Key Facts

CPPD disease encompasses a spectrum from asymptomatic chondrocalcinosis to acute pseudogout to chronic arthropathy. Unlike gout, there is no effective crystal-dissolving therapy.

Epidemiology

• Prevalence increases with age: radiographic chondrocalcinosis in 10-15% of 65-75 year olds, >25% of >80 year olds
• Equal sex ratio
• Most common crystal arthropathy in the elderly

Aetiology

• Primary (idiopathic): age-related; most common
• Familial: autosomal dominant (ANKH gene mutations); younger onset
• Secondary (metabolic): hyperparathyroidism, haemochromatosis, hypomagnesaemia, hypophosphataemia, Wilson disease, hypothyroidism, gout

Pathophysiology

• Chondrocytes produce excess inorganic pyrophosphate (PPi) which combines with calcium in cartilage
• CPPD crystals deposit in hyaline and fibrocartilage → chondrocalcinosis
• Crystal shedding into joint space → acute inflammation (similar mechanism to MSU in gout)
• NLRP3 inflammasome activation → IL-1β → neutrophilic inflammation
• Chronic CPPD can cause OA-like destructive arthropathy (pyrophosphate arthropathy)

Acute Pseudogout (CPP Crystal Arthritis)

• Acute monoarthritis: knee most common, also wrist, ankle, shoulder
• Red, hot, swollen, painful joint
• Often precipitated by: surgery, illness, dehydration, blood transfusion
• Clinically indistinguishable from gout or septic arthritis
• Self-limiting over 1-3 weeks

Chronic CPPD Arthropathy

• Resembles OA but in atypical joints (wrist, MCP, elbow, shoulder)
• "Pseudo-RA": symmetrical polyarthritis with morning stiffness
• Progressive joint damage

Asymptomatic Chondrocalcinosis

• Incidental X-ray finding
• Very common in elderly; no treatment needed

Red Flags

• Acute monoarthritis + fever → exclude septic arthritis (MUST aspirate)
• CPPD in patient <55 → screen for metabolic causes
• Recurrent pseudogout → check calcium, PTH, ferritin, magnesium

Gold Standard

• Joint aspiration: rhomboid-shaped, weakly positively birefringent crystals under compensated polarised light microscopy
• WCC usually 10,000-50,000/mm³
• Gram stain and culture to exclude infection

Bloods

• Calcium and PTH: hyperparathyroidism screen
• Ferritin and transferrin saturation: haemochromatosis screen
• Magnesium: hypomagnesaemia
• TFTs: hypothyroidism
• U&Es: renal function
• ESR/CRP: elevated during acute attack

Imaging

• X-ray: chondrocalcinosis – linear calcification within cartilage
  • Knee menisci (most common site)
  • Wrist triangular fibrocartilage
  • Pubic symphysis
  • Shoulder labrum
• Ultrasound: hyperechoic deposits within cartilage (distinct from gout's double contour sign on cartilage surface)

Acute Pseudogout

• Joint aspiration: therapeutic (removes crystals and inflammatory fluid) + diagnostic
• Intra-articular corticosteroid: triamcinolone acetonide 40mg (knee) – often most effective
• NSAIDs: naproxen 500mg BD (with PPI) for 7-14 days
• Colchicine: 500mcg BD-TDS; particularly if NSAIDs contraindicated
• Oral prednisolone: 30mg for 5 days if NSAIDs and colchicine contraindicated
• Ice and rest during acute attack

Prophylaxis (Recurrent Attacks)

• Low-dose colchicine: 500mcg OD-BD (reduces frequency of attacks)
• Low-dose prednisolone: if colchicine not tolerated
• IL-1 inhibitors (anakinra): emerging evidence for refractory cases

Chronic CPPD Arthropathy

• Manage as OA: exercise, weight management, physiotherapy
• Pharmacological: paracetamol, topical/oral NSAIDs, intra-articular steroids
• Joint replacement: for severe destructive arthropathy

Treat Underlying Metabolic Cause

• Hyperparathyroidism: parathyroidectomy (may reduce attacks)
• Haemochromatosis: venesection (may not reverse chondrocalcinosis)
• Hypomagnesaemia: magnesium supplementation

Referral Criteria

• Diagnostic uncertainty → rheumatology
• Age <55 with CPPD → metabolic workup
• Recurrent/refractory attacks → rheumatology

• Acute attacks are self-limiting (1-3 weeks)
• No disease-modifying therapy available (unlike gout)
• Chronic CPPD arthropathy: progressive; similar trajectory to OA
• Chondrocalcinosis may be incidental and asymptomatic (no treatment needed)
• Metabolic causes: treating underlying condition may reduce flare frequency
• Joint replacement: effective for severe destructive CPPD arthropathy

CPPD Disease Spectrum

Metabolic Associations (Mnemonic: WHOP)