A 52-year-old man with hereditary hemochromatosis (HFE C282Y homozygous) is managed with weekly phlebotomy until ferritin <50 ng/mL. His ferritin has normalized at 38 ng/mL after 18 months. He develops symptomatic aching in the second and third metacarpophalangeal joints bilaterally with chondrocalcinosis on X-ray. What is the mechanism of arthropathy in hemochromatosis?
- A Iron-mediated synovial inflammation via Fenton reaction
- B Urate crystal deposition from hemolysis-related hyperuricemia
- C HFE gene mutation causing direct articular cartilage damage
- D Calcium pyrophosphate dihydrate (CPPD) crystal deposition ✓
Explanation
Hemochromatosis arthropathy predominantly affects the second and third MCP joints — an unusual distribution not seen in rheumatoid arthritis or osteoarthritis — and is caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular cartilage (chondrocalcinosis). Iron promotes CPPD deposition by inhibiting pyrophosphatase. Importantly, this arthropathy does not improve with phlebotomy and iron depletion; joint involvement may even worsen after iron removal. This is one of the most distinctive and clinically important features of hemochromatosis joint disease.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.