What is the optimal treatment strategy for calcium pyrophosphate deposition disease (chondrocalcinosis) in an older adult with comorbidities that may limit non‑steroidal anti‑inflammatory drug use?

Optimal Treatment for Chondrocalcinosis (CPPD)

For older adults with comorbidities limiting NSAID use, systemic glucocorticosteroids—specifically prednisone 0.5 mg/kg/day for 5–10 days followed by discontinuation or a short taper—provide the best benefit-risk ratio and should be your first-line treatment. 1

Acute CPPD Attack Management

First-Line: Intra-articular Steroids (Monoarticular/Oligoarticular Disease)

• Intra-articular injection of long-acting glucocorticosteroids is the optimal initial treatment when only one or a few joints are involved, combined with joint aspiration, ice application, and temporary rest. 1
• Triamcinolone acetonide 60 mg injected directly into the affected joint achieves at least 50% clinical improvement in all patients within 14 days and often eliminates the need for systemic medication. 1
• Critical pitfall: Always exclude septic arthritis by joint aspiration with synovial fluid analysis and culture before injecting steroids, particularly in monoarticular presentations with fever. 1

Systemic Steroids (Polyarticular Disease or When Injection Not Feasible)

• Oral prednisone or prednisolone 0.5 mg/kg/day for 5–10 days, then discontinue is the recommended regimen for widespread joint involvement. 1
• Alternative: Full dose for 2–5 days, then taper over 7–10 days before discontinuation. 1
• Parenteral options for rapid control: Betamethasone 7 mg intramuscularly or methylprednisolone 125 mg intravenously as single doses achieve a number-needed-to-treat of 3 on day 1 (95% CI 2–16) compared to NSAIDs. 1
• Intramuscular triamcinolone acetonide 60 mg as a single dose followed by oral prednisone is an appropriate alternative. 1

Why Steroids Are Preferred in Older Adults with Comorbidities

• Steroids are particularly valuable in older patients with renal impairment, cardiovascular disease, or gastrointestinal risk who have contraindications to NSAIDs or colchicine, with an 87% strength of recommendation from EULAR guidelines. 1
• NSAIDs carry abundant evidence of gastrointestinal bleeding, cardiovascular events, and renal impairment, particularly in older patients with chronic kidney disease. 1
• Traditional colchicine dosing has a 100% incidence of side effects, and for severe renal impairment (CrCl <30 mL/min), only 0.3 mg/day is recommended. 1

Alternative Acute Treatment: ACTH

• ACTH 40–80 units (IV/IM/SC) administered three times resolves acute attacks in an average of 4.2 days, with only mild adverse effects (hypokalemia, hyperglycemia, fluid retention). 1
• This is particularly useful when both NSAIDs and steroids are contraindicated. 1

Prophylaxis Against Recurrent Attacks

• Low-dose colchicine 0.5–1 mg daily is recommended for prophylaxis in patients with normal-to-mild renal impairment (CrCl 50–80 mL/min) who experience recurrent acute CPPD attacks. 1
• Close monitoring is required, and the dose must be adjusted for renal function. 1
• Never use traditional high-dose colchicine regimens (1 mg loading then 0.5 mg every 2 hours) due to 100% incidence of marked side effects, and never use intravenous colchicine due to high risk of serious toxicity and fatality. 1

Chronic CPP Inflammatory Arthritis

• For patients with chronic inflammatory arthritis from CPPD, consider methotrexate or hydroxychloroquine after consultation with rheumatology. 2, 3
• Limited evidence suggests low-dose weekly methotrexate and hydroxychloroquine may be effective in managing persistent CPP-crystal inflammatory arthritis. 3
• Biologics inhibiting IL-1 (anakinra) and IL-6 (tocilizumab) may have a role in refractory disease. 3, 4

Metabolic Work-Up and Prevention

• Screen for metabolic contributors in patients with early-onset disease (before age 60): primary hyperparathyroidism (approximately three-fold higher odds of CPPD), hemochromatosis, hypomagnesemia, or hypophosphatasia. 2, 5, 6
• Consider magnesium supplementation in patients receiving furosemide, as magnesium depletion can promote CPP crystal formation and precipitation of acute attacks. 7
• Benefit of magnesium replacement has been reported in patients with hypomagnesemia and chondrocalcinosis. 7

Monitoring and Safety with Steroids

• Patients receiving systemic glucocorticoids should be monitored for hyperglycemia, hypokalemia, fluid retention, and hypertension. 1
• Do not use prolonged courses of steroids without a clear tapering plan, as this increases adverse effects without additional benefit. 1
• Assess cardiovascular, renal, and metabolic comorbidities before selecting steroid dose and duration, especially in elderly patients. 1

Referral to Rheumatology

• Refer patients with CPPD-associated chronic inflammatory arthritis requiring disease-modifying agents, recurrent acute attacks needing prophylaxis, polyarticular disease difficult to control, or suspected metabolic contributors. 2

Evidence Limitations

• The majority of CPPD treatment recommendations are based on expert opinion (Level IV evidence) and extrapolation from gout studies, with only 3–4 randomized controlled trials existing for CPPD treatment. 1
• No disease-modifying therapies currently exist that reduce articular calcification or dissolve CPP crystals, making control of inflammation the main therapeutic focus. 3, 4