What is the best treatment approach for a patient with hemochromatosis and arthritis?

Treatment of Hemochromatosis-Associated Arthritis

Arthropathy in hemochromatosis does not respond to phlebotomy and requires symptomatic management with analgesics, NSAIDs, physiotherapy, and ultimately joint replacement surgery when conservative measures fail. 1

Critical Understanding of Hemochromatosis Arthropathy

The joint disease in hemochromatosis is fundamentally different from typical osteoarthritis and presents unique management challenges:

• Arthropathy affects 45-57% of hemochromatosis patients, commonly presenting as the first manifestation of disease before other systemic symptoms develop 1, 2, 3
• Typical distribution involves the 2nd and 3rd metacarpophalangeal joints (46.9%), ankles (69.3%), and hips (56.8%), with earlier age of onset than primary osteoarthritis 1
• Radiographic features include joint space narrowing, exuberant osteophytes, subchondral cysts, and chondrocalcinosis in 50% of cases 1
• The arthropathy can develop even during maintenance phlebotomy therapy, distinguishing it from other iron-related complications 1

Primary Treatment: Iron Removal for Systemic Disease

While phlebotomy does not reverse arthropathy, it remains essential for preventing life-threatening complications:

• Initiate weekly therapeutic phlebotomy immediately, removing 450-500 mL of blood per session until serum ferritin reaches 50 μg/L 4, 5
• Continue lifelong maintenance phlebotomy 2-6 times per year to maintain ferritin between 50-100 μg/L 4, 5
• Phlebotomy prevents progression of liver disease, cardiac complications, and diabetes, which account for the majority of hemochromatosis-related mortality 1, 4

Important Caveat on Phlebotomy Timing

• Early phlebotomy before development of arthropathy may alleviate constitutional symptoms, but once advanced arthritis develops, phlebotomy provides no joint benefit 3
• Do not delay iron removal therapy hoping to improve joint symptoms—the primary goal is preventing organ damage and mortality 1

Symptomatic Management of Arthropathy

Since iron depletion does not reverse joint damage, treatment focuses on symptom control and functional preservation:

First-Line Symptomatic Treatment

• Analgesics and NSAIDs are the mainstay of medical management for pain control 1
• Intensive physiotherapy and occupational therapy should be implemented to maintain joint function and prevent contractures 6

Advanced Medical Options for Inflammatory Component

• For patients with inflammatory arthritis or chondrocalcinosis (CPPD), consider colchicine for crystal-induced inflammation 6
• IL-1 receptor antagonist (anakinra) may be considered for CPPD-related inflammation through NLRP3 inflammasome inhibition 6
• Intra-articular glucocorticoid injections can provide temporary relief for specific inflamed joints 3

Critical Warning About DMARDs

• Disease-modifying antirheumatic drugs (DMARDs) used for rheumatoid arthritis are contraindicated and will worsen the clinical picture due to hepatotoxicity in patients with iron-overloaded livers 7
• Hemochromatosis arthropathy can mimic rheumatoid arthritis, particularly in the MCPs, but requires fundamentally different treatment 7

Surgical Management

• Joint replacement surgery (hip and knee arthroplasty) is ultimately required for end-stage arthropathy 1
• Patients with hemochromatosis have significantly increased risk of requiring hip replacement (HR 2.77) and knee replacement (HR 2.14) compared to controls 1
• Resection osteotomies of metacarpal heads may be considered for severe hand involvement 3

Dietary and Lifestyle Modifications

These recommendations support overall hemochromatosis management but do not specifically improve arthropathy:

• Avoid iron supplements and iron-fortified foods entirely 1, 4, 5
• Avoid supplemental vitamin C, especially during iron depletion phase, as it accelerates iron mobilization and increases oxidative stress 1, 4, 5
• Limit red meat consumption and restrict alcohol intake during iron depletion 1, 4, 5

Monitoring and Prognosis

• Arthropathy symptoms significantly affect quality of life and often progress despite optimal iron management 1
• Monitor for rapid progression to cartilage loss, which is characteristic of hemochromatosis arthropathy 1
• Patients with cirrhosis require lifelong HCC screening every 6 months regardless of iron depletion status 1, 4

Clinical Algorithm Summary

1. Confirm hemochromatosis diagnosis and initiate immediate weekly phlebotomy for systemic iron overload 4, 5
2. Begin symptomatic arthropathy management with analgesics/NSAIDs and physiotherapy 1
3. For inflammatory features or chondrocalcinosis, add colchicine or consider anakinra 6
4. Avoid DMARDs entirely due to hepatotoxicity risk 7
5. Refer to orthopedic surgery when conservative measures fail for joint replacement 1
6. Continue lifelong maintenance phlebotomy to prevent other organ complications 4, 5