Degenerative joint disorder- rheumatoid arthritis

Rheumatoid disease (arthritis)

Rheumatoid disease is the most common chronic inflammatory condition affecting synovial joints and is associated with significant disability, morbidity and health-care utilization. A persistent symmetrical polyarthritis is the usual presentation; however, extra-articular disease is common. Due to its systemic nature rheumatoid arthritis should more correctly be termed rheumatoid disease.


Rheumatoid disease is common, affecting 1-3% of the population. The illness may commence at any age but predominantly affects individuals in the fifth decade of life with a 3:1 female preponderance. In older age groups the incidence is approximately equal in both sexes.


The aetiology of rheumatoid disease is unknown; however, it is likely to be multifactorial. The disease may be triggered by an environmental agent (possibly infection) acting in a genetically predisposed individual. Family and twin studies have revealed a genetic susceptibility in up to 30%. The disease is polygenic with different genes (genotype) leading to a similar clinical picture (phenotype). Caucasian patients who express the MHC class II tissue type HLA-DRB1 are particularly susceptible. No causative environmental agent has been definitively identified. It is possible that a transient infection may trigger a chronic inflammatory response in synovial joints.

Hormones may play a role as rheumatoid disease is more common in women, often improves during pregnancy and relapses in the puerperium. The incidence of rheumatoid disease appears to be falling, and this may in part be due to exogenous oestrogens in the contraceptive pill.

No consistent dietary intervention has been shown to precipitate the disease. Fish oils, especially omega-3 polyunsaturated fatty acids, may have a therapeutic effect. Smoking has been implicated as a risk and severity factor.

The pathological hallmark of rheumatoid disease is destruction of articular cartilage and subchondral bone by synovial hyperplasia. This ectopic, inflamed and invading synovium is referred to as pannus. The normal synovial lining is 2-3 cell layers thick. In the diseased state it may be 10 cells thick with an infiltrate of macrophages, B lymphocytes, Th1 CD4+ lymphocytes, plasma cells and dendritic cells. As the synovium thickens, secretion of cytokines (the immunological signal peptides) and proteolytic enzymes such as the matrix metalloproteinases leads to the degradation of cartilage and bone.

The predominant cytokines mediating the inflammation in rheumatoid disease are TNF-α, IL-1 and IL-6, however many others are present. A cytokine imbalance in favour of the pro-inflammatory factors may be the pivotal pathogenic mechanism in rheumatoid disease.

Rheumatoid disease has a variety of extra-articular manifestations, but less is known about the pathogenesis of these features. Rheumatoid nodules contain a core of fibrinoid necrosis surrounded by palisading macrophages and lymphocytes. Rheumatoid factors (immunoglobulins to the Fc portion of IgG) may be responsible for the extra-articular features.

Both inflammation and joint destruction are the characteristic features of rheumatoid disease and can progress independently. Approximately 75% of patients have two or more extra-articular features at some stage. Complications, varying in frequency and severity, include visual impairment including blindness, vocal cord dysfunction secondary to inflammation of the arytenoid cartilage, quadriparesis secondary to atlanto-axial subluxation, pleural and pericardial effusions, pulmonary fibrosis, rheumatoid nodule formation and rheumatoid vasculitis. Secondary Sjögren's syndrome, cardiovascular disease, carpal tunnel syndrome and Baker's cysts frequently occur. All these can result in substantial disability and handicap.

Clinical features

The most common presentation is symmetrical polyarthritis affecting the small joints of the hands (metacarpo-phalangeal, proximal interphalangeal joints) and wrists ). The feet (subtalar and metatarsophalangeal joints) are frequently involved early in the disease. Other features at presentation include diffuse joint stiffness, worse upon rising in the morning and after rest (gelling phenomenon). The onset may be explosive or insidious and may lead to reduced manual dexterity and mobility.

Any synovial joint may be affected in rheumatoid disease, with the knees, shoulders and elbows being frequently involved. Crico-arytenoid joint involvement in the larynx may lead to hoarseness and vocal cord collapse. Any synovium-lined structure may be involved such as tendon sheaths and bursae.

The well-described palindromic onset involves synovitis that flits from joint to joint. Occasionally rheumatoid disease may present with a polymyalgia rheumatica type onset, especially in older patients where myalgia is prominent.

With the advent of early, more aggressive effective therapies, classic features of rheumatoid disease may become less prevalent. Swan-neck and boutonnière deformities of the fingers and Z deformity of the thumb result from joint destruction and altered axis of tendon tracking. Other typical features include ulnar deviation and subluxation of the metacarpo-phalangeal and wrist joints. 'Triggering' of the fingers may result from tenosynovitis. Similar changes may occur in the feet with loss of the longitudinal arch and pes planus due to valgus deformity at the subtalar joints. The feeling of 'walking on pebbles' results from the excessive pressure on the metatarsal heads due to a cock-up deformity of the toes.

Muscle wasting is common in rheumatoid disease and is secondary to disuse atrophy. Compressive neuropathies may also occur, the most common being carpal tunnel syndrome with an equivalent syndrome occurring in the feet, tarsal tunnel syndrome.

In advanced rheumatoid disease, patient may present with severe disease, ulnar deviation of the metacarpo-phalangeal joints, rheumatoid nodules and a vasculitic lesion on the index finger of the left hand.

With the advent of early, more aggressive effective therapies, classic features of rheumatoid disease may become less prevalent. Swan-neck and boutonnière deformities of the fingers and Z deformity of the thumb result from joint destruction and altered axis of tendon tracking. Other typical features include ulnar deviation and subluxation of the metacarpo-phalangeal and wrist joints. 'Triggering' of the fingers may result from tenosynovitis. Similar changes may occur in the feet with loss of the longitudinal arch and pes planus due to valgus deformity at the subtalar joints. The feeling of 'walking on pebbles' results from the excessive pressure on the metatarsal heads due to a cock-up deformity of the toes.

Muscle wasting is common in rheumatoid disease and is secondary to disuse atrophy. Compressive neuropathies may also occur, the most common being carpal tunnel syndrome with an equivalent syndrome occurring in the feet, tarsal tunnel syndrome.In advanced rheumatoid disease, patient may present with severe disease, ulnar deviation of the metacarpo-phalangeal joints, rheumatoid nodules and a vasculitic lesion on the index finger of the left hand.


One of the most significant complications of rheumatoid disease is involvement of the articulation between the posterior aspect of the odontoid peg of C2 (the axis) and the transverse ligament of the atlas resulting in atlanto-axial subluxation. The dire outcome of this complication is spinal cord compression. Care is required during intubation and the anaesthetist must be aware of this complication. A distance greater than 4 mm from the anterior aspect of the peg to the posterior aspect of the anterior arch of C1 is abnormal. However, neurological complications are less common than might be expected as 25% of patients requiring joint replacement have some degree of C1/C2 subluxation.

Extra-articular features of rheumatoid arthritis- anemia, fever, malaise, weight loss, nodules, tendinitis, bursitis, opthalmological complication ( scleritis, scleromalacia,perforans, sicca syndrome),carpal tunnel syndrome, nail fold vasculitis,peripheral neuropathy, pleural effusion,muscle wasting, depression, infertility, osteoperosis, pulmonary edema, lymphadenopathy, Rare cases of hearing impairment, myositis, episcleritis,pericarditis, pulmonary nodule and acromegaly.

Extra-articular features usually occur in severe, seropositive (rheumatoid factor positive) disease but may occur at any time in the course of the condition. The rheumatoid nodule is the most common extra-articular manifestation, occurring in up to 25% of patients. The nodules are usually located subcutaneously adjacent to pressure points such as extensor surfaces of the forearms and elbows. Nodules may vary in diameter from millimetres to centimetres and may be solitary or multiple. A single rheumatoid nodule in the lung can mimic malignancy or an infective process such as tuberculosis. Multiple pulmonary rheumatoid nodules occur in association with coal-worker's pneumoconiosis (Caplan's syndrome).

Raynaud's phenomenon is common in rheumatoid disease and other connective tissue diseases. Upon exposure to cold the extremities characteristically turn white, blue and red during the reactive hyperaemic phase, however many patients describe 'incomplete' forms. If severe digital ulceration occurs, cryoglobulinaemia, rheumatoid vasculitis or systemic sclerosis requires exclusion.

Systemic symptoms such as fever, malaise, anorexia and weight loss frequently occur. Presence of these features increases the likelihood of premature death. Pulmonary involvement is common with pleurisy, pleural effusions, interstitial pneumonitis, pulmonary fibrosis and obliterative bronchiolitis. Nervous system involvement may manifest as neural entrapment, sensory neuropathy, sensorimotor peripheral neuropathy or mononeuritis multiplex (the latter two resulting from vasculitis of the vasa nervorum). The heart is less commonly involved but there may be pericardial chest pain and effusion. There is an increased risk of cardiovascular disease in these patients.

Rarer associations include lymphadenopathy and amyloidosis with deposition of serum amyloid A protein manifesting as proteinuria or malabsorption). Rheumatoid vasculitis may lead to nail fold infarcts in the periphery and leg ulceration. Renal involvement in rheumatoid disease is rare. Osteoporosis may occur as a result of the disease, immobility or corticosteroid therapy. There is an increased incidence of infections in patients with rheumatoid disease. Felty's syndrome (rheumatoid factor positive rheumatoid arthritis, splenomegaly and pancytopenia, most frequently neutropenia) may lead to recurrent bacterial infections, chronic leg ulcers and increased mortality.


Avascular necrosis of the femoral head and other sites occurs, especially in those treated with corticosteroids, and leads to severe pain and bone collapse.

Rheumatoid systemic vasculitis requires aggressive therapy with high-dose immunosuppression.

The diagnosis of rheumatoid disease may be difficult and several other conditions should be considered. The American College of Rheumatology devised diagnostic criteria for rheumatoid arthritis, however these were originally designed to classify patients with established disease and are therefore less sensitive and specific for early arthritis.

American College of Rheumatology diagnostic criteria for rheumatoid arthritis* (1987)

Four of the seven criteria must be met. Criteria 1-4 must have been present for at least 6 weeks:

1. Morning stiffness in and around joints lasting 1 hour or more before maximal improvement

2. Soft tissue swelling (arthritis) of three or more joint areas

3. Swelling (arthritis) of the proximal interphalangeal, metacarpo-phalangeal or wrist joints

4. Symmetrical arthritis

5. Subcutaneous nodules

6. Positive test for rheumatoid factor

7. Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints

Initial investigations

Laboratory and radiological investigations are supportive of a clinical diagnosis; however, there is no pathognomonic test for rheumatoid disease. At presentation, the investigation of polyarthritis is guided by clinical suspicion.

Full blood count

Anaemia is common and can occur as a result of chronic disease, blood loss (iron deficiency anaemia from NSAID-induced stomach ulceration), Felty's syndrome (pancytopenia) or bone marrow suppression (methotrexate treatment). Thrombocytosis develops as part of the acute phase response.

Erythrocyte sedimentation rate/C-reactive protein

The erythrocyte sedimentation rate and C-reactive protein levels are often elevated as part of the acute phase response.

Urea and electrolytes/liver profile

Baseline liver and renal function tests are performed prior to therapy. Mild alterations of liver function tests are a frequent finding but are usually not associated with significant liver disease.

Serum autoantibodies

Rheumatoid factor is present in 80% of patients but may be elevated in many other conditions. Anti-nuclear antibodies are indicators of connective tissue disease but may be present in rheumatoid arthritis. Anti-cyclic citrullinated peptide antibodies may be more sensitive and specific than rheumatoid factor.

X-rays of hands and feet

Classical features include soft tissue swelling, loss of joint space, periarticular osteopenia and juxta-articular erosions. However, radiographs are frequently normal at presentation as bone changes take at least 3 months to appear.

Joint aspiration

Aspiration of joint fluid is extremely useful to exclude infection or inflammation due to uric acid or pyrophosphate crystals.

Detection of rheumatoid factor positive is also required to confirm the presence of rheumatoid arthritis.


Monitoring of drug toxicity involves regular blood investigations such as Full Blood Count, liver function tests, renal function, ESR, CRP and urinalysis.

Further investigations

Investigations for other causes of polyarthritis

If the diagnosis is in question, investigation for other causes of a polyarthritis is mandatory including uric acid level, thyroid function tests, creatine kinase, vasculitis and infection screens.

Initial management

The principles of management of rheumatoid disease aim at symptom relief, preservation of function, retarding the erosive process and maintaining quality of life. The current focus is on early and more aggressive treatment as such intervention results in maximum long-term benefit with minimum risk.

Patient education

Patient education is a very important aspect of management. Patients should be informed of the chronic nature of rheumatoid disease and the importance of controlling the illness in order to improve prognosis.

Physiotherapy and occupational therapy

These disciplines have multiple beneficial aspects including optimization of joint movement and function and muscle strengthening by relieving pain and stiffness. Modalities utilized include heat, ice, wax baths and hydrotherapy. The use of splints, where appropriate, may be required for joint protection to avoid deformity and improve power and function of limbs.

An adequate programme of rest with graded exercise improves outcome. Orthoses are frequently required for deformed feet. Occupational therapists assess patients' disability and handicap and administer aids for daily living such as handles for cutlery and taps and long-handled combs.

Medical management

As the primary concern of the patient is pain relief, adequate analgesia is paramount. Simple analgesics such as paracetamol with or without codeine may be required (side effects are common in the elderly).

Non-steroidal anti-inflammatory drugs

NSAIDs form one of the cornerstones of medical therapy. By decreasing prostaglandin production they have analgesic, antipyretic and anti-inflammatory effects. They do not, however, alter the natural history of the disease. Traditional NSAIDs are frequently used and a large variation in response exists, therefore trials of different medications are necessary to optimize treatment. NSAIDs account for up to 20% of all cases of peptic ulcer haemorrhage and perforation, with many being fatal.


Cyclo-oxygenase-2 (COX-2) inhibitors, drugs which specifically target the COX-2 isoenzyme, were developed as an alternative to traditional NSAIDs due to their potential for less gastrointestinal toxicity. However, as an increase in cardiovascular disease was seen with certain agents, rofecoxib was withdrawn from the worldwide market in September 2004. The other COX-2 inhibitors and traditional NSAIDs are currently under close scrutiny for the emergence of data suggesting similar effects.2


Corticosteroids are extremely effective in reducing the inflammatory response. Unfortunately their long-term toxicity limits their use to the minimum dosage required to stabilize the arthritis. Higher doses are occasionally required for severe exacerbations of arthritis or extra-articular manifestations. Guidelines have been developed for the prevention of steroid-induced osteoporosis.

Intra-articular corticosteroid injections, following joint aspiration, are frequently used with excellent response and minimal side effects. Sepsis must be excluded prior to injection, with urgent Gram stain and culture of synovial fluid if infection is considered a possibility.

These medications are now introduced much earlier in the treatment of rheumatoid disease due to their efficacy in preventing progression of disease. The two main reasons for discontinuation of DMARDs are inefficacy and toxicity. The challenge is to identify patients most likely to suffer from aggressive disease and institute treatment expediently.


Due to its efficacy and tolerability, the folic acid antagonist methotrexate has emerged as the benchmark against which all other therapies for rheumatoid disease are tested. Methotrexate inhibits dihydrofolate reductase in cell metabolism. The mechanism of action in rheumatoid disease is believed to include inhibition of trafficking of white cells from blood vessels into synovium and suppression of pro-inflammatory cytokines.


The antimalarial hydroxychloroquine is effective in milder forms of rheumatoid disease. Its disease-modifying capacity is weaker than the other DMARDS and it does not appear to retard erosive disease. Monitoring for the rare event of retinal toxicity is necessary.


Sulfasalazine is a compound of sulphapyridine and 5-aminosalicylic acid. Like hydroxychloroquine, sulfasalazine is effective in mild to moderate rheumatoid disease. Serious side effects are rare but blood dyscrasias, hepatotoxicity and skin reactions may occur.

Gold salts (sodium aurothiomalate)

Gold salts have been used for over 50 years in the treatment of rheumatoid disease. Unfortunately over a third of patients develop serious side effects requiring cessation of therapy. Gold is now being used less frequently.


Leflunomide inhibits pyrimidine synthesis in T cells and has effects comparable to methotrexate. Leflunomide was designed specifically for rheumatoid disease. It has a long half-life, and if toxicity occurs, clearance of the drug is aided by the administration of colestyramine.

Other agents

Currently, ciclosporin, azathioprine and penicillamine are rarely used for rheumatoid disease due to the availability of more efficacious and less toxic compounds. Cyclophosphamide is employed for systemic rheumatoid vasculitis.

Combination therapy

Many patients are not adequately controlled on monotherapy and so combinations of DMARDs have been utilized with synergistic effect without a concomitant rise in toxicity. Various combinations have been studied, the best described being that of methotrexate, sulfasalazine and hydroxychloroquine. In practice, rheumatologists use various combinations of antirheumatic drugs in order to achieve the optimal response.


Biological response modifiers herald a new era in the treatment of rheumatic disorders.

TNF-α inhibitors have been the most extensively studied and produce rapid and sustained amelioration of the signs and symptoms of rheumatoid disease. In addition, these agents retard the radiological progression of rheumatoid disease more effectively than traditional DMARDs. In addition, 30-40% of patients do not respond to biological agents. The currently available compounds include infliximab3 and adalimumab (anti-TNF antibodies), etanercept (TNF receptor fusion protein) and anakinra (IL-1 receptor blocker). Many more biological agents such as rituximab (a β-cell antibody) are in development and are being investigated in clinical trials with promising results.

Surgical management


A surgical synovectomy and debridement/arthroplasty procedure involves excision of excess synovial tissue and rough surfaces of the joint. An alternative to surgical synovectomy is the use of the radioactive compound yttrium which, when injected intra-articularly, induces a chemical synovectomy. Details of surgical procedures are presented in the section on regional joint disease.


Not all patients with rheumatoid disease have a uniform outcome. There is good evidence that early intervention gives the maximum long-term benefit for the minimum risk. The use of suppressive drugs within 6 months of disease onset improves prognosis as it is at this stage that inflammation is present with little joint destruction. Severe joint damage and many of the extra-articular manifestations may be avoided with appropriate management.

Currently, only 50% of patients are employed after 10 years, and 40% have ceased work after 2 years from diagnosis. Approximately 75% develop at least moderate impairment of function. Factors associated with a poor prognosis include extra-articular manifestations, insidious onset, high rheumatoid factor titres, functional disability at 1 year, HLA-DR4 genotype and early erosive disease on X-ray.

In general, life expectancy is reduced by 3 years in females and 7 years in males.

statistic for rheumatoid arthritis

rheumatoid arthritis

Rheumatoid arthritis

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Sandyjunep 5 years ago from Australia

I enjoyed what I read. i must admit I skipped through some of it as it was quite long, but the heading made it easy for me to find what I wanted

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stefanwirawan1 5 years ago from Malaysia Author

Thanks for the comment and I am sorry if the content is too long.

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