What is pseudogout (calcium pyrophosphate deposition disease)?

Pseudogout (Calcium Pyrophosphate Deposition Disease)

Pseudogout is a form of inflammatory arthritis caused by the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in joints and surrounding tissues, leading to acute or chronic joint inflammation, pain, and functional impairment. 1

Clinical Presentation

• Acute attacks: Characterized by sudden onset of joint pain, swelling, redness, and warmth, most commonly affecting the knee, wrist, shoulder, and ankle joints 1, 2
• Chronic manifestations: May present as:
  • Oligoarticular or polyarticular episodes (affecting multiple joints) 3
  • Chronic inflammatory arthritis resembling rheumatoid arthritis 4
  • Progressive, destructive arthropathy (pyrophosphate arthropathy) - an accelerated form of osteoarthritis 3
• Atypical presentations: May include cervical spine involvement causing myelopathy in rare cases 5

Diagnostic Features

Imaging

• Radiography should be the initial imaging method, showing:

  • Chondrocalcinosis (calcification of cartilage) - the hallmark finding 1
  • Target sites for fibrocartilage calcification include:
    • Triangular fibrocartilage of wrists
    • Knee menisci
    • Symphysis pubis and labrum at the pelvis 1
  • Characteristic arthropathy affecting radiocarpal, metacarpophalangeal, and patellofemoral joints 1
  • Capsular or periarticular calcifications in about one-third of patients 3

• Ultrasound findings include:

  • Intra-articular microtophi
  • Echogenic synovial hypertrophy
  • "Double contour sign" (icing of the cartilage) with 83% sensitivity and 76% specificity 1

• CT can identify:

  • Chondrocalcinosis
  • Calcification of tendons, ligaments, and joint capsules
  • Osseous changes related to pseudogout 1

Laboratory Testing

• Joint fluid analysis: Reveals calcium pyrophosphate dihydrate crystals under polarized light microscopy - definitive for diagnosis 2
• Serum studies: Should include evaluation for associated metabolic conditions:
  • Calcium
  • Phosphorus
  • Parathyroid hormone (PTH)
  • Magnesium levels 1, 6

Associated Conditions

• Primary hyperparathyroidism: Patients with CPPD are three times more likely to have primary hyperparathyroidism than those without CPPD (OR=3.03) 1, 3
• Hemochromatosis: Can predispose to CPPD 1
• Hypomagnesemia: Associated with CPPD and can trigger attacks 1, 6
• Precipitating factors for acute attacks include:
  • Infection
  • Trauma
  • Surgery
  • Vascular events 3
  • Parathyroidectomy (rare) 6

Management

Acute Attacks

• NSAIDs: First-line treatment for acute attacks, with gastro-protective agents in high-risk patients 1
• Colchicine: Effective for acute attacks (0.5 mg twice daily) 1, 6
• Joint aspiration and intra-articular corticosteroids: Effective for monoarticular attacks 1
• Systemic corticosteroids: Alternative when NSAIDs and colchicine are contraindicated 1

Chronic Management

• Prophylactic treatment:

  • Low-dose colchicine (0.6 mg twice daily) has shown efficacy in preventing recurrent attacks 1
  • Consider potential side effects with long-term use

• For chronic inflammatory arthritis:

  • Hydroxychloroquine: Shown efficacy in a 6-month RCT with NNT of 2 1
  • Methotrexate (5-10 mg/week): May be valuable for severe CPPD refractory to conventional treatment 1

Management of Associated Conditions

• Treatment of underlying metabolic disorders is required when present:
  • Parathyroidectomy for primary hyperparathyroidism
  • Magnesium replacement for hypomagnesemia 1, 6

Clinical Pitfalls and Caveats

• Misdiagnosis: Pseudogout can mimic gout or septic arthritis, leading to inappropriate treatment 2
• Overlooked diagnosis: Consider pseudogout in elderly patients with acute monoarticular arthritis, especially of the knee 3
• Underlying conditions: Always screen for associated metabolic disorders, particularly hyperparathyroidism 1, 3
• Atypical presentations: Be aware that CPPD can affect unusual sites such as the spine, causing significant neurological symptoms 5
• Destructive arthropathy: Approximately one-third of cases may develop extensive joint destruction requiring surgical intervention 4

Treatment Algorithm

1. Acute attack:

   • First-line: NSAIDs with gastro-protection if needed
   • If contraindicated: Colchicine 0.5 mg twice daily
   • If monoarticular: Consider joint aspiration and intra-articular corticosteroids
   • If severe or polyarticular: Consider systemic corticosteroids

2. Chronic management:

   • For frequent recurrences: Prophylactic colchicine 0.6 mg twice daily
   • For chronic inflammatory arthritis: Hydroxychloroquine or methotrexate

3. Always:

   • Screen for and treat underlying metabolic disorders
   • Monitor for development of destructive arthropathy
   • Consider imaging to assess disease progression