{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T10:02:39Z","timestamp":1790071359966,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Small fiber neuropathy (SFN) is a clinically heterogeneous and difficult\u2010to\u2010manage condition for which intravenous immunoglobulin (IVIG) is increasingly used despite inconsistent evidence and substantial cost. We therefore systematically evaluated the clinical effectiveness of IVIG in SFN, with attention to the variation across etiological subtypes. In accordance with PRISMA 2020 guidelines, the review protocol was registered in PROSPERO (CRD420251247780). PubMed, Embase, and the Cochrane Library databases were searched from inception to 31 August 2025. Eligible studies included adults with clinically or histologically confirmed SFN receiving IVIG, reporting at least one predefined outcome. Two reviewers independently screened and extracted data. Risk of bias was assessed, and certainty of evidence was evaluated using GRADE. Due to heterogeneity, a narrative synthesis was performed. A total of seven studies (2 randomized controlled trials [RCTs], 5 observational studies) involving 165 IVIG\u2010treated patients were included. RCTs in idiopathic or broadly defined SFN showed no significant benefit of IVIG over placebo in pain reduction, autonomic symptoms, quality of life, or intraepidermal nerve fiber density. In contrast, observational studies reported improvements in pain, autonomic function, and, in some cases, nerve fiber density, particularly in autoimmune\u2010associated SFN subtypes. However, these studies were limited by small sample sizes, lack of controls, and high risk of bias. GRADE assessment indicated low to very low certainty of evidence across outcomes. Current evidence does not support routine IVIG use in SFN. Apparent benefits in selected immune\u2010mediated subtypes remain inconclusive and warrant further research with biologically stratified, adequately powered trials.<\/jats:p>","DOI":"10.1111\/jns.70138","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:17:30Z","timestamp":1783556250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of Intravenous Immunoglobulin Therapy for Small Fiber Neuropathy: A Systematic Review of Current Clinical Evidence"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8561-2513","authenticated-orcid":false,"given":"Qin Xiang","family":"Ng","sequence":"first","affiliation":[{"name":"Saw Swee Hock School of Public Health National University of Singapore and National University Health System  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klarisse Man Ling","family":"Neo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health The University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3157-9703","authenticated-orcid":false,"given":"Boxuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"NUS Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao Cheng","family":"Yeo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health The University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phireethi Natarajan","family":"Anitha","sequence":"additional","affiliation":[{"name":"School of Medicine The University of Western Australia  Crawley Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-3707","authenticated-orcid":false,"given":"Amanda Chee Yun","family":"Chan","sequence":"additional","affiliation":[{"name":"NUS Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Division of Neurology, University Medicine Cluster National University Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-019-1020-1"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-011-0181-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30329-0"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24969"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-10033-z"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2010.09.015"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27745"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000498858"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26268"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2023.04.002"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-015-0391-5"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011919"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756285617744484"},{"issue":"17","key":"e_1_2_12_16_1","article-title":"IVIG Effective in Non\u2010Length Dependent Skin Biopsies in Small Fiber Neuropathy With Plexin D1, TS\u2010HDS, and FGFR\u20103 Antibodies","volume":"102","author":"Zeidman L.","year":"2024","journal-title":"Neurology"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-33059-7"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27245"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003000"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurpra.2023.104547"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.615656"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2024.09.002"}],"container-title":["Journal of the Peripheral Nervous 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