What is the treatment for Calcium Pyrophosphate Deposition Disease (CPPD)?

Treatment for Calcium Pyrophosphate Deposition Disease (CPPD)

The optimal treatment for CPPD requires both non-pharmacological and pharmacological approaches tailored to the specific clinical presentation, with joint aspiration and intra-articular glucocorticoid injection being the most effective first-line treatment for acute attacks. 1

Treatment Algorithm Based on Clinical Presentation

1. Acute CPP Crystal Arthritis

1. First-line treatment:

   • Joint aspiration and intra-articular injection of long-acting glucocorticosteroids (GCS) 1
   • Application of ice or cool packs to affected joints 1, 2
   • Temporary rest of affected joints 1

2. If intra-articular injection not feasible or for polyarticular attacks:

   • Oral NSAIDs with gastroprotective treatment if indicated (especially in younger patients without comorbidities) 1
   • Low-dose oral colchicine (0.5 mg up to 3-4 times daily with or without an initial dose of 1 mg) 1
   • Parenteral glucocorticoids (IV methylprednisolone 125 mg or IM betamethasone 7 mg) for rapid relief when oral medications are ineffective or contraindicated (NNT of 3 compared to oral NSAIDs) 1, 2
   • ACTH (adrenocorticotrophic hormone) as an alternative for polyarticular attacks 1, 2

2. Prophylaxis Against Recurrent Attacks

• Low-dose oral colchicine (0.5-1 mg daily) 1
• Low-dose oral NSAIDs with gastroprotective treatment if indicated 1

3. Chronic CPP Crystal Inflammatory Arthritis

Pharmacological options in order of preference:

1. Oral NSAIDs with gastroprotective treatment if indicated 1
2. Low-dose colchicine (0.5-1.0 mg daily) 1
3. Low-dose corticosteroids 1
4. Methotrexate (5-10 mg/week) 1, 3, 4
5. Hydroxychloroquine 1, 4
6. IL-1 inhibitors (anakinra) or IL-6 inhibitors (tocilizumab) for refractory cases 3, 4, 5

4. CPPD with Osteoarthritis

• Treatment objectives and options are the same as for OA without CPPD 1
• Special caution with intra-articular high molecular weight hyaluronan as it might induce acute attacks 1

5. Asymptomatic Chondrocalcinosis

• No treatment required 1

Important Considerations and Caveats

Age and Comorbidity Considerations

• Elderly patients: Use caution with NSAIDs and colchicine due to higher risk of toxicity 1
• Renal impairment: Avoid or reduce doses of NSAIDs and colchicine 1
• Gastrointestinal risk factors: Always use gastroprotection with NSAIDs 1

Medication-Specific Caveats

• NSAIDs: Risk of gastrointestinal bleeding, cardiovascular events, and renal impairment 1
• Colchicine: Risk of diarrhea and other gastrointestinal side effects; avoid high-dose regimens 1
• IV colchicine: Not recommended due to high risk of serious toxicity and even fatality 1, 2
• Parenteral glucocorticoids: May cause mild hypokalaemia, hyperglycaemia, fluid retention 1

Treatment Efficacy Evidence

• The evidence for CPPD treatment is limited compared to gout, with few randomized controlled trials 3, 6
• Most treatment recommendations are extrapolated from gout management or based on expert opinion 6, 7
• For chronic CPP inflammatory arthritis, low-dose colchicine showed NNT of 2 (95% CI 1 to 4) at 4 months for >30% pain reduction 1
• Methotrexate showed significant decrease in pain intensity and joint counts in patients resistant to common treatments 1

Associated Conditions

• If detected, treat associated conditions such as hyperparathyroidism, haemochromatosis, or hypomagnesaemia 1

Disease-Modifying Limitations

• Currently, no treatment modifies CPP crystal formation or dissolution 1, 3, 4, 7
• Treatment focuses on managing inflammation and symptoms rather than addressing the underlying crystal deposition 4

By following this treatment algorithm and considering the individual patient's clinical presentation, comorbidities, and risk factors, optimal management of CPPD can be achieved to improve morbidity, mortality, and quality of life outcomes.