Fact Explanation
Patterns of disease presentation Rheumatoid arthritis (RA) is an autoimmune sero-negative inflammatory polyarthritis. The disease commonly manifests in the 30-50 yr age group with a female to male ratio of 3:1. RA is characterized by synovial inflammation and hyperplasia with gradual cartilage and bone destruction leading to deformity. The chronic inflammatory state is maintained by continuous production of chemical mediators such as cytokines, TNF etc.[1] Several patterns of disease presentations have been identified.
Gradual onset joint pain, swelling and stiffness of small joints of hands, feet and wrists Symmetrical polyarthritis involving the small joints is the most common presentation. Morning stiffness is prolonged (>I hour). Symptoms characteristically improve with rest and worsen with activity.
Acute onset polyarthritis with severe morning stiffness and pitting edema This type of presentation is mostly seen among the elderly.
Acute onset polymyalgia with severe muscle stiffness Mainly the proximal muscles are involved. This is followed by gradual development of joint symptoms. This pattern of presentation may mimic polymyalgia rheumatica.[2]
Repeated episodes of joint pain, swelling which lasts for short duration In this palindromic onset the joint symptoms last only a few hours or days.
Pain, swelling and stiffness of single large joint Monoarthritis of large joints such as knee or shoulder is seen in about 10% of patients at presentation.
Deformities Long standing RA is associated with several hand and foot deformities. These may handicap the patient in performing daily functions.
Systemic symptoms : Fatigue, anorexia, weight loss Due to the chronic inflammation associated with rheumatoid arthritis. Rheumatoid vasculitis is a rare complication with a wide range of symptoms - fever, vasculitic rashes, neuropathy, digital infarcts etc.[3]
Extra-articular features Rheumatoid arthritis is a systemic disease with multi-organ involvement due to chronic inflammation. The common organs affected are the lungs, heart, eyes, nervous system, skin & soft tissue.[4]
Extra-articular features : Skin nodules These mainly occur over the extensor surfaces of upper and lower limbs.
Extra-articular features : Ocular manifestations Common eye manifestations are redness, pain, dryness and blurring of vision. Visual impairment is a series manifestation of scleritis or corneal melting.
Extra-articular features : Respiratory - Dyspnoea & cough Pulmonary fibrosis is a known to be associated with RA. Pleural effusions may develop due to serositis.
Extra-articular features : Neurological symptoms Two common neurological conditions associated with rheumatoid arthritis are entrapment neuropathies and cervical cord compression. Carpal tunnel syndrome and tarsal tunnel syndrome present with pain, numbness and weakness of the hand and feet respectively. Atlanto-axial subluxation predisposes to cervical cord compression which presents with occipital headache and motor/ sensory symptoms involving upper and lower limbs.[5]
Clinical course of disease Rheumatoid arthritis has a prolonged course with intermittent exacerbations and remissions.
Risk factors for disease predisposition and precipitation The aetiology is unknown. Both genetic and environmental factors have being implicated in its origin. Look for a family history of the disease. Smoking, oral contraceptive pill, life style and changes associated with pregnancy are known to affect the disease process.
  1. MCINNES IAIN B., SCHETT GEORG. The Pathogenesis of Rheumatoid Arthritis. N Engl J Med [online] 2011 December, 365(23):2205-2219 [viewed 20 July 2014] Available from: doi:10.1056/NEJMra1004965
  2. CAPORALI R. Presenting features of polymyalgia rheumatica (PMR) and rheumatoid arthritis with PMR-like onset: a prospective study. [online] 2001 November, 60(11):1021-1024 [viewed 20 July 2014] Available from: doi:10.1136/ard.60.11.1021
  3. VOLLERTSEN RS, CONN DL. Vasculitis associated with rheumatoid arthritis. Rheum Dis Clin North Am [online] 1990 May, 16(2):445-61 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/2189161
  4. COJOCARU M, COJOCARU IM, SILOSI I, VRABIE CD, TANASESCU R. Extra-articular Manifestations in Rheumatoid Arthritis Maedica (Buchar) [online] 2010 Dec, 5(4):286-291 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152850
  5. MUKERJI N., TODD N. V.. Cervical Myelopathy in Rheumatoid Arthritis. Neurology Research International [online] 2011 December, 2011:1-7 [viewed 20 July 2014] Available from: doi:10.1155/2011/153628


Fact Explanation
Swelling of metacarpophalangeal joints (MCP) and proximal interphalangeal joints (PIP) Due to inflammation of the small joint of the hands and feet.
Pain on passive movement Due to inflammation of the small joint of the hands and feet.
Joint tenderness Usually seen when the joints are actively inflamed. Erythema is usually absent and suspect infection if present.
Deformities of the hand Characteristic deformities of the hand are swan neck deformity, Z thumb deformity and boutonnière deformity. Dorsal subluxation of the distal ulna can also develop.[1]
Trigger finger Trigger finger may develop due to nodule formation in the tendons or thickening of the tendon sheaths.[2]
Tendon rupture Tendon rupture of the hand due to bone deformities may present with inability to move the fingers. Rupture of the tibialis posterior tendon will result in loss of the longitudinal arch of the foot.
Deformities of the feet Characteristic deformities of the feet are cock-up’ toe deformity and calcaneovalgus.[3] Foot deformities predispose to development of callosities and secondary adventitious bursae.
Rheumatoid nodules Rheumatoid nodules are subcutaneous nodules which develop mainly on the forearm, ankle and sacral region.
Ocular examination Examine the eyes for episcleritis, scleritis, scleromalacia and corneal melting. Dry eyes (Keratoconjunctivitis sicca) is due to secondary Sjögren’s syndrome.
Cardiovascular and respiratory examination Examine the cardiovascular system to exclude conditions such as cardiomyopathy, pericardial effusion and constrictive pericarditis. Examine for signs of pulmonary fibrosis and pleural effusion.
Neurological examination Examine for upper motor neuron signs in the limbs. Examine the peripheral nerves for evidence of neuropathy.
  1. BREWERTON DA. Hand Deformities in Rheumatoid Disease Ann Rheum Dis [online] 1957 Jun, 16(2):183-197 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1006945
  2. MAKKOUK AH, OETGEN ME, SWIGART CR, DODDS SD. Trigger finger: etiology, evaluation, and treatment Curr Rev Musculoskelet Med [online] , 1(2):92-96 [viewed 20 July 2014] Available from: doi:10.1007/s12178-007-9012-1
  3. VAN DER LEEDEN M.. Forefoot joint damage, pain and disability in rheumatoid arthritis patients with foot complaints: the role of plantar pressure and gait characteristics. Rheumatology [online] 2006 January, 45(4):465-469 [viewed 20 July 2014] Available from: doi:10.1093/rheumatology/kei186

Differential Diagnoses

Fact Explanation
Osteoarthritis (OA) Osteoarthritis is common among the elderly. The disease is characterized by subchondral osteosclerosis, osteophyte formation, focal loss of articular cartilage and joint remodeling. Inflammation of the joint is minimal. Varies patterns of joint involvement have being identified. Typical joints that are involved are large joints - hips, knees, PIP and DIP joints of the hands, neck and spine. Symptoms appear insidiously in 1 or 2 joints where the of the patient develops pain and swelling with minimum stiffness. Joint pain relieved by rest and worsened by activity. Osteoarthritis can be classified according to disease presentations : Generalized nodal OA, knee OA, hip OA etc. Generalized nodal OA is more common among females and characteristically involves the finger inter-phalangeal joints. Heberden’s & Bouchard’s nodes can found as nodules in the fingers.[1]
Ankylosing spondylitis Ankylosing spondylitis is a seronegative chronic inflammatory arthritis. The disease is more common in men compared to RA with a peak incidence in the 2nd and 3rd decades. The disease primarily affects the axial skeleton. The patient presents with gradual onset back pain and stiffness. The symptoms are worse in the morning and are relieved with activity. The lumbar spine is involved initially and with time the disease ascends to higher levels. This leads to fusion/ ankylosis of the spine leading to spinal rigidity, kyphosis and reduced chest expansion. Enthesopathy is a characteristic feature with the development of plantar fasciitis, Achilles tendinitis etc.[2] Extra-articular features are rare – Apical lung fibrosis, anterior uveitis, aortic incompetence. Diagnosis is by clinical information and radiographic studies. Rheumatoid factor is usually negative.
Psoriatic arthropathy Psoriatic arthropathy is also a seronegative chronic inflammatory arthropathy. Skin psoriasis is usually present concurrently. Presentation is with pain and swelling of joints and entheses. Large and small joints of both upper and lower limbs may be affected. Joint involvement can be categorized into 5 patterns - Asymmetric inflammatory oligoarthritis, symmetrical polyarthritis, distal interphalangeal arthritis, psoriatic spondylitis and arthritis mutilans. Asymmetric inflammatory oligoarthritis is the commonest presentation where there is involvement of the small joints with tenosynovitis, enthesitis in the hands and feet which lead to the development of ‘sausage digit’ or dactylitis. Distal interphalangeal arthritis is similar to rheumatoid arthritis in presentation. Psoriatic spondylitis mimics ankylosing spondylitis. In arthritis mutilans there is destruction of joint and cartilage of the fingers and toes. On examination the fingers may appear short, mutilated and crippled. This leads to encasing and invagination of the skin (‘Telescoped’).[3]
  1. HUNTER D. J. Osteoarthritis. BMJ [online] 2006 March, 332(7542):639-642 [viewed 20 July 2014] Available from: doi:10.1136/bmj.332.7542.639
  2. BRAUN J, SIEPER J. Ankylosing spondylitis. Lancet [online] 2007 Apr 21, 369(9570):1379-90 [viewed 20 July 2014] Available from: doi:10.1016/S0140-6736(07)60635-7
  3. GLADMAN D D. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Annals of the Rheumatic Diseases [online] 2005 March, 64(suppl_2):ii14-ii17 [viewed 20 July 2014] Available from: doi:10.1136/ard.2004.032482

Investigations - for Diagnosis

Fact Explanation
A diagnosis of RA is arrived at using clinical criteria supported by investigation Clinical criteria take into account number of involved joints, type of joints involved, extra-articular features, duration of disease and presence of rheumatoid nodules, rheumatoid factor etc. The currently used criterion is the European League Against Rheumatism/American College of Rheumatology 2010 Criteria.[1]
ESR/ CRP Acute phase proteins are elevated due to chronic inflammation.
Rheumatoid factor Rheumatoid factor is an autoantibody directed against IgG antibodies. Rheumatoid factor is present in about 70% of patients. The presence of rheumatoid factor can be used as an indicator of severe disease, these patients are at higher risk of developing deformities, extra-articular features etc.
anti-citrullinated peptide antibodies (ACPA) Has high specificity for RA. Its presence is a marker of severe erosive disease. It can also be used to differentiate RA from other undifferentiated arthritis in an undiagnosed patient.[2] [3]
X-ray Typical radiographic changes in RA are periarticular osteopenia and marginal non-proliferative erosions. Radiological feature take time to develop. Hence X-ray alone is not used to diagnose RA.
Ultrasound scan/ MRI Can be used to visualize joint and synovial involvement. These are rarely used, particularly in diagnostic difficulty.
  2. JANSEN AL, VAN DER HORST-BRUINSMA I, VAN SCHAARDENBURG D, VAN DE STADT RJ, DE KONING MH, DIJKMANS BA. Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis. J Rheumatol [online] 2002 Oct, 29(10):2074-6 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12375314
  3. NIEWOLD TB, HARRISON MJ, PAGET SA. Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid arthritis. QJM [online] 2007 Apr, 100(4):193-201 [viewed 20 July 2014] Available from: doi:10.1093/qjmed/hcm015

Investigations - Fitness for Management

Fact Explanation
Full blood count Many DMARDs suppress bone marrow function. Hence a base line FBC assessment is carried out for monitoring of drug therapy. The hemoglobin value is important due to the risk of iron deficiency anemia in patients who are prescribed NSAIDs. Use of NSAIDs is a risk factor for gastrointestinal hemorrhage.[1]
Liver function tests As a baseline liver function assessment is obtained prior to initiation of DMARD therapy since some DMARDs cause hepatotoxicity.
Renal function tests Carry out baseline renal function assessment prior to initiation of drug therapy. Drug doses need to be adjusted if renal impairment is present. Also required for monitoring for drug adverse effects.
  1. LANZA FRANK L, CHAN FRANCIS K L, QUIGLEY EAMONN M M. Guidelines for Prevention of NSAID-Related Ulcer Complications. Am J Gastroenterol [online] December, 104(3):728-738 [viewed 20 July 2014] Available from: doi:10.1038/ajg.2009.115

Investigations - Followup

Fact Explanation
Monitor disease activity Visual analogue scales for pain, functional assessment or DAS28 score can be used to monitor disease activity. DAS28 score can be used to assess disease activity and measure the response to treatment. Parameters that are considered in DAS28 score include number of joints affected, number of swollen joints, ESR value and functional capabilities. Acute phase proteins can also be used to monitor disease activity.
X-rays Serial radiographs of affected segments can be used for monitoring disease progression. Further evidence is required to support its routine use. [1]
Follow up of DMARD therapy Monitor for adverse drug reactions of DMARDs. Patients on methotrexate should be monitored with regular FBC, liver function tests (LFT) and renal function tests (RFT). Monitor FBC and LFT when on sulphasalazine. Patients on gold therapy need blood count monitoring and urinalysis for proteinuria. Patients who are started on chloroquine require regular RFT and ophthalmological assessment.
  1. SCOTT DL, COULTON BL, BACON PA, POPERT AJ. Methods of X-ray assessment in rheumatoid arthritis: a re-evaluation. Br J Rheumatol [online] 1985 Feb, 24(1):31-9 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/3978364

Management - General Measures

Fact Explanation
Patient education The patient should be provided information about the natural course of the disease, exacerbating factors, complications, investigations and treatment options available. Emphasize the importance of regular follow-up and drug compliance.
Physiotherapy Arrange for formal physiotherapy sessions at a physiotherapy clinic/ center. Encourage appropriate passive and active exercise among patients.[1] Both aerobic and strengthening exercises need to be provided.
Pain relief Pain relief is can be provided with analgesics such as paracetamol and NSAIDs. There is limited evidence to support the use of combination analgesic therapy.[2]
Bed rest Acute flare-ups should be managed with adequate physical rest.
Joint protection methods Obese patients should be advised to reduce weight. Provide the patient protective footwear.
Advice patient regrading increased cardiovascular risk. Rheumatoid arthritis patients have a higher risk of cardiovascular disease and death. Chronic systemic inflammatory state, limited physical activity and normal cardiovascular risk factors predispose to this higher risk. Advice the patient on steps to minimize this risk. Pre-existing diabetes, hypertension, hyperlipidaemia should be managed appropriately.[3]
  1. KAVUNCU V, EVCIK D. Physiotherapy in Rheumatoid Arthritis MedGenMed [online] , 6(2):3 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1395797
  2. RAMIRO S, RADNER H, VAN DER HEIJDE D, VAN TUBERGEN A, BUCHBINDER R, ALETAHA D, LANDEWé RB. Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database Syst Rev [online] 2011 Oct 5:CD008886 [viewed 20 July 2014] Available from: doi:10.1002/14651858.CD008886.pub2
  3. SOLOMON DH, KARLSON EW, RIMM EB, CANNUSCIO CC, MANDL LA, MANSON JE, STAMPFER MJ, CURHAN GC. Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation [online] 2003 Mar 11, 107(9):1303-7 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12628952

Management - Specific Treatments

Fact Explanation
Treatment options Specific treatment options for rheumatoid arthritis include disease modifying anti-rheumatic drugs (DMARDs), corticosteroids, immunosuppressive drugs and newer biological agents.[1]
DMARD therapy DMARDs are used as first line therapy in RA. According to new evidence prompt initiation after diagnosis has shown better disease control and reduction in deformities, disability.[2] Polytherapy is more effective than monotherapy. DMARD therapy with methotrexate or sulfasalazine or both are considered first line therapy. DMARDs act by blocking the release or activity of cell mediators such as cytokines, TNF which maintain the disease process. The action of DMARDs is slow and may take 8-12 weeks for the effect to manifest. Many DMARDs have serious side effect profiles requiring continuous monitoring. Any individual DMARD is discontinued if no response within 6 months of therapy.
Methotrexate Methotrexate considered the current gold standard treatment in RA. Methotrexate inhibits DNA synthesis and cell replication by acting as a folic acid inhibitor. Methotrexate is administered weekly – 5 to 15mg orally. Side effects of drug : Nausea, vomiting, diarrhea, stomatitis, rashes, bone marrow toxicity, hepatotoxicity and pulmonary hypersensitivity. Hence monitor FBC, liver function tests and renal functions regularly after baseline assessment. To minimize side effects folic acid is administered concurrently on different days.
Sulphasalazine Sulphasalazine is another first line DMARD which has an efficacy is comparable to methotrexate. A dosage of 2–4 g/day is administered orally. Side effects : Nausea and vomiting, headache/dizziness, bone marrow suppression, allergic skin reactions and may precipitate hemolysis in G6PD deficiency. To avoid side effects monitor FBC and liver functions regularly.
Chloroquine and hydroxychloroquine These drugs are slightly less effective than methotrexate and sulphasalazine but are well tolerated and have fewer side effects. Dosage : 200–400 mg/day. The major side effect is ocular toxicity – maculopathy and scotoma. Conduct a baseline ophthalmological assessment and annually thereafter.
Gold therapy Gold therapy is an old DMARD and is currently less frequently used. Both oral and IM preparations could be used (auranofin and sodium aurothiomalate). IM gold is administered 50mg weekly until response occurs and then 2-4 weekly. Around 6 months is required for adequate response to occur. Disadvantages of IM gold therapy : High relapse rate and side effects. Side effects of the drug : rashes, stomatitis, proteinuria and blood dyscrasias. Monitor the patient’s FBC and urine for presence of protein. Oral gold therapy is less effective but is less toxic. Side effects are rare, diarrhea being the most common. Oral gold may be considered for treatment of mild disease.
Corticosteroid therapy Corticosteroid therapy can be administered intra-articular/intramuscular or as systemic therapy. Intra-articular steroids are primarily used to achieve rapid symptom control. Both intra-articular and IM steroids can used during acute flare-ups of joint symptoms. Systemic corticosteroids have disease modifying properties. This onset of this effect is faster than DMARDs. Hence systemic corticosteroids are started concurrently with DMARD therapy to achieve disease control in the early phase of the disease until the onset of the DMARD therapy action. Common regimes : high dose steroids (60mg/day) gradually tailed off over 3-4 months or low dose therapy (5-10mg/day) for 6-24 months. It is important to monitor for side effects of long term systemic corticosteroid therapy. Osteoporosis is an important complication in the context of rheumatoid arthritis patients.[3]
Immunosuppressive agents Immunosuppressive therapy can used to modify the disease process. Drugs which are used include azathioprine, cyclophosphamide, chlorambucil and cyclosporin. All these agents may cause bone marrow toxicity which requires regular monitoring.
Leflunomide Leflunomide is a newer DMARD which is currently used as first line therapy. It acts by inhibiting the activation of lymphocytes. Dosage : 10–20 mg/day. The efficacy of the drug is comparable to methotrexate.
Biological agents Biological agents target the activity of chemical mediators which initiate and maintain the chronic systemic and synovial inflammation – 1. Tumor necrosis factor alpha inhibitors – infliximab, adalimumab, etanercept, 2. Anti-B-cell therapy – Rituximab, 3. Interleukin 1 inhibitors – Anakinra, 4. Interleukin 6 inhibitors – Tocilizumab, 5. T cell activation inhibitors – Abatacept.[4] These agents are used in patients who fail to respond to conventional DMARD therapy. Biological agents are expensive and carry high risk of infection due to suppression of the immune system.[5]
  1. Rheumatoid arthritis: The management of rheumatoid arthritis in adults. National institute for health and care excellence, February 2009 [Viewed on 18 June 2014]. Available from : http://www.nice.org.uk/guidance/CG79
  2. SIZOVA L. Approaches to the treatment of early rheumatoid arthritis with disease-modifying antirheumatic drugs Br J Clin Pharmacol [online] 2008 Aug, 66(2):173-178 [viewed 20 July 2014] Available from: doi:10.1111/j.1365-2125.2008.03222.x
  3. HOES JN, JACOBS JW, BUTTGEREIT F, BIJLSMA JW. Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis. Nat Rev Rheumatol [online] 2010 Dec, 6(12):693-702 [viewed 20 July 2014] Available from: doi:10.1038/nrrheum.2010.179
  4. DROSOS AA. Newer immunosuppressive drugs: their potential role in rheumatoid arthritis therapy. Drugs [online] 2002, 62(6):891-907 [viewed 20 July 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/11929337
  5. CURTIS JEFFREY R., SINGH JASVINDER A.. Use of Biologics in Rheumatoid Arthritis: Current and Emerging Paradigms of Care. Clinical Therapeutics [online] 2011 June, 33(6):679-707 [viewed 20 July 2014] Available from: doi:10.1016/j.clinthera.2011.05.044