RHEUMATOID ARTHRITIS (Rheumatoid polyarthritis)

Rheumatoid arthritis is a chronic inflammation of joints, often associated with mild constitutional symptoms. It nearly always affects several joints at the same time (polyarthritis). Joint changes of a similar nature also occur in a number of other conditions such as juvenile chronic arthritis (Still’s disease), Reiter’s syndrome, psoriasis, lupus erythematosus, and other connective tissue or collagen diseases.

Cause. The cause is unknown. At present only two possibilities attract serious consideration:

The hypothesis of auto-immunity, possibly to type II collagen, is based mainly on the observation that the serum of many patients with rheumatoid arthritis contains an antibody known as rheumatoid factor, which reacts with the body protein gamma globulin. When the antibody is present the disease is termed ‘sero-positive’, as contrasted with sero-negative arthritis when the antibody is absent. The source of the antigen, and many other details of the mechanism by which rheumatoid factor is formed, are unknown.

The hypothesis of infection is likewise without sure foundation. Infection – possibly by a virus or by organisms of the mycoplasma or diphtheroid group – may result in liberation of antigenic type II collagen from the patient’s own articular cartilage.

Pathology. The synovial membrane is thickened by chronic inflammatory changes: characteristically it is infiltrated with macrophage-like cells and T-cell lymphocytes (Fig. 9.1). Later the articular cartilage is gradually softened and eroded, and the subchondral bone may also be eroded, characteristically at the joint margins – probably from the action of lytic enzymes and inflammatory mediators produced in the thickened synovial membrane. The eroded surfaces become covered by a soft membrane of inflammatory tissue known as ‘pannus’.

Fig. 9.1 Rheumatoid arthritis, with possible results. In the active phase there is marked thickening of the synovial membrane. Later, the articular cartilage is often eroded and in severe cases there may be some destruction of bone. The possible results are: 1. restoration to normal (only after mild disease of short duration); 2. continuing mildly active disease with permanently damaged joint surfaces and restricted movement; and 3. secondary osteoarthritis from wear-and-tear degeneration of the damaged joint surfaces.

The pathological changes are not confined to joints. The synovial lining of tendon sheaths may be similarly inflamed and thickened, both in the hands and in the feet. The contained tendons may become softened and may rupture, aggravating any existing deformity. Inflammatory nodules may form in the soft tissues.

After months or years of activity the disease process tends to become less active, usually leaving a number of joints that are permanently damaged, with consequent deformity, instability, or ankylosis.

Clinical features. The patient is usually a young or middle-aged adult, and is more likely to be a woman than a man. Any joint may be affected, but the incidence is higher in the more peripheral joints such as the hand joints, wrists, feet, knees, and elbows than in the lumbar or thoracic spine, shoulders, or hips. The onset is gradual, with increasing pain and swelling of a joint. Soon a number of other joints are similarly affected. Pain and stiffness are often worst when activity is resumed after resting. Often there is constitutional disturbance, with tiredness and anaemia, and occasionally fever.

On examination the affected joints are swollen from synovial thickening. The overlying skin is warmer than normal. The range of joint movements is restricted, and movement causes pain, especially at the extremes. These clinical features are often more severe in sero-positive disease than when rheumatoid factor is absent from the serum.

It is important always to study the condition of the cervical spine, which is commonly affected. Despite relatively minor symptoms, destruction of ligaments and bone may sometimes lead to subluxation of an intervertebral joint of such degree that the spinal cord is endangered, and it is important always to be wary of this possibility.

Extra-articular features may include enlargement of lymph nodes, muscle wasting, subcutaneous rheumatoid nodules, and anaemia.

Imaging. Radiographic features: At first there is no alteration from the normal. Later, there is diffuse rarefaction in the area of the joint. Eventually destruction of joint cartilage may lead to narrowing of the cartilage space and, in severe cases, to localised erosion of the bone ends (Fig. 9.2) especially in periarticular sites. Radioisotope bone scanning shows increased uptake of the isotope in the region of affected joints.

Fig. 9.2 Joint damage in rheumatoid arthritis. Left. Long-established rheumatoid arthritis of the knee. Note the rarefaction and loss of cartilage space. Right. Destruction of the elbow joint in a case of severe rheumatoid arthritis of long duration.

Investigations. Both the erythrocyte sedimentation rate and C-reactive proteins are raised during the active phase. The rheumatoid factor is present in the serum of 80% of patients with rheumatoid arthritis and is detected by the latex fixation or Rose-Waaler sheep cell agglutination tests.

Diagnosis. For a diagnosis of rheumatoid arthritis four of the following seven criteria must be present.

The clue to the diagnosis is the simultaneous involvement of several joints, with raised sedimentation rate. The presence of rheumatoid factor in the blood is highly suggestive, though the tests are not specific for rheumatoid arthritis; and rheumatoid factor may be absent in about 20% of patients even in well-established rheumatoid arthritis.

A search should always be made for evidence of one of the distinct clinical entities that may be associated with joint changes of a rheumatoid type. The most important of such conditions are:

These conditions are all sero-negative, and they may be associated with ankylosing spondylitis.

Course. There is a tendency for rheumatoid arthritis to become quiescent after remaining active for months or years. In most cases there is permanent impairment of joint function. In certain joints – especially in the knees – degenerative changes are often superimposed upon the previous rheumatoid condition, and lead to increasingly severe disability even though the original rheumatoid affection is no longer active.

Treatment. The treatment of rheumatoid arthritis is still evolving, but no specific cure has been found. Innumerable drugs have been tried, but it is by no means certain that any of them has an influence on the duration of the disease or on its eventual outcome in a particular case. Undoubtedly some drugs can mitigate the symptoms, particularly the group of non-steroidal anti-inflammatory drugs (NSAIDs) which also have an analgesic effect in addition to their action in reducing synovial inflammatory changes.

Methods of treatment may be classified into the following categories:

Rest and constitutional treatment. Rest is thought to be beneficial, especially in the early stages of the disease and during an exacerbation. At many centres patients are admitted to hospital at the outset for a period of rest, and sometimes this temporary removal from the home environment, with skilled nursing, regular food, and proper sleep, has a remarkably good effect on the general health, which is often impaired in these cases. Rest for individual joints is also helpful during the initial active stage of inflammation, provided it is not enforced for too long. Convenient light splints for this purpose may be made from expanded polystyrene, or plaster of Paris may be used. Splintage is seldom required for more than a few weeks and should be followed by graduated exercises under the supervision of a physiotherapist.

Drugs. Drugs used in rheumatoid arthritis fall mainly into the categories of the NSAIDs, and the potent anti-inflammatory agents grouped under the heading of corticosteroids. A logical plan is to use aspirin since it has both analgesic and mild anti-inflammatory properties, but to be effective it may have to be given in fairly large doses. Alternative first-line drugs should probably be chosen from the group of NSAIDs, which includes indometacin, ibuprofen, naproxen, phenoprofen and piroxicam. Due regard must be paid to the risk of side effects: gastric pain is a common complaint with most of these drugs, and more serious complications, such as gastric bleeding, are seen occasionally.

A different class of anti-rheumatic agents, to be regarded as second-line drugs, includes the potentially toxic group of compounds containing gold salts, usually given by intra-muscular injection. These must be used with care, but they are thought to be sometimes beneficial and therefore justified in severely afflicted patients who have failed to respond to the first-line drugs. Sulfasalazine, a derivative of sulphapyridine, is now also used increasingly as a second-line drug. Its mode of action is uncertain, but it has the advantage over gold salts of oral administration and fewer side effects. Another drug in this second-line category is penicillamine, the effect of which is comparable to that of gold. This also is potentially toxic for the kidneys and must be used with caution. Also included in this category are certain immuno-suppressive agents, such as azathioprine and methotrexate.

Newer developments in drug therapy have centred on biological molecules manufactured by genetic engineering that can block or reduce the production of destructive cytokines and enzymes from the cells of the rheumatoid synovium. The first of these, anti-tumour necrosis factor (TNF) has given very encouraging results in modifying the disease, but no long-term results are yet available.

The place of corticosteroids in rheumatoid arthritis is still controversial. There is wide agreement that because of their serious side effects they should be avoided altogether in the great majority of patients. There may be a small proportion of severely afflicted patients in whom the advantages outweigh the hazards.

Intra-articular injections. Injections of corticosteroids (usually hydrocortisone) into an affected joint can produce worth-while relief, but the disadvantages have precluded their widespread use. The main disadvantages are:

In general, it is wise to avoid repeated injections.

Physiotherapy. Physiotherapy is widely used and generally beneficial, even though some of the benefit may result from suggestion or ‘placebo effect’ rather than from a direct effect on the disease process. Heat in the form of infra-red radiation or short-wave diathermy is commonly used, but probably the most useful contribution of physiotherapy is active exercises including hydrotherapy, designed both to keep joints as mobile as possible and to maintain useful function in the muscles that control them.

Occupational therapy. Occupational therapy is useful mainly in helping seriously disabled patients to find ways in which they can more easily carry out the various activities of everyday life – bathing, toilet, cooking, feeding, boarding public transport, and many others. Many useful aids for the disabled are available, and those that are appropriate should be brought to the patient’s notice.

Operation. Operation has an important place in treatment, but each operation must be considered as a component in the overall plan of management and not as a substitute for other measures. Operation may be applicable to the early stages of the disease, or it may be used in the later stages to salvage a joint that has been permanently damaged and remains a source of persistent pain.

In the early stages the operation most commonly used is synovectomy – excision of thickened and inflamed synovial membrane from joint or tendon sheath. As well as relieving pain, this may possibly slow down the inflammatory process and so help to preserve articular cartilage in an affected joint. It is undertaken mainly in the knee and wrist, and in the small joints and tendon sheaths of the hand.

Operation may also be required in the hand for repair or replacement of ruptured tendons, or for correction of finger deformities. In the painful elbow there is often a place for excision of the diseased radial head, and at the wrist excision of the lower end of the ulna may bring worthwhile relief in selected cases.

Operations used in the later stages of joint disease are arthroplasty and arthrodesis. Arthroplasty is applicable particularly to the hip and knee, and sometimes to the shoulder or elbow, and to the joints of the fingers and toes. Arthrodesis is usually the operation of choice for the joints of the spine, the wrist and the ankle.

Further details are given in the sections on individual joints.

JUVENILE CHRONIC ARTHRITIS (Juvenile rheumatoid arthritis; Still’s disease)

Juvenile chronic arthritis is uncommon. In the past the general term ‘Still’s disease’ was often used broadly to cover all its manifestations, but almost certainly the disease is not a single entity. Rather it comprises a number of conditions that are more or less distinct, though features common to all are pain, swelling and stiffness of joints. Recognised types include:

These subgroups vary in age of onset, sex incidence, course, complications, and prognosis.

Sero-positive juvenile rheumatoid arthritis is similar in all respects to the same disease in adults. It tends to begin rather late in childhood and affects girls more often than boys.