Treatment of CPPD
For acute CPPD attacks, start with joint aspiration plus intra-articular corticosteroid injection combined with ice packs and rest—this approach alone is sufficient for most patients and carries the highest strength of recommendation (95%). 1
Acute CPP Crystal Arthritis
First-Line Approach (Preferred)
- Joint aspiration + intra-articular long-acting glucocorticosteroids (Strength of Recommendation: 95%)
- Add ice/cool packs and temporary rest
- This combination is often sufficient without systemic therapy 1
Systemic Therapy Options (When intra-articular injection insufficient or polyarticular)
NSAIDs or Colchicine (Strength of Recommendation: 79%)
- NSAIDs: Use with gastroprotection (proton pump inhibitors), especially in older patients
- Colchicine: 0.5 mg up to 3-4 times daily (with or without 1 mg loading dose)
- Avoid traditional high-dose regimens (100% side effect rate)
- Major limitation: Both agents have significant toxicity in elderly patients with comorbidities (GI bleeding, cardiovascular events, renal impairment, diarrhea) 1
Glucocorticoids (Strength of Recommendation: 87%) - Use when NSAIDs/colchicine contraindicated
- Short tapering course of oral glucocorticoids
- Parenteral glucocorticoids (betamethasone 7 mg IM or methylprednisolone 125 mg IV showed faster pain control than NSAIDs—NNT=3 on day 1) 1
- ACTH 40-80 units (IV/IM/SC) three times—resolved attacks in average 4.2 days 1
Clinical Reasoning
The EULAR guidelines prioritize local therapy because CPPD predominantly affects older patients with multiple comorbidities where systemic anti-inflammatory drugs pose substantial risks. Glucocorticoids become the preferred systemic option when NSAIDs/colchicine are contraindicated, which is common in this population 1.
Prophylaxis for Recurrent Acute Attacks
Low-dose colchicine 0.5-1 mg daily is the evidence-based choice for preventing recurrent flares (Strength of Recommendation: 81%) 1
- One uncontrolled trial showed reduction from 3.2 attacks/year to 1.0 attacks/year (p<0.001) with colchicine 0.6 mg twice daily 1
- Alternative: Low-dose NSAID with gastroprotection (though evidence is weaker than for colchicine)
- Critical caveat: Carefully weigh side effects against benefit, especially in elderly patients with renal impairment 1
Chronic CPP Crystal Inflammatory Arthritis
Pharmacological hierarchy (Strength of Recommendation: 79%) 1:
- First-line: NSAIDs (with gastroprotection) and/or colchicine 0.5-1.0 mg daily
- Second-line: Low-dose corticosteroids
- Third-line: Methotrexate (5-10 mg/week)
- One uncontrolled trial (n=5) showed excellent response with significant decrease in pain, joint counts, and attack frequency over 50 months 1
- Fourth-line: Hydroxychloroquine
- One RCT (n=36) showed NNT=2 for clinical response 1
Emerging Evidence
Recent data suggest potential roles for:
- Anakinra (IL-1 inhibition) for refractory acute or chronic disease 2, 3
- Tocilizumab (IL-6 inhibition) for refractory chronic polyarthritis—showed partial improvement in small case series, though corticosteroid dependence often persisted 4
- These biologics are not yet guideline-recommended but represent options when conventional therapy fails
CPPD with Osteoarthritis
Treat identically to OA without CPPD (Strength of Recommendation: 84%) 1
- Follow standard OA management guidelines
- Important warning: Avoid intra-articular high molecular weight hyaluronan—can trigger acute attacks 1
Essential Screening
Screen for and treat underlying metabolic conditions (Strength of Recommendation: 89%) 1:
- Hyperparathyroidism
- Hemochromatosis (especially in early-onset disease ≤60 years)
- Hypomagnesemia
Key Clinical Pitfalls
- Age and comorbidity dominate treatment selection: Most CPPD patients are elderly with renal impairment, making NSAIDs and colchicine high-risk despite their efficacy
- No disease-modifying therapy exists: All current treatments are symptomatic only—no drug prevents CPP crystal formation or dissolution 1
- Asymptomatic chondrocalcinosis requires no treatment 1
- Confirm diagnosis with synovial fluid analysis when possible—imaging alone is insufficient for definitive diagnosis
Practical Algorithm
Acute monoarticular/oligoarticular attack:
- → Joint aspiration + intra-articular steroid + ice/rest
- → If insufficient or contraindicated: systemic glucocorticoids (oral taper or parenteral)
- → If glucocorticoids contraindicated: NSAIDs (with gastroprotection) or colchicine
Acute polyarticular attack:
- → Systemic glucocorticoids (oral taper, parenteral, or ACTH)
- → Alternative: NSAIDs or colchicine if no contraindications
Recurrent attacks (≥2-3/year):
- → Colchicine 0.5-1 mg daily prophylaxis
Chronic inflammatory arthritis:
- → NSAIDs + colchicine → low-dose corticosteroids → methotrexate → hydroxychloroquine
- → Consider IL-1 or IL-6 inhibition if refractory