{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:47:47Z","timestamp":1780638467210,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Medical Research Program","award":["CMRPG8M0401"],"award-info":[{"award-number":["CMRPG8M0401"]}]},{"name":"Chang Gung Medical Research Program","award":["CMRPG8K0731"],"award-info":[{"award-number":["CMRPG8K0731"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Small-fiber neuropathy (SFN) is suggested to be involved in the pathogenesis of some types of autoimmune connective tissue diseases. SFN with a reduction in epidermal nerve fibers might affect sensory fibers and cause neuropathic symptoms, such as pruritus and pain, which are common in both dermatomyositis (DM) and cutaneous lupus erythematosus (CLE). Nerve growth factor (NGF) has been recognized as important in nociception by regulating epidermal nerve fiber density and sensitizing the peripheral nervous system. The present study aimed to investigate whether SFN was associated with the cutaneous manifestations of DM and CLE. We also investigated the relationship between SFN and axon guidance molecules, such as NGF, amphiregulin (AREG), and semaphorin (Sema3A) in DM and CLE. To explore the molecular signaling, interleukin (IL)-18 and IL-31, which have been implicated in the cutaneous manifestation and neuropathic symptoms in DM, were examined in keratinocytes. Our results revealed that intraepidermal nerve fiber density (IENFD) was unchanged in patients with DM, but significantly reduced in IENFD in patients with CLE compared with healthy control. Increased epidermal expression of NGF and decreased expression of Sema3A were demonstrated in patients with DM. Furthermore, IL-18 and IL-31 both induced the production of NGF from keratinocytes. Taken together, IL-18 and IL-31 mediated epidermal NGF expression might contribute to the cutaneous neuropathic symptoms in DM, while SFN might be important for CLE.<\/jats:p>","DOI":"10.3390\/ijms23169030","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T01:47:21Z","timestamp":1660528041000},"page":"9030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Increased Epidermal Nerve Growth Factor without Small-Fiber Neuropathy in Dermatomyositis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7807-4670","authenticated-orcid":false,"given":"Lai-San","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-3874","authenticated-orcid":false,"given":"Chih-Hung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ta","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Fooyin University Hospital, Pingtung 928, Taiwan"},{"name":"Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"641746","DOI":"10.3389\/fmed.2021.641746","article-title":"Neuropathic itch: Routes to clinical diagnosis","volume":"8","author":"Pereira","year":"2021","journal-title":"Front. 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