Miscellaneous Deposition Diseases

Hemochromatosis

Primary hemochromatosis is an inherited disorder that leads to massive iron deposition throughout the body. The most common genetic defect is an autosomal recessive defect in the HFE gene on chromosome 6; 1 in 200 people of northern European descent are homozygous for this mutation. Despite the relatively common prevalence of this mutation the actual clinical presentation of hemochromatosis is relatively uncommon. The initial presenting complaint of patients with hemochromatosis is joint pain, so it is critical for radiologists to be alert for the radiographic presentation of hemochromatosis. Early recognition of this disorder can prevent hepatic fibrosis, cirrhosis, and myocardiopathy through appropriate therapeutic intervention. The arthropathy is seen in 24 to 50 percent of affected patients. The arthropathy may or may not have associated radiographic chondrocalcinosis. This raises some question about the cause of the arthropathy. Although chondrocalcinosis is frequently observed, it has not been determined whether the CPPD crystals actually cause degeneration of the cartilage or the crystals are deposited secondarily in already degenerated cartilage. It is known that iron inhibits pyrophosphatase activity in the cartilage, leading to the precipitation of CPPD crystals; however, it is not known whether the iron or the CPPD crystals cause the initial degeneration of the cartilage.

The arthropathy of hemochromatosis is almost identical to that of CPPD crystal deposition in that the radiographic picture is one of osteoarthritis in atypical sites for primary osteoarthritis. As in pyrophosphate arthropathy, subchondral cysts dominate the picture, and uniform, rather than nonuniform, loss of joint space is the rule. However, there are subtle differences that distinguish hemochromatosis from CPPD arthropathy. The radiographic findings in hemochromatosis arthropathy are:

• 1.

  Osteoporosis

• 2.

  Chondrocalcinosis—there appears to be more hyaline cartilage calcification than fibrous cartilage calcification when compared to CPPD arthropathy

• 3.

  Uniform joint space loss

• 4.

  Subchondral sclerosis

• 5.

  Subchondral cyst formation

• 6.

  Beak-like osteophytes

• 7.

  Slow progression of disease—no excessive neuropathic changes as seen in CPPD

• 8.

  Bilateral symmetrical distribution

• 9.

  Distribution in hand and wrist initially and most frequently, then knee and hip; late widespread involvement throughout the skeleton

The subtle changes that may distinguish hemochromatosis arthropathy from CPPD arthropathy are best seen in the hand and wrist.

Hand and Wrist

In the hand there is specific preference for the second and third metacarpophalangeal (MCP) joints with or without involvement of the other MCP joints and wrist ( Fig. 19-1 ). There will be uniform loss of the joint space with subchondral sclerosis present. Small (1- to 3-mm) subchondral cysts may be identified. There is a characteristic osteophytic beak on the medial aspect of the second and third metacarpals. There may be flattening or collapse of the heads of the metacarpals ( Fig. 19-2 ). The fourth and fifth MCP joints may be involved, but the interphalangeal (IP) joints are usually spared. The MCP joints, particularly the fourth and fifth, are more frequently involved in hemochromatosis than they are in CPPD crystal deposition disease.

The wrist is less frequently involved in hemochromatosis than in CPPD crystal deposition disease; the distribution of the disease in the wrist also differs. Although the wrist may show involvement similar to that with CPPD arthropathy ( Fig. 19-3 ), hemochromatosis usually involves primarily the common carpometacarpal, the midcarpal and the first carpometacarpal compartments, with sparing of the radiocarpal compartment. The changes seen are those of osteoarthritis in this distribution, with subchondral sclerosis and cyst formation.

Recognition of these findings should trigger a recommendation for screening for iron overload. This is best accomplished through assessment of serum iron transferrin saturation; a level of higher than 45 percent requires further evaluation for hemochromatosis including serum ferritin level and genetic testing.

Other Joints

In some patients, in the late phase of the disease there may be widespread involvement throughout the skeleton. It may be difficult to distinguish this involvement from that of CPPD arthropathy ( Fig. 19-4 ). However, osteophytes, which have been described as “beak-like,” may dominate the radiographic picture more frequently than in CPPD arthropathy. Generally the progression of the disease is very slow, whereas that in CPPD arthropathy can be extremely rapid. The kind of neuropathic changes seen in CPPD arthropathy are not seen in hemochromatosis.

Wilson disease

Wilson disease is an extremely rare disease causing hepatolenticular degeneration. Copper is the substance deposited in the various tissues. The copper interferes with normal bone formation and causes osteogenic osteomalacia. An arthropathy occurs in 50 percent of affected patients; however, the arthropathy is usually a radiographic finding rather than a clinical problem.

Radiographic chondrocalcinosis has been reported very rarely in this already rare disease. However, there is some question about the etiology of the cartilage calcification. Pathologic proof of CPPD crystal deposition has not been made. In vitro studies have shown that copper ions inhibit pyrophosphatase activity in cartilage, allowing pyrophosphate dihydrate crystal deposition, but this phenomenon has yet to be proven in vivo. There is considerable bone fragmentation in the joint in Wilson disease, which could easily be mistaken for chondrocalcinosis.

The arthropathy of Wilson disease is quite distinctive, with marked irregularity to the cortical and subchondral areas of the articular surface giving a “paint brush” appearance. There is significant subchondral bone fragmentation, which in larger joints may resemble osteochondritis dissecans. Well-corticated ossicles may be seen in the joint. Other than these specific changes, the arthropathy resembles osteoarthritis in an unusual distribution for primary osteoarthritis. The arthropathy has been seen in the hand, wrist, foot, hip, shoulder, elbow, and knee.