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Methotrexate is a folate antagonist and one of several first-line disease-modifying drugs for treating rheumatoid arthritis. It can be given orally or parenterally: the bioavailability of oral doses of methotrexate is highly variable, being only two-thirds of that by parenteral use. The most frequent side effects are nausea and vomiting, and the most serious are toxicity of the bone marrow, liver, kidney and mucosa. Being hydrophilic, methotrexate barely penetrates the blood–brain barrier so that central nervous system toxicity is rare. However, this may follow intrathecal or high-dose intravenous administration, as used to treat haematological malignancies. There are a few case reports of leukoencephalopathy after low-dose oral methotrexate, involving the temporal and/or occipital lobes or the cerebellum.1 Subcutaneous administration of methotrexate seems to give a better clinical response and fewer side effects than oral methotrexate.2 Nevertheless, we recently observed a woman …
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