The patient is a 54 y.o man who presents to his primary care physician complaining of a loss of libido and progressive joint pain and stiffness in his hands. He also reports that his family and colleagues have noted a change in the color of his skin over the last year. Routine laboratory testing reveals a blood glucose level of 198, and abnormal liver function tests. Physical examination reveals a moderately enlarged liver, subtle cutaneous hyperpigmentation, and degenerative changes at the MCP joints bilaterally. Recalling a similar case in the past, the physician ordered a complete iron panel which showed a markedly elevated serum transferring saturation and an increased ferritin level. Plain radiographs of the hands and a CT scan of the abdomen were promptly performed.
Radiographs of the hands reveal degenerative changes at the 2nd and 3rd MCPs bilaterally (red arrows), with beak shaped osteophytes (yellow arrows) noted on the radial aspects of the metacarpal heads. A CT scan of the abdomen demonstrated an enlarged and radiodense liver.
Diagnosis and Discussion
Correct Diagnosis: Hemochromatosis
Hemochromatosis, a rare disease caused by abnormal accumulation and deposition of iron in various tissues, is a favorite among differential diagnosticians for the myriad protean ways in which it can present. The classic clinical triad of hyperpigmentation, diabetes, and chronic liver disease is a late stage manifestation of the disease. More subtle changes, such as endocrinopahies, changes in libido due to iron deposition in the affected organs, and especially arthropathy occur earlier, and are often overlooked for many years until more classic symptoms develop. Primary hemochromotosis is caused by a recessively inherited error in iron metabolism usually via mutations in the HFE gene, while secondary hemochromotosis is caused by chronic excessive iron intake and accumulation, such as occurs in patients requiring chronic transfusion therapy for hematologic disorders.
The age of onset is usually in the 5th-7th decades of life, and tends to affect men much more commonly than women. The primary articular manifestations of the disease (present in approximately 50% of patients) are a characteristic symmetric, non-inflammatory, degenerative arthritis affecting the MCPs (especially the 2nd and 3rd), and recurrent attacks of pseudogout secondary to calcium pyrophosphate deposition (CPPD). Over time, large joints such as the hips, knees, and shoulders can be affected. Radiographs show degenerative changes with some unusual features. These include involvement at non-classic sites such as the MCP, intercarpal, and wrist joints, global joint space narrowing, beak shaped osteophytosis on the radial aspects of the metacarpal heads, and chondrocalcinosis. Though often asymptomatic, diffuse osteoporosis has been reported in 25 to 60% of patients. The finding of a radiodense liver on CT scanning is relatively specific for the disease; other rare causes of a radiodense liver, such as amiodarone, gold, or thorotrast exposure can quickly be ruled out in most cases.
Diagnostic testing involves finding an elevated transferring saturation and ferritin in the setting of a suggestive history and physical examination. Confirmatory radiographs, CT scanning, and a liver biopsy complete the workup. Treatment includes phlebotomy, with chelation therapy for more severe (ie. cardiac) involvement. Unfortunately, phlebotomy has little to no effect on the arthropathy seen in hemochromatosis, and conservative treatment with NSAIDS is usually required.
- Hicken BL, Tucker DC, Barton JC. Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis. Am J Gastroenterol. 98(9):2072-7, 2003.
- Schumacher HR Jr. Hemochromatosis. Baillieres Best Pract Res Clin Rheumatol. 14(2):277-84, 2000.
- Ajioka RS, Kushner JP. Hereditary hemochromatosis. Semin Hematol. 39(4):235-41, 2002.
- Resnick D. Haemochromatosis and Wilson’s Disease. In: Resnick D, ed. Diagnosis of Bone and Joint Disorders 4th ed. Philadelphia, London, Toronto, Montreal, Sydney, Tokyo: Saunders, 4057-4070, 2002.