What is the recommended treatment for an acute calcium pyrophosphate dihydrate (CPPD) crystal arthritis flare and how can recurrent attacks be prevented?

Treatment of CPPD Arthropathy

For acute CPPD flares, joint aspiration with intra-articular corticosteroid injection is the optimal first-line treatment, while low-dose colchicine (0.5-1.0 mg daily) effectively prevents recurrent attacks. 1

Acute CPPD Crystal Arthritis (Pseudogout)

First-Line Treatment: Intra-articular Approach

• Joint aspiration combined with intra-articular long-acting glucocorticosteroid injection is the gold standard for monoarticular or oligoarticular disease, often sufficient as monotherapy without requiring systemic treatment 2, 1
• Triamcinolone acetonide 60 mg intramuscularly demonstrated at least 50% clinical improvement in all patients within 14 days 3
• This approach provides rapid symptom control while confirming the diagnosis through synovial fluid crystal analysis 2

Systemic Treatment Options When Intra-articular Injection Not Feasible

NSAIDs:

• Oral NSAIDs with gastroprotective agents (proton pump inhibitors) are effective for acute flares, particularly in younger patients without contraindications 2
• Always provide gastroprotection in older patients due to high gastrointestinal bleeding risk 1
• NSAIDs are contraindicated in patients with renal impairment, cardiovascular disease, or gastrointestinal risk factors 3

Colchicine:

• Low-dose colchicine (0.5 mg up to 3-4 times daily, with or without 1 mg initial dose) is effective for acute attacks 2
• Avoid traditional high-dose regimens (1 mg loading then 0.5 mg every 2 hours) due to 100% incidence of marked side effects 1, 3
• Never use intravenous colchicine due to serious toxicity and fatality risk 1, 3
• In severe renal impairment (CrCl <30 mL/min), reduce dose to 0.3 mg/day 3

Glucocorticosteroids:

• Prednisone 0.5 mg/kg/day for 5-10 days then discontinue, or full dose for 2-5 days then taper over 7-10 days is the recommended systemic steroid regimen 3
• Parenteral options include betamethasone 7 mg IM or methylprednisolone 125 mg IV as single doses, which showed significantly faster pain control (NNT=3 on day 1) compared to NSAIDs 2
• Systemic steroids provide the best benefit-risk ratio in older patients with comorbidities and renal impairment 3
• ACTH 40-80 units parenterally three times resolved all acute attacks in an average of 4.2 days, though mild metabolic side effects occurred 2

Critical Pitfall

• Always exclude septic arthritis before injecting corticosteroids into a joint, particularly in monoarticular presentations 3

Prophylaxis Against Recurrent Acute Attacks

Low-dose colchicine (0.5-1.0 mg daily) is the evidence-based prophylactic agent, reducing attack frequency from 3.2 episodes/year to 1.0 episode/year (p<0.001) with 90% of patients benefiting 2, 1

• Low-dose NSAIDs with gastroprotection are an alternative prophylactic option, though evidence is less robust than for colchicine 2, 1
• Carefully weigh side effect risks in older patients when selecting prophylactic therapy, as this population often has multiple comorbidities 2

Chronic CPP Crystal Inflammatory Arthritis

Treatment Algorithm (in order of preference):

First-line:

• Oral NSAIDs with gastroprotection and/or low-dose colchicine (0.5-1.0 mg daily) 2, 1
• Low-dose colchicine (0.5 mg twice daily) demonstrated NNT=2 (95% CI 1-4) for >30% pain reduction at 4 months in knee OA with persistent CPPD inflammation 2

Second-line:

• Hydroxychloroquine is the preferred second-line agent, with NNT=2 (95% CI 1-7) for clinical response (>30% reduction in swollen/tender joint count) in a 6-month RCT 2, 1, 4

Third-line for refractory disease:

• Methotrexate 5-10 mg/week should be considered for severe CPPD resistant to conventional treatment, with all patients in an uncontrolled trial showing excellent clinical response and significant decreases in pain intensity and joint counts within mean 7.4 weeks 2, 4
• Low-dose oral glucocorticoids may be used when other treatments fail 2, 1

Refractory cases:

• Anakinra (IL-1 receptor antagonist) can alleviate acute flares when other treatments have failed, with case reports showing efficacy in end-stage renal failure patients 5, 6
• Tocilizumab (IL-6 inhibitor) may be used in refractory chronic inflammatory arthritis 5, 7

Osteoarthritis with CPPD

Management objectives and treatment options are identical to OA without CPPD, following standard evidence-based OA guidelines 2, 1

• Focus on patient education, pain reduction, maintaining joint mobility, reducing disability, and improving quality of life 2
• Apply standard OA management including physical therapy and joint protection strategies 4
• Critical pitfall: Avoid intra-articular high molecular weight hyaluronan as it may induce acute attacks 2, 1, 4

Treatment of Associated Metabolic Conditions

Screen for and treat underlying conditions including hyperparathyroidism, hemochromatosis, and hypomagnesemia, as patients with CPPD are three times more likely to have primary hyperparathyroidism (OR=3.03,95% CI 1.15-8.02) 2

• Early-onset disease (before age 60) requires metabolic workup, particularly for hemochromatosis 8
• Treatment of comorbidities should follow condition-specific guidelines, though whether this affects CPPD outcomes remains unclear 2

Asymptomatic Chondrocalcinosis

No treatment is required for asymptomatic chondrocalcinosis, as currently no treatment modifies CPP crystal formation or dissolution 2, 5, 7

Special Populations: Older Adults with Renal Impairment

Systemic glucocorticosteroids (prednisone 0.5 mg/kg/day for 5-10 days) are the optimal first-line treatment in this vulnerable population, avoiding the significant toxicity risks of NSAIDs and colchicine 3

• NSAIDs carry high risk of gastrointestinal bleeding, cardiovascular events, and worsening renal function in this population 3
• Colchicine requires extreme dose reduction (0.3 mg/day) in severe renal impairment 3