Rheumatology · Crystal Arthropathy

Pseudogout (CPPD)

USMLE2PANCE
7

Bets

The facts most likely to be tested

1

Synovial fluid analysis reveals positively birefringent, rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals.

Confidence:
2

Radiographic imaging demonstrates chondrocalcinosis, characterized by linear calcification of the articular cartilage.

Confidence:
3

The knee is the most commonly affected joint in patients presenting with acute pseudogout flares.

Confidence:
4

Metabolic workup for CPPD must include screening for hemochromatosis, hyperparathyroidism, and hypomagnesemia.

Confidence:
5

First-line treatment for an acute flare in patients without contraindications is intra-articular glucocorticoid injection or oral NSAIDs.

Confidence:
6

Colchicine is the preferred agent for prophylaxis in patients with frequent, recurrent attacks of pseudogout.

Confidence:
7

Unlike gout, pseudogout is frequently associated with advanced age and underlying osteoarthritis.

Confidence:

Vignette unlocked

A 74-year-old male presents to the emergency department with a one-day history of severe pain, swelling, and erythema in his right knee. He denies recent trauma, fever, or chills, but reports a history of similar, self-limiting joint pain in the past. Physical examination reveals a warm, swollen, and tender knee with a limited range of motion. Arthrocentesis of the joint yields cloudy synovial fluid with a white blood cell count of 25,000/mm³ and 80% neutrophils. Polarized light microscopy of the fluid shows rhomboid-shaped crystals with positive birefringence.

What is the most likely diagnosis?

+Reveal answer

Pseudogout (Calcium Pyrophosphate Dihydrate Deposition Disease)

The presence of rhomboid-shaped, positively birefringent crystals is pathognomonic for CPPD, distinguishing it from the needle-shaped, negatively birefringent crystals seen in gout.

Mo

Depth

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Etiology / Epidemiology

Common in elderly patients; associated with hyperparathyroidism, hemochromatosis, and hypomagnesemia.

Clinical Manifestations

Acute, monoarticular arthritis, most commonly affecting the knee; pseudogout mimics gout.

Diagnosis

Arthrocentesis reveals positively birefringent, rhomboid-shaped crystals.

Treatment

NSAIDs are first-line; use intra-articular corticosteroids if NSAIDs are contraindicated.

Prognosis

Self-limiting acute flares; chronic CPPD arthropathy can lead to joint destruction.

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Epidemiology & Etiology

Prevalence increases significantly with age, typically affecting patients >60 years. Metabolic associations include hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatasia. Always screen for these underlying conditions in younger patients presenting with CPPD.

Pertinent Anatomy

The knee is the most frequently involved joint, followed by the wrist, shoulder, and ankle. Deposition occurs in the fibrocartilage and hyaline cartilage, visible on imaging as chondrocalcinosis.

Pathophysiology

Deposition of calcium pyrophosphate dihydrate (CPPD) crystals into the joint space triggers an inflammatory cascade. Phagocytosis of crystals by neutrophils leads to the release of inflammatory cytokines and lysosomal enzymes. This results in acute synovitis and subsequent cartilage degradation.

Clinical Manifestations

Patients present with sudden onset of severe joint pain, swelling, and erythema, often mimicking septic arthritis. The knee is the classic site of involvement. Rule out septic arthritis via synovial fluid analysis in all patients with acute monoarthritis.

Diagnosis

Arthrocentesis is the gold standard diagnostic test. Synovial fluid analysis shows positively birefringent, rhomboid-shaped crystals. Radiographs typically demonstrate chondrocalcinosis, which is the calcification of articular cartilage.

Treatment

NSAIDs are the first-line treatment for acute flares. If NSAIDs are ineffective or contraindicated, intra-articular corticosteroids are preferred. Avoid systemic steroids if infection is not ruled out. Low-dose colchicine is used for prophylaxis in patients with frequent recurrent attacks.

Prognosis

Acute attacks are self-limiting, usually resolving within weeks. Chronic CPPD arthropathy may develop, leading to progressive joint space narrowing and secondary osteoarthritis. Monitor for joint destruction and functional impairment.

Differential Diagnosis

Gout: negatively birefringent, needle-shaped crystals

Septic arthritis: fever, elevated WBC count, positive culture

Rheumatoid arthritis: symmetric, small joint involvement

Osteoarthritis: chronic, non-inflammatory joint pain

Reactive arthritis: follows infection, associated with urethritis/conjunctivitis