Publications by authors named "Vera Mahler"

122 Publications

Regulatory Requirements for the Quality of Allergen Products for Allergen Immunotherapy of Food Allergy.

Curr Allergy Asthma Rep 2021 May 10;21(5):32. Epub 2021 May 10.

Paul-Ehrlich-Institut, Langen, Germany.

Purpose Of Review: Medicinal products for allergen immunotherapy (AIT) of food allergies have gained enormous momentum in recent years. With this new class of products entering marketing authorization procedures, compliance to regulatory requirements becomes a critical element. Here, an overview is provided on specific requirements and aspects concerning the quality control and manufacturing of these products.

Recent Findings: Recent developments in the field of AIT for food allergies are divers, including products for oral, epicutaneous, and subcutaneous application, most notably targeting egg, milk, and peanut allergy. As the source materials for food AIT product are typically produced for food consumption and not for medicinal purposes, unique challenges arise in the manufacturing processes and controls of these medicinal products. Individual approaches are needed to assure acceptable quality, including control of relevant quantitative and qualitative characteristics. Major characteristics for quality verification include determination of protein content, total allergenic activity, and major allergen content. The applied manufacturing processes need to be established such that relevant process parameters are kept within justified limits and consistency of produced batches is assured. Allergen products for food AIT present specific challenges with respect to quality aspects that differentiate them from other commonly available AIT products. While established regulation is available and provides clear guidance for most aspects, other issues require consideration of new and individual settings relevant here. Consequently, as experience grows, respective amendments to currently available guidance may be needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11882-021-01008-9DOI Listing
May 2021

[New allergens for occupational dermatology?]

Authors:
Vera Mahler

Hautarzt 2021 May 5. Epub 2021 May 5.

Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Deutschland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00105-021-04825-1DOI Listing
May 2021

Allergenicity assessment of the edible cricket Acheta domesticus in terms of thermal and gastrointestinal processing and IgE cross-reactivity with shrimp.

Food Chem 2021 Apr 20;359:129878. Epub 2021 Apr 20.

University of Verona, Department of Biotechnology, Verona, Italy. Electronic address:

The allergenic potency of the cricket Acheta domesticus, a promising edible insect, has never been assessed. This work aims to study the immunoreactivity of Acheta domesticus, and its cross-reactivity with the shrimp Litopenaeus vannamei, assessing the effect of cooking and gastrointestinal digestion on their allergenic properties. Different cricket proteins were detected by immunoblotting with shrimp-allergic patients' sera. Tropomyosin was identified as the most relevant IgE-binding protein, and its cross-reactivity with shrimp tropomyosin was demonstrated by ELISA. While shrimp tropomyosin showed scarce stability to gastric digestion, cricket tropomyosin withstood the whole digestion process. The sarcoplasmic calcium-binding protein, specifically detected in shrimp, showed exceptional stability to gastrointestinal digestion. IgE-binding proteins in a model of enriched baked products were partially protected from proteolysis. In conclusion, the ingestion of A. domesticus proteins poses serious concerns to the Crustacean-allergic population. The high stability of tropomyosin may represent a risk of primary sensitization and clinical cross-reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2021.129878DOI Listing
April 2021

Practical handling of allergic reactions to COVID-19 vaccines: A position paper from German and Austrian Allergy Societies AeDA, DGAKI, GPA and ÖGAI.

Allergo J Int 2021 Apr 19:1-17. Epub 2021 Apr 19.

Allergology and Immunology, Department of Dermatology, Venereology and Allergology, Charité-University Medicine Berlin, Berlin, Germany.

Background: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty.

Methods: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI).

Results: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts.

Conclusion: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40629-021-00165-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054127PMC
April 2021

Management of anaphylaxis due to COVID-19 vaccines in the elderly.

Allergy 2021 Apr 2. Epub 2021 Apr 2.

Regional Ministry of Health of Andalusia, Seville, Spain.

Older adults, especially men and/or those with diabetes, hypertension and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritised to receive COVID-19 vaccines due to high risk of death. In very rare instances,the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society)Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14838DOI Listing
April 2021

The European baseline series: Criteria for allergen inclusion (with reference to formaldehyde releasers).

Contact Dermatitis 2021 Mar 21. Epub 2021 Mar 21.

Department of Medical Informatics, Biometry and Epidemiology, University of Erlangen/Nürnberg, Erlangen, Germany.

Existing criteria for inclusion in the European baseline series are summarized. Additional criteria are developed to aid decision making where the current criteria do not yield an unequivocal result. These include a consideration of whether an allergen (hapten) is better placed in a special series and the frequency with which an allergen cross-reacts with existing markers in the baseline series.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13836DOI Listing
March 2021

European Surveillance System on Contact Allergies (ESSCA): Characteristics of patients patch tested and diagnosed with irritant contact dermatitis.

Contact Dermatitis 2021 Mar 17. Epub 2021 Mar 17.

Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Irritant contact dermatitis (ICD) is caused by the acute locally toxic effect of a strong irritant, or the cumulative exposure to various weaker physical and/or chemical irritants.

Objectives: To describe the characteristics of patients with ICD in the population patch tested in the European Surveillance System on Contact Allergies (ESSCA; www.essca-dc.org) database.

Methods: Data collected by the ESSCA in consecutively patch-tested patients from January 2009 to December 2018 were analyzed.

Results: Of the 68 072 patients, 8702 were diagnosed with ICD (without concomitant allergic contact dermatitis [ACD]). Hand and face were the most reported anatomical sites, and 45.7% of the ICD was occupational ICD (OICD). The highest proportions of OICD were found in metal turners, bakers, pastry cooks, and confectionery makers. Among patients diagnosed with ICD, 45% were found sensitized with no relevance for the current disease.

Conclusions: The hands were mainly involved in OICD also in the subgroup of patients with contact dermatitis, in whom relevant contact sensitization had been ruled out, emphasizing the need for limiting irritant exposures. However, in difficult-to-treat contact dermatitis, unrecognized contact allergy, or unrecognized clinical relevance of identified allergies owing to incomplete or wrong product ingredient information must always be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13833DOI Listing
March 2021

Atopic skin diathesis rather than atopic dermatitis is associated with specific contact allergies.

J Dtsch Dermatol Ges 2021 02;19(2):231-240

Department of Dermatology, Venereology and Allergology, University Medical Centre Göttingen, Germany.

Background: The association of atopic dermatitis (AD) and allergic contact dermatitis has been a matter of considerable uncertainty. Study results range from lack of any association to increased sensitization for multiple allergens, but fail to identify consistent allergen associations.

Objective: We studied a large patch test cohort of patients stratified by their atopic skin diathesis using the Erlangen Atopy Score (EAS), independent of active skin disease.

Methods: Retrospective multi-center data analysis from five departments of dermatology in Germany with 4,509 patients. Patients were grouped as "no atopic skin diathesis" (n = 2,165) and "atopic skin diathesis" (n = 1,743), according to EAS.

Results: Significantly more individuals with atopic skin diathesis showed at least one positive patch test reaction to the baseline series compared to individuals without atopic skin diathesis (49.1 % vs. 38.3 %). In logistic regression analyses, atopic skin diathesis was associated with a significantly higher risk of sensitization to methylchloroisothiazolinone/methylisothiazolinone (OR 2.383) and methylisothiazolinone (OR 1.891), thiuram mix (OR 1.614), as well as nickel (OR 1.530), cobalt (OR 1.683), and chromium (OR 2.089).

Conclusions: Atopic skin diathesis proved to be the most important intrinsic risk factor for contact sensitization to few, specific allergens. Past or present AD was a less relevant variable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ddg.14341DOI Listing
February 2021

A Novel Isoallergen Dau c 1.0401 in Carrot: Stability, Allergenicity, and Comparison with Other Isoallergens.

Mol Nutr Food Res 2021 04 3;65(7):e2001110. Epub 2021 Mar 3.

Biochemie IV - Biopolymere, Universität Bayreuth, Universitätsstr. 30, Bayreuth, D-95447, Germany.

Scope: Around 25% of food allergic persons in Central Europe suffer from carrot allergy caused by the major carrot allergen Dau c 1. Three different isoallergens, Dau c 1.01, Dau c 1.02 and Dau c 1.03 are identified. However, information about the qualitative and quantitative composition of natural (n)Dau c 1 is scarce.

Methods And Results: The new carrot allergen Dau c 1.0401 is identified on the mRNA and protein level by RT-PCR and mass spectrometry. It displays only around 60% sequence identity to the other known Dau c 1 isoallergens. NMR and CD-spectra are typical for a well-folded protein containing both α-helices and β-strands. It showed a poor refolding capacity after incubation at 95 °C. IgE-binding is impaired in immunoblots, whereas in inhibition assays IgE binding to soluble Dau c 1.0401 is detected and it clearly provoked a response in mediator release assays.

Conclusion: Dau c 1.0401 is a new isoallergen which contributes to the allergenicity of carrots. The absence of immunoreactivity in immobilized assays indicates that IgE binding is impaired when the protein is blotted on a solid phase. Altogether, the results point out that its allergenicity can be reduced upon carrot processing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202001110DOI Listing
April 2021

Assessment of the effects of a work-related allergy to seafood on the reduction of earning capacity in the context of BK No. 5101.

Allergol Select 2021 14;5:33-44. Epub 2021 Jan 14.

University of Heidelberg, Heidelberg, Germany.

Fish, crustaceans, and mollusks are among the most potent allergenic foods of animal origin and are thus important triggers of work-related immediate-food allergies. In Germany, work-related seafood allergies are of great importance in the fishing and processing industries as well as in the areas of food preparation, food control, and food sales. There is no causal therapy of seafood allergy, only the strict and lifelong avoidance of allergens remains. The following recommendations serve to assess the impact of a seafood allergy with regard to the work opportunities ended by it for the assessment of the reduction of earning capacity (MdE (German for Minderung der Erwerbsfähigkeit)) in the context of the occupational disease number 5101 of the Annex to the German regulation for occupational diseases. As a special feature of work-related seafood allergy with regard to insurance law aspects, it must be taken into account that there is a potential risk of systemic reaction with subsequent multi-organ involvement. For the estimation of MdE in the general labor market, the impact of a seafood allergy can therefore be assessed, depending on its clinical severity, as generally "mild" to "severe" in justified individual cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/AL0DB380EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814778PMC
January 2021

LAMP-LFD Based on Isothermal Amplification of Multicopy Gene : Applicability for Highly Sensitive Low-Tech Screening of Allergenic Soybean () in Food.

Foods 2020 Nov 26;9(12). Epub 2020 Nov 26.

Division of Allergology, Paul-Ehrlich-Institut (PEI), D-63225 Langen, Germany.

Soybean () allergy can be life threatening. A lack of causative immunotherapy of soybean allergy makes soybean avoidance indispensable. Detection methods are essential to verify allergen labeling and unintentional allergen cross contact during food manufacture. Here, we aimed at evaluating our previously described primers for loop-mediated isothermal amplification (LAMP) of multicopy gene , combined with a lateral flow dipstick (LFD)-like detection, for their performance of soybean detection in complex food matrices. The results were compared with those obtained using quantitative real-time Polymerase Chain Reaction (qPCR) as the current standard of DNA-based allergen detection, and antibody-based commercial lateral flow device (LFD) as the current reference of protein-based rapid allergen detection. LAMP-LFD allowed unequivocal and reproducible detection of 10 mg/kg soybean incurred in three representative matrices (boiled sausage, chocolate, instant tomato soup), while clear visibility of positive test lines of two commercial LFD tests was between 10 and 10 mg/kg and depending on the matrix. Sensitivity of soybean detection in incurred food matrices, commercial retail samples, as well as various processed soybean products was comparable between LAMP-LFD and qPCR. The DNA-based LAMP-LFD proved to be a simple and low-technology soybean detection tool, showing sensitivity and specificity that is comparable or superior to the investigated commercial protein-based LFD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods9121741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760099PMC
November 2020

[Immunotherapy of allergies: current status].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Nov 2;63(11):1341-1356. Epub 2020 Nov 2.

Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225, Langen, Deutschland.

Allergen immunotherapy (AIT) is the only causally effective, disease-modifying form of therapy that, in addition to alleviating allergic symptoms, counteracts disease progression.This article provides an up-to-date overview of immunological, regulatory and practical aspects of AIT. Current literature was included and recent conceptual regulatory developments from the Division of Allergology at the higher federal authority (Paul-Ehrlich-Institut) are presented.The 62 AIT products currently approved in Germany and further 61 AIT products under the development program of the Therapy Allergen Ordinance (TAO) include 95 products for subcutaneous (SCIT) and 28 for sublingual (SLIT) treatment of birch/alder/hazel pollen, grass pollen, weed pollen, house dust mite and insect venom allergies. Native and chemically modified allergen extracts (allergoids) adsorbed to aluminium, tyrosine (partly monophosphoryl lipid A-adjuvanted) or lactose or based on lyophilisates are used as active ingredients.These 123 AIT products are subject to official state batch release testing. This does not apply to named patient products (NPPs) available for the treatment of less prevalent allergies (e.g. to olive pollen, animal hair, storage mites or moulds). There is a particular need for development of AIT products for children.As a new class of active ingredients, food allergens are in clinical phase II and III studies. A first food preparation for oral AIT of peanut allergy in children is currently undergoing a central European marketing authorization (MA) procedure. MA can only be granted if the benefit-risk balance is positive. Science and regulation are in continuous exchange on the development of AIT products that correspond to the current state of clinical research and regulation in the EU and enable early causal treatment of widespread allergies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00103-020-03224-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647996PMC
November 2020

[Recombinant allergens, peptides, and virus-like particles for allergy immunotherapy].

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2020 Nov 23;63(11):1412-1423. Epub 2020 Oct 23.

Paul-Ehrlich-Institut, Bundesinstitut für Impfstoffe und Biomedizinische Arzneimittel (PEI), Paul-Ehrlich-Straße 51-59, 63225, Langen, Deutschland.

Currently, extract-based therapeutic allergens from natural allergen sources (e.g., house dust mites, tree and grass pollen) are used for allergen-specific immunotherapy (AIT), the only causative therapy that can exhibit positive disease-modifying effects by tolerance induction and prevention of disease progression. Due to variations in the natural composition of the starting materials and different manufacturing processes, there are variations in protein content, allergen composition, and allergenic activity of similar products, which poses specific challenges for their standardization. The identification of the nucleotide sequences of allergenic proteins led to the development of molecular AIT approaches. This allows for the application of exclusively relevant structures as chemically synthesized peptides, recombinant single allergens, or molecules with hypoallergenic properties that potentially allow for an up-dosing with higher allergen-doses without allergic side effects leading more quickly to effective cumulative doses. Further modifications of AIT preparations to improve allergenic and immunogenic properties may be achieved, e.g., by including the use of virus-like particles (VLPs). To date, the herein described therapeutic approaches have been tested in clinical trials only. This article provides an overview of published molecular approaches for allergy treatment used in clinical AIT studies. Their added value and challenges compared to established therapeutic allergens are discussed. The aim of these approaches is to develop highly effective and well-tolerated AIT preparations with improved patient acceptance and adherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00103-020-03231-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648003PMC
November 2020

Patch test results with the European baseline series and additions thereof in the ESSCA network, 2015-2018.

Contact Dermatitis 2021 Feb 7;84(2):109-120. Epub 2020 Oct 7.

Dermatology Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Background: Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series.

Objectives: To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments.

Methods: Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control.

Results: In the 4 years (2015-2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), and Myroxylon pereirae resin (balsam of Peru; 5.8%).

Conclusions: While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13704DOI Listing
February 2021

Formaldehyde 2% is not a useful means of detecting allergy to formaldehyde releasers- results of the ESSCA network, 2015-2018.

Contact Dermatitis 2021 Feb 16;84(2):95-102. Epub 2020 Oct 16.

Department of Dermatology, Chapel Allerton Hospital, Leeds, UK.

Background: Studies suggest that patch testing with formaldehyde releasers (FRs) gives significant additional information to formaldehyde 1% aq. and should be considered for addition to the European baseline series (EBS). It is not known if this is also true for formaldehyde 2% aq.

Objectives: To determine the frequency of sensitization to formaldehyde 2% aq. and co-reactivity with FRs. To establish whether there is justification for including FRs in the EBS.

Materials And Methods: A 4-year, multi-center retrospective analysis of patients with positive patch test reactions to formaldehyde 2% aq. and five FRs.

Results: A maximum of 15 067 patients were tested to formaldehyde 2% aq. and at least one FR. The percentage of isolated reactions to FR, without co-reactivity to, formaldehyde 2% aq. for each FR were: 46.8% for quarternium-15 1% pet.; 67.4% imidazolidinyl urea 2% pet.; 64% diazolidinyl urea 2% pet.; 83.3% 1,3-dimethylol-5, 5-dimethyl hydantoin (DMDM) hydantoin 2% pet. and 96.3% 2-bromo-2-nitropropane-1,3-diol 0.5% pet. This demonstrates that co-reactivity varies between FRs and formaldehyde, from being virtually non-existent in 2-bromo-2-nitropropane-1,3-diol 0.5% pet. (Cohen's kappa: 0, 95% confidence interval [CI] -0.02 to 0.02)], to only weak concordance for quaternium-15 [Cohen's kappa: 0.22, 95%CI 0.16 to 0.28)], where Cohen's kappa value of 1 would indicate full concordance.

Conclusions: Formaldehyde 2% aq. is an inadequate screen for contact allergy to the formaldehyde releasers, which should be considered for inclusion in any series dependant on the frequency of reactions to and relevance of each individual allergen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13691DOI Listing
February 2021

Identification and Characterization of IgE-Reactive Proteins and a New Allergen (Cic a 1.01) from Chickpea (Cicer arietinum).

Mol Nutr Food Res 2020 10 21;64(19):e2000560. Epub 2020 Sep 21.

Division Allergology and Section Molecular Allergology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 2, 63225, Langen, Germany.

Scope: Chickpea (Cicer arietinum) allergy has frequently been reported particularly in Spain and India. Nevertheless, chickpea allergens are poorly characterized. The authors aim to identify and characterize potential allergens from chickpea.

Methods And Results: Candidate proteins are selected by an in silico approach or immunoglobuline E (IgE)-testing. Potential allergens are prepared as recombinant or natural proteins and characterized for structural integrity by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD)-spectroscopy, and mass spectrometry (MS) analysis. IgE-sensitization pattern of Spanish chickpea allergic and German peanut and birch pollen sensitized patients are investigated using chickpea extracts and purified proteins. Chickpea allergic patients show individual and heterogeneous IgE-sensitization profiles with extracts from raw and boiled chickpeas. Chickpea proteins pathogenesis related protein family 10 (PR-10), a late embryogenesis abundant protein (LEA/DC-8), and a vicilin-containing fraction, but not 2S albumin, shows IgE reactivity with sera from chickpea, birch pollen, and peanut sensitized patients. Remarkably, allergenic vicilin, DC-8, and PR-10 are detected in the extract of boiled chickpeas.

Conclusion: Several IgE-reactive chickpea allergens are identified. For the first time a yet not classified DC-8 protein is characterized as minor allergen (Cic a 1). Finally, the data suggest a potential risk for peanut allergic patients by IgE cross-reactivity with homologous chickpea proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202000560DOI Listing
October 2020

Developing a cosmetic series: Results from the ESSCA network, 2009-2018.

Contact Dermatitis 2021 Feb 29;84(2):82-94. Epub 2020 Sep 29.

Department of Dermatology, Chapel Allerton Hospital, Leeds, UK.

Background: There is considerable variability across European patch test centres as to which allergens are included in local and national cosmetics series.

Objectives: To propose a standardized, evidence-based cosmetic series for Europe based on up-to-date analysis of relevant contact allergens.

Methods: We collated data from the European Surveillance System on Contact Allergies (ESSCA) from 2009 to 2018 to determine which cosmetic allergens produce a high yield of contact allergy. Contact allergens with a prevalence of >0.3% that were considered relevant were included. Rare contact allergens were excluded if deemed no longer relevant or added to a supplemental cosmetic series for further analysis.

Results: Sensitization prevalences of 39 cosmetic contact allergens were tabulated. Thirty of these allergens yielded >0.3% positive reactions and are therefore included in our proposed European cosmetic series. Six were considered no longer relevant and therefore excluded. Three were included in a supplementary European cosmetic series. An additional nine allergens were included in either the core or supplemental European cosmetic series following literature review.

Conclusion: We have derived a potential European cosmetic series based upon the above methods. This will require ongoing investigation based upon the changing exposure profiles of cosmetic allergens as well as new and evolving substances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13690DOI Listing
February 2021

New guidance on the regulation of allergen products: key aspects and outcomes.

Curr Opin Allergy Clin Immunol 2020 12;20(6):624-630

Paul-Ehrlich-Institut, Langen, Germany.

Purpose Of Review: Key aspects and outcomes from the recently published guidance on the regulation of allergen products are summarized.

Recent Findings: A new regulatory guideline has been published to enhance harmonized national approaches on the regulation of allergen products and thereby strengthen the availability of high-quality products across the European Union (EU). As the guideline was developed, critical aspects for allergen products regulation were identified and are discussed in the document, including recommendations on the regulatory procedures to be applied for diagnostics, allergen immunotherapy products and named-patient products.

Summary: The new guidance is expected to provide clarifications on and support harmonization of the regulation of allergen products in the EU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ACI.0000000000000687DOI Listing
December 2020

Contact sensitization in metalworkers: Data from the information network of departments of dermatology (IVDK), 2010-2018.

Contact Dermatitis 2020 Dec 7;83(6):487-496. Epub 2020 Oct 7.

Information Network of Departments of Dermatology (IVDK), Institute at the University Medical Center Göttingen, Göttingen, Germany.

Background: Metalworkers are exposed to a variety of contact allergens by handling tools, metals, metalworking fluids (MWFs), oils and greases, rubber materials, and so on. Most large-scale reports on contact allergy due to MWFs are more than 10-years-old, and there are only few studies on contact allergy in mechanics and other metal workers not exposed to MWFs.

Objectives: To describe a current spectrum of contact sensitization in metalworkers with occupational dermatitis (OD).

Patients And Methods: Retrospective analysis of patch test data collected by the Information Network of Departments of Dermatology (IVDK; 2010-2018), stratifying for 804 cutting metalworkers, 2197 mechanics, and 355 other metalworkers.

Results: Cutting metalworkers were most frequently sensitized to monoethanolamine (12.6%), colophonium/abietic acid (11.4%) and formaldehyde releasers (up to 8.5%) from the MWF series, and formaldehyde (4.6%) and iodopropynyl butylcarbamate (4.6%) from the baseline series. Sensitization among mechanics and other metalworkers indicates possible occupational exposure to MWFs, glues, and resins, although this may not be expected from their job titles.

Conclusions: The spectrum of MWF contact allergens remained largely unchanged during the last years. Taking a comprehensive occupational history is indispensable in order to not miss relevant allergen exposures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13686DOI Listing
December 2020

Food Processing Does Not Abolish the Allergenicity of the Carrot Allergen Dau c 1: Influence of pH, Temperature, and the Food Matrix.

Mol Nutr Food Res 2020 09 2;64(18):e2000334. Epub 2020 Aug 2.

Biochemie IV - Biopolymere, Universität Bayreuth, Universitätsstr. 30, Bayreuth, 95447, Germany.

Scope: The major carrot allergen Dau c 1 belongs to the group of pathogenesis related class 10 (PR-10) proteins and is homologous to the birch pollen allergen Bet v 1. In contrast to most other PR-10 allergens, Dau c 1 can elicit Bet v 1 independent sensitization. Although Dau c 1 is considered heat labile, allergic reactions against cooked carrots are possible.

Methods And Results: The pH and temperature stability as well as the allergenic potential before and after treatment of purified natural (n) Dau c 1 and different recombinant (r) isoallergens is investigated: rDau c 1.0104, rDau c 1.0105, rDau c 1.0201, rDau c 1.0301. All proteins except rDau c 1.0201 are able to refold at physiological pH. pH conditions around the pI (4.4-5.5) or the presence of the carrot matrix reduce the refolding capacity. Below the pI, most isoallergens are heat resistant and still able to cause mediator release, indicating allergenicity. Moreover, cooked carrot extract is still able to provoke mediator release due to remaining soluble Dau c 1.

Conclusion: Patients allergic to carrots should avoid processed carrot containing foodstuff because heating or pH treatment do not completely abolish the allergenicity of Dau c 1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mnfr.202000334DOI Listing
September 2020

Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results.

J Allergy Clin Immunol 2020 10 10;146(4):863-874. Epub 2020 Jul 10.

Perth Children's Hospital, Nedlands, Australia.

Background: The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg).

Objective: We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study.

Methods: Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment.

Results: Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%).

Conclusions: These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.06.028DOI Listing
October 2020

Guideline on diagnostic procedures for suspected hypersensitivity to beta-lactam antibiotics: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Society of Allergology (AeDA), German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Austrian Society for Allergology and Immunology (ÖGAI), and the Paul-Ehrlich Society for Chemotherapy (PEG).

Allergol Select 2020 28;4:11-43. Epub 2020 May 28.

Department of Dermatology and Allergology am Biederstein, School of Medicine, Technical University of Munich, Munich, Germany.

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/ALX02104EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304290PMC
May 2020

[Occupationally acquired MRSA colonization and occupational dermatological assessments (BK-No. 3101 in the German list of Occupational Diseases) : Analysis of the DGUV documentation and expert opinion on a case with work-related MRSA-triggered atopic dermatitis].

Hautarzt 2020 Aug;71(8):613-623

Hautklinik Universitätsklinikum Erlangen, Erlangen, Deutschland.

Background: Person-to-person transmitted infectious diseases can cause occupational diseases (OD). These are subsumed as BK-No. 3101 in the German list of OD which applies for individuals with a considerably higher risk for infection as a consequence of their professional activity compared to the general population.

Objectives: The special medical and insurance law aspects of a work-related MRSA colonization are presented using the example of an expert opinion case and an evaluation of the BK reports of suspected occupational disease (BK No. 3101) of the German Social Accident Insurance (DGUV).

Patients And Methods: The BK documentation of the DGUV from 2007-2012 and the patient cohort from the Department of Dermatology, University Hospital Erlangen, presenting for expert assessment from 2007-2012 were retrospectively analysed for human-to-human transmitted infectious diseases of the skin (BK-No. 3101).

Results: Person-to-person transmission of infectious diseases of the skin is rare in the field of occupational dermatology. In the DGUV cohort, suspected BK-No. 3101cases amounted to 2.6% of all notified cases; recognized BK-No. 3101 cases accounted for 4.2% of all recognized cases, amongst which 9 were caused by MRSA. In contrast to a symptomatic infection, an asymptomatic MRSA colonization is not being recognized as BK-No. 3101. Bacterial superantigens can trigger atopic dermatitis (AD). In particular cases, occupationally acquired MRSA can elicit AD and may justify classification as an OD (BK-No. 3101).

Conclusions: Early detection of MRSA colonization and eradication are necessary for rehabilitation. Management of skin diseases due to infectious diseases within the framework of OD is presented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00105-020-04616-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268186PMC
August 2020

Adding a second skin prick test reading and modifying the cut-off for beta-lactam-specific IgE enhances the sensitivity in the routine diagnostic workup for immediate beta-lactam hypersensitivity.

Contact Dermatitis 2020 Nov 27;83(5):361-371. Epub 2020 Jul 27.

Allergy-Clinic of the Department of Dermatology, University Hospital of Erlangen, Erlangen, Germany.

Background: Beta-lactam (BL)-antibiotics are the most frequent reason for drug-induced hypersensitivity reactions. Because they are more efficient, less toxic, and less costly than other antibiotics, confirmation or exclusion of BL allergy is worthwhile. However, allergy tests for drug allergies are often false-negative.

Objectives: To evaluate the components of a stepwise diagnostic algorithm for immediate BL hypersensitivity with regard to sensitivity (SENS).

Methods: Consecutive patients with suspected allergy to BL antibiotics were retrospectively analyzed with regard to increasing sensitivity (plausible history of immediate BL hypersensitivity serving as external criterion) of (i) skin prick test (SPT) by adding a second reading (n = 746), (ii) BL-specific IgE-determination in vitro at two cut-offs (n = 539), and (iii) adding in vivo testing of minor and major BL determinants (n = 288).

Results: In the history-based population indicative of immediate BL hypersensitivity (n = 457), SPT with a sole 20-minute reading identified 99 (SENS: 0.21) and SPT with 20- and 40-minute-reading identified 133 cases (SENS: 0.29). in vitro specific IgE-examination identified 31 positives at a cut-off ≥0.35 kUA/L (5.8% of tested) and 99 at cut-off ≥0.11 kUA/L (18.4% of tested). In 203 SPT-negative individuals, immediate BL hypersensitivity was identified by additional tests: in 79 by specific IgE (cut-off ≥0.11 kUA/L) (thereof 53 identified solely by this test) and in 150 by in vivo testing of BL determinants in combination with Penicillin and Ampicillin intradermally (thereof 124 solely by this test); in 26 individuals both additional tests were positive. The combination of the three outpatient-based test modalities-(i) optimized SPT, (ii) specific IgE at optimized cut-off, and (iii) in vivo testing of BL determinants/Penicillin/Ampicillin-identified altogether 336/457 individuals with immediate BL-hypersensitivity (SENS: 0.73), whereas the combination of the two (i) + (ii) identified 212/457 (SENS: 0.46); (i) + (iii) 283/457 (SENS: 0.61).

Conclusions: To overcome the low sensitivity of allergological tests, optimized reading times of the SPT of BL, a lower cut-off for in vitro detection of BL-specific IgE, and intradermal testing of Penicillin, Ampicillin, and BL-determinants contribute to overall sensitivity under real life conditions to diagnose immediate BL-hypersensitivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cod.13622DOI Listing
November 2020

In-vivo diagnostic test allergens in Europe: A call to action and proposal for recovery plan-An EAACI position paper.

Allergy 2020 09;75(9):2161-2169

Allergy Section, Department of Internal Medicine, Hospital Valld'Hebron, Barcelona, Spain.

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14329DOI Listing
September 2020

ARIA guideline 2019: treatment of allergic rhinitis in the German health system.

Allergol Select 2019 30;3(1):22-50. Epub 2019 Dec 30.

Department of Dermatology, University Medical Center Mainz,Mainz, Germany.

Background: The number of patients affected by allergies is increasing worldwide. The resulting allergic diseases are leading to significant costs for health care and social systems. Integrated care pathways are needed to enable comprehensive care within the national health systems. The ARIA (Allergic Rhinitis and its Impact on Asthma) initiative develops internationally applicable guidelines for allergic respiratory diseases.

Methods: ARIA serves to improve the care of patients with allergies and chronic respiratory diseases. In collaboration with other international initiatives, national associations and patient organizations in the field of allergies and respiratory diseases, real-life integrated care pathways have been developed for a digitally assisted, integrative, individualized treatment of allergic rhinitis (AR) with comorbid asthma. In the present work, these integrated care pathways have been adapted to the German situation and health system.

Results: The present ICP (integrated care pathway) guideline covers key areas of the care of AR patients with and without asthma. It includes the views of patients and other healthcare providers.

Discussion: A comprehensive ICP guideline can reflect real-life care better than traditional guideline models.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5414/ALX02120EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066682PMC
December 2019

Year-round treatment initiation for a 6-grasses pollen allergoid in specific immunotherapy of allergic rhinoconjunctivitis and asthma.

Immunotherapy 2019 12 19;11(18):1569-1582. Epub 2019 Dec 19.

Department for Children & Adolescents, Division for Allergology, Pneumology & Cystic Fibrosis, University Hospital Goethe University, Frankfurt am Main, Germany.

Allergen immunotherapy (AIT) is an effective treatment for allergic diseases. We investigate whether treatment-initiation during the pollen season is safe. RCT-IIIb-trial of 6-grass-pollen-allergoid (Allergovit) in grass pollen-allergic patients (18-65 years) with moderate-severe rhinitis/rhinoconjunctivitis (± controlled asthma), randomized 2:1 to treatment-initiation during (Group-A) versus outside the pollen season (Group-B). Of 240 patients (32.8 ± 9.9 years, 19.5% asthma) treated, 84.9% (Group-A) and 86.6% (Group-B) reached maintenance dose without delay. Treatment-emergent adverse events occurred in 108 (68.4%/Group-A) and 41 patients (56.2%/Group-B) leading to premature trial-termination in 11 patients (7%/A) versus 3 (4.1%/B). Across groups, physicians (for 190 patients; 85.2%) and patients (192; 86.1%) rated the tolerability as 'very good'-'good'. -specific IgG4 increased in both groups (p < 0.0001). Year-round allergen immunotherapy-initiation with this preparation is safe.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2019-0086DOI Listing
December 2019