{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:48:27Z","timestamp":1791362907743,"version":"4.3.1"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aust J Dermatology"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS\/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)\u2010alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS\/TEN however remains elusive. This systematic review aimed to evaluate the case\u2013control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and\/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)\u20108 and B\u2010cell lymphoma (Bcl)\u20102 were elevated in SJS\/TEN blister fluid and skin tissue, compared with healthy controls. IL\u20102, IL\u20106, TNF\u2010alpha, tumour necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL), interferon\u2010gamma and matrix metalloproteinase\u20102 were elevated in SJS\/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL\u201033, TGF\u2010beta\u20101 and IL\u201013 were elevated in SJS\/TEN skin tissue compared with lesional lichen planus tissue, as was IL\u201013, IFN\u2010gamma, IL\u20102 and IL\u20105, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS\/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.<\/jats:p>","DOI":"10.1111\/ajd.14329","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T07:13:24Z","timestamp":1717485204000},"page":"491-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A systematic review of case\u2013control studies of cytokines in blister fluid and skin tissue of patients with Stevens Johnson syndrome and toxic epidermal necrolysis"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-2857","authenticated-orcid":false,"given":"Thomas Jonathan","family":"Stewart","sequence":"first","affiliation":[{"name":"Department of Dermatology Royal North Shore Hospital  St Leonards New South Wales Australia"},{"name":"School of Medicine University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Dermatology Royal North Shore Hospital  St Leonards New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-3632","authenticated-orcid":false,"given":"John Walter","family":"Frew","sequence":"additional","affiliation":[{"name":"School of Medicine University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Dermatology Liverpool Hospital  Liverpool New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.510"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.12.005"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2010.01176.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2006.07398.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1076029620950831"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2007.02482.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.138.1.29"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/000155599750010689"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1998.00329.x"},{"issue":"8","key":"e_1_2_9_11_1","first-page":"1868","article-title":"PIELenRed study. 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