Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease defined by persistent synovial inflammation that, if untreated, produces progressive joint destruction, disability, and excess cardiovascular mortality. It affects around 1% of the UK population with a 3:1 female-to-male predominance and peak onset between 40 and 60 years. Presentation is typically a symmetrical inflammatory polyarthritis of the small joints of the hands and feet with prolonged morning stiffness, fatigue, and constitutional symptoms. Early diagnosis is critical: NICE NG100 mandates urgent rheumatology referral for any suspected persistent synovitis, with a 3-month window of opportunity in which DMARD therapy maximises the chance of remission and prevents irreversible joint damage.
RA targets the synovial joint. In genetically susceptible individuals (HLA-DR4 shared epitope, ~60-70% of patients), environmental triggers drive autoimmunity. Smoking is the dominant modifiable risk, particularly for seropositive disease. Citrullination of self-proteins generates anti-citrullinated protein antibodies (anti-CCP), often years before clinical symptoms. Rheumatoid factor, an IgM antibody against IgG Fc, is present in around 70% but is non-specific and is also found in chronic infection, other autoimmune disease, and ~5% of healthy adults.
T cells, B cells, and macrophages infiltrate the synovium, which thickens into invasive pannus. TNF-alpha is the dominant cytokine and the target of first-line biologics; IL-6 and IL-1 amplify systemic disease. RANKL upregulation activates osteoclasts at the bare areas, producing the characteristic marginal erosions seen on radiographs. Joint destruction is progressive and irreversible if inflammation persists, while circulating cytokines drive anaemia of chronic disease, fatigue, and accelerated atherosclerosis, the leading cause of death in RA.\n\nClassic joint distribution: MCP, PIP, wrist, MTP, and cervical spine (C1/C2). DIP joints, the lumbar spine, and the sacroiliac joints are typically spared. Involvement of any spared joint argues against RA and should redirect the differential.
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