Immunology · Year 2 · from Immunology

Case 2: Rheumatoid Arthritis

Patient Demographics

  • Age: 45 years old
  • Sex: Female
  • Ethnicity: Caucasian

Chief Complaint

Painful, swollen joints in hands for 6 months

History of Present Illness

A 45-year-old woman presents with a 6-month history of joint pain and swelling primarily affecting her hands. She reports morning stiffness lasting 2-3 hours that improves with activity. The symptoms began insidiously, first affecting her fingers, and have progressively involved her wrists and feet. She has noticed difficulty making a fist and has had to remove her rings due to finger swelling. She also reports fatigue and a 5-pound unintentional weight loss.

Past Medical History

  • 20-pack-year smoking history (quit 5 years ago)
  • No prior joint problems

Family History

  • Sister with rheumatoid arthritis
  • Mother with hypothyroidism

Physical Examination

  • General: Well-appearing woman with obvious hand deformities
  • Vital Signs: Normal
  • Hands: Symmetric swelling and tenderness of MCPs (2nd-5th bilaterally) and PIPs; warmth over affected joints; boggy synovium on palpation; decreased grip strength
  • Wrists: Bilateral swelling and tenderness with limited extension
  • Feet: Tenderness at MTPs bilaterally (squeeze test positive)
  • No subcutaneous nodules palpated

Laboratory Workup

TestResultReference Range
ESR58 mm/hr0-20 mm/hr
CRP3.8 mg/dL<0.5 mg/dL
Rheumatoid Factor186 IU/mL<14 IU/mL
Anti-CCP antibody>250 U/mL<20 U/mL
ANA1:80 (speckled)Negative
CBCNormal--
Hand X-raysPeriarticular osteopenia, joint space narrowing MCPs, early erosions at 2nd and 3rd MCPNormal

Diagnosis

Seropositive Rheumatoid Arthritis with early erosive disease

Discussion

Rheumatoid arthritis is a chronic inflammatory joint disease characterized by symmetric polyarthritis with progressive joint destruction:

Pathogenesis:

  • Genetic susceptibility: HLA-DR4 "shared epitope" association
  • Environmental trigger: Smoking promotes citrullination of proteins
  • Autoimmunity: Anti-CCP antibodies target citrullinated proteins
  • Synovial inflammation: T cells, B cells, macrophages produce TNF-alpha, IL-1, IL-6
  • Pannus formation: Proliferating synovium invades and destroys cartilage and bone

Why is anti-CCP important?

  • More specific for RA than rheumatoid factor (95% vs 70%)
  • Predicts erosive disease and worse prognosis
  • Can be positive years before clinical disease onset
  • Helps distinguish RA from other causes of RF positivity

Joint involvement pattern in RA:

  • Affected: MCPs, PIPs, wrists, MTPs (symmetric)
  • Spared: DIPs (unlike osteoarthritis and psoriatic arthritis)

Extra-articular manifestations (not yet present):

  • Rheumatoid nodules (elbows, lungs)
  • Interstitial lung disease
  • Felty syndrome (splenomegaly, neutropenia)
  • Cardiovascular disease (accelerated atherosclerosis)

Treatment

  1. Early aggressive treatment: Treat-to-target strategy (low disease activity or remission)
  2. Conventional DMARDs: Methotrexate first-line (anchor drug)
  3. Biologic DMARDs if inadequate response:
  • TNF inhibitors (adalimumab, etanercept)
  • Other options: Abatacept (costimulation blockade), Rituximab (B cell depletion), JAK inhibitors
  1. Bridging therapy: Low-dose prednisone while DMARDs take effect
  2. Monitoring: Disease activity scores, inflammatory markers, imaging for erosion progression
  3. Cardiovascular risk management: Aggressive risk factor modification

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