Musculoskeletal · PANCE / PANRE

Pseudogout (CPPD Disease)

Acute crystal arthritis from calcium pyrophosphate deposition; classic site is the knee with chondrocalcinosis.

Also known as: pseudogout, CPPD, calcium pyrophosphate, chondrocalcinosis

Overview

Inflammatory arthritis caused by deposition of calcium pyrophosphate dihydrate (CPP) crystals in articular cartilage and periarticular tissues. Encompasses asymptomatic chondrocalcinosis, acute CPP crystal arthritis (classic 'pseudogout'), chronic CPP crystal inflammatory arthritis, and osteoarthritis with CPPD.

Epidemiology

Prevalence rises sharply with age; chondrocalcinosis present on imaging in ~10% of adults over 60 and >30% over 80. Equal sex distribution.

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Risk factors

Advanced age (most common)
Osteoarthritis (often coexists)
Hyperparathyroidism
Hemochromatosis
Hypomagnesemia, hypophosphatasia
Familial chondrocalcinosis (ANKH gene mutations)
Acute medical illness, surgery, trauma (common provocations)

Pathophysiology

Abnormal cartilage matrix metabolism increases extracellular pyrophosphate, which precipitates with calcium to form CPP crystals in articular and fibrocartilage. Released crystals activate the NLRP3 inflammasome, producing acute neutrophilic synovitis similar to gout.

Clinical presentation

Symptoms

Acute monoarticular or oligoarticular swelling, pain, and warmth — most often knee or wrist
Onset over hours to a day; often precipitated by surgery, trauma, or acute medical illness
Less severe than typical gout but can be incapacitating
Chronic forms: insidious polyarticular arthritis mimicking RA or OA

Signs / physical exam

Warm, swollen joint with effusion
Reduced range of motion
Low-grade fever possible
Pseudo-RA pattern: symmetric small-joint synovitis (MCP 2, 3 often involved with hook-like osteophytes if also hemochromatosis)

Differential diagnosis

Gout — Negatively birefringent needle-shaped MSU crystals; first MTP classic
Septic arthritis — Fever, immunocompromise; coexists with CPPD; arthrocentesis with Gram stain/culture mandatory
Osteoarthritis — Chronic, non-inflammatory; may coexist with CPPD (especially knees and wrists)
Rheumatoid arthritis — Symmetric polyarticular MCP/PIP/wrist; positive RF/CCP
Hemarthrosis — Trauma or anticoagulation; bloody arthrocentesis fluid

Diagnostic workup

Diagnostic criteria

ACR/EULAR 2023 classification criteria for CPPD use clinical features + imaging + crystal identification.

Labs

Arthrocentesis with polarized microscopy — rhomboid or rod-shaped, POSITIVELY birefringent CPP crystals; inflammatory fluid
Gram stain and culture to exclude septic arthritis
Screen for underlying metabolic disease in patients <55 or with polyarticular CPPD:
• Calcium, PTH, magnesium, phosphorus, alkaline phosphatase
• Iron studies and ferritin (hemochromatosis)
• TSH
CBC, ESR/CRP often elevated during attack

Imaging

Plain radiographs — linear calcification within hyaline or fibrocartilage (chondrocalcinosis), classically in knee menisci, triangular fibrocartilage complex of wrist, symphysis pubis
Ultrasound — hyperechoic deposits within cartilage
DECT — less established than for gout

Diagnostic algorithm

Feature	Pseudogout (CPPD)
Crystal	Calcium pyrophosphate dihydrate
Shape	Rhomboid or rod-shaped
Birefringence	Positive (BLUE when parallel to compensator)
Typical joints	Knee (most common), wrist (TFCC), MCP, shoulder, symphysis pubis
Radiograph clue	Chondrocalcinosis — linear calcification in cartilage
Workup if young/polyarticular	Ca, PTH, Mg, ferritin/iron studies, alkaline phosphatase, TSH
Acute therapy	Intra-articular steroid, NSAIDs, colchicine, oral steroids
Chronic prevention	Low-dose colchicine; treat underlying metabolic cause

Key CPPD features — positive birefringence and knee chondrocalcinosis are the highest-yield boards facts.

Complications

Recurrent acute attacks
Chronic destructive arthropathy of knee, shoulder ('Milwaukee shoulder' with BCP and CPP crystals)
Secondary OA with characteristic distribution (wrist radiocarpal, MCP, patellofemoral)
Spinal involvement: crowned dens syndrome — acute neck pain, fever, elevated CRP from CPPD at C1-C2 (mimics meningitis or GCA)

PANCE pearls

Patients <55 with CPPD warrant a workup for hemochromatosis, hyperparathyroidism, and hypomagnesemia.
Crowned dens syndrome (CPPD around the odontoid) causes acute neck pain + fever and can mimic meningitis — CT shows calcification.
Chondrocalcinosis on knee or wrist radiographs supports the diagnosis but is not pathognomonic.
Always perform Gram stain and culture on the aspirate — septic arthritis can coexist with crystals.

References

ACR/EULAR 2023 — 2023 ACR/EULAR Classification Criteria for Calcium Pyrophosphate Deposition Disease (Abhishek et al., Arthritis Rheumatol 2023)
EULAR 2011 — EULAR Recommendations for Calcium Pyrophosphate Deposition (Zhang et al., Ann Rheum Dis 2011)

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