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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- CPPD crystals are rhomboid/rod-shaped and weakly positively birefringent
- Most common acute joints are knee and wrist
- X-ray may show chondrocalcinosis
- Evaluate young/recurrent cases for hemochromatosis, hyperparathyroidism, hypomagnesemia, hypothyroidism
- Treat flares with aspiration, NSAIDs, colchicine, or glucocorticoids
Overview
CPPD is calcium pyrophosphate deposition in cartilage and periarticular tissue causing acute pseudogout, chronic inflammatory arthritis, or OA with chondrocalcinosis. Synovial fluid analysis is central because it mimics gout and infection.
Epidemiology
CPPD is strongly age-associated and common after age 60. Secondary causes are more important in younger or recurrent disease.
Clinical Features
Symptoms
Acute knee or wrist pain, swelling, and warmth
Fever and malaise can occur and mimic infection
Recurrent attacks after surgery, illness, or trauma
Chronic RA-like inflammatory arthritis in older adults
Acute neck pain can occur with crowned dens syndrome
Signs
Warm effused joint with painful passive ROM
Knee effusion is most common
Wrist/MCP involvement may suggest CPPD-associated OA
Severe systemic toxicity requires septic arthritis exclusion
Investigations
First-line
ArthrocentesisRhomboid weakly positively birefringent CPP crystals; send culture as well
Plain radiographsChondrocalcinosis in menisci, triangular fibrocartilage, or hyaline cartilage
CBC, ESR, CRPInflammatory markers can be elevated
Second-line
Metabolic workupCalcium, magnesium, phosphorus, alkaline phosphatase, PTH, TSH, ferritin/transferrin saturation when young or recurrent
UltrasoundCan identify cartilage calcification and guide aspiration
CT cervical spineIf crowned dens syndrome suspected
Specialist
Rheumatology referralFor recurrent, atypical, or chronic inflammatory CPPD
1
Acute flare
- Aspirate to confirm diagnosis and relieve pressure
- Intra-articular steroid is effective after infection is excluded
- NSAIDs, colchicine, or systemic glucocorticoids depending on comorbidities
2
Recurrent disease
- Low-dose colchicine prophylaxis can reduce attacks
- Treat associated OA with standard OA measures
- No therapy reliably removes CPP crystals
3
Secondary causes
- Investigate hemochromatosis, hyperparathyroidism, hypomagnesemia, hypothyroidism, and hypophosphatasia when indicated
Complications
- Recurrent flares: Repeated acute knee/wrist attacks
- Chronic inflammatory arthritis: RA-like disease in older adults
- OA acceleration: Atypical MCP/wrist OA
- Crowned dens syndrome: CPPD around odontoid causing acute neck pain
USMLE Step 2 CK Exam Tips
- 1Rhomboid weakly positively birefringent crystals = CPPD
- 2Older patient with acute swollen knee after hospitalization = CPPD
- 3Chondrocalcinosis supports CPPD but does not prove acute flare
- 4Young CPPD needs metabolic evaluation
- 5Hemochromatosis can cause hook-like MCP osteophytes plus CPPD
- 6CPP crystals do not exclude infection
- 7Allopurinol does not treat CPPD
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