Rheumatoid Arthritis (RA)

Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management | References

Definition

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that primarily affects the joints, causing inflammation, pain, and swelling. Over time, it can lead to joint destruction, deformity, and loss of function. RA can also have extra-articular manifestations, affecting other organs.

Aetiology

The exact cause of RA is unknown, but it is thought to result from a combination of genetic, environmental, and immunological factors. Key factors include:

• Genetic predisposition, particularly the presence of HLA-DRB1 alleles
• Environmental triggers, such as smoking, which is a well-established risk factor
• Hormonal factors, as RA is more common in women, suggesting a role for oestrogens
• Immune system dysregulation, where the immune system attacks the synovium (lining of the joints)

Pathophysiology

The pathophysiology of RA involves:

• Autoimmune response, where T-cells, B-cells, and other immune cells attack the synovial membrane, leading to chronic inflammation
• Synovitis, or inflammation of the synovium, resulting in thickening of the synovial membrane (pannus formation)
• Destruction of cartilage and bone due to the release of pro-inflammatory cytokines, such as tumour necrosis factor (TNF) and interleukin-6 (IL-6)
• Joint deformity and erosion due to the progressive destruction of joint structures
• Systemic inflammation, which can affect other organs, leading to complications such as cardiovascular disease, lung disease, and osteoporosis

Risk Factors

• Female gender, as women are more commonly affected than men
• Age between 40 and 60 years, although RA can occur at any age
• Family history of RA or other autoimmune diseases
• Smoking, which significantly increases the risk of developing RA
• Obesity, which is associated with a higher risk and more severe disease
• Exposure to environmental factors, such as silica dust or asbestos

Signs and Symptoms

The signs and symptoms of RA include:

• Symmetrical joint pain, swelling, and stiffness, particularly in the small joints of the hands, wrists, and feet
• Morning stiffness lasting more than 30 minutes
• Fatigue, malaise, and generalised weakness
• Joint deformities, such as ulnar deviation, swan-neck deformity, and boutonnière deformity, in advanced stages
• Extra-articular manifestations, including rheumatoid nodules, pleuritis, pericarditis, interstitial lung disease, and vasculitis
• Systemic symptoms such as low-grade fever and weight loss

Investigations

Specific investigations to diagnose RA include:

• Blood tests: Raised inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are typically positive in RA.
• Full blood count (FBC): To rule out anaemia of chronic disease, which is common in RA patients.
• X-rays: To assess joint damage, including joint space narrowing, erosions, and osteopenia near the joints.
• Ultrasound or MRI: May be used to detect early synovitis and assess joint damage in more detail.
• Joint aspiration: Synovial fluid analysis may be performed to rule out other causes of arthritis, such as gout or septic arthritis.

Management

Primary Care Management

• Referral to rheumatology: Early referral is crucial for the initiation of disease-modifying treatment.
• NSAIDs: Nonsteroidal anti-inflammatory drugs (e.g., ibuprofen, naproxen) may be used for pain relief and inflammation control.
• Glucocorticoids: Low-dose corticosteroids (e.g., prednisolone) can be used for short-term management of symptoms and to bridge the gap until disease-modifying antirheumatic drugs (DMARDs) take effect.
• Pain management: Paracetamol or mild opioids may be used as adjunctive therapy for pain relief.
• Lifestyle modifications: Encouraging regular physical activity, smoking cessation, and weight management.

Specialist Management

• DMARDs: Methotrexate is the first-line treatment for RA, often combined with other DMARDs such as sulfasalazine, hydroxychloroquine, or leflunomide. These medications slow disease progression by modulating the immune response.
• Biologic therapy: TNF inhibitors (e.g., etanercept, infliximab) or other biologics (e.g., tocilizumab, rituximab) may be used in patients with severe or refractory RA who do not respond adequately to traditional DMARDs.
• Physical therapy: Physiotherapy and occupational therapy can help maintain joint function and improve quality of life.
• Surgical intervention: Joint replacement surgery may be considered for patients with severe joint damage and disability.
• Monitoring and follow-up: Regular monitoring of disease activity, side effects of medications, and overall health is essential. This includes periodic blood tests and imaging studies.

References

1. NHS (2024) Rheumatoid Arthritis. Available at: https://www.nhs.uk/conditions/rheumatoid-arthritis/ (Accessed: 24 June 2024).
2. National Institute for Health and Care Excellence (2024) Rheumatoid Arthritis: Management and Monitoring. Available at: https://cks.nice.org.uk/topics/rheumatoid-arthritis/ (Accessed: 24 June 2024).
3. British Medical Journal (2024) Rheumatoid Arthritis: Clinical Features, Diagnosis, and Management. Available at: https://www.bmj.com/content/350/bmj.h3010 (Accessed: 24 June 2024).
4. American College of Rheumatology (2024) Rheumatoid Arthritis. Available at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Rheumatoid-Arthritis (Accessed: 24 June 2024).
5. National Rheumatoid Arthritis Society (2024) Living with Rheumatoid Arthritis. Available at: https://www.nras.org.uk/ (Accessed: 24 June 2024).

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