{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:12:06Z","timestamp":1785499926155,"version":"3.56.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30\u2010AR053503"],"award-info":[{"award-number":["P30\u2010AR053503"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["T32AR048522"],"award-info":[{"award-number":["T32AR048522"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis Care &amp; Research"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Scleromyxedema (SMX) is a rare systemic sclerosis mimic that often responds to intravenous immunoglobulin (IVIG) therapy, yet the resulting clinical and biochemical changes have not been well characterized. To better understand the pathogenesis of the disease and the efficacy of IVIG, we sought to explore whether IVIG would introduce a measurable biologic effect corresponding with clinical improvement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen patients with SMX were recruited for the study. Clinical information and peripheral blood mononuclear cells for flow cytometry were obtained immediately before and again 1\u20132 weeks after patients received IVIG therapy. Ten patients also underwent skin biopsies for gene expression analysis both before and after IVIG therapy. Clinical data included measures of skin involvement (modification of the modified Rodnan skin thickness score [MMRSS] and percentage of body surface area) and several patient\u2010reported outcome measures assessing patients\u2019 skin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Posttreatment, the average MMRSS score decreased from mean \u00b1 SD 13.6 \u00b1 2.6 to 10.3 \u00b1 1.9; <jats:italic>P<\/jats:italic> = 0.003. There were also significant improvements in skin flexibility (mean \u00b1 SD 5.4 \u00b1 0.8 to 3.2 \u00b1 0.7; <jats:italic>P<\/jats:italic> = 0.003) and softening (mean \u00b1 SD 4.9 \u00b1 0.9 to 2.6 \u00b1 0.6; <jats:italic>P<\/jats:italic> = 0.022). Baseline levels of Tc17 cells (CD8+CCR6+CXCR3+CCR4\u2013) correlated with the extent of skin involvement as measured by MMRSS pretreatment (r = 0.69, <jats:italic>P<\/jats:italic> = 0.012) and decreased after IVIG therapy (mean \u00b1 SD 3.4% \u00b1 3.2% to 1.3% \u00b1 1.7%; <jats:italic>P<\/jats:italic> = 0.008). Posttreatment analysis of RNA in skin tissue revealed a decrease in gene expression of transforming growth factor \u03b2 (TGF\u03b2) cytokines as well as several interferon\u2010inducible proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This open\u2010label study further supports the evidence that patients with SMX respond both objectively and subjectively to IVIG therapy. Biologic studies suggest a role for T lymphocytes in the pathogenesis of the disease and reveal the potential significance of TGF\u03b2 and interferon pathways.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr.23908","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T07:20:01Z","timestamp":1555917601000},"page":"761-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Clinical and Molecular Phenotyping in Scleromyxedema Pretreatment and Posttreatment With Intravenous Immunoglobulin"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-8392","authenticated-orcid":false,"given":"Christopher A.","family":"Mecoli","sequence":"first","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"C. Conover","family":"Talbot","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fava","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Cheadle","sequence":"additional","affiliation":[{"name":"Elsevier, Washington, DC, and Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Boin","sequence":"additional","affiliation":[{"name":"University of California  San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4864-4011","authenticated-orcid":false,"given":"Laura K.","family":"Hummers","sequence":"additional","affiliation":[{"name":"Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40674-016-0038-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000118"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.53.3063"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.01.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2012.01882.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.12.021"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-017-8625-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0b013e3181630835"},{"key":"e_1_2_7_10_1","first-page":"263","article-title":"Intravenous immunoglobulin therapy for scleromyxedema: a case report and review of literature","volume":"9","author":"Sroa N","year":"2010","journal-title":"J Drugs Dermatol"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14244"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2001.111630"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0722-x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63681"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014108"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-622662"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900368"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.11.010"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.137"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.07.029"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10363"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4823"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38288"},{"key":"e_1_2_7_25_1","first-page":"S37","article-title":"Repeated teaching courses of the modified Rodnan skin score in systemic sclerosis","volume":"28","author":"Ionescu R","year":"2010","journal-title":"Clin Exp Rheumatol"}],"container-title":["Arthritis Care &amp; Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Facr.23908","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.23908","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/acr.23908","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/acr.23908","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T17:28:16Z","timestamp":1759426096000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/acr.23908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,14]]},"references-count":24,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/acr.23908"],"URL":"https:\/\/doi.org\/10.1002\/acr.23908","archive":["Portico"],"relation":{},"ISSN":["2151-464X","2151-4658"],"issn-type":[{"value":"2151-464X","type":"print"},{"value":"2151-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,14]]},"assertion":[{"value":"2018-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}