Introduction

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease characterized by persistent synovitis, progressive destruction of articular cartilage and bone, and a wide range of extra-articular manifestations. The disease primarily affects the small synovial joints of the hands and feet but may progressively involve larger joints and multiple organ systems. Without early diagnosis and treatment, RA can lead to irreversible joint damage, deformity, disability, reduced quality of life, and increased cardiovascular mortality.

RA affects approximately 0.5–1% of the adult population worldwide and occurs about two to three times more frequently in women than men. Early initiation of disease-modifying antirheumatic drugs (DMARDs) is the cornerstone of management and significantly improves long-term outcomes.

Epidemiology

• Prevalence approximately 0.5–1% worldwide.

• Female-to-male ratio approximately 3:1.

• Most commonly develops between 30 and 60 years of age.

• May occur at any age.

• More common among first-degree relatives of affected individuals.

• Increased cardiovascular morbidity and mortality compared with the general population.

Etiology

The exact cause remains unknown. Rheumatoid arthritis results from a complex interaction between genetic susceptibility and environmental triggers leading to loss of immune tolerance.

Genetic factors

• HLA-DRB1 shared epitope alleles

• Family history

• PTPN22 polymorphism

Environmental factors

• Cigarette smoking

• Periodontal disease

• Obesity

• Silica exposure

• Female hormonal factors

Pathophysiology

Rheumatoid arthritis develops when genetically susceptible individuals lose immunological tolerance to self-antigens, particularly citrullinated proteins. Environmental triggers such as cigarette smoking and periodontal infections promote protein citrullination, leading to activation of T lymphocytes and B lymphocytes within the synovium. Activated immune cells produce autoantibodies, including rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA), together with inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6).

Persistent cytokine production causes proliferation of the synovial membrane, forming an invasive inflammatory tissue known as pannus. The pannus progressively erodes cartilage, subchondral bone, tendons, and ligaments through activation of osteoclasts and matrix-degrading enzymes. Ongoing inflammation eventually results in joint space narrowing, deformity, instability, tendon rupture, and irreversible loss of function. Because RA is a systemic disease, chronic inflammation may also affect the eyes, lungs, heart, blood vessels, skin, and other organs.

Risk factors

• Female sex

• Increasing age

• Family history

• Cigarette smoking

• Obesity

• Periodontal disease

• HLA-DRB1 genotype

• Previous autoimmune disease

Clinical presentation

Articular manifestations

• Morning stiffness lasting longer than one hour

• Symmetrical polyarthritis

• Painful swollen joints

• Involvement of three or more joints

• Small joints commonly affected:

  • Metacarpophalangeal (MCP)

  • Proximal interphalangeal (PIP)

  • Wrist

  • Metatarsophalangeal (MTP)

• Progressive involvement of elbows, shoulders, knees and ankles

• Reduced grip strength

• Joint tenderness

• Reduced range of motion

Chronic joint deformities

• Ulnar deviation

• Swan-neck deformity

• Boutonnière deformity

• Z-thumb deformity

• Joint subluxation

• Tendon rupture

Extra-articular manifestations

• Rheumatoid nodules

• Fatigue

• Low-grade fever

• Weight loss

• Anaemia

• Vasculitis

• Dry eyes (secondary Sjögren syndrome)

• Episcleritis and scleritis

• Interstitial lung disease

• Pleural effusion

• Pericarditis

• Peripheral neuropathy

Target population for classification

The 2010 ACR/EULAR classification criteria should be applied only to patients who have:

• At least one joint with definite clinical synovitis (swelling).

• Synovitis that is not better explained by another disease such as gout, lupus, psoriatic arthritis, or septic arthritis.

Diagnostic criteria (2010 ACR/EULAR classification criteria)

A total score of 6 or more out of 10 classifies a patient as having definite rheumatoid arthritis.

Domain A. Joint involvement (0–5 points)

Domain B. Serology (0–3 points)

At least one serological test is required.

Domain C. Acute-phase reactants (0–1 point)

At least one acute-phase reactant is required.

Domain D. Duration of symptoms (0–1 point)

Interpretation

• Total score ≥6/10: Definite rheumatoid arthritis.

• Total score <6/10: Does not currently meet classification criteria; reassessment is recommended if symptoms persist.

Investigations

Laboratory investigations

• Full blood picture (FBP) with differential

• Erythrocyte sedimentation rate (ESR)

• C-reactive protein (CRP)

• Rheumatoid factor (RF)

• Anti-citrullinated protein antibody (ACPA/anti-CCP) – highly specific

• Antinuclear antibody (ANA) when connective tissue disease is suspected

• Liver function tests

• Renal function tests

• Serum uric acid when crystal arthritis is suspected

Synovial fluid analysis

Typical findings:

• Inflammatory appearance

• White blood cell count >2,000/mm³ (often 5,000–50,000/mm³)

• Predominantly neutrophils

• Negative Gram stain and culture unless infection coexists

Imaging

Plain X-ray

Early findings:

• Soft tissue swelling

• Juxta-articular osteopenia

Late findings:

• Joint space narrowing

• Marginal erosions

• Joint deformity

• Subluxation

Ultrasound

• Synovitis

• Power Doppler activity

• Early erosions

• Tenosynovitis

MRI

Most sensitive for early disease.

Demonstrates:

• Bone marrow oedema

• Synovitis

• Cartilage damage

• Early erosions

Differential diagnosis

• Osteoarthritis

• Psoriatic arthritis

• Reactive arthritis

• Systemic lupus erythematosus

• Crystal arthritis

• Septic arthritis

• Viral arthritis

• Ankylosing spondylitis

Management

Treatment aims to:

• Control inflammation

• Achieve remission or low disease activity

• Prevent joint destruction

• Preserve function

• Improve quality of life

• Reduce extra-articular complications

Pharmacological treatment

NSAIDs should be used in combination with corticosteroids or DMARDs. Once DMARDs become effective, NSAIDs and corticosteroids should be reduced or discontinued where possible.

Non-selective COX inhibitors

Ibuprofen

• 400–800 mg orally every 8 hours for 5 days

OR

Meloxicam

• 7.5–15 mg orally every 12 hours for 5–14 days

OR

Piroxicam

• 20 mg orally once daily

or

• 10 mg orally every 12 hours for 5–14 days

Selective COX-2 inhibitors

Ketoprofen

• 50–75 mg orally every 8 hours for 7–14 days

OR

Dexketoprofen trometamol

• 12.5 mg orally every 6 hours

or

• 25 mg orally every 8 hours for 7–14 days

Corticosteroid therapy

Prednisolone

• 40 mg orally daily for 3 days, then gradually taper over 2–4 weeks

OR

Triamcinolone

• 40 mg intramuscularly every 6 weeks

• Additional 20–100 mg IM may be administered as clinically indicated

OR

Betamethasone dipropionate 2 mg plus betamethasone sodium phosphate 10 mg

• Intralesional injection once

• Maximum 4 mL per treatment

• Repeat every 2–12 weeks

• Maximum four injections annually for up to two years

Disease-modifying antirheumatic drugs (DMARDs)

Hydroxychloroquine

• 400–600 mg orally once daily for 4–12 weeks

• Then 200–400 mg orally once daily for a further 12 weeks

OR

Sulfasalazine

• 0.5–1 g orally daily in two divided doses

• Increase weekly to a maintenance dose of 2 g/day for 12 weeks

OR

Methotrexate

• Initial dose 7.5 mg orally once weekly

• Increase gradually according to clinical response

• Maximum 20 mg/week for 12 weeks

Important treatment notes

• Repeat CRP and ESR every two weeks to determine whether treatment should be escalated, maintained, or tapered.

• Patients receiving NSAIDs for more than two weeks should receive proton pump inhibitor therapy for gastrointestinal protection.

• Oral corticosteroids or NSAIDs should be combined with one DMARD until the DMARD becomes clinically effective.

• Patients receiving long-term corticosteroids should undergo random blood glucose (RBG) testing at least twice yearly.

• Patients taking methotrexate should also receive folic acid supplementation according to local protocols and undergo regular monitoring of liver function, renal function, and full blood count.

Surgical treatment

Surgery may be indicated in patients with severe pain, deformity, tendon rupture, or irreversible joint destruction.

Procedures include:

• Synovectomy

• Tenosynovectomy

• Tendon realignment

• Reconstructive surgery

• Arthroplasty

• Arthrodesis

Rehabilitation

Orthotics and assistive devices

• Wrist splints

• Hand splints

• Well-padded footwear

• Walking aids

• Braces

Physiotherapy

• Daily range-of-motion exercises

• Muscle strengthening

• Joint protection techniques

• Aerobic exercise for at least 30 minutes on four or more days each week

Occupational therapy

Occupational therapy assists patients by:

• Maintaining independence in activities of daily living

• Teaching energy conservation techniques

• Providing adaptive devices

• Recommending workplace modifications

Monitoring and follow-up

Patients should be monitored regularly for:

• Disease activity

• Functional status

• ESR and CRP

• Complete blood count

• Liver function

• Renal function

• Drug toxicity

• Development of joint deformities

• Extra-articular complications

Complications

• Progressive joint destruction

• Permanent deformity

• Tendon rupture

• Cervical spine instability

• Osteoporosis

• Cardiovascular disease

• Interstitial lung disease

• Vasculitis

• Secondary Sjögren syndrome

• Functional disability

• Increased mortality

Prognosis

Rheumatoid arthritis is a chronic progressive disease; however, early diagnosis and prompt initiation of DMARD therapy substantially improve long-term outcomes. Patients treated early are more likely to achieve sustained remission, preserve joint function, and prevent irreversible structural damage. Delayed treatment is associated with progressive deformity, disability, extra-articular complications, and increased cardiovascular mortality.