{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:37:48Z","timestamp":1784162268676,"version":"3.55.0"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation primarily driven by the cytokine interferon gamma. It can be either a genetic or acquired disorder associated with infection, malignancy, and rheumatologic disorders. Trisomy 21 can express a wide range of phenotypes which include immune dysregulation and shares inherent pathophysiology with a group of disorders termed interferonopathies. Knowledge of this overlap in seemingly unrelated conditions could provide a basis for future research, and most importantly, alternative therapeutic interventions in acute life threatening clinical scenarios. Herein, we describe two patients with trisomy 21 presenting with HLH that was refractory to conventional treatment. Both patients were successfully managed with novel interventions targeting the interferon pathway.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We describe a 17-month-old male and 15-month-old female with trisomy 21 presenting with a myriad of signs and symptoms including fever, rash, cytopenias, and hyperferritinemia, both ultimately diagnosed with HLH. Each had relapsing, refractory HLH over time requiring several admissions to the hospital receiving conventional high dose corticosteroids and interleukin-1 inhibition therapy. Successful steroid-free remission was achieved after targeting interferon inhibition with emapalumab induction followed by long-term maintenance on baricitinib.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>To our knowledge, these are the first reported cases of relapsed, refractory HLH in patients with trisomy 21 successfully treated with emapalumab and transitioned to a steroid-sparing regimen with oral baricitinib for maintenance therapy. Trisomy 21 autoimmunity and HLH are both thought to be driven by interferon gamma. Targeting therapy toward interferon signaling in both HLH and autoimmunity in trisomy 21 may have potential therapeutic benefits. Further investigation is needed to determine if trisomy 21 may predispose to the development of HLH given this common pathway.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12969-022-00764-w","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T12:03:38Z","timestamp":1668773018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hemophagocytic lymphohistocytosis in trisomy 21: successful treatment with interferon inhibition"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6392-7757","authenticated-orcid":false,"given":"Allison","family":"Guild","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Fritch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachit","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Reinhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Acquazzino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"764_CR1","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.1056\/NEJMra1706537","volume":"382","author":"MJ Bull","year":"2020","unstructured":"Bull MJ. Down syndrome. N Engl J Med. 2020;382:2344\u201352.","journal-title":"N Engl J Med"},{"issue":"13","key":"764_CR2","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2147\/PHMT.S282646","volume":"14","author":"JT Jones","year":"2022","unstructured":"Jones JT, Kitchen J, Talib N. Down syndrome-associated arthritis (DA): diagnostic and management challenges. Pediatric Health Med Ther. 2022;14(13):53\u201362.","journal-title":"Pediatric Health Med Ther"},{"issue":"2","key":"764_CR3","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.1365-2249.2009.03890.x","volume":"156","author":"MA Kusters","year":"2009","unstructured":"Kusters MA, Verstegen RH, Gemen EF, de Vries E. Intrinsic defect of the immune system in children with Down syndrome: a review. Clin Exp Immunol. 2009;156(2):189\u201393.","journal-title":"Clin Exp Immunol"},{"key":"764_CR4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3389\/fped.2020.00073","volume":"8","author":"D Huggard","year":"2020","unstructured":"Huggard D, Doherty DG, Molloy EJ. Immune dysregulation in children with Down syndrome. Front Pediatr. 2020;8:73.","journal-title":"Front Pediatr"},{"issue":"2","key":"764_CR5","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1684\/ecn.2012.0307","volume":"23","author":"M Nateghi Rostami","year":"2012","unstructured":"Nateghi Rostami M, Douraghi M, Miramin Mohammadi A, Nikmanesh B. Altered serum pro-inflammatory cytokines in children with Down\u2019s syndrome. Eur Cytokine Netw. 2012;23(2):64\u20137.","journal-title":"Eur Cytokine Netw"},{"issue":"48","key":"764_CR6","doi-asserted-by":"publisher","first-page":"84489","DOI":"10.18632\/oncotarget.21060","volume":"8","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Che M, Yuan J, et al. Aberrations in circulating inflammatory cytokine levels in patients with Down syndrome: a meta-analysis. Oncotarget. 2017;8(48):84489\u201396.","journal-title":"Oncotarget"},{"key":"764_CR7","doi-asserted-by":"publisher","first-page":"14818","DOI":"10.1038\/s41598-017-13858-3","volume":"1","author":"KD Sullivan","year":"2017","unstructured":"Sullivan KD, Evans D, Pandey A, et al. Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation. Sci Rep. 2017;1:14818.","journal-title":"Sci Rep"},{"issue":"48","key":"764_CR8","doi-asserted-by":"publisher","first-page":"24231","DOI":"10.1073\/pnas.1908129116","volume":"116","author":"P Araya","year":"2019","unstructured":"Araya P, Waugh KA, Sullivan KD, N\u00fa\u00f1ez NG, Roselli E, Smith KP, Granrath RE, Rachubinski AL, Enriquez Estrada B, Butcher ET, Minter R, Tuttle KD, Bruno TC, Maccioni M, Espinosa JM. Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity. Proc Natl Acad Sci USA. 2019;116(48):24231\u201341.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"6","key":"764_CR9","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s10875-020-00803-9","volume":"40","author":"XF Kong","year":"2020","unstructured":"Kong XF, Worley L, Rinchai D, Bondet V, Jithesh PV, Goulet M, Nonnotte E, Rebillat AS, Conte M, Mircher C, G\u00fcrtler N, Liu L, Migaud M, Elanbari M, Habib T, Ma CS, Bustamante J, Abel L, Ravel A, Lyonnet S, Munnich A, Duffy D, Chaussabel D, Casanova JL, Tangye SG, Boisson-Dupuis S, Puel A. Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome. J Clin Immunol. 2020;40(6):807\u201319.","journal-title":"J Clin Immunol"},{"key":"764_CR10","doi-asserted-by":"publisher","first-page":"16220","DOI":"10.7554\/eLife.16220","volume":"5","author":"KD Sullivan","year":"2016","unstructured":"Sullivan KD, et al. Trisomy 21 consistently activates the interferon response. Elife. 2016;5:16220.","journal-title":"Elife"},{"key":"764_CR11","doi-asserted-by":"publisher","unstructured":"Waugh KA, Minter R, Baxter J, et al. Interferon receptor gene dosage determines diverse hallmarks of Down syndrome. bioRxiv. 2022. https:\/\/doi.org\/10.1101\/2022.02.03.478982.","DOI":"10.1101\/2022.02.03.478982"},{"issue":"2","key":"764_CR12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/pbc.21039","volume":"48","author":"JI Henter","year":"2007","unstructured":"Henter JI, Horne A, Aric\u00f3 M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124\u201331.","journal-title":"Pediatr Blood Cancer"},{"issue":"6","key":"764_CR13","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1309\/AJCP4ZDKJ4ICOUAT","volume":"139","author":"FG Rosado","year":"2013","unstructured":"Rosado FG, Kim AS. Hemophagocytic Lymphohistiocytosis: an update on diagnosis and pathogenesis. Am J Clin Pathol. 2013;139(6):713\u201327.","journal-title":"Am J Clin Pathol"},{"key":"764_CR14","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1182\/blood-2011-03-278127","volume":"118","author":"MB Jordan","year":"2011","unstructured":"Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood. 2011;118:4041\u201352.","journal-title":"Blood"},{"key":"764_CR15","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1159\/000312628","volume":"153","author":"DS Selmi","year":"2010","unstructured":"Selmi DS, Teuber SS, et al. Macrophage activation syndrome in autoimmune disease. Int Arch Allergy Immunol. 2010;153:109\u201320.","journal-title":"Int Arch Allergy Immunol"},{"issue":"3","key":"764_CR16","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1182\/blood-2003-10-3413","volume":"104","author":"MB Jordan","year":"2004","unstructured":"Jordan MB, Hildeman D, Kappler J, Marrack P. An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder. Blood. 2004;104(3):735\u201343.","journal-title":"Blood"},{"key":"764_CR17","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1182\/blood-2017-06-788349","volume":"130","author":"E Bergsten","year":"2017","unstructured":"Bergsten E, Horne A, Aric\u00f3 M, et al. Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood. 2017;130:2728\u201338.","journal-title":"Blood"},{"key":"764_CR18","unstructured":"U.S. Food & Drug Administration. FDA approves first treatment specifically for patients with rare and life-threatening type of immune disease. 2018. https:\/\/www.fda.gov. Accessed 10 Jan 2022."},{"issue":"7","key":"764_CR19","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1016\/j.celrep.2019.10.038","volume":"29","author":"KA Waugh","year":"2019","unstructured":"Waugh KA, Araya P, Pandey A, Jordan KR, Smith KP, Granrath RE, Khanal S, Butcher ET, Estrada BE, Rachubinski AL, McWilliams JA, Minter R, Dimasi T, Colvin KL, Baturin D, Pham AT, Galbraith MD, Bartsch KW, Yeager ME, Porter CC, Sullivan KD, Hsieh EW, Espinosa JM. Mass Cytometry Reveals Global Immune Remodeling with Multi-lineage Hypersensitivity to Type I Interferon in Down Syndrome. Cell Rep. 2019;29(7):1893\u2013908.","journal-title":"Cell Rep"},{"issue":"8","key":"764_CR20","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1007\/s00277-017-2993-y","volume":"96","author":"M Lin","year":"2017","unstructured":"Lin M, Park S, Hayden A, Giustini D, Trinkaus M, Pudek M, Mattman A, Schneider M, Chen LYC. Clinical utility of soluble interleukin-2 receptor in hemophagocytic syndromes: a systematic scoping review. Ann Hematol. 2017;96(8):1241\u201351.","journal-title":"Ann Hematol"},{"key":"764_CR21","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/nrrheum.2009.237","volume":"6","author":"J Hall","year":"2010","unstructured":"Hall J, Rosen A. Type I interferons: crucial participants in disease amplification in autoimmunity. Nat Rev Rheumatol. 2010;6:40\u20139.","journal-title":"Nat Rev Rheumatol"},{"key":"764_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.631329","author":"DM D'Angelo","year":"2021","unstructured":"D\u2019Angelo DM, Di Filippo P, Breda L, Chiarelli F. Type I Interferonopathies in Children: An Overview. Front Pediatr. 2021. https:\/\/doi.org\/10.3389\/fped.2021.631329.","journal-title":"Front Pediatr"},{"key":"764_CR23","doi-asserted-by":"publisher","unstructured":"Volpi S, Picco P, Caorsi R, et al. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol. 2016.https:\/\/doi.org\/10.1186\/s12969-016-0094-4","DOI":"10.1186\/s12969-016-0094-4"},{"key":"764_CR24","doi-asserted-by":"publisher","first-page":"5187","DOI":"10.2147\/JIR.S280953","volume":"14","author":"H Chung","year":"2021","unstructured":"Chung H, Green PH, Wang TC, Kong XF. Interferon-driven immune dysregulation in Down syndrome: a review of the evidence. J Inflamm Res. 2021;14:5187\u2013200.","journal-title":"J Inflamm Res"},{"key":"764_CR25","doi-asserted-by":"crossref","unstructured":"Lazea C, Blag C. Hemophagocytic Lymphohistiocytosis Secondary to Mycoplasma Pneumoniae Infection in a Trisomy 21 girl. Revista Romana de Medicina de Laborator. 2018;26:113\u20137.","DOI":"10.1515\/rrlm-2017-0039"},{"key":"764_CR26","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1093\/jpids\/piaa148","volume":"10","author":"S Kim-Hellmuth","year":"2021","unstructured":"Kim-Hellmuth S, Hermann M, et al. SARS-CoV-2 triggering severe acute respiratory distress syndrome and secondary Hemophagocytic Lymphohistiocytosis in a 3-year-old child with Down syndrome. J Pediatric Infect Dis Soc. 2021;10:543\u20136.","journal-title":"J Pediatric Infect Dis Soc"},{"issue":"3","key":"764_CR27","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/0090-1229(84)90312-X","volume":"33","author":"MP Nair","year":"1984","unstructured":"Nair MP, Schwartz SA. Association of decreased T-cell-mediated natural cytotoxicity and interferon production in Down\u2019s syndrome. Clin Immunol Immunopathol. 1984;33(3):412\u201324.","journal-title":"Clin Immunol Immunopathol"},{"key":"764_CR28","first-page":"204","volume":"7","author":"AG Ugazio","year":"1990","unstructured":"Ugazio AG, Maccario R, Notarangelo LD, Burgio GR. Immunology of Down syndrome: a review. Am J Med Genet Suppl. 1990;7:204\u201312.","journal-title":"Am J Med Genet Suppl"},{"key":"764_CR29","first-page":"213","volume":"7","author":"A Cossarizza","year":"1990","unstructured":"Cossarizza A, Monti D, Montagnani G, Ortolani C, Masi M, Zannotti M, Franceschi C. Precocious aging of the immune system in Down syndrome: alteration of B lymphocytes, T-lymphocyte subsets, and cells with natural killer markers. Am J Med Genet Suppl. 1990;7:213\u20138.","journal-title":"Am J Med Genet Suppl"},{"key":"764_CR30","doi-asserted-by":"publisher","unstructured":"Tuttle KD, Waugh KA, Araya P, et al. JAK1 Inhibition Blocks Lethal Immune Hypersensitivity in a Mouse Model of Down Syndrome. Cell Rep. 2020.https:\/\/doi.org\/10.1016\/j.celrep.2020.108407","DOI":"10.1016\/j.celrep.2020.108407"},{"issue":"2","key":"764_CR31","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1002\/emmm.200900009","volume":"1","author":"J Pachlopnik Schmid","year":"2009","unstructured":"Pachlopnik Schmid J, Ho CH, Chr\u00e9tien F, et al. Neutralization of IFN-gamma defeats haemophagocytosis in LCMV-infected perforin- and Rab27a-deficient mice. EMBO Mol Med. 2009;1(2):112\u201324.","journal-title":"EMBO Mol Med"},{"key":"764_CR32","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1182\/blood-2016-02-700013","volume":"128","author":"S Maschalidi","year":"2016","unstructured":"Maschalidi S, Sepulveda FE, Garrigue A, et al. Therapeutic effect of JAK1\/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice. Blood. 2016;128:60\u201371.","journal-title":"Blood"},{"key":"764_CR33","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1182\/blood-2015-12-684399","volume":"127","author":"R Das","year":"2016","unstructured":"Das R, Guan P, Sprague L, et al. Janus kinase inhibition lessens inflammation and ameliorates disease in murine models of hemophagocytic lymphohistiocytosis. Blood. 2016;127:1666\u201375.","journal-title":"Blood"},{"issue":"19","key":"764_CR34","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1056\/NEJMoa1911326","volume":"382","author":"F Locatelli","year":"2020","unstructured":"Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti M-C, et al. Emapalumab in children with primary hemophagocytic lymphohistiocytosis. N Engl J Med. 2020;382(19):1811\u201322.","journal-title":"N Engl J Med"},{"key":"764_CR35","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1182\/blood-2021-147596","volume":"138","author":"F De Benedetti","year":"2021","unstructured":"De Benedetti F, Grom A, Bracaglia C, et al. Macrophage Activation Syndrome (MAS) in Systemic Juvenile Idiopathic Arthritis (sJIA): Treatment with Emapalumab, an Anti-Interferon Gamma (IFN\u03b3) Monoclonal Antibody. Blood. 2021;138:2058.","journal-title":"Blood"},{"issue":"14","key":"764_CR36","doi-asserted-by":"publisher","first-page":"887","DOI":"10.21037\/atm-20-3127","volume":"8","author":"JB Gabr","year":"2020","unstructured":"Gabr JB, Liu E, Mian S, Pillittere J, Bonilla E, Banki K, Perl A. Successful treatment of secondary macrophage activation syndrome with emapalumab in a patient with newly diagnosed adult-onset Still\u2019s disease: case report and review of the literature. Ann Transl Med. 2020;8(14):887.","journal-title":"Ann Transl Med"},{"issue":"1","key":"764_CR37","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1182\/bloodadvances.2018025858","volume":"3","author":"DT Lounder","year":"2019","unstructured":"Lounder DT, Bin Q, de Min C, Jordan MB. Treatment of refractory hemophagocytic lymphohistiocytosis with emapalumab despite severe concurrent infections. Blood Adv. 2019;3(1):47\u201350.","journal-title":"Blood Adv"},{"key":"764_CR38","unstructured":"Swedish Orphan Biovitrum. Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults with MAS in Still\u2019s or SLE. Identifier NCT05001737. https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05001737. Accessed 2 Feb 2022."},{"issue":"7","key":"764_CR39","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.3324\/haematol.2020.253781","volume":"106","author":"Q Zhang","year":"2021","unstructured":"Zhang Q, Wei A, Ma HH, Zhang L, Lian HY, Wang D, Zhao YZ, Cui L, Li WJ, Yang Y, Wang TY, Li ZG, Zhang R. A pilot study of ruxolitinib as a front-line therapy for 12 children with secondary hemophagocytic lymphohistiocytosis. Haematologica. 2021;106(7):1892\u2013901.","journal-title":"Haematologica"},{"issue":"3","key":"764_CR40","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.hemonc.2017.07.002","volume":"12","author":"JH Sin","year":"2019","unstructured":"Sin JH, Zangardi ML. Ruxolitinib for secondary hemophagocytic lymphohistiocytosis: First case report. Hematol Oncol Stem Cell Ther. 2019;12(3):166\u201370.","journal-title":"Hematol Oncol Stem Cell Ther"},{"issue":"5","key":"764_CR41","doi-asserted-by":"publisher","first-page":"e210","DOI":"10.3324\/haematol.2019.222471","volume":"105","author":"J Wang","year":"2020","unstructured":"Wang J, Wang Y, Wu L, Wang X, Jin Z, Gao Z, Wang Z. Ruxolitinib for refractory\/relapsed hemophagocytic lymphohistiocytosis. Haematologica. 2020;105(5):e210\u20132.","journal-title":"Haematologica"},{"issue":"12","key":"764_CR42","doi-asserted-by":"publisher","first-page":"614704","DOI":"10.3389\/fimmu.2021.614704","volume":"16","author":"C Keenan","year":"2021","unstructured":"Keenan C, Nichols KE, Albeituni S. Use of the JAK inhibitor Ruxolitinib in the treatment of Hemophagocytic Lymphohistiocytosis. Front Immunol. 2021;16(12):614704.","journal-title":"Front Immunol"},{"key":"764_CR43","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1182\/bloodadvances.2017007526","volume":"1","author":"L Broglie","year":"2017","unstructured":"Broglie L, Pommert L, Rao S, et al. Ruxolitinib for treatment of refractory hemophagocytic lymphohistiocytosis. Blood Adv. 2017;1:1533\u20136.","journal-title":"Blood Adv"},{"issue":"7","key":"764_CR44","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1172\/JCI98814","volume":"128","author":"GA Montealegre Sanchez","year":"2018","unstructured":"Montealegre Sanchez GA, Reinhardt A, Ramsey S, et al. JAK1\/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest. 2018;128(7):3041\u201352.","journal-title":"J Clin Invest"},{"key":"764_CR45","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.jdcr.2019.02.007","volume":"5","author":"AL Rachubinski","year":"2019","unstructured":"Rachubinski AL, Enriquez-Estrada B, Norris D, Dunnick CA, Boldrick JC, Espinosa JM. JAK inhibition in Down syndrome: two cases of therapeutic benefit for alopecia reata. JAAD Case Rep. 2019;5:365\u20137.","journal-title":"JAAD Case Rep"},{"key":"764_CR46","unstructured":"University of Colorado, Denver.\u00a0Tofacitinib for Immune Skin Conditions in Down Syndrome. Identifier NCT04246372.\u00a02020\u00a0https:\/\/clinicaltrials.gov\/ct2\/show\/record\/NCT04246372. Accessed 2 Feb 2022."}],"container-title":["Pediatric Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-022-00764-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12969-022-00764-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12969-022-00764-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T12:12:05Z","timestamp":1668773525000},"score":1,"resource":{"primary":{"URL":"https:\/\/ped-rheum.biomedcentral.com\/articles\/10.1186\/s12969-022-00764-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,18]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["764"],"URL":"https:\/\/doi.org\/10.1186\/s12969-022-00764-w","relation":{},"ISSN":["1546-0096"],"issn-type":[{"value":"1546-0096","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,18]]},"assertion":[{"value":"1 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent for publication has been obtained from patients\u2019 parents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"104"}}