{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:42:02Z","timestamp":1791474122151,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Reliable quality of epicutaneous patch test (PT) preparations is a prerequisite for establishing a robust diagnosis in patients with suspected allergic contact dermatitis due to delayed-type sensitization. It is difficult to identify potential quality issues in daily practice, since confirmatory methods are lacking and assessment of PT-relevance is predominantly based on patients\u2019 history and exposure. The quality of PT products can be affected, e.g., by the properties of the active substance, an insufficient development of the PT preparation or issues during manufacturing. Resulting quality deficiencies can cause both false-negative and false-positive test results. As PT preparations are medicinal products according to Directive 2001\/83\/EC, they require a marketing authorization (MA) entailing assessment of quality, safety and efficacy by the competent authorities. The corresponding product dossier is the basis for MA. It is continuously updated, e.g., upon change of a source material supplier, ensuring comparability of the respective product over time. Compliance with regulatory requirements is a crucial foundation for sustainable quality to prevent product deficiencies, ensuring reliable test results in practice. Harmonization across the EU is important to ensure the widespread availability of high-quality PT products. This review presents the MA requirements of PT preparations in the EU, as well as challenges previously reported by physicians.<\/jats:p>","DOI":"10.3390\/jcm14217521","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T02:34:45Z","timestamp":1761273285000},"page":"7521","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Patch Test Preparations: Basis and State-of-the-Art Modern Diagnostic Tools for Contact Allergy"],"prefix":"10.3390","volume":"14","author":[{"given":"Julia","family":"Zimmer","sequence":"first","affiliation":[{"name":"Allergology Division, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Neimanis","sequence":"additional","affiliation":[{"name":"Allergology Division, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Allergology Division, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Schubert","sequence":"additional","affiliation":[{"name":"Information Network of Departments of Dermatology (IVDK), Institute at the University Medical Centre G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Mahler","sequence":"additional","affiliation":[{"name":"Allergology Division, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Duus Johansen, J., Mahler, V., Lepoittevin, J.-P., and Frosch, P.J. (2021). Mechanisms of Irritant and Allergic Contact Dermatitis. Contact Dermatitis, Springer International Publishing AG. [6th ed.].","DOI":"10.1007\/978-3-030-36335-2"},{"key":"ref_2","unstructured":"Groot, A.C.d. (2022). Patch Testing: Test Concentrations and Vehicles for 5100 Chemicals, Acdegroot Publishing. [5th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3109\/1547691X.2015.1008656","article-title":"The lymphocyte transformation test in allergic contact dermatitis: New opportunities","volume":"13","author":"Popple","year":"2016","journal-title":"J. Immunotoxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1111\/all.14322","article-title":"TCRs with segment TRAV9-2 or a CDR3 histidine are overrepresented among nickel-specific CD4+ T cells","volume":"75","author":"Riedel","year":"2020","journal-title":"Allergy"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"212","DOI":"10.5414\/ALX02505E","article-title":"Regulatory framework for development and marketing authorization of allergen products for diagnosis of rare type I and type IV allergies: The current status","volume":"8","author":"Zimmer","year":"2024","journal-title":"Allergol. Select"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/cod.14580","article-title":"Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces \u2018Contact Dermatitis\u2019 and \u2018Occupational Skin Disease\u2019 position paper","volume":"91","author":"John","year":"2024","journal-title":"Contact Dermat."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1097\/ACI.0000000000000687","article-title":"New guidance on the regulation of allergen products: Key aspects and outcomes","volume":"20","author":"Bonertz","year":"2020","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_8","first-page":"339","article-title":"Post Launch Approval Process for Allergens in Italy (presented atI PES 2023\u201416th International Paul-Ehrlich-Seminar; September 6\u20149, 2023, Langen, Germany)","volume":"47","author":"Mitrevski","year":"2024","journal-title":"Allergologie"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/cod.12432","article-title":"European Society of Contact Dermatitis guideline for diagnostic patch testing\u2014Recommendations on best practice","volume":"73","author":"Johansen","year":"2015","journal-title":"Contact Dermat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1600-0536.2007.01098.x","article-title":"Recommendation of appropriate amounts of petrolatum preparation to be applied at patch testing","volume":"56","author":"Bruze","year":"2007","journal-title":"Contact Dermat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/cod.14332","article-title":"Patch testing hydroperoxides of limonene and linalool in consecutive patients-Results of the IVDK 2018\u20132020","volume":"89","author":"Schubert","year":"2023","journal-title":"Contact Dermat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"CD01","DOI":"10.1093\/bjd\/ljad113.200","article-title":"Sodium benzoate: An important allergen to patch test to\u2014Is 5% in petrolatum too irritant?","volume":"188","author":"Lawrance","year":"2023","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/cod.14812","article-title":"Frequent Positive Patch Test Reactions to Glucosides in Children: A Call for Caution?","volume":"93","author":"Kanokrungsee","year":"2025","journal-title":"Contact Dermat."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0190-9622(94)70220-9","article-title":"Reproducibility of patch tests: A multicenter study of synchronous left-versus right-sided patch tests by the German Contact Dermatitis Research Group","volume":"31","author":"Brasch","year":"1994","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1053\/ajcd.2000.8011","article-title":"Patch testing with methyldibromoglutaronitrile","volume":"11","author":"Geier","year":"2000","journal-title":"Am. J. Contact Dermat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s00105-019-04517-x","article-title":"Dauerbrenner Konservierungsmittelallergie: Was geht, was kommt, was bleibt?","volume":"71","author":"Kreft","year":"2020","journal-title":"Hautarzt"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/DER.0000000000000471","article-title":"Linalool Hydroperoxides","volume":"30","year":"2019","journal-title":"Dermatitis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cod.14064","article-title":"Limonene and linalool hydroperoxides review: Pros and cons for routine patch testing","volume":"87","author":"Ogueta","year":"2022","journal-title":"Contact Dermat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/cod.14255","article-title":"The European baseline series and recommended additions: 2023","volume":"88","author":"Wilkinson","year":"2023","journal-title":"Contact Dermat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/DER.0000000000000465","article-title":"Limonene Hydroperoxides","volume":"30","year":"2019","journal-title":"Dermatitis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.0105-1873.2005.00646.x","article-title":"Patch testing with p-toluene diamine preparations of different ages","volume":"53","author":"Geier","year":"2005","journal-title":"Contact Dermat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1111\/j.1600-0536.2006.00964_1.x","article-title":"Both mercaptobenzothiazole and mercapto mix should be part of the standard series","volume":"55","author":"Geier","year":"2006","journal-title":"Contact Dermat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1600-0536.1993.tb03320.x","article-title":"Stability of the mercaptobenzothiazole compounds","volume":"28","author":"Hansson","year":"1993","journal-title":"Contact Dermat."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/cod.12300","article-title":"Fragrance patch tests prepared in advance may give false-negative reactions","volume":"71","author":"Mowitz","year":"2014","journal-title":"Contact Dermat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/cod.14701","article-title":"Comparison of patch testing Brazilian (Green) propolis and Chinese (poplar-type) propolis: Clinical epidemiological study using data from the Information Network of Departments of Dermatology (IVDK)","volume":"92","author":"Piontek","year":"2025","journal-title":"Contact Dermat."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1111\/cod.14748","article-title":"Results of Concurrent Patch Testing of Brazilian and Chinese Propolis","volume":"92","author":"Ipenburg","year":"2025","journal-title":"Contact Dermat."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1111\/cod.13263","article-title":"Myroxylon pereirae resin (balsam of Peru)\u2014A critical review of the literature and assessment of the significance of positive patch test reactions and the usefulness of restrictive diets","volume":"80","year":"2019","journal-title":"Contact Dermat."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/DER.0000000000000241","article-title":"Essential Oils, Part VI: Sandalwood Oil, Ylang-Ylang Oil, and Jasmine Absolute","volume":"28","author":"Groot","year":"2017","journal-title":"Dermatitis"},{"key":"ref_29","first-page":"117","article-title":"Risks Associated with Adulterated Essential Oils","volume":"24","author":"Shakeel","year":"2023","journal-title":"IJCBS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/cod.12088","article-title":"Investigation of the homogeneity of methacrylate allergens in commercially available patch test preparations","volume":"69","author":"Mose","year":"2013","journal-title":"Contact Dermat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1111\/cod.12169","article-title":"Concentrations and stability of methyl methacrylate, glutaraldehyde, formaldehyde and nickel sulfate in commercial patch test allergen preparations","volume":"70","author":"Siegel","year":"2014","journal-title":"Contact Dermat."},{"key":"ref_32","first-page":"20","article-title":"Gas chromatographic and mass spectrometric purity analysis of acrylates and methacrylates used as patch test substances","volume":"8","author":"Kanerva","year":"1997","journal-title":"Am. J. Contact Dermat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1600-0536.2007.01298.x","article-title":"Chemical investigations of disperse dyes in patch test preparations","volume":"58","author":"Ryberg","year":"2008","journal-title":"Contact Dermat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1600-0536.2007.01228.x","article-title":"Current patch test results in consecutive patients with, and chemical analysis of, disperse blue (DB) 106, DB 124, and the mix of DB 106 and 124","volume":"57","author":"Uter","year":"2007","journal-title":"Contact Dermat."},{"key":"ref_35","unstructured":"John, S.M., Johansen, J.D., Rustemeyer, T., Elsner, P., and Maibach, H.I. (2025). Dyes, pigments and inks. Kanerva\u2019s Occupational Dermatology, Springer International PU. (In Press)."},{"key":"ref_36","first-page":"1187","article-title":"S3 Guidelines: Epicutaneous patch testing with contact allergens and drugs\u2014Short version, Part 2","volume":"17","author":"Mahler","year":"2019","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00228-015-1886-z","article-title":"It is time to review how unlicensed medicines are used","volume":"71","author":"Sutherland","year":"2015","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_38","unstructured":"European Pharmacopoeia Monograph on Allergen Products (1063). Strasbourg, France: Council of Europe."},{"key":"ref_39","unstructured":"European Medicines Agency (2025, October 18). Guideline on Allergen Products: Production and Quality Issues (EMEA\/CHMP\/BWP\/304831\/2007). Available online: https:\/\/www.ema.europa.eu\/en\/allergen-products-production-quality-issues-scientific-guideline."},{"key":"ref_40","unstructured":"European Medicines Agency (2025, October 18). Guideline on Allergen Products Development for Immunotherapy and Allergy Diagnosis in Moderate to Lowsized Study Populations (EMA\/161669\/2025). Available online: https:\/\/www.ema.europa.eu\/en\/allergen-products-development-immunotherapy-allergy-diagnosis-moderate-low-sized-study-populations-scientific-guideline."},{"key":"ref_41","unstructured":"European Medicines Agency (2025, October 18). Guideline on Process Validation for Finished Products\u2014Information and Data to be Provided in Regulatory Submissions (EMA\/CHMP\/CVMP\/QWP\/BWP\/70278\/2012-Rev1,Corr.1). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-process-validation-finished-products-information-and-data-be-provided-regulatory-submissions-revision-1_en.pdf."},{"key":"ref_42","unstructured":"European Medicines Agency (2025, October 18). Guideline on Clinical Evaluation of Diagnostic Agents (CPMP\/EWP\/1119\/98\/Rev. 1). Available online: https:\/\/www.ema.europa.eu\/en\/clinical-evaluation-diagnostic-agents-scientific-guideline."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1600-0536.1992.tb05267.x","article-title":"The reaction index: A parameter to assess the quality of patch test preparations","volume":"27","author":"Brasch","year":"1992","journal-title":"Contact Dermat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1600-0536.2008.01360.x","article-title":"How to use the reaction index and positivity ratio","volume":"59","author":"Brasch","year":"2008","journal-title":"Contact Dermat."},{"key":"ref_45","unstructured":"(2025, October 18). Commission Regulation (EC) No 1234\/2008 of 24 November 2008 Concerning the Examination of Variations to the Terms of Marketing Authorisations for Medicinal Products for Human Use and Veterinary Medicinal Products. Available online: https:\/\/eur-lex.europa.eu\/eli\/reg\/2008\/1234\/oj\/eng."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/DER.0b013e3182a0a19d","article-title":"Stability of patch test allergens","volume":"24","author":"Joy","year":"2013","journal-title":"Dermatitis"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7521\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T02:46:43Z","timestamp":1761274003000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/21\/7521"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,23]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14217521"],"URL":"https:\/\/doi.org\/10.3390\/jcm14217521","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,23]]}}}