Rheumatoid arthritis (RA) affects 0.5-1% of most populations worldwide. The average age of onset is 55 years but it can occur at any time, even in infancy (juvenile idiopathic arthritis). It is more common in women and smokers. It is a leading cause of disability and risks premature mortality by 5-10 years due to:

• Extra-articular involvement of the renal and respiratory tracts.
  
• Opportunistic infections in the presence of immunosuppressive drug therapy.
  
• Accelerated atheroma and subsequent coronary artery disease.

The underlying cause is unknown but is likely to encompass genetic factors, sex hormones and an unidentified initiating agent. B-cells, T-cells (particularly T_H17 and T_H1) and thepro-inflammatory cytokines interleukin 1 (IL-1), IL-6, IL-17 and tumour necrosis factorα (TNFα) generate persistent cellular activation, autoimmunity and inflammation of synovial joints and of a number of extra-articular sites.

See Chapter 22, Pathogenesis of rheumatoid arthritis, for more details.

The diagnosis of RA rests on a number of clinical and laboratory features. For the original 1987 American College of Rheumatology (ACR) criteria, at least four of the following following criteria must be met to make a diagnosis of RA. There are no exclusion criteria. Note that joint symptoms must be present for at least 6 weeks to differentiate RA from the post-viral arthropathies (e.g. parvovirus), which generally have a shorter time course and more benign prognosis.

Other radiographic features include soft tissue swelling, periarticular osteopaenia, and joint fusion or destruction. N.B. Rheumatoid factor (RF) is present in only 70% of patients and up to 15% of the normal population have RF but not RA. Anti-citrullinated protein antibody (ACPA, also known as anti-cyclic citrullinated peptide anti-CCP) is more specific for RA and is only found in 3% of the general population. The presence of either or both are linked to increased disease severity. The presence of rheumatoid nodules on examination indicates seropositivity for RF and thus a worse prognosis.

In 2010, new criteria were devised by collaboration between ACR and the European League Against Rheumatism (EULAR) to increase the sensitivity in early disease. The diagnosis of RA is based on the presence of synovitis in at least one joint (for which there is no better alternative diagnosis) and a score of ≥6 out of 10 from the following:

• Number and size of joints involved (score 0–5).
  
• Serologic abnormality (score 0–3).
  
• Elevated acute phase response (score 0–1).
  
• Symptom duration (score 0–1).

The most common presentation is insidious pain, swelling and stiffness of the small joints of the hands (metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, with characteristic sparing of the distal interphalangeals (DIPs)), although any synovial joint may be affected. In contrast to osteoarthritis, the symptoms are most marked in the morning, exacerbated by rest and improve with activity. In a minority of cases the disease can present acutely with widespread synovitis, with a migratory arthritis (palindromic RA) or with marked systemic features of pyrexia, fatigue and weight loss.

As the disease progresses, joint instability leads to subluxation and persistent deformity. Classic changes include:

• Subluxation at the MCP joints with palmar and ulnar deviation of the fingers.
  
• Disease at the PIP joints causes: