Making a Diagnosis of Rheumatoid Arthritis

Common symptoms of rheumatoid arthritis (RA):

•   Stiffness in the joints, particularly in the morning. Typically this affects the hands and feet, and is symmetrical, but often the dominant hand is more severely affected. 

•   Swollen, painful joints (called synovitis). The joints are soft and boggy, quite different from the square, hard, bony swelling of osteoarthritis (OA). The swelling is due to an inflamed joint membrane (the synovial lining). There may be fluid in the joint (an effusion). 

•   Fatigue; most people have little energy, feel ill and often describe flu-like symptoms. 

•   One of the most important pointers to the diagnosis is rapid loss of function. People with RA find buttons and bra straps are very difficult to fasten and they frequently drop cups or other household items. 

When the disease starts suddenly, with involvement of the hands, feet or large joints, the diagnosis is often made rapidly. However, many people have symptoms that may be flitting and transient before becoming permanent, with a general feeling of non-specific illness (flu–like), depression and lethargy. These latter symptoms may be obvious to both the patient and doctor, but the additional joint symptoms may not have triggered the possible diagnosis of RA and the correct response of referral to secondary care. This situation can be a diagnostic challenge for GPs, as laboratory tests can be normal in the early stages of disease.

What conditions may be confused with RA?

Fibromyalgia

People with this condition often feel pain “all over”, in all their muscles and joints, and have multiple tender points when examined. They will also often have a degree of early morning stiffness. Poor unrestorative sleep is often present, with associated fatigue and low mood, and often there are associated symptoms of headaches and irritable bowels and bladder. It is important to distinguish this condition from rheumatoid arthritis, although sometimes both conditions are present.

Polymyalgia Rheumatica (PMR)

This condition causes pain and stiffness of the shoulders and thighs and tends to occur in people over 65 years of age. Sometimes elderly people with RA present with similar symptoms, and the correct diagnosis of RA usually becomes apparent when the patient is unable to reduce the steroid dosage below 10mg. 

Post-viral arthritis

Acute, post-infective, self-limiting arthritis can follow influenza and other viral illness, particularly parvovirus. It may be extremely painful with swollen ankles, wrists or knees. This usually resolves over several weeks or months. A clue may be that other family members or friends were also affected by symptoms of a viral infection around the same time.

Osteoarthritis

Osteoarthritis (OA) is the most common type of joint disease, and often affects the hands. It occurs more frequently in women than men, and often starts around or just after the time of the menopause.  Hands affected by OA often have small lumps (nodes) on either side of the finger joints, most commonly found at the ends of the fingers, near to the finger nails (called Heberden’s  nodes). The base of the thumb is also frequently affected.  OA hands usually function quite well, even though they may look unsightly i.e. look larger, squarer and have hard lumps. Osteoarthritis can usually be distinguished from rheumatoid arthritis, although some people can suffer from both types of arthritis.

What is the best management of rheumatoid arthritis?

Drugs are only part of the overall treatment for people with RA, all of whom require a holistic team approach involving both the primary and secondary care teams. 

Any person who is suspected of having RA should be referred to a specialist rheumatologist. Early referral is important so that disease modifying anti-rheumatic drugs (DMARDs) may be prescribed as soon as possible so as to slow or halt the disease process.  Delay in referral or receiving a definitive diagnosis and treatment can result in significant costs to the individual, particularly those who are employed. This is because joint damage occurs most rapidly in the early stages of the disease and often the treatment drugs can take several months to work.

Many areas now offer “Early Arthritis Clinics” where a rapid assessment is performed by specialists/specialist nurses in order to limit any delays.  An ultrasound of the affected joints may be performed during this assessment.  

The first goal of treatment is symptom control, with pain management being the most important priority: this may require non-steroidal anti-inflammatory drugs (NSAIDs or COX 2 drugs) either alone or in combination with analgesic drugs (painkillers). The choice of drug will depend on the person’s co-morbidities (other conditions) such as cardiovascular risk and gastrointestinal disease. All NSAIDs should be given for the shortest time possible with a proton-pump inhibitor drug to protect the stomach. Other analgesic drugs may also be required (paracetamol, co-codamol, tramadol etc): the dose of which can be varied from day to day depending upon symptoms or what activities are planned for a particular day. 

What are the common drugs used to control RA?

After pain control, the most important strategy is to start Disease Modifying drugs (DMARDs) as soon as possible; any delay will affect symptom control, quality of life, and functional ability up to 5 years after diagnosis. This ‘window of opportunity’, i.e. the time from symptom onset to initiation of a DMARD, should ideally be less than 3 months. 

Many rheumatologists will prescribe two DMARDs simultaneously, as this is likely to provide better initial symptom control and ability to achieve remission, without an increase in toxicity. Because it can take a few weeks to obtain a DMARD response, glucocorticoids (often termed “steroid” drugs)  are often used as an additional short-term ‘bridge’ to gain more rapid symptom control.  All people who start steroids should be considered for osteoporosis prophylaxis (drug treatments that prevent steroids from causing thinning of the bones or osteoporosis).

The most frequently used initial DMARDs are methotrexate or sulfasalazine, with other drugs such as hydroxychloroquine and leflunomide used less commonly. Although other agents have been used in the past (e.g. gold, D-penicillamine, azathioprine, ciclosporin), these are rarely used in routine care due to greater toxicity and less efficacy.

What are the practical points about taking methotrexate (MTX)?

Methotrexate is the preferred initial drug of most rheumatologists, and compared with other DMARDs, has greater efficacy, quicker onset of action, and fewer treatment withdrawals. 

Every person who takes this drug should have received the NPSA (National Patient Safety Agency) methotrexate booklet www.ncas.nhs.uk, which contains detailed information and highlights that the drug should only be taken once a week. The usual dose is between 7.5-20mg once weekly (which works out at between 3-8 x 2.5mg tablets), though some hospitals will go up to a slightly higher dose when necessary. Folic acid 5mg is also given (at least weekly) to reduce the risk of side effects. Elderly people may require lower doses. If the maximum oral dose is not effective or causes side effects, weekly subcutaneous (under the skin) injection is an effective alternative. 

The most serious early side effect is a lung allergy (pneumonitis), which causes fever, dry cough and breathlessness. Although this is a rare complication, people taking this drug are advised to stop their methotrexate and contact their doctor or nurse if these symptoms occur.  People taking this drug should also avoid taking certain antibiotics (if in doubt check) and men and women of child-rearing age should use adequate contraception as methotrexate can affect the unborn foetus.

It is important to be protected by appropriate immunisations (eg pneumovax for pneumonia and annual influenza (flu) jab) but live vaccines should be avoided, so consult your doctor if you are planning to travel abroad. 

Blood tests are usually monitored every 2 weeks until the dose and results are stable for 6 weeks, then monthly until the dose and disease is stable for 1 year. Thereafter the monitoring can be reduced to 2–3 monthly.

What are the practical points about taking sulfasalazine?

The use of this drug as first-line treatment is declining, as it has greater toxicity and slower onset than methotrexate. It does have the advantage that it can be used in women who wish to conceive; in this situation folic acid should be added. It can cause a reversible reduction in sperm count in men. The usual dose is 500mg once daily, increased by 500mg each week up to 2-3g per day. It should not be used if there is any known allergy to either sulphonamide drugs or aspirin. An early side effect can be feeling sick (nausea) in the first few weeks, but this usually settles and then the dose may be increased. Very rarely, it can cause a rash: if this occurs the drug should be stopped. Monitoring blood tests are usually required for the first 3 months, and then 3-monthly.

Other DMARDS

Leflunomide is a newer immunomodulatory drug that has similar efficacy to methotrexate but a higher incidence of side effects and so is usually used after methotrexate or sulfasalazine. The usual dose is 10–20 mg daily. The most common side effects include gastointestinal (GI) intolerance, rash and a mild increase in blood pressure..

The half-life of the drug is long (1–4 weeks) and therefore if side effects occur the drug may need to be “washed out” with a drug called colestyramine. Blood tests need monitoring every 2 weeks for 6 months, then, if stable, reduced to 2 monthly unless co-prescribed with another immunosuppressant drug. 

Blood pressure and weight should be checked regularly. The drug lasts in the body for a long time and women planning to have children should either discontinue the drug 2 years prior to conception or have a rapid removal of its active metabolite by following the washout procedure. Men should continue to use effective contraception for 3 months after stopping leflunomide.

Hydroxychloroquine is an older DMARD which is less potent than other drugs and so often used in combination rather than on its own. It has an extremely good safety profile, does not require routine blood monitoring and also has a mild beneficial effect on lipid profiles (cholesterol levels). Potential side effects include skin rashes/allergy, mild gastrointestinal disturbance and eye disorders, though the latter is rare. Anyone experiencing changes in their vision they should stop the drug and seek advice from a GP or rheumatologist who will usually arrange an appointment with an eye specialist.

What are the recent advances in Drug Management?

A major breakthrough in understanding the cause of RA was the identification that the chemical tumour necrosis factor-alpha (TNF) was the cause of many of the consequences of RA, including joint pain and damage, fatigue and weight loss. These effects were confirmed when clinical trials of anti-TNF drugs resulted in a rapid and sustained clinical improvement in the symptoms of RA. 

Five anti-TNF agents are currently approved for clinical use: etanercept, adalimumab, certolizumab pegol and golimumab which are given by subcutaneous injection, and infliximab which is given as an intravenous infusion.  The drugs work very quickly, usually within a few weeks. 

Anti-TNF therapy costs approximately £9,000 per year and the UK healthcare system, which has finite resources, tries to strike a balance between the needs of an individual patient and the needs of the community as a whole. These drugs are currently approved for use when the disease remains highly active despite an adequate trial for at least 6 months of at least two DMARDs, one of which should be methotrexate.

Despite gaining approval from NICE (National Institute for Health and Clinical Excellence), there is still wide geographical variation in the ability of people to access anti-TNF therapy, and if you are concerned that you should be receiving this treatment you should discuss this with your rheumatology team or GP. 

Anti-TNF therapy will accelerate current tuberculosis (TB), and reactivate latent TB and viral hepatitis: all patients should have been screened for these conditions prior to treatment. 

One of the early side effects is an increased risk of infections. Specialist advice should be sought when any patient taking anti-TNF therapy develops an unusual or severe infection, and treatment stopped until the infection has cleared.

The long-term outcome of therapy of these drugs is not yet known, but a national registry of those who have received treatment has not shown any long term concern to date. 

Other biological drugs

The success of anti-TNF has led to the development of other drugs that target different aspects of the immune response. Rituximab is given by infusion (drip) and is an antibody that binds to the surface of B cells, resulting in their depletion from the peripheral circulation for at least 6 months. It has similar efficacy to anti-TNF therapy, and is currently approved for use in combination with methotrexate if anti-TNF therapy fails to work.

Tocilizumab is a drug that targets cells called interleukin-6 (or IL6) which has similar efficacy and is approved for use in the same way as anti-TNF drugs.

Abatacept is another biologic drug, that can be used after failure of at least one anti-TNF drug (or tocilizumab) and rituximab, and it targets the T cells.

What vaccinations are required before starting biological drugs?

Immunization with live vaccines is not recommended for patients on biologicals, immuno-suppressants and methotrexate. Where possible, immunisation status should be reviewed before starting these drugs especially if a person is of child bearing age and/or likely to visit countries where yellow fever vaccination is required. This is an ever-changing area and specialist advice may be required for patients already taking these drugs who wish to go abroad or have children or grandchildren who are being given live vaccines. Chicken Pox and Shingles are potentially a serious threat to patients taking biologicals or methotrexate. If a patient develops either of these infections they should seek urgent advice re anti-viral medication.

Practical Help

A new diagnosis of RA can be a time of emotional distress due to the potential impact on quality of life and the difficulties that accompanies living with disease and treatment. This includes concerns about drugs, family life, no longer being able to enjoy a favourite hobby, no longer able to work, etc. Fear, loneliness, depression, anger and anxiety are common and, if unacknowledged, can be overwhelming and disabling. The best ways to tackle these problems are by your medical team providing:

•   good symptom control (pain relief) is essential

•   simple strategies of listening, acknowledging the normality of distressing emotion, helping people to recognise and develop simple coping strategies, e.g. pacing, distraction, relaxation, gentle exercise

•   provision of practical help, e.g. helping to get financial support, child care, disabled badges for parking, devices to aid ADL, help with employment

•   some people may require more specialist skilled help from trained counsellors or psychologists.

There may be a need to change occupation or reduce working hours; for further information see the NRAS guide for people with RA and their employers, which cover aspects of fatigue, benefits and driving (DVLA) advice. The ‘Access to Work’ programme can also be used to provide practical support for adjustments needed to return to work.

On another practical note, footwear is also important; comfortable, air-cushioned shoes (such as Hotter, Ecco or Clarks Springer sandals) will help. Try to avoid slip on shoes, slippers or bare feet as this can put more stress on the joints. Don’t be afraid to ask for advice. Fatigue may be a problem but try to continue with hobbies and develop new ones. 

Many patients will also look for ways to help their condition themselves through diet, exercise and complementary therapies. Further information about this is available in other articles, in the lifestyle section of the NRAS website.

Conclusion

Fortunately, the management of RA has undergone a revolution in care during the past decade, and continues to be an area of great research interest, with many new treatments currently in trial stages. There is now a much greater medical understanding of the disease, better ways to assess disease activity, and, for the first time, targeted biological therapies that have a real prospect of inducing disease remission. 

Management has many more facets than mere drug treatments but drugs remain the mainstay. Drug management may be likened to a pressure cooker. The pressure cooker represents the disease of RA. DMARDs are represented by the weights on the top of the pressure cooker but whilst there is steam hissing out of the vent the patient has to take analgesics and NSAIDs / Cox-2s to control the everyday pain and stiffness. Biologic drugs appear to have the potential to turn the heat off under the pressure cooker, i.e. if a patient responds to these drugs then the disease is virtually turned off.

Despite these advances, recent studies have shown that it can sometimes be difficult for people in the early stages of rheumatoid arthritis to access the health care that they need. If you are concerned that you may have RA, you should consult your GP about referral to a specialist.  Likewise, if you are currently receiving care but are concerned that it isn’t working as well as you need it to, you should also discuss your concerns with your GP or rheumatologist. 

Information Standard logoReferences available on request

Dr John Dickson, Dr Peter Lanyon, Dr Elspeth Wise, Primary Care Rheumatology Society

Original article: 22/05/2003
Reviewed: 03/02/2014
Next review due: 03/02/2017  

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