ABSTRACT Autoimmune diseases are an important field for the development of bone marrow transplantation, or hematopoietic stem cell transplantation. In Europe alone, almost 3000 procedures have been registered so far. The Brazilian Society for Bone Marrow Transplantation (Sociedade Brasileira de Transplantes de Medula Óssea) organized consensus meetings for the Autoimmune Diseases Group, to review the available literature on hematopoietic stem cell transplantation for autoimmune diseases, aiming to gather data that support the procedure for these patients. Three autoimmune diseases for which there are evidence-based indications for hematopoietic stem cell transplantation are multiple sclerosis, systemic sclerosis and Crohn's disease. The professional stem cell transplant societies in America, Europe and Brazil (Sociedade Brasileira de Transplantes de Medula Óssea) currently consider hematopoietic stem cell transplantation as a therapeutic modality for these three autoimmune diseases. This article reviews the evidence available.

Abstract Background: In the past 20 years, hematopoietic stem cell transplantation (HSCT) has been investigated as treatment for systemic sclerosis (SSc). The goal of HSCT is to eradicate the autoreactive immune system, which is replaced by a new immune repertoire with long-lasting regulation and tolerance to autoantigens. Here, we describe the clinical outcomes of severe and refractory SSc patients that underwent HSCT at a single Brazilian center. Patients and methods: This is a longitudinal and retrospective study, including 70 adult SSc patients, with an established diagnosis of SSc, and who underwent autologous HSCT from 2009 to 2016. The procedure included harvesting and cryopreservation of autologous hematopoietic progenitor cells, followed by administration of an immunoablative regimen and subsequent infusion of the previously collected cells. Patients were evaluated immediately before transplantation, at 6 months and then yearly until at least 5-years of post-transplantation follow-up. At each evaluation time point, patients underwent clinical examination, including modified Rodnan's skin score (mRSS) assessment, echocardiography, high-resolution computed tomography of the lungs and pulmonary function. Results: Median (range) age was 35.9 (19–59), with 57 (81.4%) female and median (range) non-Raynaud's disease duration of 2 (1–7) years. Before transplantation, 96% of the patients had diffuse skin involvement, 84.2%, interstitial lung disease and 67%, positive anti-topoisomerase I antibodies. Skin involvement significantly improved, with a decline in mRSS at all post-transplantation time points until at least 5-years of follow-up. When patients with pre-HSCT interstitial lung disease were analyzed, there was an improvement in pulmonary function (forced vital capacity and diffusing capacity of lung for carbon monoxide) over the 5-year follow-up. Overall survival was 81% and progression-free survival was 70.5% at 8-years after HSCT. Three patients died due to transplant-related toxicity, 9 patients died over follow-up due to disease reactivation and one patient died due to thrombotic thrombocytopenic purpura. Conclusions: Autologous hematopoietic progenitor cell transplantation improves skin and interstitial lung involvement. These results are in line with the international experience and support HSCT as a viable therapeutic alternative for patients with severe and progressive systemic sclerosis.

Abstract Background The reproducibility and reliability of the modified Rodnan's Skin Score (mRSS) are debated due to investigator-related subjectivity. Here, we evaluate if durometry correlates with mRSS in patients with diffuse systemic sclerosis (SSc). Methods This cross-sectional study was conducted from December 2018 to June 2019, including 58 diffuse SSc patients. Two certified researchers, blind to each other's scores, performed the mRSS, followed by durometry at 17 predefined skin sites. For durometry and mRSS, individual scores per skin site were registered. Durometry and mRSS results measured by each researcher, as well as scores from different researchers, were compared. Skin thickness measurements from forearm skin biopsies were available in a subset of the patients, for comparisons. Statistical analyses included Cohen's Kappa Coefficient, Intraclass Correlation Coefficient, Kendall's Coefficient and Spearman's test. Results Mean (standard deviation, SD) patient age was 44.8 (12.9) years, and 88% were female. Inter-rater agreement varied from 0.88 to 0.99 (Intraclass correlation coefficient) for durometry, and 0.54 to 0.79 (Cohen's Kappa coefficient) for mRSS, according to the specific evaluated sites. When data were compared with skin thickness assessed in forearm biopsies, durometry correlated better with skin thickness than mRSS. Conclusion Durometry may be considered as an alternative method to quantify skin involvement in patients with diffuse SSc. The strong inter-rater agreement suggests that the method may be useful for the assessment of patients by multiple researchers, as in clinical trials.

INTRODUÇÃO: A hipermobilidade articular (HA) é uma condição clínica hereditária em que há aumento da elasticidade articular em movimentos passivos. Na população em geral, a frequência varia entre 10% e 20%, podendo ser estimada por métodos específicos como o Escore de Beighton, e o The five part questionnaire for identifying hipermobility, um questionário de autoavaliação para a identificação da HA. OBJETIVOS: Validar o The five part questionnaire for identifying hipermobility para a língua portuguesa e determinar sua sensibilidade e especificidade quando comparado ao escore de Beighton no diagnóstico da HA. MÉTODOS: O The five part questionnaire for identifying hipermobility foi traduzido para a língua portuguesa e aplicado em 2.523 universitários brasileiros. A seguir, o escore de Beighton foi aplicado em uma amostra de 394 estudantes selecionados aleatoriamente do primeiro grupo, a fim de estabelecer o diagnóstico de HA. Finalmente, ambos os métodos foram estatisticamente comparados. RESULTADOS: A frequência da HA foi de 37,01% quando avaliada através do questionário de autoavaliação, e 34% com o escore de Beighton. As frequências da doença, quando o questionário de autoavaliação e o escore de Beighton foram aplicados, foram, respectivamente, 43,5% e 44,2% no sexo feminino, e 28,44% e 16% no masculino. A sensibilidade do questionário de autoavaliação foi de 70,9%, e a especificidade, de 77,4%, com área sob a curva ROC (receiver operating characteristic) de 0,786%. CONCLUSÕES: A HA é frequente em universitários brasileiros e mais comum no sexo feminino. O questionário de autoavaliação para identificação de HA, traduzido e validado para a língua portuguesa, foi um método efetivo para sua identificação, quando comparado ao escore de Beighton

INTRODUCTION: Joint hypermobility (JH) is an inherited clinical condition with increased joint elasticity in passive movements. In the general population, its frequency, which can be estimated through specific methods, such as the nine-point Beighton hypermobility score (Beighton score) and the self-reported five-part questionnaire for identifying hypermobility (five-part questionnaire), ranges from 10% to 20%. OBJECTIVES: To validate the Portuguese version of the five-part questionnaire and to determine its sensitivity and specificity when compared with the Beighton score for diagnosing JH. METHODS: The five-part questionnaire for identifying hypermobility was translated into Portuguese and applied to 2,523 Brazilian university students. Then, a sample with 394 randomly selected students was evaluated by use of the Beighton score, aiming at establishing the JH diagnosis. Finally, the two methods were statistically compared. RESULTS: The JH frequency was 37.01% when using the five-part questionnaire, and 34% when using the Beighton score. Considering sex, the JH frequencies according to the five-part questionnaire and Beighton score were 43.54% and 44.26% in females, and 28.44% and 16% in males, respectively. The sensitivity of the self-reported questionnaire was 70.9% and its specificity was 77.4%, with an area under the receiver operating characteristic (ROC) curve of 0.786. CONCLUSIONS: JH is frequent in Brazilian university students, and more common in women. The self-reported five-part questionnaire for JH identification, translated into Portuguese and validated, was an effective method when compared with the Beighton score for identifying JH

A mucosite oral (MO) afeta pacientes que são submetidos ao transplante de células-tronco hematopoéticas (TCTH) devido as altas doses de quimioterapia e/ou radioterapia. A proposta desta investigação foi realizar um estudo comparativo da freqüência e a evolução da MO entre os pacientes submetidos ao laser terapêutico e da terapia convencional (uso de solução de bochecho chamada "Fórmula para Mucosite").Os pacientes foram submetidos ao regime de condicionamento mieloablativo antes da realização do TCTH alogênico.Vinte e dois pacientes foram selecionados e divididos em 2 grupos: grupo I foi irradiado com laser AlGaInP (660 nm) e laser GaAlAs (780 nm), potência de 25 mW, dose de 6,3J/cm², tempo 10 s, seguido do tratamento convencional; grupo II submetido apenas ao tratamento convencional. Ambas as escalas da World Health Organization (WHO) e Oral Mucositis Assessment Scales (OMAS) foram utilizadas para avaliar os resultados. Os dados foram analizados pelo teste não-paramétrico de Wilcoxon, com p<0,05 considerado estatisticamente significante. O grupo I apresentou menor frequência de MO (p=0,02) e menor média de acordo com as escalas WHO e OMAS (p<0,01 e p=0,01, respectivamente). Em conclusão, o laser reduziu a frequência e gravidade da MO, sugerindo que o laser terapêutico pode ser usado para ambos como uma nova forma de prevenção e tratamento da MO.

Oral mucositis (OM) affects patients who are submitted to hematopoietic stem cell transplantation (HSCT) due to high doses of chemotherapy and/or radiotherapy. The purpose of this investigation was to perform a comparative study of the frequency and evolution of OM among patients subjected to therapeutic laser and to the conventional therapy (use of mouthwash called "Mucositis Formula"). The patients were subjected to a myeloablative conditioning regimen before the allogeneic HSCT. Twenty-two patients were selected and divided into 2 groups: group I was irradiated with InGaAlP laser (660 nm) and GaAlAs laser (780 nm), 25 mW potency, 6.3J/cm² dose, in 10-s irradiation time, followed to conventional treatment; group II was subjected only to the conventional treatment. Both World Health Organization (WHO) scale and the Oral Mucositis Assessment Scale (OMAS) were used to evaluate the results. Data were analyzed by the non-parametric Wilcoxon test, with p<0.05 considered as statistically significant. Group I presented a lower frequency of OM (p=0.02) and lower mean scores, according to WHO and OMAS scales (p<0.01 and p=0.01, respectively). In conclusion, laser reduced the frequency and severity of OM, suggesting that therapeutic laser can be used both as a new form of prevention and treatment of OM.