Background:Systemic juvenile idiopathic arthritis (sJIA) is one of the most perplexing diseases of childhood, with a wide range of presentation features and severity. Advances in treatment have improved the outcome, such as the use of modulators of proinflammatory cytokines and their receptors, but in a considerable number of children, especially in polyarticular or sJIA, refractoriness tends to be progressive. As of late, extreme cases have required Autologous Stem Cell Transplantation (ASCT) as a last resort.Objectives:To describe an extremely refractory clinical evolution in a sAIJ patient, the first one to be submitted to an ASCT for an autoinflammatory condition in Brasília, Brazil’s capital.Methods:Case ReportThe patient was classified according to the Pediatric International League of Associations for Rheumatology for sJIA.I.T.S.M, female, 15-years-old, was diagnosed with sJIA at 6 with the onset of polyarthritis, daily fever for 6 weeks, rash and enlargement of liver and spleen. In the initial investigation infectious and neoplastic causes were ruled out.The use of prednisone and methotrexate lead to a preliminary effective clinical control, however after an year, there was clinical deterioration and etanercept was associated, leading to a short term improvement. At that time, in addition to anti-tumour necrosis factor medications, no other biological drugs were available in Brazil.Despite some brief periods of clinical improvement, after different regimes, the patient manifested recurrent flares. Since the diagnosis she has already been treated with:[1]Methotrexate (2011 to 2014*, 2016 to 2020). *In 2015, it was replaced by Leflunomide (up to May 2016, discontinued due to intolerance);[2]Etanercept (2012);[3]Cyclosporine (August to December 2012);[4]Adalimumab (2013);[5]Tocilizumab (May 2014 to January 2015);[6]Canaquinumab (March 2015 to April 2016);[7]Mycophenolate Mofetil (February 2016, discontinued in May 2017 due to start of Cyclophosphamide);[8]Rituximab (May 2016 to April 2017);[9]Cyclophosphamide at a dose of 2 grams /m2 as well as Filgrastim for mobilization and collection of stem cells (May 2017, in a attempt of ASCT), but the parents were unable to reach a mutual agreement to consent to the continuation of this therapy;[10]Cyclophosphamide (500mg /m2) in a mensal scheme application for nine consecutive months since June 2017, once was observed a clinical improvement after the intensive immunosuppression previous to ASCT attempt;[11]Several courses of methylprednisolone and human immunoglobulin since the initial diagnosis;[12]Abatacept (November 2019 to October 2020);[13]ASCT was suggested again in 2020, this time with the consent of all family members.Results:An intensive immunosuppression [Cyclophosphamide and anti-thymocyte globulin (ATG)] followed by ASCT (October 2020) resulted in apparent sustained remission. The patient’s evolution since the transplant has been optimistic. She is currently on a low dose prednisone prescription. To ensure a less profound depletion of T cells, a better control of systemic disease and antimicrobial and antiviral prophylaxis after transplantation, slow tapering of corticosteroids were performed.Conclusion:The goal of hematopoietic stem cell transplantation in patients with autoimmune disease is to reprogram the immune system with the eradication of autoreactive cells, renew the population of regulatory T cells and restore the diversity of T cell receptor function.ASCT has been used in some refractory children with sJIA as well as hematologic malignancy and some progressive autoimmune diseases. However it is associated with significant morbidity and mortality, due to prolonged and severe depression of T cell immunity.References:[1]D.M.C. Brinkman et al. Arthritis Care & Research (2007)[2]Voltarelli Júlio C. et al. Rev. Bras. Hematol. Hemoter. (2010)[3]Angelo De Cata et al. Clin Exp Med. (2016)[4]Joost F. Swart et al. Nature Reviews Rheumatology (2017)Acknowledgements:We kindly thank the Hematology service of Hospital da Criança de Brasília, where the patient was subjected to the autologous stem-cell transplantation.Disclosure of Interests:None declared
Decrease of Skin Infiltrating and Circulating CCR10+ T Cells Coincides with Clinical Improvement after Topical Tacrolimus in Omenn Syndrome
