Calcium Pyrophosphate Deposition Disease (Pseudogout)
Rheumatology
Illness script · Rheumatology
Calcium Pyrophosphate Deposition Disease (Pseudogout)
Acute crystal-induced arthritis caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition, most commonly affecting the knee.
This illness script for Calcium Pyrophosphate Deposition Disease (Pseudogout) covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.
01
Predisposing factors
- Older adults (>60 years); prevalence increases sharply with age
- Equal sex distribution; slight female predominance in older cohorts
- Hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia predispose
- Joint trauma or surgery can precipitate acute flares
- Associated with OA — often overlapping in elderly patients
- Familial (rare autosomal dominant ANKH gene mutation)
02
Presentation
- Acute monoarthritis — knee most common (~50%), then wrist, ankle
- Warmth, erythema, effusion; mimics septic arthritis or gout
- Onset over hours; self-limiting flare lasting days to weeks
- May be precipitated by acute illness, surgery, or trauma
- Chronic polyarticular form can mimic rheumatoid arthritis
03
Pathophysiology
- CPPD crystals deposit in fibrocartilage and hyaline cartilage (chondrocalcinosis)
- Crystal shedding into synovial space triggers NLRP3 inflammasome activation
- IL-1β–mediated neutrophil influx causes acute synovial inflammation
- Metabolic disturbances (↑Ca²⁺, ↓Mg²⁺, ↑Fe) promote crystal nucleation
04
Diagnostics
- Synovial fluid analysis is gold standard — weakly POSITIVE birefringent rhomboid-shaped crystals under polarized light
- SF: turbid/inflammatory (WBC 2,000–100,000, PMN predominant)
- X-ray: chondrocalcinosis (calcification of menisci, triangular fibrocartilage of wrist)
- Check metabolic screen: Ca²⁺, PTH, ferritin/transferrin sat, Mg²⁺, phosphate (esp. in younger patients)
- Ultrasound can detect CPPD deposits as echogenic deposits within cartilage
05
Management
- NSAIDs (e.g., indomethacin) first-line if no contraindications
- Intra-articular corticosteroid injection — highly effective for monoarticular flare
- Systemic corticosteroids or colchicine when NSAIDs contraindicated (renal disease, elderly)
- Colchicine (low-dose) can be used for prophylaxis of recurrent flares
- Treat underlying metabolic disorder; no proven disease-modifying therapy for CPPD itself
06
Clinical pivots
How to separate this script from the look-alikes that show up on exams and on the wards.
Gout
Gout crystals are needle-shaped and NEGATIVELY birefringent (yellow parallel to compensator); pseudogout crystals are rhomboid and weakly POSITIVELY birefringent.
Septic arthritis
Septic arthritis has SF WBC typically >50,000 with no crystals; always send cultures — crystals and infection can coexist.
Osteoarthritis
OA is non-inflammatory (SF WBC <2,000) without acute flares; chondrocalcinosis on X-ray favors CPPD.
Rheumatoid arthritis
Chronic CPPD polyarthritis resembles RA but is seronegative (RF/anti-CCP negative) and shows chondrocalcinosis on imaging.
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Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.