What is CPPD (Calcium Pyrophosphate Deposition) arthropathy?

CPPD Arthropathy: Definition and Management

CPPD arthropathy is a form of crystal-induced joint disease caused by the deposition of calcium pyrophosphate dihydrate crystals in articular tissues, primarily affecting cartilage, and manifesting as various clinical presentations including acute inflammatory attacks, chronic arthritis, and osteoarthritis with crystal deposition. 1

Pathophysiology and Clinical Presentations

CPPD (Calcium Pyrophosphate Deposition) disease results from the accumulation of calcium pyrophosphate crystals within joints and surrounding tissues, leading to:

• Four distinct clinical presentations 1, 2:

  1. Asymptomatic CPPD (incidental finding)
  2. Osteoarthritis with CPPD
  3. Acute CPP crystal arthritis (pseudogout)
  4. Chronic CPP inflammatory crystal arthritis

• Prevalence increases with age:

  • 10-15% in people aged 65-75 years

  • 40% in those over 80 years 3

• Common sites of involvement:

  • Knee (most common)
  • Wrist
  • Shoulder
  • Hip
  • Spine (particularly atlantoaxial joint causing crowned dens syndrome) 2

Diagnosis

Diagnosis of CPPD arthropathy relies on:

1. Synovial fluid analysis:

   • Identification of weakly positive birefringent rhomboid-shaped crystals under compensated polarized light microscopy 2
   • Initial screening with non-polarized microscopy based on crystal morphology 2

2. Imaging findings:

   • Conventional radiography: punctate and linear radiodense deposits in fibrocartilage and hyaline cartilage (chondrocalcinosis) 3
   • Ultrasonography: increasingly used for detection 4
   • CT: particularly useful for axial joints and crowned dens syndrome 4

Associated Conditions

CPPD is associated with several metabolic conditions that require evaluation:

• Hyperparathyroidism: Patients with CPPD are 3 times more likely to have primary hyperparathyroidism 5
• Hemochromatosis: Particularly important in early-onset disease (before age 60) 3
• Hypomagnesemia
• Hypophosphatemia/Hypophosphatasia
• Genetic variants: Mutations in ANKH and osteoprotegerin genes 4

Management Approaches

Acute CPP Crystal Arthritis (Pseudogout)

1. First-line treatment:

   • Joint aspiration with intra-articular glucocorticoid injection 1
   • NSAIDs with gastroprotection if no contraindications 1
   • Low-dose colchicine (0.5-1.0 mg daily) if NSAIDs are contraindicated 1

2. Alternative options:

   • IV methylprednisolone (125 mg) for rapid relief when oral medications are ineffective (NNT of 3) 1
   • IM betamethasone (7 mg) as an injectable alternative 1

Chronic CPP Inflammatory Arthritis

Treatment algorithm:

1. Start with NSAIDs or low-dose colchicine
2. If ineffective, progress to low-dose corticosteroids
3. If still inadequate control, consider methotrexate (5-10 mg/week) or hydroxychloroquine 1
4. For refractory cases, IL-1 inhibitors (anakinra) or IL-6 inhibitors (tocilizumab) may be considered 6, 4

Prevention of Recurrent Attacks

• Low-dose colchicine has shown effectiveness in preventing recurrent attacks 3
• Methotrexate may be beneficial in recurring cases that fail to respond to other treatments 3

Special Considerations

• Elderly patients: Higher risk of toxicity with NSAIDs and colchicine; require careful monitoring 1
• Renal impairment: Increases risk of adverse effects; requires dose adjustment 1
• Early-onset disease: Thorough metabolic workup needed, particularly for hemochromatosis 1, 3

Treatment Limitations

Unlike gout, there are currently no effective treatments to dissolve or prevent the formation of CPP crystals 6, 4:

• Magnesium supplementation has shown possible clinical benefits in pain reduction but does not reduce radiographic chondrocalcinosis 5
• Research into agents that could modulate pyrophosphate levels (probenecid, polyphosphates, phosphocitrate) remains theoretical 5

Monitoring and Follow-up

Regular follow-up is essential to:

• Assess treatment response
• Monitor for medication side effects
• Evaluate for progression of joint damage
• Reassess for any underlying metabolic disorders 1

CPPD arthropathy remains challenging to manage due to limited high-quality evidence, with most treatment approaches extrapolated from gout management protocols 7.