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Abstract Background Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. Methods A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. Results Six recommendations were elaborated regarding the pharmacological treatment of Raynaud’s phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. Conclusion These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren’s syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database.Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months.Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population.

Abstract Nailfold capillaroscopy (NFC) is a reproducible, simple, low-cost, and safe imaging technique used for morphological analysis of nail bed capillaries. It is considered to be extremely useful for the investigation of Raynaud’s phenomenon and for the early diagnosis of systemic sclerosis (SSc). The capillaroscopic pattern typically associated with SSc, scleroderma (“SD”) pattern, is characterized by dilated capillaries, microhemorrhages, avascular areas and/or capillary loss, and distortion of the capillary architecture. The aim of these recommendations is to provide orientation regarding the relevance of NFC, and to establish a consensus on the indications, nomenclature, the interpretation of NFC findings and the technical equipments that should be used. These recommendations were formulated based on a systematic literature review of studies included in the database MEDLINE (PubMed) without any time restriction.

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 doençaOBJECTIVES: 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

Nem sempre é possível estabelecer uma clara distinção entre as doenças musculares de causa infecciosa e as miosites idiopáticas. Há situações, inclusive, em que se considera existir uma relação causal entre ambas as doenças. Descrevemos o caso de uma paciente com manifestações clínicas e laboratoriais de polimiosite que apresentou infecção precedente de leptospirose, em que se considera a hipótese de ação de "gatilho" do agente infeccioso no quadro muscular inflamatório.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.

Arterite de Takayasu (AT) é uma doença rara caracterizada por vasculite dos grandes vasos, principalmente aorta e seus ramos. A inflamação vascular leva a irregularidades na parede do vaso, causando estenoses e aneurismas. O envolvimento da artéria pulmonar (AP) é freqüente na AT. Apesar disso, o desenvolvimento de hipertensão arterial pulmonar (HAP) é menos comum, alterando o tratamento e o prognóstico dos pacientes. Descrevemos um caso de uma paciente com AT com estenoses múltiplas em artérias pulmonares, HAP e doença cerebrovascular, além de revisão de literatura sobre o assunto.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.

Na síndrome de Sjögren, o acometimento subclínico dos túbulos renais pode afetar uma parcela significativa de pacientes. A maioria apresenta acidose tubular renal distal (tipo 1), que pode se constituir na primeira manifestação da doença auto-imune e contribuir para sua maior duração e gravidade. A depleção de potássio, resultante da acidose tubular renal distal, pode ser extremamente grave e colocar em risco a vida do paciente se não diagnosticada e tratada. A paralisia periódica hipocalêmica foi observada em quase 40% dos pacientes com síndrome de Sjögren e acidose tubular renal distal. Descrevemos, a seguir, o caso de uma paciente com diagnóstico de síndrome de Sjögren, estabelecido há quatro anos, que apresentou amortecimento e fraqueza em membros inferiores com dificuldade respiratória. Houve agravamento dos sintomas e necessidade de internamento em Unidade de Terapia Intensiva. À admissão, verificou-se potássio sérico de 2 mEq/L. Com o diagnóstico de paralisia hipocalêmica, procedeu-se ao tratamento imediato com reposição parenteral de KCl 19,1% e oxigênio suplementar (máscara). Não houve necessidade de ventilação mecânica. A paciente recebeu alta com potássio sérico corrigido para 3,4 mEq/L.Subclinical renal tubular dysfunction in Sjögren'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 Sjögren's syndrome and distal renal tubular acidosis. The case that follows describes a patient who was diagnosed with Sjögren'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.

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

Abstract 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.

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.Autoantibodies possibly influence clinical manifestations of systemic sclerosis (SSc). This clinical-serological correlation, associated with the paucity of autoantibodies concomitance, gave rise to the historical paradigm of autoantibodies mutual exclusivity. However, one can question this assumption. Does autoantibodies concomitance mean coexistence of two different entities? On the other hand, if considered a unique disease, is this phenomenon a random event or does it represent a distinct subgroup of patients, with peculiar clinical, pathogenic, and immunogenetic characteristics? The autoantibodies' prevalence in early SSc is high. However, anti-centromere antibody (ACA) and antitopoisomerase 1 antibody (ATA) duplicity is a rare event. Similarly, the ACA, ATA, and anti-RNA polymerase (anti-RNA-P) III coexistence have not been described yet in single patient. In the reported case, with ACA, ATA, and anti-RNA-P III positivity, we have noted early vascular manifestations and late limited cutaneous involvement. This is, to our knowledge, the first report of three concomitant specific autoantibodies in a patient with SSc. We do believe this coexistence represents a rare serologic subgroup of a unique disease, with possible clinical and prognostic value, although this remains to be confirmed.

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.BACKGROUND: There is no appropriate and reliable method of evaluating and monitoring severity in rosacea. OBJECTIVE: To determine the importance of nailfold capillaroscopy as a diagnostic and prognostic method for patients with rosacea. METHODS: A cross-sectional study where eight patients with rosacea and 8 control subjects were submitted to nailfold capillaroscopy from May to July 2009. We collected clinical data related to gender, age, skin phototype, and rosacea stage according to Plewig and Kligman classification and the classification of the National Rosacea Society. Additionally, we evaluated the progression of the disease and treatment therapies previously used. RESULTS: The majority of the patients evaluated (6 out of 8 patients) had rosacea subtype I (vascular) or erythematotelangiectatic rosacea. The mean duration of the disorder was 5.96 years, and 87.5% of the patients were under treatment with topical metronidazole. Nailfold cappilaroscopy showed that evidence of devascularization was absent in both groups. CONCLUSION: Nailfold capillaroscopy presents a nonspecific pattern and does not seem to help in the diagnosis or prognosis of rosacea.

Abstract: 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.