II Brazilian Society of Rheumatology consensus for lupus nephritis diagnosis and treatment.

OBJECTIVE: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN). METHODS: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion. RESULTS: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy. CONCLUSION: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil.

Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Doenças osteoarticulares degenerativas periféricas / Peripheral degenerative joint diseases

A osteoartrite é uma afecção degenerativa da cartilagem hialinaarticular que acomete, mais frequentemente, pessoas acimados 50 anos de idade. Manifesta-se por dor, rigidez e prejuízofuncional da articulação atingida. Classifi ca-se em primária (ouidiopática) e secundária. Alguns fatores de risco são genética,etnia, idade, sexo, obesidade, atividades ocupacionais e alteraçõesbiomecânicas articulares. Quaisquer que seja a localização e acausa, a patogênese se constitui em mudanças catabólicas, cominibição da síntese e tentativa de reparo da matriz cartilaginosa.Ações de metaloproteinases e de citocinas (IL-1, IL-6 e TNF-α)são responsáveis pelos sinais infl amatórios que ocorrem e peladegradação da cartilagem. As formas mais freqüentes de osteoartriteperiférica ocorrem em joelho, coxofemoral e mão, sendo a dor osintoma mais importante, quase sempre desproporcional aosachados radiológicos. O diagnóstico se fundamenta nos aspectosclínicos, laboratoriais e de imagem. As associações científi casrecomendam um roteiro de tratamento que envolve recursos nãofarmacológicos (educação, fi sioterapia, órteses), farmacológicos(analgésicos, antiinfl amatórios, infi ltrações de corticóides,viscossuplementação, medicamentos de ação lenta) e cirurgia. Aartroplastia parece ser a mais efetiva das medidas, mas é restrita acasos que não responderam às outras ações.