How can I differentiate between CPPD and other forms of arthritis in a patient presenting with joint pain and swelling?

To differentiate calcium pyrophosphate deposition disease (CPPD) from other forms of arthritis in a patient presenting with joint pain and swelling, focus on clinical presentation, joint involvement pattern, and diagnostic investigations.

CPPD often presents with acute or chronic episodes of joint inflammation, commonly affecting the knees, wrists, and sometimes the shoulders, hips, or ankles, which can mimic osteoarthritis or gout but typically involves larger joints more than gout does ¹.

Unlike gout, which usually affects the first metatarsophalangeal joint, CPPD can cause pseudogout attacks characterized by sudden joint pain and swelling, often in the knee, with less frequent involvement of small joints (Ferrone et al., 2012).

Radiographically, CPPD is distinguished by chondrocalcinosis—linear or punctate calcifications in cartilage visible on X-rays, especially in the knee menisci or wrist cartilage, which is not a feature of gout or typical osteoarthritis ¹.

Synovial fluid analysis is critical: CPPD shows rhomboid-shaped, positively birefringent calcium pyrophosphate crystals under polarized light microscopy, whereas gout shows negatively birefringent monosodium urate crystals (Sekeramayi et al., 2025).

Osteoarthritis typically presents with joint space narrowing, osteophyte formation, and subchondral sclerosis on imaging without crystal deposition, and usually has a more chronic, progressive course ¹.

In summary, differentiation relies on clinical pattern (joint distribution and attack characteristics), radiographic evidence of chondrocalcinosis, and synovial fluid crystal analysis.