Initially, it was thought to work through its anti-proliferative effects on lymphocytes. MTX was introduced as a therapy for RA without a clear understanding of its mechanism of action in this disease. The use of MTX in RA was first reported in the 1950s, although its routine use did not occur until 30 years later. It was initially introduced in oncology for the treatment of childhood acute leukaemia. MTX was first developed as a folate antagonist inhibiting the proliferation of malignant cells through inhibition of synthesis of purines and pyrimidines. MTX is one of the most commonly used drugs in the treatment of RA. English language papers only were reviewed. Search terms used were ‘rheumatoid arthritis’, ‘infection’, ‘methotrexate’, ‘disease modifying agents’ and ‘varicella zoster’. Data for this review were identified by searches of MEDLINE, EMBASE, author's personal files and references from relevant articles. The aim of this review is to summarize the literature on infection risk associated with low-dose MTX use in patients with RA. However, concern remains regarding the vulnerability to infection and increased severity of infections in patients taking low-dose MTX. Low-dose MTX is now the most widely used first-line DMARD in the treatment of RA and is also used as the backbone in treatment with newer biological anti-TNF agents. It is the most common inflammatory arthritis, with an estimated incidence in the UK of 1.16% in women and 0.44% in men. RA is a chronic inflammatory disease of unknown aetiology that principally affects the smaller synovial joints in a symmetrical fashion leading, in the majority of cases, to joint destruction. Rheumatoid arthritis, Methotrexate, Infection, Varicella zoster, Immunosuppression Introduction
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