The basics - Rheumatoid arthritis

Early referral and treatment is essential in this debilitating disease, writes Dr Louise Warburton.

Rheumatoid arthritis (RA) affects 1-2 per cent of the population. An average GP with a list of 2,000 patients will therefore have 10-20 patients with RA in his or her care.

However, the number presenting with new-onset inflammatory arthritis in one year will be small, and the challenge for GPs is to recognise cases when they present.

Treatment for RA has to be started early in the disease to prevent disease progression. Patients who wait over a year from symptom onset to referral to a rheumatologist still have a 73 per cent risk of developing erosive change prior to treatment being initiated.1

Symmetrical pain and swelling across the MTP joint is common

Patients with erosive disease have more progressive disease and greater disability.

The British Society for Rheumatology suggests that the goal should be to commence patients on disease-modifying antirheumatic drug (DMARD) therapy within three months of the start of their disease.2

There are various models to aid the diagnosis of RA; most include:

  • Symmetrical joint involvement, usually of three joint areas, which must include the metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints.
  • Joint involvement means both pain and swelling (synovitis).
  • Tenderness on palpation of these joints; for example, squeezing or compressing the metacarpals or metatarsals may be painful.
  • Morning stiffness of at least 30 minutes.
  • Raised inflammatory markers (ESR and CRP).
  • Positive rheumatoid factor.

However, having normal inflammatory markers and a normal rheumatoid factor should not stop a GP referring a patient for further assessment in the rheumatology clinic. These markers may develop later in the disease and valuable treatment time will be lost if GPs wait for positive markers.

Sometimes only one joint is involved at one time, as in palindromic rheumatism. Lots of patients with osteoarthritis complain of stiffness. It is important to clarify exactly what is 'morning stiffness'.

Stiffness and fatigue
As GPs we should be alerted by any patient complaining of difficulties getting out of bed in the morning due to joint pain. Ask about what it is like to go to the bathroom in the night.

Patients with inflammatory arthritis become stiff after any period of resting. Sometimes just sitting in a chair for a few minutes will cause painful 'gelling' and an inability to straighten up fully when first standing.

Similarly, getting out of bed in the night will be painful and gait will be slow until the joints have loosened up.

Ask the patient if there is anything that they have stopped doing or are unable to do now. Patients with RA will often find ways around problematic movements, such as lowering their washing line because they can't reach as high due to painful shoulders.

Patients with RA will also complain of fatigue. Combined with joint stiffness and gelling, fatigue may be a clue to inflammatory arthritis. Ask specifically about reduced exercise tolerance, difficulties carrying out day-to-day tasks due to tiredness, and adaptation of routines to cope with the fatigue.

If a diagnosis of RA is made in secondary care, it is likely that the patient will be put on DMARD therapy. The commonest two drugs used are methotrexate and sulfasalazine.

Methotrexate is given as a once-weekly dose starting at 7.5mg and increasing where necessary to 25mg weekly. Folic acid is also prescribed weekly, usually two days after the methotrexate.

Sulfasalazine is given daily, starting at 500mg per day and increasing weekly by 500mg to a final dosage of 1g twice daily.

Both these therapies initially require, fortnightly blood monitoring for FBC and LFTs to detect early signs of bone marrow toxicity and liver fibrosis.

Methotrexate can cause pulmonary fibrosis, and a chest X-ray and LFTs are obligatory investigations before treatment is commenced. If a patient develops breathlessness on methotrexate, the drug should be stopped and further guidance from rheumatology colleagues should be sought.

Leflunomide is used if methotrexate and sulfasalazine do not work or cause side-effects. It cannot be used in hypertensive patients.

Recent research suggests that combinations of DMARDs work better than single DMARDs and it may become more commonplace for patients to be commenced on corticosteroid therapy and two DMARDs at the same time.3,4

Anti-TNF therapies
If standard DMARDs do not work, patients can be offered anti-tumour necrosis factor therapy (anti-TNF). Three drugs are currently available: infliximab, etanercept and adalimumab. They can only be used if a patient has failed on two standard DMARD regimens and has a disease activity score of 5.2 or more.

They are expensive and funding has to be approved by each patient's PCT on an individual basis.

If the anti-TNF therapies are not effective then treatment with rituximab, a specific anti-B cell monoclonal antibody is the next step in the treatment ladder. NICE is currently recommending trials of only one anti-TNF therapy in each patient with RA.5

These drugs are effective treatments but predispose the patient to infections. Latent TB can be re-activated.

All patients with active RA and those on DMARD or biologic therapies such as anti-TNFs and rituximab, should be offered an annual influenza vaccination and a one-off pneumococcal vaccination.

RA is a relatively common condition but can be difficult to spot in the early stages. Referral should be prompt to enable DMARD therapy - probably as combination therapies - to be started as soon as possible.

Regular blood monitoring is required for patients on DMARD therapy regimens but not biologic therapies. GPs should be alert for signs of infection in both regimens, but particularly the biologic regimens, and treat promptly with antibiotics.

  • Dr Warburton is a GPSI in rheumatology in Ironbridge, Shropshire

Learning points

  • RA is common but it is important to diagnose early.
  • Disease-modifying treatment should begin ideally within three months of onset of symptoms.
  • It is useful to establish exactly what the patient means by 'morning stiffness' - ask about any pain or stiffness on getting out of bed during the night.
  • Patients taking methotrexate or sulfasalazine require initial fortnightly FBC and LFT monitoring.
  • Patients on disease-modifying drugs are more susceptible to infections, and should be vaccinated against influenza and pneumococcal diseases.


1. Irvine S, Munro R, Porter D. Early referral, diagnosis and treatment of rheumatoid arthritis: evidence for changing medical practice. Ann Rheum Diseases 1999; 58: 510-3.

2. Luqmani R, Hennell S, Estrach C et al. British Society for Rheumatology and British Health Professionals in Rheumatology Guideline for the Management of Rheumatoid Arthritis (The first 2 years). Rheumatology (Oxford) 2006; 45: 1,167-9.

3. Grigor C, Capell H, Stirling A et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004; 364: 263-9.

4. Makinen H, Kautiainen H, Hannonen P et al. Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis. J Rheumatol 2007; 34: 316-21.

5. NICE Technology Assessment 130: Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis. London: NICE, October 2007.

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