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. (SSc manifestations decade (RCTs PatientPopulation Patient Population Patient/Population Intervention Comparison PICO (PICO Assessment GRADE (GRADE methodology recommendation 75 needed Raynauds Raynaud s phenomenon healing (healing ulcers ILD (ILD drugs rituximab placebocontrolled placebo controlled found decisionmaking decision making practice 7

Abstract Background Cognitive dysfunction (CD) is a widespread manifestation in adult systemic lupus erythematosus (SLE) patients, but this subject is rarely examined in patients with childhood-onset SLE (cSLE). This study aimed to assess the frequency of CD, its associations with lupus clinical manifestations and its impact on the health-related quality of life (HRQL) in young adult cSLE patients. Methods We evaluated 39 cSLE patients older than 18 years. They underwent a rheumatologic evaluation and extensive neuropsychological assessment, encompassing all cognitive domains described by the American College of Rheumatology. HRQL was assessed with the WHOOQOL-BREEF, General Activities of Daily Living Scale (GADL) and Systemic Lupus Erythematosus-specific quality-of-life instrument (SLEQOL). The activity of SLE was evaluated with the modified sle disease activity index (sledai-2k). Results Impairment in at least one cognitive domain was found in 35 (87.2%) patients. The most compromised domains were attention (64.1%), memory (46.2%), and executive functions (38.5%). Patients with cognitive impairment were older, had more accumulated damage and had worse socioeconomic status. Regarding the association between cognitive dysfunction and HRQL, memory impairment was correlated with worse environmental perception and a worse relationship with the treatment. Conclusion In this study, the frequency of CD in cSLE patients was as high as that in the adult SLE population. CD can significantly impact the response of cSLE patients to treatment, justifying preventive measures in the care of this population. (CD (SLE childhoodonset childhood onset cSLE. . (cSLE) healthrelated health related (HRQL 3 1 years assessment Rheumatology WHOOQOLBREEF, WHOOQOLBREEF WHOOQOL BREEF, BREEF WHOOQOL-BREEF GADL (GADL Erythematosusspecific Erythematosus specific qualityoflife SLEQOL. SLEQOL (SLEQOL) sledai2k. sledai2k sledaik sledai 2k k (sledai-2k) 87.2% 872 87 2 (87.2% 64.1%, 641 64.1% , 64 (64.1%) 46.2%, 462 46.2% 46 (46.2%) 38.5%. 385 38.5% 38 5 (38.5%) status treatment population (cSLE (SLEQOL (sledai-2k 87.2 8 (87.2 64.1 6 (64.1% 46.2 4 (46.2% 38.5 (38.5% 87. (87. 64. (64.1 46. (46.2 38. (38.5 (87 (64. (46. (38. (8 (64 (46 (38 ( (6 (4 (3

A síndrome de ativação macrofágica (SAM) é uma doença rara e potencialmente fatal, normalmente associada às doenças reumáticas crônicas, em especial a artrite idiopática juvenil. É incluída no grupo das formas secundárias de síndrome hemofagocítica, cujas outras causas podem ser as doenças linfoproliferativas e infecções. As manifestações clínicas e laboratoriais mais importantes são a febre não remitente, esplenomegalia, hemorragias, disfunção hepática, citopenias, hipoalbuminemia, hipertrigliceridemia e hiperferritinemia. O tratamento deve ser iniciado rapidamente, e a maioria dos casos responde bem aos corticosteroides e à ciclosporina (CSA). O vírus Epstein-Barr (EBV) é descrito como possível gatilho para muitos casos de SAM, especialmente naqueles em tratamento com bloqueadores do fator de necrose tumoral (TNF). Nos casos refratários ao tratamento convencional, etoposide (VP16) deve ser administrado, em associação com corticosteroides e CSA. Nosso objetivo foi descrever um caso raro de síndrome hematofagocítica provavelmente secundária à infecção pelo vírus Epstein-Barr (EBV), em paciente com artrite idiopática juvenil sistêmica, confirmada pelas manifestações clínicas e laboratoriais típicas, mielograma e sorologia positiva contra o EBV, que atingiu remissão completa após inclusão no protocolo de tratamento HLH-04.

Machrophage activation syndrome (MAS) is a rare and potentially fatal disease, commonly associated with chronic rheumatic diseases, mainly juvenile idiopathic arthritis. It is included in the group of secondary forms of haemophagocytic syndrome, and other causes are lymphoproliferative diseases and infections. Its most important clinical and laboratorial manifestations are non-remitting fever, splenomegaly, bleeding, impairment of liver function, cytopenias, hypoalbuminemia, hypertriglyceridemia, hypofibrinogenemia and hyperferritinemia. The treatment needs to be started quickly, and the majority of cases have a good response with corticosteroids and cyclosporine. The Epstein–Barr virus is described as a possible trigger for many cases of MAS, especially in these patients in treatment with tumor necrosis factor (TNF) blockers. In these refractory cases, etoposide (VP16) should be administered, associated with corticosteroids and cyclosporine. Our objective is to describe a rare case of MAS probably due to EBV infection in a subject with systemiconset juvenile idiopathic arthritis, which achieved complete remission of the disease after therapy guided by 2004-HLH protocol.

O pioderma gangrenoso (PG) faz parte do espectro das dermatoses neutrofílicas, processos que têm em comum um padrão histológico similar, formado por infiltrado de leucócitos polimorfonucleares, de caráter não infeccioso e não neoplásico e sem vasculite primária. Caracteriza-se por úlceras dolorosas, com bordas imprecisas, de variados tamanhos e profundidade, localizadas principalmente nos membros inferiores, mas outras partes da pele, mucosas e outros órgãos podem estar envolvidos. A doença tem grande morbidade e seu curso pode ser crônico ou recidivante. A patogênese não é bem conhecida. Em 50 a 70% dos pacientes, está associado a uma doença de base, como doença inflamatória intestinal, doenças reumáticas, hematológicas ou malignidades; pode apresentar-se de forma isolada. São analisados dois pacientes com o diagnóstico de pioderma gangrenoso e artrite associada, para ressaltar a importância do conhecimento dessa dermatose pelo reumatologista, já que o acometimento articular ocorre em cerca de 37% dos pacientes que apresentam essa síndrome neutrofílica.

Pyoderma gangrenosum (PG) is a necrotizing neutrophilic dermatosis, a condition with polymorphonuclear infiltrates, which is non-infective, non neoplastic and has no primary vasculitis. It may be idiopathic or associated with a systemic disorder. It is characterized by painful ulcers with undermined edge, of variable depth and size. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. The course can be mild or malignant, chronic or relapsing, and has a remarkable morbidity. The pathogenesis is unknown. In 50 to 70% of the patients, PG is associated with underlying systemic diseases such as inflammatory bowel disease, myeloproliferative disorders, hematological or malignancies; it can appear in isolated form. This is a report of two patients with PG and arthritis which intends to show the importance, for rheumatologists, of considering this dermatosis, since articular complaints are present in 37% of the PG patients.

A pancreatite aguda é uma manifestação incomum do lúpus eritematoso sistêmico (LES) e a freqüência desta associação não é conhecida. Contudo, a pancreatite aguda é um diagnóstico diferencial importante na avaliação da dor abdominal em pacientes com LES. Os pacientes, normalmente, apresentam dor de intensidade variável, algumas vezes simulando abdome agudo. Vários fatores têm sido implicados na patogênese desta condição, tais como fenômenos autoimunes, vasculite, anticorpos antifosfolípides e drogas. O papel dos corticosteróides como um fator etiológico é ainda controverso. Além disso, em alguns relatos a manutenção do corticosteróide foi fundamental na recuperação dos pacientes. Relatamos duas pacientes com lúpus eritematoso sistêmico que apresentaram pancreatite aguda. Em nenhum dos casos havia evidências de quaisquer fatores predisponentes conhecidos para a pancreatite aguda, portanto esta condição foi considerada uma manifestação de atividade lúpica. Uma das pacientes faleceu por síndrome da resposta inflamatória sistêmica secundária à pancreatite. No outro caso, utilizouse corticóide em doses de estresse durante o tratamento, com boa evolução.

Acute pancreatitis is an uncommon manifestation of systemic lupus erythematosus (SLE) and the frequency of this association is unknown. Nevertheless, acute pancreatitis is an important differential diagnosis in the evaluation of abdominal pain in individuals with SLE. Patients usually present with pain of variable intensity, sometimes simulating acute abdomen. Several factors have been implicated in the pathogenesis of this condition, such as autoimmune events, vasculitis, antiphospholipid antibodies and drugs. The role of corticosteroids as an etiological factor is still controversial. Moreover, in some reports the maintenance of corticosteroids was crucial in the patients' recovery. We report two patients with SLE, who presented with acute pancreatitis. In neither of the cases evidence of any known predisposing factors was present and, therefore, the condition was considered a manifestation of lupus activity. One of the patients died as a consequence of systemic inflammatory response secondary to pancreatitis. In the other case, stress doses of corticoids were used in the treatment, resulting in a good outcome.