Case Report
Microbial contamination in water-based metalworking fluid as trigger for occupational hypersensitivity pneumonitis – development of specific IgG tools for a suspected clinical case
Sabine Kespohl, Isabell Warfolomeow, Gerd Schneider, Silke Maryska, Ursula Meurer, and Monika Raulf
Volume 4 (2020) p. 110 - 117
Abstract
Allergologie select, Volume 4/2020 (110-117)
Microbial contamination in water-based metalworking fluid as trigger for occupational hypersensitivity pneumonitis – development of specific IgG tools for a suspected clinical case
Sabine Kespohl1, Isabell Warfolomeow2, Gerd Schneider3, Silke Maryska1, Ursula Meurer1, and Monika Raulf1
1Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, 2German Social Accident Insurance Institution for the Woodworking and Metalworking Industries, BGHM, Mainz, and 3Institute for Occupational Safety and Health of the German Social Accident Insurance (IFA), St. Augustin, Germany
Microbially contaminated metal-working fluid (MWF) can cause respiratory symptoms in exposed workers in the form of exogenous allergic alveolitis/hypersensitivity pneumonitis (HP). The diagnosis of HP is based, among others, on the identification of the culprit and the detection of corresponding specific IgG antibodies (sIgG) in the patient’s serum. Commercial antigen tools for the detection of these HP triggers are rarely available; therefore, antigens from contaminated MWF workplace samples were isolated exemplarily for diagnosis of a suspected HP case. Various MWF-specific bacteria were identified in the workplace samples, including Pseudomonas oleovorans, Pseudomonas alcaliphila, Pseudomonas spec., Paenibacillus glucanolyticus, and Corynebacterium amycolatum. The sIgG antigen binding, detected by ImmunoCAP system against MWF antigens from workplace samples and against the identified bacterial antigens, was much stronger in the patient serum compared to selected reference sera. The highest sIgG concentrations in the patient’s serum could be determined against Pseudomonas antigens. Inhibition tests showed cross-reactions of MWF and Pseudomonas antigens, whereby the Pseudomonas antigens cross-reacted less with each other. For in-vitro diagnosis in case of suspected HP caused by contaminated MWF, workplacerelated antigens are now available.Correspondence to:
Dr. Sabine Kespohl, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum
Email: [email protected]
Original
What should be tested in patients with suspected mold exposure? Usefulness of serological markers for the diagnosis
Sabine Kespohl, Verena Liebers, Silke Maryska, Ursula Meurer, Claudia Litzenberger, Rolf Merget, and Monika Raulf
Volume 6 (2022) p. 118 - 132
Abstract
Allergologie select, Vol. 6/2022 (118-132)
What should be tested in patients with suspected mold exposure? Usefulness of serological markers for the diagnosis
Sabine Kespohl, Verena Liebers, Silke Maryska, Ursula Meurer, Claudia Litzenberger, Rolf Merget, and Monika Raulf
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany
The associations of mold exposure, IgE-mediated sensitization, inflammatory markers, and respiratory symptoms were analyzed in 46 exposed and 23 nonexposed individuals. Both exposure and clinical symptoms were assessed by questionnaire. Specific (s)IgE to mold mixture (mx1) was significantly higher and found more frequently in exposed (41%) than non-exposed individuals (17%), which was not observed for sIgG to mold mix (Gmx6). Notably, exposed asthmatics were more frequently sensitized to molds (55%) compared to exposed non-asthmatics (18%). In addition, the serum concentrations of club cell protein (CC16) were significantly lower in exposed subjects, especially in asthmatics. Positive associations were observed among mold sensitization, asthma, and mold exposure, but not in subjects with predominantly environmental sensitizations without mold sensitization. Thus, sIgE to mx1 but not sIgG to Gmx6 is a useful diagnostic marker to verify mold-associated respiratory symptoms.Correspondence to:
Dr. rer. nat. Sabine Kespohl, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Deutsche Gesetzliche Unfallversicherung e.V. (DGUV), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
Email: [email protected]
Original
Is in vitro cytokine release a suitable marker to improve the diagnosis of suspected mold-related respiratory symptoms? A proof-of-concept study
Verena Liebers, Sabine Kespohl, Gerda Borowitzki, Heike Stubel, and Monika Raulf
Volume 6 (2022) p. 133 - 141
Abstract
Allergologie select, Vol. 6/2022 (133-141)
Is in vitro cytokine release a suitable marker to improve the diagnosis of suspected mold-related respiratory symptoms? A proof-of-concept study
Verena Liebers, Sabine Kespohl, Gerda Borowitzki, Heike Stubel, and Monika Raulf
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Germany
Indoor mold infestation can lead to a variety of adverse health effects, including allergic and non-allergic respiratory complaints. Especially if no evidence of an allergic reaction can be found for the complaints, diagnostic tools that might explain mold-associated health problems are missing. As a proof-of-concept, in the present study whole blood assay (WBA) was used to determine cellular response by measuring cytokine release (IL-1β and IL-8) after in vitro stimulation. Blood was available from a total of 48 subjects. By questionnaire, complaints and possible mold exposure were documented. Specific in vitro blood stimulation was tested with Escherichia coli endotoxin and extracts of different molds (Aspergillus fumigatus, Penicillium chrysogenum, Aspergillus versicolor, and Cladosporium herbarum). To characterize the relevance of WBA in describing the mold-induced immune response, we compared the following groups: asthmatics vs. non-asthmatics, mx1-sensitized vs. non-mx1-sensitized, mold-exposed vs. non-mold-exposed. In response to endotoxin stimulation, a significantly higher IL-1β release was found in mx1-sensitized than in non-mx1-sensitized subjects. Furthermore, the blood of asthmatics showed significantly higher IL-8 and IL-1β release after stimulation with Penicillium chrysogenum and endotoxin, respectively, compared to non-asthmatics. However, no significant difference in the level of cytokine release was observed between the mold-exposed and non-exposed group, neither after endotoxin nor mold stimulation. In conclusion, the WBA used in this study is not a suitable tool for clinical routine diagnostic workup. Our data suggests that WBA reflects cellular differences that are disease-related but not directly attributable to mold exposure. However, in combination with further data, WBA will be a helpful und interesting tool in research, e.g., in description of the complex immune response to molds.Correspondence to:
Dr. rer. nat. Verena Liebers, Institut für Prävention und Arbeitsmedizin, der Deutschen Gesetzlichen Unfallversicherung, Institut der Ruhr-Universität Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
Email: [email protected]
Letter to the Editor
Authors’ response to comment to “What should be tested in patients with suspected mold exposure? Usefulness of serological markers for the diagnosis” Allergol Select. 2022; 6: 118-132
Sabine Kespohl und Monika Raulf
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Jahrgang 46 (2023) p. 476 - 477
Abstract
Allergologie, Jahrgang 46, Nr. 7/2023, S. 476-477
Authors’ response to comment to “What should be tested in patients with suspected mold exposure? Usefulness of serological markers for the diagnosis” Allergol Select. 2022; 6: 118-132
Sabine Kespohl und Monika Raulf
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA)
Correspondence to:
Dr. rer. nat. Sabine Kespohl
Institute for Prevention and Occupational Medicine
of the German Social Accident Insurance
Institute of the Ruhr University Bochum (IPA), Germany
Email: [email protected]
Review
Diagnostics of IgE-mediated occupational allergies: Between reality, requirements, and opportunities
Monika Raulf and Sabine Kespohl
Volume 8 (2024) p. 220 - 227
Abstract
Allergologie select, Vol. 8/2024 (220-227)
Diagnostics of IgE-mediated occupational allergies: Between reality, requirements, and opportunities
Monika Raulf and Sabine Kespohl
Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Bochum, Germany
Occupational skin and respiratory allergies are among the most common occupational diseases in Germany. The identification of the allergy trigger is essential for the recognition of an occupational allergy as well as for effective individual prevention. However, occupational type I allergens are among the “rare” allergens and the possibilities of guideline-compliant diagnosis using quality-tested skin test solutions is becoming increasingly difficult due to the reduction in commercially available test allergens. In order to guarantee meaningful diagnostic workup for all affected insured persons with suspected occupational type I allergies and to ensure this in the future, a durable optimization, standardization, and availability of allergy tests for occupational allergic diseases is urgently required. The need for action has been recognized by the German Social Accident Insurance (DGUV), and steps to eliminate the diagnostic gaps have been initiated by a joint research project at the Institute for Prevention and Occupational Medicine of the DGUV (IPA) and the Paul Ehrlich Institut (PEI). The evaluation of alternative methods for the production of standardized test allergen solutions can also be used for newly emerging allergens in the workplace. New allergen sources at workplaces and thus also sensitization and allergies among employees can be expected as a result of changes in work processes and the introduction of new technologies and/or working materials, which are also introduced in connection with climate change and the concept of sustainability.Correspondence to:
Prof. Dr. Monika Raulf, Institute for Prevention and Occupational Medicine of the German
Social Accident Insurance, Institute of the Ruhr-University Bochum (IPA), Germany and Department Competence Center Allergology/Immunology, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
Email: [email protected]
Original
Procedure for a standardized preparation of skin prick test solutions for the diagnosis of occupational type I allergies in the absence of commercial extracts
Sabine Kespohl, Robin Jost, Silke Maryska, Lena-Maria Altin, Ingrid Sander, Stefan Schülke, Kathrin E. Paulus-Tremel, Andreas Bonertz, Thomas Klose, Vera Mahler, and Monika Raulf
Volume 8 (2024) p. 238 - 250
Abstract
Allergologie select, Vol. 8/2024 (238-250)
Procedure for a standardized preparation of skin prick test solutions for the diagnosis of occupational type I allergies in the absence of commercial extracts
Sabine Kespohl1, Robin Jost2, Silke Maryska1, Lena-Maria Altin3, Ingrid Sander1, Stefan Schülke2, Kathrin E. Paulus-Tremel2, Andreas Bonertz2, Thomas Klose3, Vera Mahler2, and Monika Raulf1
1Institute for Prevention and Occupational Medicine of the DGUV, Ruhr-University Bochum (IPA), Bochum, 2Division Allergology, Paul-Ehrlich-Institut, Langen, and 3Sonnenschein Apotheke, Koblenz, Germany
In order to ensure valid diagnostics for occupational test allergen solutions despite the ongoing reduction in the availability of commercial test extracts, a plan B was initiated for the possible production of skin prick test (SPT) solutions in public pharmacies. For important occupational allergen sources (wheat and rye, storage mites, animal epithelia, mold material) laboratory extraction methods were analyzed in comparison to pharmacy compatible extraction methods regarding protein quantity and quality in SDS-PAGE combined with silver staining. Subsequently, using the example of bovine epithelia, adapted extraction procedures as well as in-process and final product controls were transferred to a public pharmacy. Allergen sources with a high protein content, such as wheat and rye grains as well as storage mites, showed good comparability of the extractable protein quantity and protein pattern, regardless of the applied extraction method. In contrast, allergen source materials with a low total protein content, such as animal epithelia and molds, can benefit from laboratory extraction conditions such as mechanical disruption and specific buffer additives. In the qualitative protein silver staining, characteristic protein patterns were identified for each allergen source. Depending on the extraction method, only minor differences in total protein patterns were observed in animal epithelia and molds. Using source materials from two suppliers, the resulting allergen extracts displayed clear differences in protein content in storage mites and quantitative and qualitative differences in molds. A practical preparation attempt of SPT solutions in a public pharmacy was successful. SPT solutions prepared with adapted pharmacy extraction methods showed a comparable protein and Bos d 2 allergen content and equivalent qualities in the protein pattern compared to a previously available commercial SPT solution. Accordingly, it can be assumed that standardized SPT solutions with sufficient allergen quality for occupational allergen sources can be prepared in public pharmacies if certified allergen sources with appropriate protein content are available.Correspondence to:
Dr. Sabine Kespohl, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Department Competence Center Allergology/Immunology, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany
Email: [email protected]
Review
Possible manufacture of test allergens in public pharmacies for the diagnosis of type I allergies: Legal aspects
Robin Jost, Sabine Kespohl, Kathrin E. Paulus-Tremel, Julia Zimmer, Andreas Bonertz, Ingrid Sander, Thomas Klose, Lena-Maria Altin, Simone Heller, Ralph Heimke-Brinck, Frank Dörje, Susanne Philippus, Matthias Meyer, Sabrina Segebrecht, Torsten Wessel, Dieter Starke, Stefan Schülke, Monika Raulf, and Vera Mahler
Volume 8 (2024) p. 251 - 264
Abstract
Allergologie select, Vol. 8/2024 (251-264)
Possible manufacture of test allergens in public pharmacies for the diagnosis of type I allergies: Legal aspects
Robin Jost1,2, Sabine Kespohl3, Kathrin E. Paulus-Tremel1, Julia Zimmer1, Andreas Bonertz1, Ingrid Sander3, Thomas Klose4, Lena-Maria Altin4, Simone Heller4, Ralph Heimke-Brinck5, Frank Dörje5, Susanne Philippus6, Matthias Meyer7, Sabrina Segebrecht8, Torsten Wessel9, Dieter Starke10, Stefan Schülke1, Monika Raulf3, and Vera Mahler1,2
1Allergology Division, Paul-Ehrlich-Institut (PEI), Langen (Hesse), 2Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, 3Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (DGUV), Institute of the Ruhr-Universität Bochum (IPA), Bochum, 4Sonnenschein Apotheke, Koblenz, 5Pharmacy Department, Erlangen University Hospital, Erlangen, 6Thuringian State Authority for Consumer Protection, Department Pharmacy, Bad Langensalza, 7Bundeswehr Commissioner for the Surveillance of Medicinal Products, Supervisory Agency for Public Law Tasks of the Bundeswehr Medical Service South, Munich, 8Drug Supervision, State Social Services Agency of Land Schleswig-Holstein, Neumünster, 9Pharmacy Inspector, Local inspectorate for pharmacies, District of Wesel, Moers, and 10 State Agency for Social Affairs, Youth and Care, Rhineland-Palatinate, Koblenz, Germany
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.Correspondence to:
Prof. Dr. Vera Mahler, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225 Langen, Germany
Email: [email protected]
Case Report
Legumes in bread baking: A hidden risk for an IgE-mediated inhalant allergy
Sabine Kespohl, Christian Eisenhawer, Silke Maryska, Ingrid Sander, Irene Mittermann, Martina Aumayr, and Monika Raulf
Volume 9 (2025) p. 58 - 65
Abstract
Allergologie select, Vol. 9/2025 (58-65)
Legumes in bread baking: A hidden risk for an IgE-mediated inhalant allergy
Sabine Kespohl1, Christian Eisenhawer1, Silke Maryska1, Ingrid Sander1, Irene Mittermann2, Martina Aumayr2, and Monika Raulf1
1Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany, and 2MacroAssay Diagnostics, Vienna, Austria
New protein-rich flour blends from legumes are increasingly being processed for gluten-free bakery products, which may increase the risk of IgE-mediated sensitization through inhalation exposure. In the described case of a 29-year-old baker, work incapacity occurred due to respiratory complaints following exposure to various gluten-free baking ingredients. Occupationrelated sensitization to “chestnut pea flour” (flour from lightly roasted and ground yellow peas) was identified, while the patient showed no IgE sensitization to five other ingredients. Significant allergic respiratory reactions occurred during bronchial challenge test with “chestnut pea” extract. Based on the test results and typical workplace-related symptoms, recognition of occupational disease was recommended. Further identification of potential causal allergens using IgE blot and allergen component-resolved diagnostics revealed IgE bindings to typical storage proteins, 2S albumin and vicilin, as well as to Bet v 1 homologous of “chestnut pea” and non-specific lipid transfer proteins. This case illustrates that the processing of protein-rich legume flours can pose new sensitization risks for workers, which should be considered in the future.Correspondence to:
Dr. Sabine Kespohl, Department Competence Centre for Allergology/Immunology, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp Platz 1, 44789 Bochum, Germany
Email: [email protected]
Case Report
Airborne exposure-induced occupational type I allergy to Tenebrio molitor: Case report and studies on immunological reactivity
Laura Weißenborn, Sabine Kespohl, Silke Maryska, Ingrid Sander, Jakob Bickhardt, Thomas Henle, and Monika Raulf
Volume 9 (2025) p. 66 - 74
Abstract
Allergologie select, Vol. 9/2025 (66-74)
Airborne exposure-induced occupational type I allergy to Tenebrio molitor: Case report and studies on immunological reactivity
Laura Weißenborn1, Sabine Kespohl2, Silke Maryska2, Ingrid Sander2, Jakob Bickhardt3, Thomas Henle1, and Monika Raulf2
1Chair of Food Chemistry, Technische Universität Dresden, Dresden, 2Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, and 3Pulmonary Specialist Practice and Training Center, Dresden, Germany
This occupational case report describes a 28-year-old woman, employed since November 2020 as a research assistant working with mealworms (Tenebrio molitor), who developed symptoms of mild shortness of breath and severe redness and swelling of the eyes in early 2022, leading to the diagnosis of occupational allergic asthma due to respiratory sensitization to mealworm. Subsequent tests confirmed mono-sensitization to T. molitor and additional cross-sensitization to flour beetle (Tribolium confusum). Further studies aimed to determine the antigenic and allergenic potency of different protein fractions and rearing material isolated from T. molitor regarding protein pattern and immunological activity by T. molitor-specific polyclonal rabbit IgG and human IgE. The highest antigen content of T. molitor was measured in the rearing material, followed by mealworm flour and aqueous extraction. Allergenic proteins are particularly detected in mealworm flour and aqueous fraction at molecular weights of 24 and 11 kDa, which appear to be specific for primary airway sensitization. In addition, the airborne T. molitor antigen levels in the workplace were monitored using electrostatic dust collectors to identify hotspots of exposure. The disposal of dry insect material was shown to be responsible for the unintentional release of potential allergens. Therefore, awareness of the potential risk of a type I allergy due to the release of airborne insect allergens in the workplace should be raised.Correspondence to:
Laura Weißenborn, Technische Universität Dresden, Professur für Lebensmittelchemie, Bergstraße 66, 01062 Dresden, Germany
Email: [email protected]
