What are the typical presentation, differential diagnosis (DDX), investigations (INVX), management (MX), and complications of Rheumatoid Arthritis (RA)?

Rheumatoid Arthritis: Clinical Presentation, Diagnosis, Management, and Complications

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis affecting small joints, with potential for extra-articular manifestations and progressive joint damage if not treated early with disease-modifying antirheumatic drugs (DMARDs).

Typical Presentation (Signs and Symptoms)

Joint Manifestations

• Pattern: Symmetric polyarthritis predominantly affecting:
  • Metacarpophalangeal joints
  • Proximal interphalangeal joints
  • Wrists
  • Metatarsophalangeal joints
  • Knees 1
• Morning stiffness: Lasting at least 1 hour before maximal improvement, duration correlates with disease activity 1
• Joint symptoms: Swelling, tenderness, pain, and severe motion impairment 1

Onset Patterns

• Insidious onset (most common): Gradual development of pain with symmetric small joint swelling
• Acute/subacute onset (25% of patients)
• Other patterns:
  • Palindromic onset (recurrent episodes of oligoarthritis)
  • Monoarticular presentation
  • Extra-articular synovitis (tenosynovitis, bursitis)
  • Polymyalgic-like onset (resembling polymyalgia rheumatica in elderly)
  • Constitutional symptoms (malaise, fatigue, weight loss, fever) 1

Extra-articular Manifestations

• Rheumatoid nodules
• Vasculitis
• Hematologic abnormalities
• Interstitial lung disease
• Scleritis/episcleritis
• Felty's syndrome
• Cardiac involvement 1, 2

Differential Diagnosis (DDX)

• Osteoarthritis
• Systemic lupus erythematosus
• Psoriatic arthritis
• Crystal arthropathies (gout, pseudogout)
• Adult-onset Still's disease
• Reactive arthritis
• Seronegative spondyloarthropathies
• Polymyalgia rheumatica
• Viral arthritis 3, 4

Investigations (INVX)

Laboratory Tests

1. Rheumatoid Factor (RF):

   • Sensitivity: 69-84%
   • Specificity: 78-85% 5

2. Anti-citrullinated protein antibody (Anti-CCP):

   • Sensitivity: 67-78.5%
   • Specificity: 95-98%
   • Highest specificity for RA diagnosis 5, 4

3. Inflammatory markers:

   • Erythrocyte sedimentation rate (ESR)
   • C-reactive protein (CRP)
   • Both provide information about acute phase response 1, 4

4. Complete blood count: May show anemia of chronic disease, thrombocytosis, leukocytosis 1

5. Baseline renal and hepatic function tests: Important before starting treatment 3

Imaging

1. Plain radiographs:

   • Initial findings: Soft tissue swelling, juxtaarticular osteoporosis
   • Later findings: Joint space narrowing, erosions
   • Recommended at baseline and every 6-12 months during first few years 5, 1

2. Ultrasonography:

   • Detects synovial thickening even in early disease
   • Useful for assessing joint, tendon, and bursal involvement 1

3. MRI/CT (selected cases):

   • More sensitive for early erosions and synovitis
   • Helpful in complex cases 1

Management (MX)

Treatment Goals

• Minimize joint pain and swelling
• Prevent radiographic damage and visible deformity
• Maintain work and personal activities
• Achieve remission or lowest disease activity possible 5, 4

Pharmacological Treatment

1. First-line therapy:

   • Methotrexate: 7.5-15mg weekly, escalating to 20-25mg
   • Should be started within 3 months of symptom onset 5, 6

2. Combination therapy:

   • Methotrexate + hydroxychloroquine + short-term steroids (preferred first-line combination) 5

3. Glucocorticoids:

   • Used at lowest effective dose for shortest time possible (<6 months)
   • Options: oral prednisone (5-10 mg daily) as bridging therapy
   • Intra-articular injections for specific affected joints 5

4. Biologic DMARDs (if inadequate response to conventional DMARDs):

   • TNF inhibitors (etanercept, adalimumab, infliximab)
   • IL-6 inhibitors (tocilizumab)
   • T-cell co-stimulation modulator (abatacept)
   • B-cell depleting therapy (rituximab) 5, 6

5. NSAIDs:

   • For symptomatic relief
   • Use after evaluation of gastrointestinal, renal, and cardiovascular status 5

Non-Pharmacological Treatment

• Patient education on self-management techniques
• Physical therapy and muscle strengthening exercises
• Proper footwear
• Joint protection techniques 5

Monitoring and Follow-up

• Regular assessment of disease activity using validated measures (CDAI, DAS28, SDAI)
• Follow-up every 1-3 months until remission, then every 3-6 months
• Treatment modification if target not achieved within 3-6 months 5

Complications

1. Joint-related:

   • Progressive joint destruction
   • Deformities (swan neck, boutonnière, ulnar deviation)
   • Joint ankylosis
   • Need for joint replacement surgery 3, 2

2. Extra-articular:

   • Cardiovascular disease (leading cause of death in RA patients)
   • Interstitial lung disease
   • Rheumatoid vasculitis
   • Amyloidosis
   • Increased risk of infections
   • Osteoporosis 2

3. Psychosocial:

   • Disability and functional impairment
   • Depression and anxiety
   • Fatigue
   • Reduced quality of life 2

Common Pitfalls to Avoid

• Delayed referral to a rheumatologist (should be within 6 weeks of symptom onset)
• Failing to start DMARDs early in patients at risk for persistent disease
• Inadequate monitoring of disease activity and treatment response
• Overreliance on a single test for diagnosis
• Overlooking RA in patients with only one or few affected joints initially 5

Early diagnosis and aggressive treatment within the "window of opportunity" are crucial for preventing joint damage and improving long-term outcomes in patients with rheumatoid arthritis.