be considered.9.In occupational Hymenoptera allergy, venom immunotherapy should be started.10.Workers with compromised skin and especially atopic individuals should not wear gloves containing natural rubber latex (NRL) – to primarily prevent sensitization. In secondary prevention a “NRL-free” strategy should be followed.11.In occupations at greater risk for occupational anaphylaxis, surveillance and awareness campaigns are recommended.12.We call for awareness, documentation, and registration of occupational anaphylaxis in registries., (© Dustri-Verlag Dr. K. Feistle.)

Not available., (© Dustri-Verlag Dr. K. Feistle.)