ABC of Rheumatology: RHEUMATOID ARTHRITIS—II: TREATMENTBMJ 1995; 310 doi: https://doi.org/10.1136/bmj.310.6980.652 (Published 11 March 1995) Cite this as: BMJ 1995;310:652
- M Akil,
- R S Amos
Except for the mildest cases, rheumatoid arthritis cannot be adequately managed by one specialist in isolation from others. Most people with rheumatoid arthritis cope better if they understand their condition and have realistic expectations of the benefits and disadvantages of treatment. Therefore, education of patients is an important aspect of treatment. Specialist rheumatology nurses have become well established in many rheumatology departments; their role includes monitoring drugs used to treat rheumatoid arthritis and differentiating minor or unrelated symptoms from those that require action.
Goals of treatment in rheumatoid arthritis
Relief of symptoms
Preservation of function
Prevention of structural damage and deformity
Maintenance of patient's normal lifestyle
In a physiotherapy department local measures such as heat, cold, and electrotherapy may be used to reduce pain and generally form part of a rehabilitation programme of exercises designed to improve muscle strength and encourage mobility in affected joints. The aims of occupational therapy are to educate patients; to protect joints; to analyse function and to improve it by means of exercise and use of aids and appliances; and to provide splints when necessary.
Role of physiotherapy for rheumatoid arthritis
Education of patients
Reduction of pain and swelling
Mobilisation of joints to minimise deformity
Strengthening of muscles and prevention of disuse atrophy
Increase range of movements and function
Few of the individual techniques used in physiotherapy and occupational therapy have been subjected to controlled trials, but there is no doubt that therapists who are skilled in handling atrophied, inflamed, and stiff tissues and familiar with the problems faced by patients with arthritis greatly help in treatment and rehabilitation.
Role of podiatry for rheumatoid arthritis
Local redistribution of loading to prevent formation of calluses
Provision of specialised footwear
Provision of customised orthoses and insoles to improve foot and toe posture and function
Provision of foot care to prevent local infection
The aims of surgery are to relieve pain and to restore function. Indications for urgent treatment are septic arthritis, ruptured tendons, and compression of nerves and spinal cord.
Although synovectomy may slow down damage for a relatively short period, it does not alter the final outcome. This procedure is becoming less popular among surgeons who specialise in treating arthritis. When surgery is being considered the patient must be part of the decision making process, as must the patient's rheumatologist as well as the surgeon, and should have a realistic understanding of the procedure. The timing of surgery is crucial: for example, forefoot arthroplasty, if indicated, should usually precede knee or hip arthroplasty to minimise the risk of infection.
Corrective surgical procedures
Cervical fusion for subluxation
Drugs for relief of symtpoms
These drugs provide symptomatic relief but do not modify the course of the disease. For the mildest cases they may be used alone, but they are usually used in combination with disease modifying drugs. The response of individual patients varies, and several drugs may be tried in succession to find a suitable one. A single large dose at night, especially if the drug is in a slow release form, often helps to relieve early morning stiffness. Gastrointestinal toxicity is the commonest side effect. Inflammation, erosion, and ulceration occur in the oesophagus, stomach, duodenum, and small bowel. These are often chronic and asymptomatic, presenting with anaemia or occasionally with acute upper gastrointestinal bleeding. H2 blockers reduce the risk of duodenal ulceration but have little protective effect against gastric ulcers. Misoprostol, a synthetic analogue of prostaglandin E1, protects against gastric and duodenal ulcers, but its use is limited by the high incidence of diarrhoea and abdominal pain. It should not be used in women who are or may become pregnant. Proton pump inhibitors are used for gastro-oesophageal reflux, which can be exacerbated by non-steroidal anti-inflammatory drugs. Routine prophylaxis against peptic ulcer disease is controversial, but it is required for patients with a previous history of ulceration. Non-steroidal anti-inflammatory drugs should be used with caution in patients with renal failure, cardiac failure, or uncontrolled hypertension to avoid decompensation due to renal prostanoid blockade. Interstitial nephritis may present idiosyncratically. Concomitant administration of non-steroidal anti-inflammatory drugs with anticoagulants is best avoided if possible. Administration of non-steroidal anti-inflammatory drugs in the later stages of pregnancy delays the onset and increases the duration of labour. It may lead to the closure of ductus arteriosus in utero and possibly persistent pulmonary hypertension of the newborn. The drugs are safe for use by lactating mothers except for aspirin, which may increase the risk of Reye's syndrome in children.
Non-steroidal anti-inflammatory drugs
Side effects of non-steroidal anti-inflammatory drugs
Dyspepsia and gastritis
Gastric or duodenal ulceration
Central nervous system
Headache and dizziness
Precipitation of acute renal failure
Paracetamol, dextropropoxyphene, and codeine are used for simple pain relief. The choice is not critical but depends on patients' preferences. Stronger, narcotic analgesics should be avoided.
Intra-articular corticosteroids can help to settle a flare. Long acting (depot) drugs such as triamcinolone or methylprednisolone are usually used for injection of large joints, but hydrocortisone or prednisolone is preferable for superficial joints or flexor tendon sheaths because of the lower incidence of subcutaneous and skin atrophy.
Bolus intravenous or intramuscular corticosteroids can be used as an adjunct to the slower acting second line drugs. This procedure has not become popular, but it may be suitable for managing some of the systemic complications of rheumatoid arthritis. The potential hazards include avascular bone necrosis, spread of systemic sepsis, and cardiac arrhythmias.
Daily oral corticosteroids—Such regular use of corticosteroids for rheumatoid synovitis is controversial. There is speculation about whether corticosteroids may modify the disease process and, if so, whether this can be achieved in small doses. Prednisolone should be used as an early treatment for rheumatoid arthritis only in cases of severe disability due to persistent disease activity and as an adjunct to treatment with second line drugs. Continual corticosteroid treatment exacerbates the local and systemic osteopenia that accompanies active and chronic rheumatoid arthritis, and no dose avoids risk.
Drugs that suppress the disease process
These drugs play a key role in the treatment of rheumatoid arthritis, and recent recommendations have focused on their early and continued use. This is because of the serious long term outcome of rheumatoid arthritis and therefore the need to intervene early with the most effective drugs. All these drugs are potentially toxic, and regular monitoring for toxicity is necessary. There is considerable variation in the monitoring schedules followed by different rheumatologists, and those given below reflect the authors' experience and practice.
Treatment schedule for sulphasalazine
Starting dose of 0.5 g or 1.0 g daily
Increased over 3-4 weeks to
Maintenance dose of 2.0 g daily
After 3 months dose may be increased further to 2.5-3.0 g daily if required (and tolerated)
This is a popular first choice drug. Benefit develops progressively after about six weeks, so a non-steroidal anti-inflammatory drug should be continued. About 60% of patients given the drug continue taking it after three years, while it is withdrawn in 15% because of toxicity.
The irritating, though rarely serious, side effects include nausea, headache, and abdominal discomfort, and the incidence of such side effects is probably reduced by the use of enteric coated tablets. A skin rash is occasionally a problem, and the drug should not be used for patients who are allergic to sulphonamides.
Bone marrow toxicity and hepatitis are among the more serious side effects. These are more common in the first six months of treatment. Patients' blood count and liver function should be checked before starting treatment, at monthly intervals for the first three months, and then once every three to six months. Other side effects include reversible oligospermia and, since sulphasalazine is excreted in most body fluids, yellow discoloration of urine and soft contact lenses.
Desensitisation of patients who are allergic to sulphasalazine is possible by use of a series of very low doses of increasing strength (this is available in a special pack)
These are less effective but safer than some other disease modifying drugs. Retinopathy is the main serious side effect and is commoner with chloroquine than hydroxychloroquine. Ophthalmic monitoring is advisable.
This has a wide variety of potential side effects. A metallic taste and nausea are common early problems but resolve with continued use. Skin rashes, bone marrow toxicity, and proteinuria are more serious. Monitoring of blood and urine should initially be monthly; the interval is often increased thereafter, but toxicity may develop at any time.
Injectable gold (sodium aurothiomalate) can cause remission of rheumatoid arthritis, but the chances of tolerating long term treatment are modest. The commonest adverse reactions are skin rashes, but not all such rashes require a permanent end of treatment. Proteinuria can be the precursor to serious renal problems; if persistent, it should be investigated and gold treatment withheld. Blood dyscrasia is potentially lethal; the data sheet recommends that a blood count be obtained before each injection, but this is not always practical and many rheumatologists consider regular blood monitoring to be sufficient.
Auranofin is an oral preparation of gold. Diarrhoea is more common but is not a major problem, although it often leads to discontinuation of the drug. It is less effective than injectable gold, and the two drugs should not be regarded as interchangeable. Regular monitoring of blood and urine is necessary.
This is used for synovitis and systemic complications of rheumatoid arthritis. The main initial limiting factor is nausea. Regular blood monitoring is necessary for early detection of bone marrow toxicity or derangement of liver function. Prolonged treatment may be associated with an increased risk of lymphoma. The usual dose is 2.5 mg/kg daily.
This has been used predominantly in North America and, more recently, in Europe in small once weekly oral or injectable doses. This regimen has helped many patients with rheumatoid arthritis, and in some centres methotrexate is the disease modifying drug of choice.
The most common side effect is nausea, which is not usually severe and may settle. More serious side effects include bone marrow toxicity and alveolitis. The risk of hepatic fibrosis and possibly cirrhosis appears to be extremely low in patients given intermittent low doses, though it should be used with reluctance in people who have more than a modest intake of alcohol. The need for regular liver biopsies is debatable, but they are hard to justify in patients with low risk.
How much immunosuppressant effect methotrexate actually has in intermittent low doses is debatable. There may be an increased risk of certain viral infections and possibly a slightly higher risk of some bacterial infections. If antibiotics are needed it seems important to avoid co-trimoxazole and probably trimethoprim. Certainly, the former can precipitate a blood dyscrasia, probably because of folic acid deficiency in patients taking methotrexate. A case could be made out for giving all such patients folic acid supplements. Certainly, red cell folate or at least mean corpuscular volume should be regularly monitored.
This has been used to treat severe rheumatoid synovitis resistant to other treatments and to treat systemic vasculitis. It carries the risk of all the side effects of immunosuppressive drugs and very careful monitoring is mandatory. Patients must understand the risk involved.
New and experimental treatments
Cyclosporin is expensive and potentially toxic, with a 40% risk of renal impairment and hypertension. It is best reserved for patients resistant to other drugs. Treatments to target specific immune mediated changes in rheumatoid arthritis are currently being investigated. The value of these treatments has not yet been established, but initial results are promising.
Experimental treatments targeting specific immune mediated changes in rheumatoid arthritis
Cytokine inhibitors—such as recombinant human interleukin I receptor antagonist
Recombinant soluble tumour necrosis factor receptor
Antibodies to tumour necrosis factor (alpha)
Antibodies to CD4 cells
Since there is no cure for rheumatoid arthritis with conventional treatment, many patients turn to complementary medicine. Some of the treatments available are getting closer to the practice of orthodox medicine. Patients may take supplements to their diet or may turn to homoeopathy or, more recently, reflexology or iridology.
For centuries sufferers from rheumatic disease have been advised to alter their diet in the hope of improving their condition. There is no evidence that this changes the natural course of the disease, but some symptomatic relief might be obtained. Whether the basis of diet therapy lies in supplements of trace elements or antioxidants or in avoiding “toxic” or “allergenic” constituents remains to be determined. However, there is evidence that starvation produces short term improvement in the activity of rheumatoid arthritis, and this raises the possibility that dietary manipulation may have something to offer.
Food supplements claimed to help people with rheumatoid arthritis
Extracts from New Zealand green lipped mussel
Evening primrose oil
Dietary therapy involves the avoidance of foods thought to worsen synovitis, particularly dairy products, cereals, and eggs. An elimination diet consists of “non-allergenic” foods such as rice, carrots, and fish followed by graded reintroduction of other foods. Whichever way the diet is pursued, it is important that suspected foodstuffs are tested by repeated reintroduction. Extreme dietary exclusions may induce deficiency disorders.
Food supplements—A wide variety of supplements have been tried by patients suffering from rheumatoid arthritis, some of which may have anti-inflammatory properties. The benefits for rheumatoid arthritis that are claimed have yet to be proved.