Musculoskeletal · PANCE / PANRE

Pseudogout (CPPD Disease)

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

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.

Try two board-style Pseudogout questions

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Question 1MusculoskeletalEasy
A 68-year-old woman presents with acute severe left knee pain and swelling that began after a minor fall two days ago. She has a history of hypothyroidism. On examination the knee is warm, swollen, and tender with painful range of motion; she is afebrile. Radiographs show linear calcification of the articular cartilage. Joint aspiration reveals a cloudy effusion with rhomboid-shaped crystals that are weakly positively birefringent under polarized light. Which of the following is the most likely diagnosis?
  • AOsteoarthritis flare
  • BSeptic arthritis
  • CGout
  • DPseudogout
Reveal answer & full explanation
Correct answer: D — Pseudogout
  • AOsteoarthritis flare
  • BSeptic arthritis
  • CGout
  • DPseudogout✓

Why Pseudogout is correct

  • Pseudogout (calcium pyrophosphate deposition disease, CPPD) is identified by the combination of acute monoarticular knee arthritis, chondrocalcinosis (linear cartilage calcification) on radiograph, and rhomboid-shaped, weakly positively birefringent crystals on synovial fluid analysis
  • CPPD most often affects large joints such as the knee and wrist in older adults and may be triggered by trauma, illness, or surgery
  • Treatment is with NSAIDs, colchicine, or intra-articular corticosteroids
  • A search for associated metabolic conditions (hemochromatosis, hyperparathyroidism, hypothyroidism) is warranted

Why the others are wrong

  • Gout — key distractor because it is also a crystal arthropathy, but gout crystals are needle-shaped and negatively birefringent (yellow when parallel to the compensator), the opposite of the rhomboid, positively birefringent crystals seen here
  • Osteoarthritis flare — degenerative knee disease is common at this age and chondrocalcinosis often coexists with it, but an osteoarthritic effusion is noninflammatory and crystal-free, whereas the rhomboid, weakly positively birefringent crystals here are diagnostic of CPPD
  • Septic arthritis — must always be excluded in an acute hot joint and typically shows a markedly elevated synovial white cell count with a positive Gram stain or culture; importantly, infection and crystals can coexist, so crystals do not exclude septic arthritis, but this afebrile patient with diagnostic crystals and no systemic signs of sepsis fits pseudogout

Additional high-yield points

  • Recognizing crystal shape and birefringence distinguishes pseudogout from gout at the bedside
Question 2MusculoskeletalEasy
A 40-year-old male has sudden-onset severe right knee pain, swelling, and redness after a long airline flight. Knee aspirate shows 42,000 WBCs (88% PMNs) and positively birefringent rhomboid-shaped crystals. Gram stain is negative. Serum calcium is 11.2 mg/dL. Which of the following is the most likely diagnosis?
  • AGout
  • BReactive arthritis
  • CSeptic arthritis
  • DPseudogout
Reveal answer & full explanation
Correct answer: D — Pseudogout
  • AGout
  • BReactive arthritis
  • CSeptic arthritis
  • DPseudogout✓

Why Pseudogout is correct

  • Caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition in the joint
  • Crystals are positively birefringent (blue when parallel to the polarizer axis) and rhomboid-shaped — both match this aspirate
  • Contrasts with gout, whose crystals are negatively birefringent and needle-shaped
  • Radiography classically shows chondrocalcinosis (calcification of fibrocartilage)
  • This patient's hypercalcemia (11.2 mg/dL) points toward primary hyperparathyroidism as a metabolic driver — check PTH

Why the others are wrong

  • Gout — confused-with pseudogout: gout crystals are negatively birefringent and needle-shaped, opposite to the positively birefringent rhomboid crystals seen here
  • Reactive arthritis — right-concept-wrong-setting: follows a GI or GU infection and produces a sterile inflammatory effusion without crystals
  • Septic arthritis — should still be considered and the fluid cultured, but crystal-proven CPPD with hypercalcemia makes it the less likely diagnosis; note a negative Gram stain does NOT exclude infection (only ~50% sensitive), and the presence of crystals does NOT rule out coexisting septic arthritis, so culture is warranted whenever infection is clinically possible

Additional high-yield points

  • Metabolic associations (especially early-onset or recurrent CPPD): (1) hyperparathyroidism (elevated calcium and PTH); (2) hemochromatosis (iron deposition inhibits pyrophosphatase); (3) hypomagnesemia; (4) hypophosphatasia; (5) hypothyroidism
  • Acute attack treatment: NSAIDs, colchicine, or intra-articular corticosteroids
  • Prophylaxis: colchicine 0.6 mg daily if recurrent attacks
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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

FeaturePseudogout (CPPD)
CrystalCalcium pyrophosphate dihydrate
ShapeRhomboid or rod-shaped
BirefringencePositive (BLUE when parallel to compensator)
Typical jointsKnee (most common), wrist (TFCC), MCP, shoulder, symphysis pubis
Radiograph clueChondrocalcinosis — linear calcification in cartilage
Workup if young/polyarticularCa, PTH, Mg, ferritin/iron studies, alkaline phosphatase, TSH
Acute therapyIntra-articular steroid, NSAIDs, colchicine, oral steroids
Chronic preventionLow-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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Commonly confused with

vs Goutvs Septic Arthritisvs Osteoarthritis

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Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.