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Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Background: The current subclassification of systemic sclerosis into cutaneous subtypes does not fully capture the heterogeneity of the disease. We aimed to compare the performances of stratification into LeRoy's cutaneous subtypes versus stratification by autoantibody status in systemic sclerosis. Methods: For this cohort study, we assessed people with systemic sclerosis in the multicentre international European Scleroderma Trials and Research (EUSTAR) database. Individuals positive for systemic-sclerosis autoantibodies of two specificities were excluded, and remaining individuals were classified by cutaneous subtype, according to their systemic sclerosis-specific autoantibodies, or both. We assessed the performance of each model to predict overall survival, progression-free survival, disease progression, and different organ involvement. The three models were compared by use of the area under the curve (AUC) of the receiver operating characteristic and the net reclassification improvement (NRI). Missing data were imputed. Findings: We assessed the database on July 26, 2019. Of 16 939 patients assessed for eligibility, 10 711 patients were included: 1647 (15·4%) of 10 709 were male, 9062 (84·6%) were female, mean age was 54·4 (SD 13·8) years, and mean disease duration was 7·9 (SD 8·2) years. Information regarding cutaneous subtype was available for 10 176 participants and antibody data were available for 9643 participants. In the prognostic analysis, there was no difference in AUC for overall survival (0·82, 95% CI 0·81–0·84 for cutaneous only vs 0·84, 0·82–0·85 for antibody only vs 0·84, 0·83–0·86 for combined) or for progression-free survival (0·70, 0·69–0·71 vs 0·71, 0·70–0·72 vs 0·71, 0·70–0·72). However, at 4 years the NRI showed substantial improvement for the antibody-only model compared with the cutaneous-only model in prediction of overall survival (0·57, 0·46–0·71 for antibody only vs 0·29, 0·19–0·39 for cutaneous only) and disease progression (0·36, 0·29–0·46 vs 0·21, 0·14–0·28). The antibody-only model did better than the cutaneous-only model in predicting renal crisis (AUC 0·72, 0·70–0·74 for antibody only vs 0·66, 0·64–0·69 for cutaneous only) and lung fibrosis leading to restrictive lung function (AUC 0·76, 0·75–0·77 vs 0·71, 0·70–0·72). The combined model improved the prediction of digital ulcers and elevated systolic pulmonary artery pressure, but did poorly for cardiac involvement. Interpretation: The autoantibody-only model outperforms cutaneous-only subsetting for risk stratifying people with systemic sclerosis in the EUSTAR cohort. Physicians should be aware of these findings at the time of decision making for patient management. Funding: World Scleroderma Foundation.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

To evaluate the influence of geographic variation on the risk of digital ulcer (DU) development in systemic sclerosis (SSc) patients.This cross-sectional, multicentre study evaluated patients with SSc from centres located in different geographic regions of Brazil (subtropical and tropical climate zones). Demographic and clinical data were collected.The study included 141 patients with SSc (26 from the subtropical and 115 from the tropical zone). In total, 43 DUs were observed in 23 (16%) of the patients. By a simple logistic regression model, the presence of DUs was associated with a higher modified Rodnan skin score, previous necrosis or amputation of the extremities, flexion contracture of the fingers, active smoking, higher avascular score on capillaroscopy, higher severity of Raynaud's phenomenon, a higher Health Assessment Questionnaire Disability Index (HAQ-DI) score, a higher visual analogue scale score for Raynaud's phenomenon and overall disease, and the subtropical climate zone. Using multiple logistic regression, the presence of DUs was significantly associated with patients living in the subtropical climate zone [odds ratio (OR) = 5.4, p = 0.002], necrosis or amputation (OR = 5.2, p = 0.011), and a higher HAQ-DI score (OR = 2.6, p = 0.021).In this multicentre study in a continental country with different climates, patients with SSc living in a subtropical climate region had a 5.4 times higher risk of developing DUs than patients living in a warmer region (tropical climate), suggesting a more severe course of peripheral vasculopathy among patients living in geographic regions with relatively cold weather.

Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are prevalent complications of systemic sclerosis (SSc) and are currently the leading causes of death related to the disease. The accurate recognition of these conditions is therefore of utmost importance for patient management. A study was carried out with 24 SSc patients being followed at the Rheumatology Department of the Hospital de Clínicas of Universidade Federal do Paraná (UFPR) and 14 healthy volunteers, with the objective of evaluating the usefulness of lung magnetic resonance imaging (MRI) when assessing ILD in SS patients. The results obtained with lung MRI were compared to those obtained by computed tomography (CT) of the chest, currently considered the examination of choice when investigating ILD in SS patients. The assessed population was predominantly composed of women with a mean age of 50 years, limited cutaneous SS, and a disease duration of approximately 7 years. In most cases, there was agreement between the findings on chest CT and lung MRI. Considering it is a radiation-free examination and capable of accurately identifying areas of lung tissue inflammatory involvement, lung MRI showed to be a useful examination, and further studies are needed to assess whether there is an advantage in using lung MRI instead of chest CT when assessing ILD activity in SS patients. Resumo A doença intersticial pulmonar (DIP) e a hipertensão arterial pulmonar (HAP) são complicações prevalentes na esclerose sistêmica (ES) e constituem atualmente as principais causas de morte relacionadas à doença. O reconhecimento preciso dessas condições é, portanto, de fundamental importância no manejo dos pacientes. Fez-se um estudo com 24 pacientes com ES em acompanhamento no serviço de reumatologia do Hospital de Clínicas da Universidade Federal do Paraná (UFPR) e 14 voluntários sadios com objetivo de avaliar a utilidade do exame de ressonância magnética (RM) do pulmão na avaliação da DIP em pacientes com ES. Os resultados obtidos com a RM pulmonar foram comparados com os obtidos na tomografia computadorizada (TC) de tórax, exame atualmente considerado de eleição na investigação da DIP em pacientes com ES. A população avaliada era predominantemente composta por mulheres com idade média de 50 anos, ES cutânea limitada e tempo de doença de aproximadamente sete anos. Na maioria dos casos, houve concordância entre os achados na TC de tórax e RM do pulmão. Em se tratando de um exame isento de radiação e capaz de identificar com adequada precisão áreas de acometimento inflamatório do tecido pulmonar, a RM do pulmão de revelou um exame útil. São necessários mais estudos para avaliar se há vantagem da RM do pulmão sobre a TC de tórax na avaliação da atividade da DIP em pacientes com ES.

Description of the method to elaborate the evidenceThe members of the Comissão de Esclerose Sistêmica da Sociedade Brasileira de Reumatologia (Systemic Sclerosis Commission of the Brazilian Society of Rheumatology, SBR) 2010- 2012 took part in the Evidence Preparation Course given by the Associação Médica Brasileira (Brazilian Medical Association, AMB) in São Paulo in the first semester of 2011. The questions were formulated and discussed via internet in the second semester of 2011. The 15 clinical questions considered to be relevant were structured using the P.I.C.O. method (patient; intervention or indicator; comparison; outcome). The literature search was conducted by searching the databases MEDLINE, EMBASE, SciElo/Lilacs, and the Cochrane Library through February, 2012 (Appendix). Critical assessment of the evidence in the selected articles was performed using the Jadad score. The observational studies and case series were considered for analysis when randomised clinical trials could not be located. A manual search located the relevant studies that were included in the analysis. The answers to the questions included in the Recommendations were refined and elaborated, and all of the selected references exhibited the corresponding grade of recommendation and the strength of scientific evidence. The references were updated through December, 2012, entered into a single file by the coordinator, and sent to the co-authors in four successive rounds for preparation of the final version.Grades of recommendation and strength of evidenceA.Most consistent experimental and observational studies.B.Less consistent experimental and observational studies.C.Case reports (uncontrolled studies).D.Opinion that is not substantiated by critical evaluation, based on consensus, physiological studies or animal models.ObjectiveTo establish recommendations for the management and treatment of systemic sclerosis.

ObjectivesTo determine the causes of death and risk factors in systemic sclerosis (SSc).MethodsBetween 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation.ResultsWe identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile.ConclusionCombining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients’ survival.

OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. RESULTS: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p

Due to mounting evidences of interaction between Hansen's bacilli with endothelial cells and the paucity of studies addressing the presence of nailfold capillaroscopic alterations in patients with Hansen's disease, a study was carried out in order to verify the presence of capillaroscopic alterations in patients with leprosy in its various forms and its correlation with clinical parameters. Ten patients were evaluated at a specialized university service. Sixty percent of those had some capillaroscopic change, such as micro-hemorrhages, ectatic, bushy and corkscrew capillaries. Such changes were unspecific, which suggests there is not a specific pattern for this disease.

Os autoanticorpos possivelmente influenciam as manifestações clínicas da esclerose sistêmica (ES). Essa correlação clínico-sorológica, associada à insuficiência de casos de concomitância de autoanticorpos, originou o paradigma histórico de que seriam mutuamente excludentes. Porém, pode-se questionar essa tese. Poderia a multiplicidade de autoanticorpos significar a coexistência de duas patologias distintas? Por outro lado, se assumidos como anticorpos específicos de uma doença única, essa multiplicidade seria um evento aleatório ou representaria um subgrupo distinto de pacientes, com características clínicas, patogênicas e imunogenéticas próprias? A prevalência de autoanticorpos na ES precoce é elevada. Entretanto, a duplicidade do anticorpo anticentrômero (AAC) e do anticorpo antitopoisomerase 1 (AAT) é um evento raro. Já a coexistência de AAC, AAT e anticorpo anti-RNA polimerase (anti-RNA-P) III ainda não foi descrita em um paciente isolado. Neste relato, com positividade para AAC, AAT e anti-RNA-P III, notamos manifestações vasculares precoces e posterior comprometimento cutâneo limitado. Este parece ser o primeiro relato de concomitância de três autoanticorpos específicos em um paciente com ES. Acreditamos que essa coexistência representa um subgrupo sorológico raro de uma única doença, com possível valor clínico e prognóstico - porém, ainda há necessidade de confirmação.

OBJETIVOS: Este estudo visou à análise das manifestações da esclerose sistêmica (ES), com ênfase na pesquisa dos autoanticorpos e de suas correlações clínicas, na população de pacientes em acompanhamento no ambulatório de ES do Hospital de Clínicas da Universidade Federal do Paraná. METODOLOGIA: Realizou-se um estudo transversal com 96 pacientes em acompanhamento no ambulatório de ES do hospital, entre setembro de 2007 e setembro de 2009. RESULTADOS: A maioria dos pacientes era do sexo feminino, com idade entre a quarta e quinta décadas e tempo de doença com mediana de 10 anos. A forma cutânea limitada de ES foi a mais prevalente. Na análise dos autoanticorpos, o anticorpo anticentromérico (ACA) associou-se a ES forma limitada, idade mais avançada ao diagnóstico, maior tempo de doença, intervalo maior entre o surgimento do fenômeno de Raynaud (FRy) e o primeiro sintoma não FRy, maior prevalência de hipertensão arterial sistêmica (HAS) e de bloqueios de condução cardíaca. O anticorpo antitopoisomerase-1 (antitopo-1, previamente denominado anti-Scl-70) foi mais comum na forma difusa da ES, na presença de doença ativa e de úlceras digitais. O anticorpo anti-RNA polimerase III (antipol III) correlacionou-se com a forma difusa de ES, presença de doença ativa e sinovite. CONCLUSÕES: Este estudo vem ressaltar e ratificar o papel relevante dos autoanticorpos na avaliação dos pacientes com ES, sendo possível correlacionar o perfil autoimune dessa população com manifestações específicas da doença OBJECTIVES: To assess the manifestations of systemic sclerosis (SSc), with an emphasis on the analysis of autoantibodies and their clinical correlations, in a population of patients followed up at the SSc Outpatient Clinics of the Hospital de Clínicas of the Universidade Federal do Paraná. METHODOLOGY: Cross-sectional study with 96 patients followed up at the SSc Outpatient Clinics of the hospital between September 2007 and September 2009. RESULTS: Most patients were of the female sex, in their forties or fifties, and the median time of disease was ten years. The limited cutaneous form of SSc was more prevalent. The analysis of the autoantibodies showed the association of anticentromere antibody (ACA) with the following: the limited form of SSc; more advanced age at the time of diagnosis; longer disease time; longer interval between the appearance of the Raynaud's phenomenon (RyP) and the first non-RyP symptom; systemic arterial hypertension (SAH); and cardiac conduction blocks. The antitopoisomerase-1 antibody (ATA-1, previously called anti-Scl-70) was more common in the presence of the diffuse form of SSc, active disease, and digital ulcers. The anti-RNA polymerase III antibody (anti-Pol III) correlated with the diffuse form of SSc, disease activity, and synovitis. CONCLUSIONS: This study emphasizes and confirms the important role of autoantibodies in assessing patients with SSc, allowing the correlation between the autoimmune profile of patients with SSc and specific manifestations of the disease

FUNDAMENTOS: Não há um método adequado e fidedigno de avaliação e seguimento da severidade na rosácea. OBJETIVO: Determinar a importância da capilaroscopia periungueal como método diagnóstico e prognóstico em pacientes portadores de rosácea. MÉTODOS: Estudo transversal onde foram submetidos ao exame da capilaroscopia periungueal 8 pacientes com rosácea e 8 controles no período entre maio e julho de 2009. Foram coletados dados clínicos relacionados ao sexo, idade, fototipo, classificação da rosácea de acordo com a classificação de Plewig e Kligman e a classificação da National Rosacea Society. Adicionalmente, avaliamos o tempo de evolução da doença e tratamentos previamente utilizados. RESULTADOS: A grande maioria das pacientes avaliadas (6 das 8 pacientes) apresentavam rosácea grau I (vascular) ou eritêmato-teleangiectásica. A idade média de duração da rosácea foi de 5,96 anos, sendo que 87,5% faziam tratamento com metronidazol tópico. Nenhum paciente tanto do grupo rosácea como controle demonstrou evidência de desvascularização ao exame capilaroscópico. CONCLUSÃO: A capilaroscopia periungueal apresenta um padrão inespecífico e não parece auxiliar no diagnóstico ou prognóstico da rosácea.

Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.

Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are prevalent complications of systemic sclerosis (SSc) and are currently the leading causes of death related to the disease. The accurate recognition of these conditions is therefore of utmost importance for patient management. A study was carried out with 24 SSc patients being followed at the Rheumatology Department of the Hospital de Clínicas of Universidade Federal do Paraná (UFPR) and 14 healthy volunteers, with the objective of evaluating the usefulness of lung magnetic resonance imaging (MRI) when assessing ILD in SS patients. The results obtained with lung MRI were compared to those obtained by computed tomography (CT) of the chest, currently considered the examination of choice when investigating ILD in SS patients. The assessed population was predominantly composed of women with a mean age of 50 years, limited cutaneous SS, and a disease duration of approximately 7 years. In most cases, there was agreement between the findings on chest CT and lung MRI. Considering it is a radiation-free examination and capable of accurately identifying areas of lung tissue inflammatory involvement, lung MRI showed to be a useful examination, and further studies are needed to assess whether there is an advantage in using lung MRI instead of chest CT when assessing ILD activity in SS patients.

Aproximadamente, 98% dos pacientes que sao avaliados pelo reumatologista apresentam a dor como queixa principal. Porem, somente em 50% dos casos a dor e bem explicada pelo medico. Ate pouco tempo, a maioria dos livros-texto de reumatologia nao tratava da fisiopatologia e do tratamento da dor nas doencas reumaticas. Esta tendencia esta mudando, com cada vez mais artigos, conferencias e capitulos de livros analisando a dor como sintoma, dissecando os seus aspectos fisiopatologicos e estabelecendo estrategias de tratamento. Esta serie de artigos inclui um editorial chamando a atencao dos reumatologistas para o problema da dor, um artigo da dor na artrite reumatoide (AR), uma serie de artigos no uso de opioides na reumatologia e estudos sobre uma terapeutica nao-farmacologica (acupuntura) e uma nova terapeutica farmacologica.

About a quarter of sclerodermic patients present calcinosis. However, patients with limited form of the disease are more likely to have calcinosis than patients with diffuse form. We report a case of a 54-year-old female patient with limited cutaneous scleroderma using rituximab (RTX) to treat lung fibrosis and arthritis. Into RTX treatment, she also had a complete resolution of calcinosis in her hands. The patient reported improvement in dyspnea and synovitis after two courses of RTX (four weekly infusions 375 mg/m(2) each). After 7 months of the first infusion, the calcinosis in her fingers had a complete remission, especially the right thumb. Based on current evidences, we discuss the use of rituximab as a promising therapy to treat not only lung disease but also calcinosis in patients with scleroderma.

Descricao do metodo de elaboracao das evidencias Os integrantes da Comissao de Esclerose Sistemica da Sociedade Brasileira de Reumatologia (bienio 2010-2012) participaram do Curso de Elaboracao de Evidencias da Associacao Medica Brasileira, em Sao Paulo, durante o primeiro semestre de 2011. As questoes foram propostas e discutidas pela internet, no segundo semestre de 2011. As 15 questoes clinicas consideradas relevantes foram estruturadas por meio da estrategia do P.I.C.O. (Paciente; Intervencao ou Indicador; Comparacao; Outcome). As estrategias de busca avaliaram as bases de dados MEDLINE, EMBASE, Scielo/Lilacs, Cochrane Library ate setembro de 2012 (Apendice). Os artigos selecionados na primeira estrategia de busca foram submetidos a avaliacao critica das evidencias, utilizando-se o escore de Jadad. Foram considerados tambem estudos observacionais e series de casos na ausencia de ensaios clinicos randomizados. Foi realizada insercao de estudos relevantes obtidos por busca manual. Posteriormente, foram elaboradas as respostas as perguntas das Recomendacoes, em que cada referencia bibliografica selecionada apresentava o correspondente grau de recomendacao e forca de evidencia cientifica. Para as Recomendacoes finais, as referencias bibliograficas foram atualizadas ate dezembro de 2012, redigidas em texto unico pelo coordenador, e submetidas aos coautores em quatro turnos, para elaboracao do texto final. Grau de recomendacao e forca de evidencia A: Estudos experimentais e observacionais de melhor consistencia. B: Estudos experimentais e observacionais de menor consistencia. C: Relatos de casos (estudos nao controlados). D: Opiniao desprovida de avaliacao critica, baseada em consensos, estudos fisiologicos ou modelos animais. Objetivo Estabelecer as recomendacoes para o manejo e para o tratamento da esclerose sistemica.

Pacientes com Esclerose Sistêmica (ES) podem apresentar envolvimento muscular na forma de miosite ou miopatianão inflamatória. É verificada também associação entre acometimento muscular e disfunção ventricular esquerda (DVE) em pacientes com ES, o que lhes confere pior prognóstico. Avaliamos 87 pacientes do Hospital de Clínicas da Universidade Federal do Paraná, com diagnóstico de ES, quanto à presença de manifestações da musculatura esquelética e a relação destas com DVE. Verificamos uma prevalência de 42,5% de acometimento muscular nos pacientes avaliados, observando uma correlação positiva com a forma difusa da doença. Afastadas outras causas de DVE, três dos quatro pacientes com fração de ejeção abaixo do valor de normalidade apresentaram alteração de força muscular, atrofia e/ou elevação de enzima creatinofosfoquinase sérica (CPK) Patients with systemic sclerosis (SSc) can have muscle involvement in the form of myositis or non-infl ammatory myopathy. The muscle involvement can be associated with left ventricular dysfunction (LVD) in patients with SSc, resulting in worse prognosis. Eighty-seven patients of the Hospital de Clínicas of the Universidade Federal do Paraná, diagnosed with SSc, were assessed regarding the presence of skeletal muscle manifestations and their relation with LVD. A 42.5% prevalence of muscle involvement was observed in the patients studied, as well as a positive correlation with the diffuse form of the disease. Excluding other causes of LVD, three of the four patients with ejection fraction below the normal reference value had alteration of the muscle strength, atrophy and/or serum creatine phosphokinase (CPK) elevation

To assess the manifestations of systemic sclerosis (SSc), with an emphasis on the analysis of autoantibodies and their clinical correlations, in a population of patients followed up at the SSc Outpatient Clinics of the Hospital de Clínicas of the Universidade Federal do Paraná.Cross-sectional study with 96 patients followed up at the SSc Outpatient Clinics of the hospital between September 2007 and September 2009.Most patients were of the female sex, in their forties or fifties, and the median time of disease was ten years. The limited cutaneous form of SSc was more prevalent. The analysis of the autoantibodies showed the association of anticentromere antibody (ACA) with the following: the limited form of SSc; more advanced age at the time of diagnosis; longer disease time; longer interval between the appearance of the Raynaud's phenomenon (RyP) and the first non-RyP symptom; systemic arterial hypertension (SAH); and cardiac conduction blocks. The antitopoisomerase-1 antibody (ATA-1, previously called anti-Scl-70) was more common in the presence of the diffuse form of SSc, active disease, and digital ulcers. The anti-RNA polymerase III antibody (anti-Pol III) correlated with the diffuse form of SSc, disease activity, and synovitis.This study emphasizes and confirms the important role of autoantibodies in assessing patients with SSc, allowing the correlation between the autoimmune profile of patients with SSc and specific manifestations of the disease.

Patients with systemic sclerosis (SSc) can have muscle involvement in the form of myositis or non-infl ammatory myopathy. The muscle involvement can be associated with left ventricular dysfunction (LVD) in patients with SSc, resulting in worse prognosis. Eighty-seven patients of the Hospital de Clínicas of the Universidade Federal do Paraná, diagnosed with SSc, were assessed regarding the presence of skeletal muscle manifestations and their relation with LVD. A 42.5% prevalence of muscle involvement was observed in the patients studied, as well as a positive correlation with the diffuse form of the disease. Excluding other causes of LVD, three of the four patients with ejection fraction below the normal reference value had alteration of the muscle strength, atrophy and/or serum creatine phosphokinase (CPK) elevation.

ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting.ConclusionThe three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.

Systemic Sclerosis (SSc) is an inflammatory disease that decreases functional capacity through muscular atrophy, skin sclerosis and loss of joint function. Scleroderma patients suffer from movement's restriction. In addition, the disease affects the nutritional status, compromising the quality of life in varying degrees. The gastrointestinal involvement appears to be the main responsible for the nutritional impairment.To evaluate the physical and nutritional status of patients with SSc.We conducted a cross-sectional and descriptive study in 20 patients with SSc. All patients were evaluated in Physioteraphy Clinic of the Catholic University of Paraná, from July 2003 to April 2004. The evaluation was performed by Bioimpedance Body (BIA), the questionnaires Nutritional Risk Assessment (Determine), Mini Nutritional Assessment of Aging and Health Assessment Questionnaire (HAQ) and Visual Analogue Scale (VAS) for pain. The work muscle ability was assessed by measuring the peak torque of flexor and extensor muscles of the elbow in the isokinetic dynamometer Cybex Norm model 7000. We have calculated the mean and standard deviation for each variable analyzed, in addition to the percentage of peak torque deficit.The values of the VAS ranged from zero to 97.8 mm (mean: 48.9 +/- 32.9 mm). The HAQ scores ranged from zero to 2.75 (average: 0.95 +/- 0.8). The average BMI was 22.4 +/- 3.9 kg / m2. The average deficit of mass was: 1.3 +/- 2.1 kg. Ten patients had high nutritional risk. 1 patient was malnourished and 15 were at high risk for malnutrition. The average peak torque to the muscle groups of elbows was 19.2 +/- 5 N / m to the flexor and 21.9 +/-6.6 N/m for the extensors, with an average deficit of 17% and 13% for the both groups.We found that SSc patients were in poor nutritional status and had decreased functional and physical capacity by the weakening of the muscles of the elbow demonstrated by the isokinetic evaluation. We concluded that our SSc patients were at high risk for malnutrition and this may indicate that scleroderma patients need a better nutritional orientation. We do consider that SSc patients also must be included in physical activity programs in order to achieve better physical performance.

Sometimes, it is not possible to establish an obvious distinction between the muscular manifestations due to infectious diseases and the idiopathic myositis. In fact, in some situations it is believed there is a causal relationship between those diseases. We describe the case of a patient with clinical and laboratorial features of polymyositis who had developed leptospirosis previously. The hypothesis of the infectious agent acting as a "trigger" to the muscular disease is discussed.

Takayasu arteritis (TA) is a rare illness characterized by vasculitis of great vessels, mainly of aorta and its branches. The vascular inflammation leads to irregularities of the vessel wall causing stenosis and aneurysms. The pulmonary artery (PA) involvement is frequent in TA. Despite this, the development of pulmonary arterial hypertension is less common, modifying the treatment and the prognosis of the patients. We describe a case of a patient with TA with multiple stenosis in pulmonary arteries, pulmonary arterial hypertension and cerebrovascular disease, as well as review of the literature on the subject.

Subclinical renal tubular dysfunction in Sjogren's syndrome can affect a significant number of patients, the majority presenting with distal renal tubular acidosis (type 1). Such findings may be the first symptom of the auto-immune disease, and can contribute for a prolonged disease duration and severity. Potassium depletion resulting from distal renal tubular acidosis can be extremely severe, and can jeopardise patient's life, if its diagnosis and treatment are delayed. Hypocalemic periodic paralysis was observed in almost 40% of patients who suffer from Sjogren's syndrome and distal renal tubular acidosis. The case that follows describes a patient who was diagnosed with Sjogren's syndrome four years ago. Three days before being admitted to hospital, the patient complained that her lower limbs were numb and weak, and that breathing was difficult. Symptoms intensified, the patient was broght to the Intensive Care Unit, where the serum potassium was 2 mEq/L at admittance. Hypocalemic paralysis was diagnosed, and the patient was immediately treated with IV KCl 19.1% and supplementary oxygen by mask. Mechanical ventilation was not required. The patient was discharged with serum potassium corrected to 3.4 mEq/L.

Objectives To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. Methods We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. Results The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n = 971/2959) and 22% (n = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted-R2 = 0.06, P Conclusions GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed.

A esclerose sistêmica (ES) é uma doença crônica autoimune caracterizada por uma associação de processos fisiopatológicos, como disfunção vascular, inflamação e fibrose progressiva da pele e de órgãos internos. A lesão microvascular na ES é um processo complexo, com diversos aspectos disfuncionais simultâneos que interagem entre si. A injúria inicial de células endoteliais desencadeia diversas alterações que culminarão em fibrose, fazendo com que a ES possa ser definida como \"doença microvascular fibrosante\". Nas últimas décadas, o transplante autólogo de células tronco hematopoiéticas (TCTH) vem ganhando espaço no tratamento dos pacientes com ES, com resultados relevantes quanto à melhora da pele e do acometimento pulmonar. Contudo, existem poucos estudos sobre o impacto desta opção terapêutica sobre a vasculopatia associada à doença. Assim, este estudo tem como objetivo geral avaliar se o TCTH afeta a microvasculatura de pacientes com ES. Para esse fim, propusemos um estudo longitudinal e retrospectivo, com 35 pacientes com diagnóstico de ES submetidos ao TCTH e seguidos pelo período de 36 meses. Durante o seguimento, os pacientes foram semestralmente submetidos a capilaroscopia, tomografia computadorizada de tórax, espirometria com avaliação de difusão de monóxido de carbono (DLCO), ecocardiograma, pontuação do escore modificado de Rodnan e coleta de exames laboratoriais que incluíram marcadores de lesão e ativação endotelial (IL6, fator de Von Willebrand, CXCL8, EGF, VEGFA, pentraxina 3, E-selectina, trombomodulina, P-selectina, CXCL4, VCAM1, ICAM1, endotelina 1, IL18). Como resultados clínicos, encontramos melhora progressiva e sustentada do quadro cutâneo e estabilização do quadro pulmonar. Na avaliação de capilaroscopia periungueal, houve melhora do padrão de arquitetura e distribuição capilar. Os marcadores séricos associados ao endotélio mantiveram-se estáveis durante o período de acompanhamento. Concluímos que o TCTH melhora alguns aspectos da vasculopatia presente na ES, o que reforça a ideia de que esta terapia é uma alternativa viável de tratamento para pacientes selecionados e em momento oportuno da doença. Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by an association of pathophysiological processes, including vascular dysfunction, inflammation and progressive fibrosis of the skin and internal organs. The microvascular lesion in SSc is a complex process with simultaneous dysfunctional aspects that interact with each other. The initial injury to the endothelium triggers several alterations that culminate in fibrosis, defining SSc as a \"fibrotic microvascular disease\". In the last decades, autologous hematopoietic stem cell transplantation (HSCT) has been chosen as treatment for SSc patients, with significant results in the improvement of skin and lung involvement. However, few studies have evaluated the impact of this therapeutic option on SSc-associated vasculopathy. Thus, this study aims to assess whether HSCT affects the microvasculature of patients with SSc. To that end, we proposed a longitudinal and retrospective study, with 35 SSc patients undergoing HSCT, followed for a period of 36 months. During follow-up, patients underwent semiannual periungueal capillaroscopy evaluations, high-resolution pulmonary computed tomography, spirometry with DLCO assessment, echocardiogram, modified Rodnans score and collection of blood samples for laboratory tests that included markers of injury and activation of the endothelium (IL6, Von Willebrand factor, CXCL8, EGF, VEGFA, pentraxin 3, E-selectin, thrombomodulin, P-selectin, CXCL4, VCAM1, ICAM1, endothelin 1, IL18). As results, we found progressive and sustained improvement of the skin condition and stabilization of the pulmonary involvement. The capillaroscopy evaluations showed improvement in the pattern of microvascular architecture and distribution. The endothelial markers remained stable in the serum during the follow-up period. We conclude that HSCT is able to at least partially improve the vasculopathy present in SSc, which reinforces the idea that procedure is a viable treatment alternative for selected patients and at an opportune time in disease course.