{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:45:56Z","timestamp":1791909956141,"version":"4.3.4"},"reference-count":14,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:p>Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) is associated with recessive mutations in SLC29A3, encoding the equilibrative nucleoside transporter hENT3 expressed in mitochondria, causing PHID and H syndromes, familial Rosai-Dorfman disease, and histiocytosis-lymphadenopathy-plus syndrome. Autoinflammation is increasingly recognized in these syndromes. We previously reported a 16-year-old girl with PHID syndrome associated with severe autoinflammation that was recalcitrant to interleukin-1 and tumor necrosis factor-\u03b1 blockade. Tocilizumab is a humanized, monoclonal, anti-human interleukin-6 receptor antibody routinely used to treat arthritis in children and adults. Herein we report the first case of successful treatment of PHID syndrome using tocilizumab. Before commencing tocilizumab, there was evidence of significant systemic inflammation, and progressive sclerodermatous changes (physician global assessment [PGA] 7\/10). Twelve weeks after starting tocilizumab (8 mg\/kg every 2 weeks, intravenously) systemic inflammatory symptoms improved, and acute phase response markers normalized; serum amyloid A reduced from 178 to 8.4 mg\/L. After a dose increase to 12 mg\/kg every 2 weeks her energy levels, appetite, fevers, and night sweats further improved. Less skin tightness (PGA 5\/10) was documented 12 months later. This excellent clinical and serological response was sustained over 48 months, and cutaneous sclerosis had improved further (PGA 3\/10). Her height remained well below the 0.4th centile, and tocilizumab also had no impact on her diabetes or exocrine pancreatic insufficiency. Although the mechanism of autoinflammation of PHID remains uncertain, we suggest that tocilizumab should be the first choice when considering treatment of the autoinflammatory or cutaneous manifestations of this genetic disease.<\/jats:p>","DOI":"10.1542\/peds.2016-3148","type":"journal-article","created":{"date-parts":[[2017,10,27]],"date-time":"2017-10-27T03:30:15Z","timestamp":1509075015000},"source":"Crossref","is-referenced-by-count":35,"title":["Tocilizumab for the Treatment of SLC29A3 Mutation Positive PHID Syndrome"],"prefix":"10.1542","volume":"140","author":[{"given":"Nadia K.","family":"Rafiq","sequence":"first","affiliation":[{"name":"Department of Paediatric Rheumatology, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Hussain","sequence":"additional","affiliation":[{"name":"Developmental Endocrinology Research Group, Molecular Genetics Unit, Great Ormond Street Institute of Child Health, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Brogan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Rheumatology, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2017,11,1]]},"reference":[{"issue":"9\u201310","key":"2021121100384327200_B1","first-page":"877","article-title":"Pigmentary hypertrichosis and non-autoimmune insulin-dependent diabetes mellitus (PHID) syndrome is associated with severe chronic inflammation and cardiomyopathy, and represents a new monogenic autoinflammatory syndrome.","volume":"26","author":"Senniappan","year":"2013","journal-title":"J Pediatr Endocrinol 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trial.","volume":"74","author":"Brunner","year":"2015","journal-title":"Ann Rheum Dis"},{"issue":"12","key":"2021121100384327200_B8","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1093\/hmg\/ddp161","article-title":"SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway.","volume":"18","author":"Cliffe","year":"2009","journal-title":"Hum Mol Genet"},{"issue":"36","key":"2021121100384327200_B9","doi-asserted-by":"crossref","first-page":"28343","DOI":"10.1074\/jbc.M110.109199","article-title":"Human equilibrative nucleoside transporter-3 (hENT3) spectrum disorder mutations impair nucleoside transport, protein localization, and stability.","volume":"285","author":"Kang","year":"2010","journal-title":"J Biol Chem"},{"issue":"2","key":"2021121100384327200_B10","doi-asserted-by":"crossref","first-page":"e1000833","DOI":"10.1371\/journal.pgen.1000833","article-title":"Mutations in SLC29A3, encoding an equilibrative nucleoside transporter ENT3, cause a familial histiocytosis syndrome (Faisalabad histiocytosis) and familial Rosai-Dorfman disease.","volume":"6","author":"Morgan","year":"2010","journal-title":"PLoS Genet"},{"issue":"2","key":"2021121100384327200_B11","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1097\/DAD.0b013e3181b28572","article-title":"H syndrome: recently defined genodermatosis with distinct histologic features. A morphological, histochemical, immunohistochemical, and ultrastructural study of 10 cases.","volume":"32","author":"Doviner","year":"2010","journal-title":"Am J Dermatopathol"},{"issue":"6064","key":"2021121100384327200_B12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1126\/science.1213682","article-title":"Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis.","volume":"335","author":"Hsu","year":"2012","journal-title":"Science"},{"issue":"2","key":"2021121100384327200_B13","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/01.RHU.0000442576.41537.de","article-title":"Interleukin 6 blockade for hyperimmunoglobulin D and periodic fever syndrome.","volume":"20","author":"Shendi","year":"2014","journal-title":"J Clin Rheumatol"},{"issue":"3","key":"2021121100384327200_B14","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1476-5381.2009.00206.x","article-title":"Current status and challenges of cytokine pharmacology.","volume":"157","author":"Z\u00eddek","year":"2009","journal-title":"Br J Pharmacol"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2016-3148\/908424\/peds_20163148.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/doi\/10.1542\/peds.2016-3148\/908424\/peds_20163148.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T03:20:24Z","timestamp":1639192824000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/140\/5\/e20163148\/37763\/Tocilizumab-for-the-Treatment-of-SLC29A3-Mutation"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,1]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,11,1]]},"published-print":{"date-parts":[[2017,11,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2016-3148","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,1]]},"article-number":"e20163148"}}