Rheumatoid arthritis

Rheumatoid arthritis (RA) is a common, chronic, systemic disease producing:
• A symmetrical inflammatory polyarthritis
• Extra-articular involvement, e.g. in the lungs and many other organs
• Progressive joint damage causing severe disability in young people, demanding considerable resources in terms of doctors, drugs and surgery


RA affects about 2% of the population worldwide and is just as common in tropical countries as in cold, damp Britain. It is about three times as common in women as in men. It can begin at any age from 10 to 70 years but it most often starts between the ages of 30 and 40 years. There is an increased incidence in those with a family history of RA (5-10%) and an association with HLA-DR4 (70%) in most ethnic groups. HLA-DRl is found in the majority of HLA-DR4-negative patients, particularly in Indians and Israelis.


The cause of RA is unknown. Toxic substances produced by the inflammatory reaction in the synovium are thought to lead to the destruction of cartilage, the characteristic feature of progressing RA.
Many immunological disturbances are seen and RA is considered to be an autoimmune disease for the following reasons.
AUTOANTIBODIES are seen. Rheumatoid factor is also found in other diseases and therefore may play little part in the pathogenesis of RA.
IMMUNE COMPLEXES are common in the synovial fluid and the circulation.
ASSOCIATION OF OTHER ORGAN-SPECIFIC AUTOIMMUNE DISEASES such as primary hypothyroidism and pernicious anaemia.
A likely hypothesis for the chronicity of the inflammatory process is a persistent foreign antigen, perhaps a bacterium or virus, that is taken up by macro phages but not destroyed or removed. This leads to a systemic inflammatory reaction, not unlike adjuvant arthritis in rats, mediated by the immune system and characterized by an inflammation of many joints, vasculitis and granuloma formation (nodules). Shows possible pathogenic mechanisms leading to joint damage and destruction.


RA is a disease of the synovium. There are two main pathological characteristics-inflammation and proliferation. The synovium shows signs of a chronic inflammatory reaction, with infiltration of lymphocytes, plasma cells and macro phages. It then proliferates and grows out over the surface of the cartilage, producing a tumour-like mass called ‘pannus’.
The subcutaneous nodules seen in RA, usually called rheumatoid nodules, have a central area of necrosis surrounded by a palisade of macrophages and fibrous tissue. Similar lesions occur in the pleura, pericardium and lung. The lymph nodes are often hyperplastic.


RA usually presents with the insidious onset of pain and stiffness in the small joints of the hands and feet, which eventually goes on to the characteristic chronic bilateral symmetrical peripheral polyarthritis. In 25% of cases it presents as arthritis of a single joint, such as the knee. An acute onset of the disease is characteristic in the elderly and is sometimes called ‘explosive RA’.


JOINT PAIN. The pain is worst on waking in the morning and may improve with activity. There is often pain at night and disturbed sleep.
MORNING STIFFNESS, often lasting for several hours.
GENERAL SYMPTOMS. Fatigue and general malaise are common.
DISABILITY depends upon the changes in individual joints.
NON-ARTICULAR SYMPTOMS are discussed below.
Patients may present with carpal tunnel syndrome or disease of other systems.


SWELLING: soft tissue swelling caused by effusion or synovial proliferation.
TENDERNESS on pressure or movement.
LIMITATION OF MOVEMENT with muscle wasting around affected joints.
DEFORMITIES occurring LD the later stages of the disease.
NODULES and other extra-articular features.

Pathogenesis of rheumatoid arthritis.
Pathogenesis of rheumatoid arthritis.

Pattern of joint involvement

The characteristic pattern of joint involvement is shown. Most patients eventually have many joints involved, including the hands, wrists, elbows, shoulders, cervical spine, knees, ankles and feet. The dorsal and lumbar spines are not involved.
THE HIPS. The hip joint is involved in about 50% of patients. This seldom occurs at the onset of the disease but usually develops within the first few years.
THE HANDS AND WRISTS. The pattern of joint involvement is shown in Fig. 8.9. In contrast to OA the distal interphalangeal joints are only involved in 30% of cases. Early in the disease there is spindling of the fingers due to swelling of the proximal but not distal interphalangeal joints; the metacarpophalangeal and wrist joints are also swollen. As the disease progresses, there is weakening of joint capsules causing laxity and deformity. The characteristic deformities of the rheumatoid hand are shown.
THE FEET. Deformities in the feet are similar to those seen in the hands and wrists. There is lateral deviation of the toes and subluxation of the metatarsophalangeal joints so that the heads of the metatarsals become palpable in the soles of the feet. Patients often describe a sensation of walking on marbles.
THE KNEES. Synovial effusions and quadriceps wasting are early features. Later flexion, valgus or varus deformities appear with joint instability. The pressure of fluid within the knee leads to the formation of a Baker’s cyst in the popliteal fossa. With the increased pressure, the knee joint may rupture, releasing irritant synovial fluid into the muscles of the calf. The sudden onset of pain with swelling of the ankle and a positive Homan’s sign may be mistaken for deep vein thrombosis but the correct diagnosis can be confirmed by ultrasound or arthrogram.

The pattern of hand involvement in rheumatoid ritis.
The pattern of hand involvement in rheumatoid
Characteristichand deformities in rheumatoid arthritis.
Characteristichand deformities in rheumatoid

Progression and prognosis of joint involvement The activity and rate of progression of joint changes in RA are very variable. New joints are involved in an additive pattern in most cases. The pattern of joint involvement is usually established within months of its onset.
Partial remissions and relapses follow. In some, the disease is mild with little or no progression. In others, the characteristic deformities and complications occur. About 10% of patients become seriously disabled and 40% develop significant disability.
PALINDROMIC RHEUMATISM. Episodes of arthritis may precede the development of chronic RA. Palindromic rheumatism is described.

Non-articular features

1 Rheumatoid nodules are found in about 20% of cases. They are most often felt on the ulnar surface of the forearm just below the elbow but they can appear almost anywhere. Patients with nodules are usually seropositive.
2 Bursitis. The olecranon and other bursae may be swollen.
3 Tenosynovitis, particularly affecting the flexor tendons in the palm of the hand, can cause trigger finger as well as pain and swelling and may contribute to flexion deformities. Swelling of the extensor tendon sheath over the dorsum of the wrist is common.
4 Muscle wasting. There is wasting of muscles around affected joints, particularly in the hands.

THE EYES. The commonest eye problem in RA is secondary Sjogren’s syndrome, occurring in about 15% of cases. It comprises dry eyes (keratoconjunctivitis sicca), a dry mouth (xerostomia) and RA. This syndrome is also seen in other connective tissue disorders, e.g. SLE. The lacrimal and salivary glands are infiltrated with lymphocytes and plasma cells, suggesting that this syndrome is part of the immunological process of rheumatoid disease. The development of dry eyes is particularly important because tear production protects the cornea. Artificial tears such as hypromellose 0.3% eyedrops should be prescribed. Primary Sjogren’s syndrome is described.
2 Scleritis may occur, causing a painful red eye. Scleromalacia presents as a bluish discoloration of the sclera around the iris; perforation rarely occurs.


1 Carpal tunnel syndrome is the commonest neurological abnormality .
2 Atlanto-axial subluxation can cause serious neurological abnormality. In this condition rheumatoid involvement
of an adjacent bursa leads to weakening of the transverse ligament of the atlas. This in turn allows the odontoid process to separate from the anterior arch of the atlas and to move posteriorly on flexion of the cervical spine with potential infringement on the cervical cord. Atlanto-axial subluxation is a common X-ray finding, but cervical cord compression is fortunately rare.
3 Polyneuropathy occurs rarely causing glove and stocking sensory loss and sometimes motor weakness. It is usually symmetrical and often involves the legs. Multiple mononeuropathy (mononeuritis multiplex) can also occur as a result of vasculitis.

The non-articular manifestations of rheumatoid arthritis.
The non-articula  manifestations of rheumatoid arthritis.

1 Palpable lymph nodes are common, usually in the distribution of affected joints.
2 The spleen may be enlarged. RA with splenomegaly and neutropenia is known as Felty’s syndrome. Recurrent infections may occur. HLA-DRW4 is found in 95% of such patients compared with 70% of patients with RA and 30% of controls. Skin pigmentation also  occurs.
3 Anaemia is almost universal in RA and is proportional to the activity of the inflammatory process. The anaemia is usually normochromic and normocytic-the anaemia of chronic disease; it may be iron-deficientdue  to gastrointestinal blood loss from NSAID ingestion, or rarely, haemolytic (positive Coombs’ test) or
part of a pancytopenia due to hypersplenism in Felty’s syndrome.
3 Thrombocytosis correlates with disease activity. THE LUNGS. The lungs are commonly affected; the abnormalities are described in detail. They include:
1 Pleural effusion-this is the commonest lung problem and occurs particularly in middle-aged men but seldom in women. It may precede the development of arthritis. The fluid has a high protein and low sugar content.
2 Diffuse .fibrosing alveolitis is rare.
3 Rheumatoid nodules in the lungs can be up to 3 ern in diameter and mistaken for carcinoma.
4 Caplan’s syndrome is the occurrence of nodular pulmonary fibrosis in patients with RA exposed to various industrial dusts.
5 Small airway disease is commoner in patients with RA who smoke than in normal people who smoke.

THE HEART. A pericardial rub is often heard in patients with RA (up to 30%). Pericarditis is seldom a clinical problem but occasionally a large pericardial effusion causes tamponade. Constrictive pericarditis is rare.
THE KIDNEYS. RA is a common cause of amyloidosis affecting the kidneys. It usually presents as proteinuria and may go on to renal failure or to the nephrotic syndrome. Analgesic nephropathy is nowadays very rare .
THE SKIN. The skin is not directly involved in RA but leg ulcers may occur, particularly in patients with Felty’s syndrome and in those with a vasculitis. Vasculitis most often appears as nail fold lesions in the hands and, very occasionally, it produces gangrene of the fingers or toes. Ankle oedema is often seen in active RA and is due to increased vascular permeability.

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