What is the recommended approach for diagnosing and treating calcium pyrophosphate crystal deposition?

From the Guidelines

The recommended approach for diagnosing calcium pyrophosphate crystal deposition (CPPD) involves a combination of clinical assessment, imaging, and targeted therapies, with diagnosis beginning with joint aspiration and synovial fluid analysis to identify characteristic rhomboid-shaped, weakly positively birefringent crystals under polarized light microscopy, as recommended by the EULAR guidelines 1. Diagnosis of CPPD should include:

• Joint aspiration and synovial fluid analysis to identify characteristic crystals under polarized light microscopy
• Imaging studies such as X-rays to reveal chondrocalcinosis (calcification of cartilage) in affected joints, particularly knees, wrists, and pubic symphysis
• Clinical assessment to identify symptoms and signs of CPPD, such as joint pain and swelling For acute attacks (pseudogout), treatment typically includes:
• Joint rest and ice application
• Anti-inflammatory medications such as NSAIDs (e.g. naproxen 500mg twice daily or indomethacin 25-50mg three times daily for 7-14 days) 1
• Colchicine (0.6mg once or twice daily) or corticosteroids (intra-articular injection of methylprednisolone 40-80mg or oral prednisone 30-40mg daily with taper over 7-14 days) For chronic CPPD, treatment may include:
• Low-dose daily colchicine (0.6mg once daily) to prevent flares
• Methotrexate (10-25mg weekly) or hydroxychloroquine (200-400mg daily) for chronic inflammatory arthritis
• Individualized treatment based on comorbidities, with NSAIDs avoided in those with renal impairment or gastrointestinal risks It is also important to identify and treat any underlying metabolic conditions that may contribute to CPPD development, such as hyperparathyroidism, hemochromatosis, or hypomagnesemia 1.

From the Research

Diagnosis of Calcium Pyrophosphate Crystals

• The diagnosis of calcium pyrophosphate crystal deposition disease (CPPD) is based on the evaluation of history and clinical features, conventional radiology, and synovial fluid examination 2.
• Non-polarized light microscopy should be used initially to screen for CPPD crystals based on their characteristic morphology, and compensated polarized light microscopy is recommended for definitive identification 2, 3.
• The use of a novel polarized light microscope with a polarized digital camera and multi-focal depth imaging capabilities has been shown to enhance crystal detection rates and sensitivity for both CPP and monosodium urate (MSU) crystals 4.

Clinical Presentations of CPPD

• CPPD disease can present in four different clinical forms: asymptomatic CPPD, osteoarthritis (OA) with CPPD, acute CPP crystal arthritis, and chronic CPP inflammatory crystal arthritis 2.
• Acute CPP crystal arthritis is characterized by sudden onset of pain, swelling, and tenderness with overlying erythema, usually in a large joint, while chronic inflammatory arthritis is characterized by joint swelling, morning stiffness, pain, and high ESR and CRP 2.

Synovial Fluid Analysis

• Synovial fluid analysis for crystals is a simple procedure that allows for immediate and definite diagnosis of gout and CPPD arthritis when clinics are fitted with a proper microscope and the rheumatologists are appropriately trained 3.
• The sensitivity and specificity of synovial fluid analysis for crystal detection can vary depending on the observer and the concentration of crystals in the fluid, with a threshold concentration of 10-100 micrograms/ml for reliable identification of MSUM and CPPD crystals 5.

Treatment and Prevention

• The main goals of CPPD therapy are control of the acute or chronic inflammatory reaction and prevention of further episodes 2.
• The relationship between OA and CPPD is still unclear, with some studies suggesting that CPPD crystals may contribute to acute and chronic inflammation in OA, while others suggest that they may be the result of joint degeneration 2, 6.