Epidemiology

Age of onset: adults > 60 years

Etiology

The primary (idiopathic) form is most common, with age as a major risk factor.
Secondary forms
- Joint trauma/damage: including joint surgery, previous juvenile idiopathic arthritis, and Osteoarthritis
- Metabolic disorders: including hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia, and possibly gout
- Familial chondrocalcinosis: due to mutations in the CCAL1 or CCAL2 genes

Pathophysiology

Deposition of calcium pyrophosphate dihydrate (CPP or CPPD) crystals in articular cartilage → paroxysmal joint inflammation and cartilage destruction → inflammatory arthritis (crystalline arthritis)

Clinical features

Acute CPP crystal arthritis (pseudogout)

Clinical features
- Acute attack of pain and swelling in the affected joint(s)
- Monoarthritis (occasionally oligoarthritis)
- Most commonly affects the knee and wrist; can also affect other large joints (e.g., hips, ankles)
- Typically self-limited
Features that differ from acute gout
- Longer duration of acute attacks
  - Up to several months
- Possible systemic symptoms
  - E.g., fever, chills, altered mental status in the elderly

Chronic CPP crystal arthritis

Osteoarthritis-like presentation (osteoarthritis with CPPD; pseudo-osteoarthritis)
- Most common form of CPPD disease
- Characterized by progressive joint degeneration
  - Usually polyarticular; can occur in joints not typically affected by OA
  - More severe than typical OA
  - Often associated with pseudogout-like flares of acute inflammatory arthritis

Diagnostics

Arthrocentesis and synovial fluid analysis (SFA)

Cloudy fluid
Polarized light microscopy (with a red filter) appearance of CPP crystals (opposite to findings in Gout)
- Rhomboid-shaped crystals that are weakly positively birefringent
- Crystals appear blue when their optical axis is oriented parallel to the polarizer.
- Crystals appear yellow when their axis is perpendicular to the polarizer.
Cell count: WBC > 2000/μL with > 50% neutrophils

Imaging

X-ray of the affected joint(s)
- Chondrocalcinosis: calcification of cartilage in the affected joints

Differential diagnostics

Feature	Gout	Pseudogout (CPPD)
Crystal	Monosodium Urate (MSU)	Calcium Pyrophosphate Dihydrate (CPPD)
Crystal Shape	Needle-shaped	Rhomboid-shaped (rhomboids, rods)
Birefringence	Negatively birefringent (Yellow when parallel)	Positively birefringent (Blue when parallel)
Classic Joint	1st MTP (Podagra)	Knee
X-Ray Finding	Punched-out erosions (“rat-bite”)	Chondrocalcinosis (cartilage calcification)
Key Associations	Diuretics, EtOH, CKD, red meat	Hyperparathyroidism, Hemochromatosis, OA
Acute Tx	NSAIDs > Colchicine > Steroids	Steroids (intra-articular) > NSAIDs > Colchicine
Chronic Tx	Allopurinol, Febuxostat	None to dissolve crystals; manage underlying cause

Treatment