Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune multisystemic inflammatory disease which affects many organs but predominantly attacks the synovial tissues and joints.

The overall prevalence is 0.5-1% and the disease is 2-3 times more common in women 1.

Onset is generally in adulthood, peaking in the 4th and 5th decades. The paediatric condition, juvenile rheumatoid arthritis, is discussed separately.

Onset may be insidious or abrupt. Early features commonly include tiredness, malaise, and generalised aches. Arthritis symptoms typically first develop in the hands and wrists in a symmetric, proximal distribution. Feet and large joints may also be involved.

Aetiology is unknown but is probably multifactorial. It is generally considered that a genetic predisposition (HLA-DR B1 which is the most common allele of HLA-DR4 involved in RA) and an environmental trigger (Epstein-Barr virus postulated as a possible antigen, but not proven) lead to an autoimmune response that is directed against synovial structures and other organs.

Activation and accumulation of T CD4 cells in the synovium starts a cascade of inflammatory responses which result in:

  • activation of the macrophages and synovial cells and production of cytokines such as IL4 and TNF, which in turn cause proliferation of the synovial cells and increase production of destructive enzymes such as elastase and collagenase by macrophages
  • activating B cell lymphocytes to produce various antibodies including rheumatoid factor (RF-IgM antibodies against Fc portion of the IgG) which makes immune complexes that deposit in different tissues and contribute to further injury 
  • directly activate endothelial cells via increased production of VCAM1, which increases the adhesion and accumulation of inflammatory cells
  • producing RANKL which in turn activate osteoclasts causing subchondral bone destruction 

The inflammatory response leads to pannus formation. Pannus is an oedematous thickened hyperplastic synovium infiltrated by lymphocytes T and B, plasmocytes, macrophages and osteoclasts. Pannus will gradually erode bare areas initially, followed by the articular cartilage. It causes a fibrous ankylosis which eventually ossifies 2,3.

Diagnosis is based on a combination of clinical, radiographic, and serological criteria. The 2010 ACR - EULAR classification criteria for Rheumatoid Arthritis 4 has a maximal score of 10 and requires a score of >6 for a diagnosis of RA to be made:

  • joint involvement
    • 0: large joint
    • 1: 2-10 large joints
    • 2: 1-3 small joints (with or without involvement of large joints)
    • 3: 4-10 small joints (with or without involvement of large joints)
    • 5: >10 joints (at least 1 small joint)
  • serology
    • 0: negative RF and negative anti-CCP
    • 2: low-positive RF or low-positive anti-CCP
    • 3: high-positive RF or high-positive anti-CCP
  • acute phase reactants
    • 0: normal CRP and normal ESR
    • 1: abnormal CRP and abnormal ESR
  • duration of symptoms
    • 0: <6 weeks
    • 1: >6 weeks

Non-musculoskeletal features of RA tend to occur late in the disease and include:

  • pulmonary involvement
    • disease may involve the interstitum, airway, and/or pleura
  • cardiovascular disease
    • accelerated coronary artery and cerebrovascular atherosclerosis 8 contributing significantly to the excess mortality of RA
    • pericarditis
    • vasculitis: occurs more commonly with a severe erosive disease, rheumatoid nodules, high RF titres
  • cutaneous involvement
    • rheumatoid nodules are usually seen in pressure areas: elbows, occiput, lumbosacral 3
    • occurs in RF-positive patients 9
  • ocular involvement

There are several serological markers for rheumatoid arthritis:

  • rheumatoid factor (RF): is an IgM antibody against FC portion of the IgG antibodies, and is a traditional marker but is nonspecific; associated with several autoimmune and chronic infectious diseases
  • anti-cyclic citrullinated peptide (anti-CCP)/anti-citruillated plasma antibody (ACPA): it is more than 80% sensitive and more than 95% specific
  • elevated ESR or C-reactive protein

Musculoskeletal manifestations are the earliest and the dominant features of rheumatoid arthritis.

For further details, please refer to musculoskeletal manifestations of rheumatoid arthritis.

Pulmonary disease may involve the airway, interstitum, and/or pleura; a full description is available in respiratory manifestations of rheumatoid arthritis.

Splenomegaly may be seen as part of Felty syndrome, usually in longstanding RA.

Treatment of RA is aimed at improving the symptoms and slowing disease progression. Therapy is with a combination of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and TNF antagonists (e.g. etanercept) The anti-TNF treatments and variants of, which suppress the immune system, are known collectively as biological therapies.

The disease carries a significant burden of disability. There is also a reduction in life expectancy, with excess mortality usually related to its non-articular manifestations 5,6.

Rheumatoid arthritis was a term first coined by British physician Sir Alfred Baring Garrod (1819-1907) in 1859 11.

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Article information

rID: 12369
Synonyms or Alternate Spellings:
  • Rheumatoid arthritis (RA)
  • Rheumatoid arthritis (General)

Cases and figures

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    Case 1: rheumatoid hands
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    Case 2: dens involvement
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    Case 4: cervical spine involvement
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