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Gout, Pseudogout, Ankylosing Spondylitis, & Other Arthitides for the American Board of Internal Medicine (ABIM) Exam

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Gout
  • Definition: A disorder of purine metabolism leading to hyperuricemia and monosodium urate crystal deposition in joints, causing recurrent acute arthritis.
Pathophysiology
  • Hyperuricemia: Caused by overproduction or underexcretion of uric acid.
  • Crystal-Induced Inflammation: Monosodium urate crystals activate inflammatory mediators in the synovium.
Clinical Features
  • Acute Gouty Arthritis: Sudden, severe joint pain, erythema, and swelling; classic initial presentation in the 1st MTP joint (podagra).
  • Tophi Formation: Subcutaneous nodules in chronic gout; can affect ears, fingers, and tendons.
Diagnosis
  • Joint Aspiration: Negatively birefringent, needle-shaped crystals on polarized light microscopy.
  • Serum Uric Acid Levels: May be elevated but can be normal during an acute attack.
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Pseudogout (Calcium Pyrophosphate Deposition Disease - CPPD)
  • Definition: A form of arthritis resulting from the deposition of calcium pyrophosphate crystals in joints.
Pathophysiology
  • Calcium Pyrophosphate Crystal Deposition: Crystals deposit in articular cartilage, triggering inflammation (chondrocalcinosis).
Clinical Features
  • Acute Pseudogout: Pain, redness, and swelling in large joints (commonly the knee).
  • Chronic CPPD: Resembles osteoarthritis or rheumatoid arthritis, with progressive joint degeneration.
Diagnosis
  • Synovial Fluid Analysis: Rhomboid-shaped, positively birefringent crystals.
  • Radiographic Findings: Chondrocalcinosis and joint space narrowing.
Gout vs Pseudogout
Urate and CPPD Histological Image References
Gout Pseudogout
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Reactive Arthritis
  • Definition: An inflammatory arthritis following a genitourinary or gastrointestinal infection.
Pathophysiology
  • Post-Infectious Autoimmunity: Triggered by infections like Chlamydia, Salmonella, Shigella, or Campylobacter.
Clinical Features
  • Triad: Arthritis, urethritis, and conjunctivitis/uveitis.
  • Asymmetric Joint Involvement: Usually affects the lower extremities and sacroiliac joints.
Diagnosis
  • Clinical Diagnosis: Based on symptoms and history of recent infection.
  • HLA-B27: Often positive but not specific.
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Ankylosing Spondylitis (AS)
  • Definition: A chronic inflammatory arthritis predominantly affecting the axial skeleton, leading to spinal rigidity and ankylosis.
Pathophysiology
  • Genetic Predisposition: Strongly associated with HLA-B27.
  • Inflammation and Bone Remodeling: Chronic inflammation leads to new bone formation and vertebral fusion.
Clinical Features
  • Low Back Pain and Stiffness: Gradual onset, worsens with rest, improves with activity.
  • Extra-Articular Manifestations: Uveitis, aortic regurgitation, and pulmonary fibrosis.
Diagnosis
  • Imaging Studies: X-ray showing sacroiliitis, "bamboo spine" on advanced imaging.
  • Laboratory Findings: Elevated ESR/CRP, HLA-B27 testing.
Ankylosing spondylitis - bamboo spine
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Psoriatic Arthritis (PsA)
  • Definition: An inflammatory arthritis associated with psoriasis, affecting both peripheral and axial joints.
Pathophysiology
  • Autoimmune Inflammation: Affects the skin and synovial joints, leading to joint damage.
Clinical Features
  • Patterns of Joint Involvement: Asymmetric oligoarthritis, DIP joint involvement, dactylitis ("sausage digits"), nail pitting.
  • Variable Disease Presentation: Can mimic rheumatoid arthritis or ankylosing spondylitis.
Diagnosis
  • Clinical Diagnosis: Psoriatic skin changes plus joint symptoms.
  • Radiographic Findings: "Pencil-in-cup" deformity, joint erosions.
Psoriatic Arthritis. Penci-in-cup deformity. Dactylitis.
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Septic Arthritis
  • Definition: An infection of the joint space, requiring urgent diagnosis and treatment.
Pathophysiology
  • Bacterial Infection: Most commonly caused by Staphylococcus aureus; in sexually active adults, consider Neisseria gonorrhoeae.
Clinical Features
  • Acute Monoarticular Arthritis: Pain, erythema, warmth, and fever, typically affecting a large joint (e.g., knee, hip).
  • Systemic Signs: Fever, malaise, leukocytosis.
Diagnosis
  • Synovial Fluid Analysis: Purulent fluid, high WBC count (>50,000 cells/mm³), positive Gram stain and culture.
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Essential Points
  • Gout vs. Pseudogout: Distinct crystal types and microscopy findings; gout (monosodium urate, negatively birefringent), pseudogout (calcium pyrophosphate, positively birefringent).
  • Seronegative Spondyloarthropathies: Includes ankylosing spondylitis, reactive arthritis, and psoriatic arthritis; associated with HLA-B27.
  • Septic Arthritis: A medical emergency requiring prompt synovial fluid analysis and initiation of antibiotics.
  • Pattern Recognition: Recognize clinical patterns, triggers, and extra-articular manifestations for accurate diagnosis and management.

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