Applied Radiology

cHe denied illicit drug use or any recent fevers or chills. Radiographs of the left knee at that time were significant only for a joint effusion (not shown). He was given nonsteroidal anti-inflammatory medication and was referred to physical therapy for range-of-motion (ROM) exercises and modalities for pain and swelling control. Although the pain and swelling gradually decreased over a 4-week period, the patient experienced progressive loss of motion and represented 10 months later with significant joint contractures. Repeat radiographs (Figure 1) were obtained, followed by magnetic resonance (MR) imaging of the left knee (Figure 2).

DIAGNOSIS

Hemophilic arthropathy

IMAGING FINDINGS

Radiographs of the right knee were normal. The radiographic images of the left knee reveal extensive erosive and degenerative change about the femoral-tibial and femoral-patellar joints and diffuse, severe osteopenia (Figure 1). MR imaging shows extensive subchondral cystic change and edema. The T2-weighted MR image shows, particularly well, multiple, intra-articular dark irregular foci corresponding to hemosiderin deposits (Figure 2).

DISCUSSION

The coagulation dysfunction in hemophilia A is a sex-linked deficiency or abnormality of a plasma protein called factor VIII (FVIII) found in 1 of 5000 male births. Physiologically, FVIII is found circulating in the plasma bound to von Willebrand's factor, which acts as a carrier protein. The degree of FVIII deficiency correlates with the extent of bleeding, and hemophilia A can be classified as severe (<1% activity), moderate (1% to 5%), or mild (5% to 25%). Typically, symptoms begin in childhood associated with hemorrhage after minor trauma. As the individual ages and becomes more prudent, symptoms become less frequent. Although a presumptive diagnosis can be made based on age, sex, family history, and clinical presentation, the presentation is not always classic. Up to 30% of patients may have a normal family history due to mild disease or lack of males in the family tree. Mild disease, however, may not present until well into adulthood; there has even been a case in which the patient was diagnosed during his 60s. ¹ Hemophilia has been well documented in females in whom X chromosome inactivation occurs at an early stage of embryogenesis, resulting in unusually low levels of FVIII. ² The differential diagnosis for congenital bleeding disorders includes hemophilia B (deficiency of factor IX), factor XI deficiency, and von Willebrand's disease (deficiency of vWF). Acquired coagulation disorders should also be considered, such as vitamin K deficiency, liver disease, and factor deficiencies that may be seen in conditions like systemic lupus erythematosus or lymphoma.

Radiographically, the diagnosis is often suggested by recurring changes of hemarthrosis in the knees, elbows, and ankles. ³ Although there is no universally accepted classification system, several common patterns of joint disease in hemophilic arthropathy have been described by Arnold and Hilgartner. ⁴ The initial episode of intra-articular bleeding, often following minor trauma, is usually associated with joint effusion without osseous or articular involvement. With recurrent small bleeds or after a large bleed, peri-articular osteoporosis and regional soft-tissue swelling are common sequelae. In adolescents, the hyperemic joint may lead to localized, accelerated growth and limb-length discrepancies. Eventually osseous irregularity and erosion develop, accompanied by subchondral cysts. Synovial effusions are common and may appear radiodense due to hemosiderin deposition. An important diagnostic clue to hemophilic arthropathy during this phase is the preservation of joint space. As osseous erosions continue, however, joint space narrowing is seen, associated with progressive, symmetric cartilaginous destruction. Eventually, complete obliteration of the joint space will occur and secondary degenerative signs, including osteophytes and eburnation, develop. With chronic disease, muscle imbalances and joint contractures may develop.

MR imaging can detect early erosions not visualized on conventional radiography and is probably the best modality for assessing intra-articular abnormalities associated with hemophilic arthropathy. Generally, hemarthrosis can be seen as areas of low to intermediate signal on T1-weighted MR images and increased signal on T2-weighted MR images. ⁵ Chronic peri-articular changes are often visualized as decreased signal intensity on both T1- and T2-weighted MR images. Synovial hypertrophy results from fibrosis and appears as nodular areas of low to intermediate signal intensity on T1- and T2- weighted MR images. Subchondral cysts containing inflammatory fluid show increased signal on T2-weighted MR images, while fibrotic cysts are hypointense. ⁶ Because articular cartilage is well visualized on MR imaging, focal areas of thinning or absent cartilage can be easily detected.

Treatment for hemophilia typically involves some form of factor replacement depending on the severity of the disease. The pain and swelling associated with joint injuries can be treated with conservative measures such as immobilization, cooling, and nonsteroidal anti-inflammatory medication, which do not interfere with the coagulation pathway or platelet function. Aspiration therapy is contraindicated unless necrosis, due to joint tension or compartment pressure, is imminent. Radiotherapy for vascular sclerosis can be useful in the treatment of soft-tissue masses and acute joint hemarthrosis. When irreversible osseous and cartilaginous changes have occurred, and pain and joint contractures limit activities of life, joint replacement should be considered.

CONCLUSION

Hemophilic arthropathy is a rare joint-destroying disorder that is more prevalent before adulthood. A wide spectrum of radiographic and MR changes are possible depending on the stage of the disorder. Correlating a good history with characteristic imaging findings can result in prompt diagnosis and treatment and may prevent, or at least delay, the need for joint replacement.

Prepared by Michael W. Matchette, MD from the University of Texas Health Science Center, San Antonio, TX and Justin Q. Ly, MD from Wilford Hall Medical Center, San Antonio, TX.