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Pseudogout (Calcium Pyrophosphate Dihydrate, CPPD)

BASICS

  • Description: Autoinflammatory disease from deposition of calcium pyrophosphate dihydrate (CPPD) crystals within joints.
  • Synonyms: Pseudogout, CPPD, pyrophosphate arthropathy, chondrocalcinosis.
  • Definitive diagnosis: Identification of CPPD crystals in synovial fluid.
  • Systems affected: Endocrine/metabolic, musculoskeletal

EPIDEMIOLOGY

  • Prevalence: 4–7% of adults in US/Europe; 80% of patients >60 years
  • Chondrocalcinosis: 1:10 adults age 60–75, 1:3 over age 80
  • Gender: No strong predominance; men acute, women atypical presentations

ETIOLOGY & PATHOPHYSIOLOGY

  • Pathogenesis:
  • Overproduction of anionic pyrophosphate in articular cartilage
  • Formation of CPPD crystals → neutrophil-mediated inflammation
  • Inflammation/damage from repeated crystal deposition
  • Genetics: Rare autosomal dominant forms (ANKH gene mutation), mostly sporadic
  • Precipitating events: Trauma, medical illness, surgery (notably post-parathyroidectomy)

RISK FACTORS

  • Advanced age
  • Joint trauma

GENERAL PREVENTION

  • Colchicine 0.6 mg BID may reduce frequency of recurrent attacks

COMMONLY ASSOCIATED CONDITIONS

  • Gout
  • Hyperparathyroidism
  • Hemochromatosis
  • Amyloidosis
  • Hypothyroidism
  • Wilson disease
  • Hypomagnesemia
  • Familial hypocalciuric hypercalcemia
  • X-linked hypophosphatemic rickets
  • Acromegaly

DIAGNOSIS

History

  • Mimics gout: acute pain/swelling in ≥1 joint (knee > ankle/wrist/toe/shoulder)
  • May develop after intra-articular hyaluronic acid injection
  • Chronic CPPD: Progressive degenerative arthritis + acute inflammatory attacks

Physical Exam

  • Erythema, warmth, joint tenderness/effusion, decreased ROM
  • 50% may have fever

Differential Diagnosis

  • Gout, septic arthritis, trauma, Reiter syndrome, Lyme disease, acute RA

Diagnostic Tests

  • Synovial fluid: Inflammatory effusion (2,000–100,000 WBCs/mL, 80–90% neutrophils)

  • 50,000 WBCs/mL: increased likelihood of sepsis

  • Polarized microscopy: positively birefringent crystals (may have false negatives)
  • Exclude metabolic diseases: serum Ca, P, Mg, iPTH, iron, ferritin, TSH, ALP
  • Imaging:
  • X-ray: linear/punctate calcification of fibrocartilage (knees, hips, symphysis pubis, wrists)
  • US: effusion, synovial thickening, hyperechoic deposits
  • MRI: hypointense chondrocalcinosis in menisci
  • Key: Synovial fluid analysis is required for diagnosis

TREATMENT

General Measures

  • Rest, elevate joint, apply ice/cool compresses
  • Non-weight bearing during pain

First Line

  • Acute: Joint aspiration ± intra-articular steroid, oral NSAIDs, colchicine
  • NSAIDs: Ibuprofen 600–800 mg PO TID–QID (max 3.2 g/day), naproxen 500 mg PO BID
    • Avoid in peptic ulcer, GI bleeding, renal/cardiac disease
    • Use PPI/misoprostol for GI protection if at risk
  • Colchicine: 0.5 mg up to 3–4× daily, or 1.2 mg at onset, 0.6 mg after 1 hr
    • No loading dose in elderly (renal risk)
  • Intra-articular steroids: Prednisolone sodium phosphate 4–20 mg or triamcinolone diacetate 2–40 mg
  • Chronic: Prophylactic NSAIDs and/or colchicine

Second Line

  • Oral prednisone: 30–50 mg/day x 7–10 days
  • IM triamcinolone acetonide: 40 mg, repeat in 1–4 days if needed

Other/Experimental

  • ACTH, anakinra (anti-IL-1), hydroxychloroquine, infliximab, probenecid, magnesium, EDTA (limited data)
  • Methotrexate: not effective in chronic-recurrent CPPD

Physical Therapy

  • Isometric exercises acutely; ROM as pain subsides; resume weight bearing when improved

Surgery/Procedures

  • Arthrocentesis for diagnosis and symptom relief
  • Surgical removal of large tophaceous lesions (rare)

ISSUES FOR REFERRAL

  • Rheumatology/orthopedics for septic joint, non-response to treatment, or diagnostic uncertainty

ADMISSION, INPATIENT, & NURSING

  • Admit if septic arthritis suspected (WBC >50,000/mL)
  • Begin empiric antibiotics pending culture

ONGOING CARE

  • Reevaluate 48–72 hours after therapy starts; follow up in 1 week and as needed

DIET

  • No known dietary relationship

PATIENT EDUCATION

  • Rest affected joint; symptoms typically resolve in 7–10 days

PROGNOSIS

  • Acute: Excellent, resolves in ~10 days
  • Chronic/recurrent: Risk of progressive joint damage, functional limitation

COMPLICATIONS

  • Recurrent acute attacks
  • Osteoarthritis
  • Functional loss

GERIATRIC CONSIDERATIONS

  • Elderly: higher risk of GI/renal side effects from NSAIDs; avoid colchicine loading

ICD-10 Codes

  • M11.20 Other chondrocalcinosis, unspecified site
  • M11.269 Other chondrocalcinosis, unspecified knee
  • M11.29 Other chondrocalcinosis, multiple sites

CLINICAL PEARLS

  • Suspect CPPD in arthritis not fitting classic degenerative pattern.
  • Arthrocentesis is essential for confirmation.
  • Always exclude septic arthritis if clinical suspicion is high; start antibiotics if necessary.
  • NSAIDs are preferred for acute attacks; oral/intra-articular steroids are alternatives if NSAIDs contraindicated.