{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:45:50Z","timestamp":1790279150374,"version":"4.1.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T00:00:00Z","timestamp":1660003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Symptomatic vitamin C deficiency, scurvy, is a relatively rare disease in developed countries, but it has been reported in patients with autism spectrum disorder or developmental delay who tend to have selective diets. Patients with scurvy often demonstrate musculoskeletal manifestations with unknown pathophysiology. Herein, we report a case of scurvy in an 11-year-old boy who presented with iron-deficiency anaemia, systemic osteomyelitis, myositis predominantly in the lower extremities, and right ventricular volume overload with mild pulmonary hypertension and was diagnosed with scurvy. He had a mild developmental disorder and a selective diet, which resulted in severe vitamin C deficiency. He received intravenous and oral vitamin C supplementation, which relieved his arthralgia and muscle pain in a week. Following 4\u2009months of vitamin C supplementation, he demonstrated no abnormal manifestations on laboratory or imaging examination and recovered without sequelae. Inflammatory cytokine and chemokine evaluations demonstrated elevated levels of interleukin (IL)-6, IL-17A, and IL-23, which are associated with T-helper (Th) 17 cell activation. This study is the first to suggest the association between the inflammation seen in scurvy, rheumatic manifestations in the patient, and Th17 cell activation. Further analysis of the association between the inflammation and vitamin C supplementation may contribute to new insights for the comprehension and treatment of other inflammatory diseases, such as rheumatic diseases.<\/jats:p>","DOI":"10.1093\/mrcr\/rxac059","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T08:08:11Z","timestamp":1660032491000},"page":"302-306","source":"Crossref","is-referenced-by-count":5,"title":["Rheumatologic manifestations with elevated levels of IL-6, IL-17A, and IL-23 in a patient with scurvy"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-4874","authenticated-orcid":false,"given":"Masahiro","family":"Ueki","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keita","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo, Hokkaid\u00f4, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo, Hokkaid\u00f4, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ohata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takiko","family":"Nobuta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichiro","family":"Takezaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Manabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"},{"name":"Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo, Hokkaid\u00f4, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital , Sapporo, Japan"},{"name":"Department of Pediatrics, Faculty of Medicine and Graduate School of Medicine, Hokkaido University , Sapporo, Hokkaid\u00f4, Japan"},{"name":"Department of Food and Human Wellness, Rakuno Gakuen University , Ebetsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,9]]},"reference":[{"key":"2023010315532604500_R1","doi-asserted-by":"publisher","DOI":"10.3390\/nu13020615","article-title":"Vitamin C-sources, physiological role, kinetics, deficiency, use, toxicity, and determination","volume":"13","author":"Dosed\u011bl","year":"2021","journal-title":"Nutrients"},{"key":"2023010315532604500_R2","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jcot.2014.12.003","article-title":"Scurvy in pediatric age group - a disease often forgotten?","volume":"6","author":"Agarwal","year":"2015","journal-title":"J Clin Orthop Trauma"},{"key":"2023010315532604500_R3","doi-asserted-by":"publisher","first-page":"7180","DOI":"10.4049\/jimmunol.165.12.7180","article-title":"Vitamin C inhibits NF-kappa B activation by TNF via the activation of p38 mitogen-activated protein kinase","volume":"165","author":"Bowie","year":"2000","journal-title":"J Immunol (Baltimore, Md: 1950)"},{"key":"2023010315532604500_R4","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1182\/blood.V99.9.3205","article-title":"Vitamin C inhibits granulocyte macrophage-colony-stimulating factor-induced signaling pathways","volume":"99","author":"C\u00e1rcamo","year":"2002","journal-title":"Blood"},{"key":"2023010315532604500_R5","doi-asserted-by":"publisher","first-page":"12995","DOI":"10.1021\/bi0263210","article-title":"Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation","volume":"41","author":"C\u00e1rcamo","year":"2002","journal-title":"Biochemistry"},{"key":"2023010315532604500_R6","doi-asserted-by":"publisher","first-page":"3405","DOI":"10.2147\/DDDT.S83144","article-title":"Effect of vitamin C on inflammation and metabolic markers in hypertensive and\/or diabetic obese adults: a randomized controlled trial","volume":"9","author":"Ellulu","year":"2015","journal-title":"Drug Des Devel Ther"},{"key":"2023010315532604500_R7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1556\/1886.2019.00016","article-title":"Immunomodulatory and antimicrobial effects of vitamin C","volume":"9","author":"Mousavi","year":"2019","journal-title":"Eur J Microbiol Immunol (Bp)"},{"key":"2023010315532604500_R8","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-020-02730-w","article-title":"The neuropsychiatric effects of vitamin C deficiency: a systematic review","volume":"20","author":"Plevin","year":"2020","journal-title":"BMC Psychiatry"},{"key":"2023010315532604500_R9","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.semarthrit.2010.10.005","article-title":"Rheumatic manifestations of scurvy: a report of three recent cases in a major urban center and a review","volume":"41","author":"Mertens","year":"2011","journal-title":"Semin Arthritis Rheum"},{"key":"2023010315532604500_R10","doi-asserted-by":"publisher","first-page":"e1699","DOI":"10.1542\/peds.2012-3054","article-title":"Pulmonary hypertension associated with scurvy and vitamin deficiencies in an autistic child","volume":"132","author":"Duvall","year":"2013","journal-title":"Pediatrics"},{"key":"2023010315532604500_R11","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-015-0020-1","article-title":"Childhood scurvy: an unusual cause of refusal to walk in a child","volume":"13","author":"Alqanatish","year":"2015","journal-title":"Pediatr Rheumatol Online J"},{"key":"2023010315532604500_R12","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jpeds.2018.12.068","article-title":"Pulmonary hypertension secondary to scurvy in a developmentally typical child","volume":"208","author":"Frank","year":"2019","journal-title":"J Pediatr"},{"key":"2023010315532604500_R13","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1213\/XAA.0000000000001087","article-title":"Pulmonary hypertensive crisis during general anesthesia in a 3-year-old autistic boy with undiagnosed scurvy, undergoing cardiac catheterization: a case report","volume":"13","author":"Ichiyanagi","year":"2019","journal-title":"A A Pract"},{"key":"2023010315532604500_R14","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-2824","article-title":"Scurvy due to selective diet in a seemingly healthy 4-year-old boy","volume":"144","author":"Nastro","year":"2019","journal-title":"Pediatrics"},{"key":"2023010315532604500_R15","doi-asserted-by":"publisher","DOI":"10.1186\/s12969-020-00439-4","article-title":"Vitamin C deficiency mimicking inflammatory bone disease of the hand","volume":"18","author":"Liebling","year":"2020","journal-title":"Pediatr Rheumatol Online J"},{"key":"2023010315532604500_R16","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.jpeds.2019.10.059","article-title":"Scurvy masquerading as juvenile idiopathic arthritis or vasculitis with elevated inflammatory markers: a case series","volume":"218","author":"Perkins","year":"2020","journal-title":"J Pediatr"},{"key":"2023010315532604500_R17","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.immuni.2015.12.003","article-title":"Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions","volume":"43","author":"Patel","year":"2015","journal-title":"Immunity"},{"key":"2023010315532604500_R18","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1042\/BST20180169","article-title":"Vitamin C and immune cell function in inflammation and cancer","volume":"46","author":"Ang","year":"2018","journal-title":"Biochem Soc Trans"},{"key":"2023010315532604500_R19","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/JLB.1MR1219-245R","article-title":"A comparative view on vitamin C effects on alphabeta- versus gammadelta T-cell activation and differentiation","volume":"107","author":"Peters","year":"2020","journal-title":"J Leukoc Biol"},{"key":"2023010315532604500_R20","doi-asserted-by":"publisher","first-page":"6056","DOI":"10.1073\/pnas.1919893117","article-title":"Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism","volume":"117","author":"Cribbs","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023010315532604500_R21","doi-asserted-by":"publisher","first-page":"49","DOI":"10.5483\/BMBRep.2017.50.1.193","article-title":"Vitamin C enhances the expression of IL17 in a Jmjd2-dependent manner","volume":"50","author":"Song","year":"2017","journal-title":"BMB Rep"},{"key":"2023010315532604500_R22","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.ijscr.2020.03.002","article-title":"Scurvy: forgotten diagnosis, but still exist","volume":"68","author":"Miraj","year":"2020","journal-title":"Int J Surg Case Rep"},{"key":"2023010315532604500_R23","doi-asserted-by":"publisher","first-page":"71","DOI":"10.5114\/ceji.2014.42128","article-title":"Imbalance of Th17 and T-regulatory cells in peripheral blood and synovial fluid in treatment naive children with juvenile idiopathic arthritis","volume":"39","author":"Szymanska-Kaluza","year":"2014","journal-title":"Cent Eur J Immunol"},{"key":"2023010315532604500_R24","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1093\/rheumatology\/kez252","article-title":"Using peripheral blood immune signatures to stratify patients with adult and juvenile inflammatory myopathies","volume":"59","author":"Wilkinson","year":"2020","journal-title":"Rheumatology (Oxford)"},{"key":"2023010315532604500_R25","doi-asserted-by":"publisher","first-page":"1311","DOI":"10.1038\/oby.2005.159","article-title":"Diet induction of monocyte chemoattractant protein-1 and its impact on obesity","volume":"13","author":"Chen","year":"2005","journal-title":"Obes Res"}],"container-title":["Modern Rheumatology Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/mrcr\/advance-article-pdf\/doi\/10.1093\/mrcr\/rxac059\/45534694\/rxac059.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mrcr\/article-pdf\/7\/1\/302\/48482464\/rxac059.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/mrcr\/article-pdf\/7\/1\/302\/48482464\/rxac059.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T15:57:09Z","timestamp":1672761429000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mrcr\/article\/7\/1\/302\/6658562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,9]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,8,9]]},"published-print":{"date-parts":[[2023,1,3]]}},"URL":"https:\/\/doi.org\/10.1093\/mrcr\/rxac059","relation":{},"ISSN":["2472-5625"],"issn-type":[{"value":"2472-5625","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,1]]},"published":{"date-parts":[[2022,8,9]]}}}