A 53-year-old man comes to the office due to progressive pain and stiffness in his hands for the past several months. The patient's symptoms are worse in the morning, and he has difficulty shaving or holding a coffee cup. The stiffness lasts for about 15 minutes and the pain gradually improves through the course of the day, but he often has to take acetaminophen for complete relief. For the past 3 weeks, he has experienced pain in the left knee, especially after prolonged rest. The patient has also had progressive fatigue over the past year. Medical history is notable for type 2 diabetes mellitus, which was diagnosed 6 months ago and is treated with metformin. He works as a sales representative and does not use tobacco, alcohol, or illicit drugs. Family history is remarkable for diabetes mellitus in his father. Temperature is 37.1 C (98.8 F), blood pressure is 126/78 mm Hg, and pulse is 82/min. Physical examination shows normal jugular venous pressure, clear lung fields, and normal heart sounds. The abdomen is nondistended, soft, and nontender. The liver is palpable 1 cm below the right costal margin. There is moderate swelling, warmth, and mild tenderness and decreased range of motion of the second and third metacarpophalangeal joints in both hands. A small effusion and tenderness of the left knee is present without any redness. Radiography of the hand reveals narrowing of the joint space, particularly of the second and third metacarpophalangeal joints, along with subchondral sclerosis, curved osteophytes, subchondral cysts, and osteopenia. An arthrocentesis of the knee is performed, and the synovial fluid analysis shows a leukocyte count of 20,000 cells/mm³ with 80% neutrophils. Gram stain shows no organisms, and polarization microscopy reveals positively birefringent rhomboid-shaped crystals. Additional studies are performed and the diagnosis is established. If this patient's current condition remains untreated, he is at greatest risk for which of the following?

Question

Quizplus · Accepted Answer

Explanation: The initial evaluation of hereditary hemochromatosis (HH) includes serum iron studies, which show increased levels of iron, ferritin, and transferrin saturation. The diagnosis can be confirmed with genetic testing for hemochromatosis-associated mutations (eg, HFE). Long-term management of HH involves serial phlebotomy to deplete excess iron stores. Due to the associated chronic liver disease, patients with HH have an approximately 20-fold increased risk for hepatocellular cancer, accounting for 30%-45% of deaths in patients with HH. Treatment of HH with phlebotomy can lead to improved hepatocellular function, with reduced progression to cirrhosis and an associated reduction in the risk of hepatocellular carcinoma. Phlebotomy also typically alleviates fatigue, reduces skin pigmentation, lowers the risk of heart failure, and may improve glycemic control. (Choice A) Myeloproliferative disorders (eg, polycythemia vera, idiopathic myelofibrosis) can cause hepatosplenomegaly due to hepatic congestion and extramedullary hematopoiesis. They can also cause gouty arthropathy due to increased red cell turnover. However, these disorders are not associated with calcium pyrophosphate dihydrate deposition. (Choice B) Compression radiculopathy is a potential complication of spinal stenosis, which typically presents in patients age >60 and is characterized by lower extremity pain, numbness, and weakness. (Choice D) Interstitial lung disease is a potential extraarticular manifestation of rheumatoid arthritis but is not seen in HH. (Choice E) Uric acid nephrolithiasis can occur in patients with gout, which typically causes an episodic, acute inflammatory arthritis affecting the 1st metatarsophalangeal joint or knee. HH is not associated with nephrolithiasis. Educational objective: Due to the associated chronic liver disease, patients with hereditary hemochromatosis have an increased risk for hepatocellular cancer. Treatment with phlebotomy can lead to improved hepatocellular function, with reduced progression to cirrhosis and an associated reduction in the risk of hepatocellular carcinoma.

A 53-Year-Old Man Comes to the Office Due to Progressive