Rheumatoid arthritis

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

RA has an overall prevalence of 0.5-1%. There is a female predominance, with the disease being 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, will be discussed separately.

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

Aetiology is unknown, and 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 requires a score of >6/10 for a diagnosis of RA to me made:

A- 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)

B- Serology

  • 0: negative RF and negative ACPA
  • 2: low-positive RF or low-positive ACPA
  • 3: high-positive RF or high-positive ACPA

C- Acute Phase Reactants

  • 0: normal CRP and Normal ESR
  • 1: abnormal CRP and Abnormal ESR

D- Duration of Symptoms

  • 0: <6 weeks
  • 1: >6 weeks
  • pulmonary involvement
  • cardiovascular disease
    • accelerated coronary artery and cerebrovascular atherosclerosis 8 which contribute 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

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): 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.

Please refer to the article on 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, NSAIDs, DMARDs (disease modifying antirheumatic drugs) and TNF antagonists (e.g.etanercept - Enbrel TM) 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.

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Article information

rID: 12369
Section: Pathology
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 3: rheumatoid lung
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    Case 4: cervical spine involvement
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    Rheumatoid Arthri...
    Case 5
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    Case 6
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