Rheumatoid arthritis

Rheumatoid Arthritis: A Comprehensive Overview

Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by systemic inflammation primarily affecting synovial joints. Understanding its pathophysiology and management is crucial for pharmacists, as RA significantly impacts patients' quality of life and often requires long-term treatment strategies.

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Definition

Rheumatoid arthritis is an autoimmune disorder that primarily targets the synovium (lining of joints), leading to joint inflammation, pain, swelling, and eventual joint destruction. The condition affects multiple joints symmetrically and can involve extra-articular manifestations such as cardiovascular, pulmonary, and ocular systems.

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Types of Rheumatoid Arthritis

1. Seropositive RA: The most common form, characterized by the presence of specific autoantibodies—rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP).
2. Seronegative RA: Lacks the presence of these autoantibodies, making diagnosis more challenging but the clinical presentation remains similar.

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Etiology

The exact cause of RA is unknown, but it is considered multifactorial, involving:

• Genetic predisposition: Specific genes like HLA-DRB1 are linked to RA susceptibility.
• Environmental factors: Smoking, infections (such as Epstein-Barr virus), and hormonal imbalances contribute to the risk.
• Autoimmune mechanism: Abnormal immune responses trigger synovial inflammation and systemic complications.

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Pathophysiology

RA initiates when autoantibodies (RF and anti-CCP) form immune complexes that deposit in joints. These complexes trigger an inflammatory response, involving cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). The inflammatory cascade causes:

1. Synovial membrane inflammation (synovitis), leading to pannus formation—a destructive layer of granulation tissue.
2. Erosion of cartilage and bone within the joint.
3. Chronic joint damage with resultant deformity, stiffness, and loss of function.

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Clinical Manifestations

1. Articular Symptoms:

   • Morning stiffness lasting more than 30 minutes.
   • Symmetrical joint swelling, particularly in the small joints (e.g., hands, wrists, feet).
   • Joint pain, tenderness, and warmth.
   • Decreased range of motion and deformities (e.g., ulnar deviation, swan-neck deformity).

2. Extra-articular Symptoms:

   • Rheumatoid nodules: Firm, subcutaneous lumps.
   • Cardiovascular involvement: Increased risk of atherosclerosis and pericarditis.
   • Pulmonary: Interstitial lung disease, pleuritis.
   • Ocular: Sjögren’s syndrome (dry eyes), scleritis.

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Diagnosis

1. Clinical assessment: Symmetrical polyarthritis lasting more than 6 weeks, with hallmark symptoms such as morning stiffness and joint swelling.
2. Laboratory Tests:
   • Rheumatoid factor (RF) and anti-CCP antibodies: Diagnostic markers.
   • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Indicators of systemic inflammation.
3. Imaging:
   • X-rays: Show joint space narrowing, bone erosions, and deformities.
   • Ultrasound/MRI: Useful for early detection of synovitis and bone erosions.

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Treatment

Pharmacological Treatment

1. Nonsteroidal Anti-inflammatory Drugs (NSAIDs):

   • Provide symptomatic relief by reducing inflammation and pain. Common agents include ibuprofen and naproxen.

2. Corticosteroids:

   • Used short-term to control acute flare-ups (e.g., prednisone). They are effective anti-inflammatory agents but come with long-term side effects like osteoporosis.

3. Disease-Modifying Antirheumatic Drugs (DMARDs):

   • Conventional DMARDs: Methotrexate is the gold standard due to its ability to slow disease progression. Other options include leflunomide, sulfasalazine, and hydroxychloroquine.
   • Biologic DMARDs: Target specific inflammatory cytokines (e.g., TNF inhibitors like infliximab, IL-6 inhibitors like tocilizumab).
   • Janus kinase (JAK) inhibitors: Tofacitinib, a newer class of oral DMARDs, disrupts cytokine signaling involved in RA.

Non-Pharmacological Treatment

1. Physical Therapy and Occupational Therapy: To improve joint mobility and maintain function.

2. Lifestyle Modifications:

   • Regular low-impact exercise (e.g., swimming, walking) to strengthen muscles and joints.
   • Weight management to reduce stress on weight-bearing joints.
   • Smoking cessation: Reduces inflammation and slows disease progression.

3. Surgical Options: For severe, unmanageable cases, joint replacement or synovectomy may be required.

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FAQs about Rheumatoid Arthritis

1. What is the difference between rheumatoid arthritis and osteoarthritis? RA is an autoimmune disease causing systemic inflammation, while osteoarthritis is a degenerative joint disease caused by wear and tear.

2. Can RA affect organs other than joints? Yes, RA can affect organs like the lungs, heart, and eyes due to systemic inflammation.

3. How is RA diagnosed? Through clinical evaluation, blood tests for RF and anti-CCP, and imaging studies like X-rays and MRIs.

4. Is RA curable? No, RA is a chronic condition, but early diagnosis and treatment can help manage symptoms and prevent joint damage.

5. Are biologics the same as DMARDs? Biologics are a subset of DMARDs that target specific components of the immune system, while conventional DMARDs affect overall immune response.