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.