Medicine – Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that predominantly affects the synovial joints. It typically produces a symmetrical inflammatory polyarthritis, particularly involving the small joints of the hands and feet. Persistent synovial inflammation can progressively damage cartilage, bone, tendons, and ligaments, eventually resulting in characteristic joint deformities and functional impairment. Although joint disease is the dominant manifestation, RA is a systemic condition and may also affect the skin, lungs, heart, eyes, nervous system, and other organs.

Revised American College of Rheumatology Criteria for Rheumatoid Arthritis

The 1987 revised American College of Rheumatology (ACR) criteria historically classified a patient as having rheumatoid arthritis when at least four of seven criteria were present. For the first four criteria, the abnormalities were required to have been present for at least six weeks. These are historical classification criteria; modern practice generally uses the 2010 ACR/EULAR classification criteria.

1. Morning Stiffness

Patients characteristically experience morning stiffness lasting for more than one hour. The stiffness usually improves gradually with movement and activity. Under the 1987 criteria, it needed to persist for at least six weeks.

2. Arthritis of Three or More Joint Areas

There should be objective evidence of arthritis affecting at least three joint areas simultaneously. Affected joints demonstrate soft-tissue swelling or synovial fluid accumulation rather than enlargement caused solely by bony changes. This pattern should persist for at least six weeks.

3. Arthritis of the Hand Joints

RA has a strong tendency to involve the hands. At least one area involving the wrist, metacarpophalangeal (MCP), or proximal interphalangeal (PIP) joints should demonstrate inflammatory arthritis for at least six weeks.

4. Symmetrical Arthritis

Joint involvement is typically symmetrical, meaning that corresponding joint areas on both sides of the body are affected. Perfect symmetry is not always present, particularly early in the disease, but a bilateral pattern becomes characteristic as established RA develops.

5. Rheumatoid Nodules

Rheumatoid nodules are firm subcutaneous nodules that commonly develop over pressure points and extensor surfaces, such as around the elbows. They are particularly associated with seropositive and more severe rheumatoid arthritis.

6. Serum Rheumatoid Factor

The presence of rheumatoid factor (RF) supports the diagnosis. Rheumatoid factors are autoantibodies, most commonly IgM antibodies, directed against the Fc portion of IgG. However, RF is not specific to RA and may occur in other diseases and in healthy individuals.

7. Radiological Changes

Characteristic radiographic abnormalities include marginal erosions and periarticular osteopenia, particularly in the hands and wrists. More advanced disease produces joint-space narrowing, deformity, subluxation, and progressive joint destruction.

Joint Involvement in Rheumatoid Arthritis

RA typically causes a symmetrical polyarthropathy. The small joints of the hands and feet are particularly frequently affected, although larger joints and the cervical spine may become involved as the disease progresses.

The MCP, PIP, and metatarsophalangeal (MTP) joints are among the most frequently affected, traditionally reported in approximately 90% of patients with established disease. The wrists, knees, ankles, and subtalar joints have historically been reported as affected in around 80%. Shoulder involvement may occur in approximately 60%, while the hips and elbows may be affected in around 50%. The cervical spine can also become involved, particularly in longstanding disease, and older sources report this in approximately 40% of patients.

Features of the Rheumatoid Hand

1. Symmetrical Deforming Polyarthropathy

Established RA produces a characteristic symmetrical deforming polyarthropathy involving predominantly the MCP, PIP, and wrist joints. Chronic synovitis damages cartilage, bone, tendons, and supporting ligaments, gradually altering the normal alignment and stability of the hand.

2. Sparing of the DIP Joints

The distal interphalangeal (DIP) joints are usually spared in rheumatoid arthritis. Significant DIP involvement should therefore raise consideration of other conditions, particularly osteoarthritis or psoriatic arthritis.

3. Active Synovitis

During active inflammation, affected joints are typically warm, swollen, tender, and painful on movement. The swelling results primarily from synovial inflammation and effusion.

4. Ulnar Deviation

Chronic inflammation and ligamentous damage can cause ulnar deviation of the fingers at the MCP joints. The fingers progressively deviate toward the ulnar side of the hand, producing one of the classic deformities of longstanding RA.

5. Subluxation

Progressive destruction of the supporting structures can lead to subluxation of the MCP joints and wrists. This contributes to instability, deformity, reduced grip strength, and impaired hand function.

6. Swan-Neck Deformity

A swan-neck deformity consists of hyperextension of the PIP joint with flexion of the DIP joint. It develops because chronic inflammatory damage disrupts the normal balance between the tendons and ligaments controlling the finger.

7. Boutonnière Deformity

A boutonnière deformity has the opposite configuration, with flexion of the PIP joint and hyperextension of the DIP joint. It results from damage to the central portion of the extensor tendon mechanism.

8. Z-Deformity of the Thumb

The thumb may develop a characteristic Z-shaped deformity, resulting from abnormal flexion and extension at different thumb joints. This can interfere significantly with pinch and grip function.

9. Wasting of the Dorsal Interossei

Chronic disease may cause wasting of the dorsal interosseous muscles, producing visible hollowing between the metacarpal bones. Disuse, joint dysfunction, and neurological involvement can contribute to this finding.

10. Absence of Psoriatic Nail Changes

Typical psoriatic nail abnormalities, such as nail pitting and onycholysis, are not characteristic of rheumatoid arthritis. Their presence may suggest psoriatic arthritis rather than RA.

11. Nail-Fold Infarcts and Vasculitic Lesions

Severe rheumatoid vasculitis can compromise small blood vessels and produce nail-fold infarcts or other vasculitic skin lesions. These manifestations are more likely in longstanding, severe, seropositive disease.

12. Carpal Tunnel Syndrome

Inflammatory swelling around the wrist may compress the median nerve within the carpal tunnel, producing numbness, tingling, pain, and sometimes weakness in the median nerve distribution. Carpal tunnel syndrome is therefore a recognised neurological complication of RA.

13. Palmar Erythema

Some patients develop palmar erythema, producing diffuse redness of the palms. Although nonspecific, it may accompany active systemic inflammatory disease.

Extra-Articular Features of Rheumatoid Arthritis

Extra-articular disease is more likely in patients with severe, longstanding, and seropositive RA.

Non-Organ-Specific Features

Systemic inflammation may cause constitutional manifestations such as weight loss and fever, while lymphoid activation may result in lymphadenopathy. Rheumatoid nodules are particularly associated with RF-positive disease.

Felty syndrome is an important complication characterised classically by the combination of rheumatoid arthritis, splenomegaly, and neutropenia. Patients may consequently have an increased susceptibility to infection.

Longstanding inflammatory disease may rarely lead to secondary AA amyloidosis, which can particularly affect the kidneys. Patients with RA also have an increased susceptibility to infections, resulting from the disease itself and from immunosuppressive therapy. Osteoporosis may develop because of chronic inflammation, reduced physical activity, and corticosteroid exposure.

Organ-Specific Features

1. Cardiac Manifestations

Cardiac involvement may include pericarditis and pericardial effusion. Valvular abnormalities can also occur, although they are less characteristic. Chronic RA additionally increases the risk of atherosclerotic cardiovascular disease.

2. Pulmonary Manifestations

RA can produce several pulmonary complications, including pleurisy and pleural effusions. Interstitial lung disease may cause pulmonary fibrosis, resulting in progressive breathlessness and impaired gas exchange.

Rheumatoid pulmonary nodules may also occur. Bronchiectasis is another recognised association. Caplan syndrome refers to the development of rheumatoid pulmonary nodules in individuals with pneumoconiosis, classically coal workers exposed to mineral dust.

3. Neurological Manifestations

Neurological disease may result from nerve compression, vasculitis, or cervical spine involvement. Carpal tunnel syndrome is a common example of a compressive neuropathy.

Rheumatoid vasculitis may cause mononeuritis multiplex, in which several individual peripheral nerves become damaged. In the cervical spine, particularly at the atlantoaxial joint, instability or subluxation can compress the spinal cord and produce cervical myelopathy.

4. Renal Manifestations

The kidneys are not usually directly affected by classic rheumatoid synovitis, but renal complications can occur. Longstanding uncontrolled inflammation may rarely result in AA amyloidosis, while medications historically used for RA can cause glomerulonephritis or interstitial nephritis.

5. Ocular Manifestations

Eye involvement may include episcleritis, which is generally relatively mild, and scleritis, which is more painful and potentially serious. Severe destructive scleral inflammation may produce scleromalacia perforans, particularly in longstanding RA.

RA may also coexist with secondary Sjögren’s syndrome, producing reduced lacrimal and salivary secretion and resulting in dry eyes and dry mouth.

Laboratory Findings in Rheumatoid Arthritis

1. Anaemia

Anaemia is common and frequently has the pattern of anaemia of chronic inflammation, usually producing a normocytic, normochromic picture. Iron deficiency may coexist and can produce hypochromic or microcytic changes.

2. Thrombocytosis

Active systemic inflammation may produce reactive thrombocytosis, with an elevated platelet count. The degree of thrombocytosis may broadly reflect inflammatory activity.

3. Raised ESR and CRP

Both the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are commonly elevated during active disease. They are nonspecific inflammatory markers but are useful for assessing and monitoring disease activity.

4. Iron and Ferritin Changes

The inflammatory response alters iron metabolism. Serum iron concentration and total iron-binding capacity may be reduced, while ferritin may be normal or elevated because it acts as an acute-phase reactant. These findings are typical of anaemia associated with chronic inflammation.

5. Raised Globulins

Chronic immune activation may result in increased immunoglobulin production and therefore raised serum globulin concentrations.

6. Alkaline Phosphatase

Alkaline phosphatase (ALP) may occasionally be elevated, particularly in active systemic disease, although it is not a specific diagnostic marker for RA.

Rheumatoid Factor

Rheumatoid factor refers to autoantibodies directed against the Fc portion of IgG. The classic rheumatoid factor is an IgM autoantibody, although other immunoglobulin classes may also occur.

Older sources report RF positivity in approximately 70–80% of patients with established RA. However, it is not specific for the disease and can occur in other autoimmune disorders, chronic infections, and healthy individuals. The frequency of positive RF also increases with age.

Modern evaluation commonly includes anti-cyclic citrullinated peptide (anti-CCP/ACPA) antibodies, which have greater specificity for RA and can help predict a greater likelihood of erosive disease.

Radiological Features of Rheumatoid Arthritis

1. Soft-Tissue Swelling

An early radiographic finding is soft-tissue swelling around affected joints, reflecting active synovitis and joint effusion.

2. Joint-Space Narrowing

Progressive destruction and loss of articular cartilage cause narrowing of the joint space. In RA, this narrowing is often relatively uniform across the affected joint.

3. Juxta-Articular Osteopenia

Inflammation around affected joints may produce juxta-articular or periarticular osteopenia, causing the bone close to the joint to appear less dense on radiographs.

4. Marginal Bone Erosions

Persistent synovitis produces invasive inflammatory tissue that damages the bone at the joint margins. This leads to characteristic marginal erosions, which are an important radiological sign of established RA.

5. Joint Deformities

Advanced disease can result in subluxation, malalignment, and fixed deformities because of progressive destruction of cartilage, bone, tendons, and ligaments.

Drug Treatment of Rheumatoid Arthritis

Treatment aims not only to relieve symptoms but also to suppress inflammation, achieve remission or low disease activity, prevent structural joint damage, and preserve physical function. Modern management emphasises early use of disease-modifying therapy rather than relying solely on symptomatic treatment.

1. Symptom-Modifying Treatment

Analgesics may be used to relieve pain but do not control the underlying autoimmune disease or prevent joint destruction.

NSAIDs can reduce inflammatory pain and stiffness and may improve short-term function. However, they do not prevent progression of joint damage, so they should not replace disease-modifying treatment.

2. Disease-Modifying Antirheumatic Drugs

Methotrexate is generally the preferred first-line conventional synthetic disease-modifying antirheumatic drug (DMARD) for patients with active RA unless contraindicated. Other conventional DMARDs include sulfasalazine, hydroxychloroquine, and leflunomide, either alone or in combination depending on disease severity and response.

Corticosteroids may provide rapid suppression of inflammation and are sometimes used as short-term bridging therapy or for significant flares. Because of their numerous long-term adverse effects, prolonged corticosteroid exposure should be minimised whenever possible.

Other immunosuppressive drugs, including azathioprine and ciclosporin, have historically been used in selected cases but are much less central to routine modern RA treatment. Similarly, gold salts and penicillamine are older DMARDs that are now rarely used because more effective and better-tolerated alternatives are available.

Patients who remain inadequately controlled despite conventional DMARD therapy may receive biologic or targeted synthetic DMARDs. These include TNF inhibitors such as infliximab and other therapies directed against specific inflammatory pathways or immune cells. Treatment selection is individualised according to disease activity, previous therapy, comorbidities, infection risk, and other clinical factors.

Key Clinical Pattern

Rheumatoid arthritis is characterised by chronic symmetrical inflammatory polyarthritis, especially involving the MCP, PIP, wrist, and MTP joints while usually sparing the DIP joints. Persistent inflammation may produce characteristic deformities such as ulnar deviation, swan-neck deformity, boutonnière deformity, and Z-deformity of the thumb. Important investigations include RF, anti-CCP antibodies, ESR, CRP, and radiographs, while early treatment with DMARDs, particularly methotrexate, is central to preventing irreversible joint damage.