{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:11:08Z","timestamp":1767211868942,"version":"3.37.3"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Growing and sustainable consumption of health\u2010care products raises a controversial issue underlying the reliability of an <jats:italic>in\u00a0vitro<\/jats:italic> diagnostic approach for adverse skin reaction. This report aimed to: (i) discuss the causative nature of a commercial dietary supplement composed of natural ingredients, particularly an <jats:italic>Euglena<\/jats:italic>\u2010containing product, suspicious for erythema multiforme in our exemplified case; and (ii) to address the assay suitability of the lymphocyte transformation test (<jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content>) for identifying allergic reaction to any ingredient(s) of the product. A Japanese elderly man developed erythema multiforme after intake of a commercially available natural dietary product, whose <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> was positive. His clinical course and positive <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> suggested a provisional diagnosis of natural dietary product\u2010induced eruption. We conducted an inquiry survey for the standard <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> with any commercial products containing <jats:italic>Euglena<\/jats:italic> in three major Japanese laboratory services and identified 22 subjects, almost all of whom (21\/22, 95.6%) showed a positive <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> for any <jats:italic>Euglena<\/jats:italic>\u2010containing products as a suspected causative. Seven normal healthy volunteers who had no intake history of <jats:italic>Euglena<\/jats:italic>\u2010containing products showed an equivalent <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> positivity rate with the same product taken by our case; culprit components of the product included <jats:italic>Euglena<\/jats:italic>,<jats:italic> Angelica keiskei<\/jats:italic>, Barley grass and <jats:italic>Chlorella<\/jats:italic>. A cell\u2010free culture system and enzyme\u2010linked immunoassay suggest that the high <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content> positivity relies on the non\u2010specific lymphoproliferative activity, and not contamination of uncharacterized microorganisms and endotoxins. Because of the constitutive false positivity of <jats:styled-content style=\"fixed-case\">LTT<\/jats:styled-content>, this assay is unreliable for <jats:italic>in\u00a0vitro<\/jats:italic> supportive diagnosis of adverse skin events caused by dietary products containing particular natural ingredients, as well as herbal materials.<\/jats:p>","DOI":"10.1111\/1346-8138.14739","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T09:45:48Z","timestamp":1547027148000},"page":"234-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dietary supplement product composed of natural ingredients as a suspected cause of erythema multiforme: A case report and identification for the confident false positivity of lymphocyte transformation test"],"prefix":"10.1111","volume":"46","author":[{"given":"Natsuko","family":"Utsunomiya","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4934-5205","authenticated-orcid":false,"given":"Noritaka","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takenao","family":"Chino","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1164-6088","authenticated-orcid":false,"given":"Akira","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukio","family":"Hida","sequence":"additional","affiliation":[{"name":"Clinical Laboratories Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-2682","authenticated-orcid":false,"given":"Minoru","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medical Sciences University of Fukui Fukui Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.212.49"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02180.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.2340\/00015555-0695"},{"key":"e_1_2_6_5_1","first-page":"1543","article-title":"Evaluation of diagnostic significance of the drug\u2010induced lymphocyte stimulation test in drug eruptions","volume":"110","author":"Muto M","year":"2000","journal-title":"Jpn J Dermatol"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.07-3088"},{"key":"e_1_2_6_7_1","first-page":"479","article-title":"Lymphocyte transformation test for medicinal herbs yields false\u2010positive results for first\u2010visit patients","volume":"10","author":"Mantani N","year":"2003","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.122.399"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.140.6.723"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.2000.03463.x"},{"key":"e_1_2_6_11_1","unstructured":"Specifications and Standards for Food Food Additives etc.Under the Food Sanitation Act. Japan External Trade Organization 2011."},{"volume-title":"The Biology of Euglena","year":"1968","author":"Buetow DE","key":"e_1_2_6_12_1"},{"key":"e_1_2_6_13_1","first-page":"323","article-title":"Possiblse extent of the contribution of Euglena as a high nutritional food resource \u2010physiological functions and application of Euglena cells","volume":"91","author":"Nakano Y","year":"2017","journal-title":"J Nutr Sci Vitaminol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-483X(00)00290-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni777"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3358\/shokueishi.47.164"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2011.03.010"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2004.00547.x"},{"key":"e_1_2_6_19_1","first-page":"272","article-title":"Lymphocyte\u2010stimulation tests and patch tests to carbamazepine hypersensitivity","volume":"29","author":"Houwerzijl J","year":"1977","journal-title":"Clin Exp Immunol"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1346-8138.14739","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.14739","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T05:25:47Z","timestamp":1694669147000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.14739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,9]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,3]]}},"alternative-id":["10.1111\/1346-8138.14739"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.14739","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"type":"print","value":"0385-2407"},{"type":"electronic","value":"1346-8138"}],"subject":[],"published":{"date-parts":[[2019,1,9]]},"assertion":[{"value":"2018-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}