Show Summary Details
Page of

Rheumatoid arthritis 

Rheumatoid arthritis

Chapter:
Rheumatoid arthritis
Author(s):

Ravinder Nath Maini

DOI:
10.1093/med/9780199204854.003.1905_update_002

August 28, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Chapter reviewed in December 2013—minor updates made

Updated on 29 May 2014. The previous version of this content can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE (www.oxfordmedicine.com). © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 23 April 2017

Rheumatoid arthritis (RA) is a common, painful, and disabling disease affecting 0.8 to 1.0% of the adult population worldwide, with a female:male ratio of 3:1.

Clinical features

The predominant feature of the disease is a deforming and destructive polyarthritis, with (less commonly) extra-articular manifestations such as subcutaneous nodule formation, serositis, vasculitis, fibrosing alveolitis, amyloidosis, and Felty’s syndrome. Patients also exhibit systemic features of inflammation, including fatigue, anaemia, weight loss, a raised erythrocyte sedimentation rate (ESR), and elevated concentrations of acute phase proteins.

Severe disease is associated with comorbidities including cardiovascular disease, serious infections, and B-cell lymphomas; although iatrogenic factors are contributory factors to some or all of these, there is good evidence that endogenous mechanisms involved in rheumatoid disease also play an important part. Severe disease is a cause of premature death.

Aetiology, pathogenesis, and diagnosis

Aetiology is multifactorial, with a role for genetic factors, such as HLA DR genes coding a pentapeptide sequence in the antigen-binding region, PTDN22 (a signalling molecule in T cells), and several other genes, many of which regulate immunity and inflammation. Genetic factors interact with environmental and host factors, including smoking and sex hormones, and initiate a biological response to an unidentified trigger that results in the recruitment of cells derived from the bone marrow into the joints and other sites of disease, where a chronic immune-inflammatory reaction ensues. Production by B cells of autoantibodies, such as rheumatoid factors and antibodies to citrullinated peptides, as well as interactions between activated T cells and monocyte-macrophages and synoviocytes mediated by cell contact and cytokines, sustain and amplify the inflammatory reaction. Invasion and enzymatic degradation of cartilage by synoviocytes and of bone by osteoclasts follows and leads to irreversible structural damage and joint failure.

The 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria include: (1) the presence for at least 6 weeks of an observable involvement of a minimum of 1-3 small joints (metacarpophalangeal, interphalangeal, 2nd-5th metatarsophalangeal and wrist joints); (2) the presence of IgM rheumatoid factor and/or anticitrullinated protein antibody (ACPA); and (3) abnormal CRP or ESR.

Prognosis and management

The disease follows a relentless progressive course of variable trajectory in individual patients if untreated. Symptoms, signs, laboratory tests, and imaging are used to monitor inflammatory disease activity, damage to joints, and extra-articular disease.

Mild disease—is treated with judicious use of analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), and DMARDs in patients with persistent active disease. Corticosteroid injections into individual affected joints, tendon sheaths, and bursas for persistent swelling, tenderness, or loss of normal range of movement can be very effective.

Moderate or severe disease—this occurs when there is an unremitting pattern of polyarthritis with evidence of significant functional impairment and joint damage in early stages of presentation. In these circumstances, the aim of drug treatment is to achieve rapid reduction in disease activity to a low level and, if possible, remission. This always requires the use of synthetic or biological DMARDs, supplemented by NSAIDs, and corticosteroids.

(1) NSAIDs are used for control of pain and stiffness, with naproxen, low-dose celecoxib, and low-dose ibuprofen being relatively free of cardiovascular risk. These alleviate symptoms and signs of inflammation but have no effect on preventing structural damage, hence they should be used at the lowest effective dose and for the shortest time during disease flares or in the induction period of DMARD therapy.

(2) DMARDs should be used in all patients with moderate or severe disease. Methotrexate, is the drug of choice because of its reliable and durable efficacy. It can be used alone, or concomitantly with other synthetic DMARDs or anti-tumour necrosis factor (anti-TNF) drugs, as the standard of care in patients with continuing disease activity, before consideration of other biological DMARDs.

(3) Corticosteroids are required in over 50% of patients with moderate or severe disease. If continuing long-term use appears necessary, the aim should be to reduce the dose to the equivalent of 5 to 7.5 mg of prednisolone daily by more aggressive use of DMARDs or instigation of anti-TNF therapy.

(4) Biological monoclonal antibody and recombinant protein drugs that have proved efficacious in rheumatoid arthritis include: (a) five TNF inhibitors: four monoclonal antibodies and a fragment (infliximab, adalimumab, golimumab and certolizumab); and a TNF receptor-Fc IgG fusion protein, (etanercept); (b) an interleukin-1 receptor antagonist (anakinra); (c) an anti-CD20 B-cell-depleting monoclonal antibody (rituximab); (d) CTLA4-Ig, a receptor-fusion-FcIgG recombinant protein (abatacept); and (e) IL-6 receptor blocker (tocilizumab). Anti-TNF therapy should ideally be instituted in the early stages of an established diagnosis as soon as it becomes apparent that remission or near-remission is not induced by the best use of synthetic DMARDs. Another biological DMARD is indicated in patients who fail to respond to TNF inhibitors (NICE recommends rituximab only in this context). Cost constraints or safety concerns may limit the institution of biological DMARDs.

Systemic rheumatoid vasculitis is potentially a life-threatening complication: therapy with high-dose corticosteroids and cyclophosphamide is favoured by many specialists.

Long-term outcome: with a holistic approach, judicious use of drugs and non-pharmacological measures such as patient education, physiotherapy, aids, appliances, and surgical treatment, mobility and pain-free quality of life can be maintained in most patients for many years. Effective control of disease prevents progressive disability, comorbidity, and premature death. The goal of reliable cure of disease has not yet been achieved.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.