Intended for healthcare professionals

Education And Debate


BMJ 1995; 310 doi: (Published 04 March 1995) Cite this as: BMJ 1995;310:587
  1. M Akil,
  2. R S Amos
  1. M Akil is registrar in rheumatology and R S Amos is consultant rheumatologist at Sheffield Centre for Rheumatic Diseases, Neither Edge Hospital, Sheffield.
  2. The ABC of Rheumatology is edited by Michael L Snaith, senior lecturer in rheumatology at Nether Edge Hospital, Sheffield.

    Rheumatoid arthritis is the commonest disorder of connective tissues and is an important cause of disability, morbidity, and mortality. Life expectancy is reduced by four years in men and by 10 years in women, though this reduction is accounted for by a minority of patients with more severe disease. Nevertheless, patients with this condition may be offered life insurance only on the basis of loaded premiums.

    Rheumatoid arthritis occurs worldwide with variable incidence and severity. In Western countries, it affects up to 1-3% of the population, although many are not severely affected and may not seek medical advice at all. Overall, there is a 3:1 female preponderance, but this excess is greater in young people and the age related incidence is approximately equal in elderly people.

    Factors associated with poorer prognosis in rheumatoid arthritis

    • Insidious polyarticular onset

    • Male patients

    • Extra-articular manifestations

    • Functional disability at one year after start of disease

    • Substantially raised concentration of rheumatoid factors

    • Presence of HLA-DR4

    • Radiographic evidence of erosions within three years of start of disease

    The aetiology of rheumatoid arthritis remains unclear, but there is evidence of genetic predisposition to the disease. The presence of HLA-DR4 is significantly commoner among sufferers of rheumatoid arthritis who are white. Rheumatoid arthritis is associated with only certain subtypes of HLA-DR4 (HLA-Dw4 and HLA-Dw14); susceptibility is related to a shared epitope on the HLA molecule.

    Rheumatoid arthritis in women

    • Higher incidence of disease in women of child bearing age

    • Disease tends to go into remission during pregnancy and to flare after giving birth

    • Use of contraceptive pill or high gravidity adds some protection against later development of disease

    Clinical features Joint damage

    The start of the disease is usually insidious but can be episodic or acute. Rheumatoid arthritis usually presents as a polyarthritis affecting small joints or small and large joints. Early disease is characterised by pain and other cardinal signs of inflammation (heat, swelling, functional loss, and possible erythema over the joints) but not by damage and deformity. If the disease remains active and uncontrolled the inflammation will usually spread to additional joints and gradual irreversible tissue damage will occur, causing deformity and instability of joints. The most serious long term disability is associated with damage to the larger weight bearing joints.

    FIG 1
    FIG 1

    Effect of rheumatoid arthritis on the hand: (left) early changes and (right) later deformity

    Inflammation of other synovial structures is common, and a similar process may occur in tendon sheaths, progressing to serious dysfunction and rupture. The typical rheumatoid deformities—such as ulnar deviation of the fingers, z deformity of the thumb, and swan neck and boutonniere deformities—are mostly due to damage or displacement of tendons. Palpable thickening or nodularity of tendons is common.

    Causes of impaired hand function in rheumatoid arthritis

    • Active synovitis

    • Joint deformity

    • Rupture of tendon

    • Carpal tunnel syndrome

    • Mononeuritis

    • Compression of nerve root at T1

    • Compression of spinal cord

    The spine—Although rheumatoid arthritis predominantly affects peripheral joints, discovertebral joints of the cervical spine are often affected. This may lead to atlantoaxial subluxation or, less commonly, subluxation at lower levels, with subsequent compression of the spinal cord. The earliest and most common symptom of cervical subluxation is pain radiating up into the occiput. Other symptoms include paraesthesia, sudden deterioration in hand function, sensory loss, abnormal gait, and urinary retention or incontinence.

    Effusion of the knee may produce a popliteal (Baker's) cyst. This may rupture to cause diffuse pain and swelling in the calf that mimics deep vein thrombosis.

    FIG 2
    FIG 2

    Magnetic resonance image of cervical spine showing spinal cord compression at C1 and C2.

    FIG 3
    FIG 3

    Rheumatoid nodule (above) and rheumatoid vasculitis (right).

    Extra-articular manifestations of rheumatoid arthritis

    • Rheumatoid nodules

    • Vasculitis

    • Pulmonary

      Pleural effusion

      Fibrosing alveolitis


    • Cardiac


      Mitral valve disease

      Conduction defects

    • Skin

      Palmar erythema

      Cutaneous vasculitis

      Pyoderma gangrenosum

    Non-articular manifestations

    Non-articular manifestations of rheumatoid arthritis are common. Rheumatoid nodules—which affect about a fifth of patients—may occur anywhere but are most common at sites of pressure, notably the extensor surfaces of the forearms and the posterior surface of the Achilles tendon.

    A wide variety of other systems may be damaged by the rheumatoid process. Disease of small and sometimes larger blood vessels may be caused by deposition of immune complex in the vascular walls. This can lead to digital infarction, larger skin ulcers, and mononeuritis because of damage to the vasa nervorum.

    Renal disease is rare but may occur as a result of amyloidosis, which presents as proteinuria or drug toxicity.

    FIG 4
    FIG 4

    Renal amyloid (Congo red stain.)

    Eye complications

    Sjogren's syndrome—The sicca complex results in dry gritty eyes with slight redness but normal vision. It is confirmed with the Schirmer test, which measures the wetting of a strip of sterilised filter paper when one end is placed under the eyelid. It is usually a late feature in women with seropositive rheumatoid arthritis.

    Episcleritis is ocular irritation with nodules. Vision is normal.

    Scleritis causes severe pain and occasionally reduces vision. There is diffuse or nodular redness, and the end stage of the condition is healing, with atrophy producing a bluish-grey sclera.

    FIG 5
    FIG 5

    Scleritis associated with rheumatoid arthritis

    Felty's syndrome

    This is a combination of seropositive rheumatoid arthritis (often with relatively inactive synovitis) with splenomegaly and neutropenia. It is associated with serious infections, vasculitis (leg ulcers, mononeuritis), anaemia, thrombocytopenia, and lymphadenopathy.

    Neurological complications

    These include entrapment of peripheral nerves (carpal tunnel, ulnar, lateral popliteal, tarsal, etc); mononeuritis multiplex; peripheral neuropathy—either associated with the disease or caused by drugs; compression of nerve roots; and compression of the cervical region of the spinal cord.

    Complications of rheumatoid arthritis

    • Joint failure causing physical disability

    • Osteoporosis

    • Depression

    • Increased risk of infections

    • Amyloidosis

    • Complications of medical and surgical treatment

    Investigations Immune abnormalities

    Rheumatoid factors are antiimmunoglobulins, and anti-IgG IgM is the immunological hallmark of rheumatoid arthritis. It is detected with the Rose-Waaler assay, but it is neither universally present in, nor specific for, rheumatoid arthritis: it is found in the sera of 80% of patients with rheumatoid arthritis, but the remainder are persistently seronegative despite otherwise typical disease. These patients may, however, be found to carry rheumatoid factors of other isotypes. The extra-articular features of rheumatoid arthritis are much commoner in patients with high concentrations of rheumatoid factor, but it is a poor guide to the severity of joint disease and to the success or otherwise of treatment.

    Laboratory findings in rheumatoid arthritis

    • Anaemia—normochromic or hypochromic, normocytic (if microcytic consider iron deficiency)

    • Thrombocytosis

    • Raised erythrocyte sedimentation rate

    • Raised C reactive protein concentration

    • Raised ferritin concentration as acute phase protein

    • Low serum iron concentration

    • Low total iron binding capacity

    • Raised serum globulin concentrations

    • Raised serum alkaline phosphatase activity

    • Presence of rheumatoid factor

    Antinuclear antibodies may be present in some patients. The test for antinuclear antibody is widely used to screen for systemic lupus erythematosus, but it should be remembered that some patients with lupus will have positive tests for rheumatoid factor while some patients with rheumatoid arthritis will have positive tests for antinuclear antibody. Thus neither test is a universal diagnostic tool.

    Other causes of positive test for rheumatoid factor

    • Other connective tissue diseases

    • Viral infections

    • Leprosy

    • Leishmaniasis

    • Subacute bacterial endocarditis

    • Tuberculosis

    • Liver diseases

    • Sarcoidosis

    • Mixed essential cryoglobulinaemia

    Indicators of acute phase response

    A raised erythrocyte sedimentation rate (or plasma viscosity) and the presence of acute phase proteins such as C reactive protein are commonly found in patients with rheumatoid arthritis, especially when the disease is active. They reflect the severity of acute inflammation and thus may be a reasonable guide to the success of drug treatment, though they are not specific to rheumatoid arthritis. The disease is likely to progress if a raised erythrocyte sedimentation rate (or presence of C reactive protein) persists, but progression can still occur if they do not persist.

    Causes of anaemia in rheumatoid arthritis

    • Anaemia of chronic disease

    • Iron deficiency—blood loss caused by non-steroidal anti-inflammatory drugs

    • Suppression of bone marrow function—caused by sulphasalazine, penicillamine, gold, and cytotoxic drugs

    • Folate deficiency—caused by sulphasalazine, methotrexate

    • Vitamin B-12 deficiency—caused by associated pernicious anaemia

    • Haemolysis—caused by sulphasalazine and dapsone

    • Felty's syndrome

    Liver function

    Tests for liver function may give abnormal results in patients with rheumatoid arthritis. Serum concentrations of transaminases and alkaline phosphatase may be moderately elevated when the disease is active.


    Radiographs of the hands often are normal at presentation or may show swelling of soft tissue, loss of joint space, or periarticular osteoporosis. Erosions typical of rheumatoid arthritis develop within three years of the start of the disease in over 90% of patients who ultimately develop the erosions.

    FIG 6
    FIG 6

    Radiograph of hands showing rheumatoid erosions.

    Unusual presentations

    Symmetrical small joint polyarthritis, with or without large joints also being affected, is the commonest presentation. In elderly patients the start of rheumatoid arthritis may be indistinguishable from polymyalgia rheumatica. Occasionally, rheumatoid arthritis may present as a monoarthritis. Other conditions (such as infection, crystal arthritis, other inflammatory arthritis, etc) must be excluded before a diagnosis of rheumatoid arthritis is made.

    Unusual patterns of start of rheumatoid arthritis

    • Palindromic

    • Monoarthritic

    • Asymmetrical

    • Polymyalgic

    • Oligoarthritic

    Palindromic rheumatism is characterised by recurrent episodes of mostly oligoarticular arthritis that leave no residual clinical or radiological changes. Up to half of patients with this condition later develop typical rheumatoid arthritis, often accompanied by conversion to seropositivity for rheumatoid factor.

    Differential diagnosis of rheumatoid arthritis

    Psoriatic arthritis—always seronegative

    Primary nodal osteoarthritis

    Other connective tissue diseases

    Calcium pyrophosphate deposition disease

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