Hemophilic joint disease - current perspective and potential future strategies.
Recurrent hemarthroses can lead to hemophilic joint disease (HJD), which is one of the most disabling complications of these X-linked recessive disorders characterized by a deficiency of clotting factors VIII/IX. The pathogenesis of HJD is not well understood and there is evidence to suggest that iron may play a central role in the pathogenetic process causing changes at the molecular level and through the release of cytokines and perpetuation of a chronic inflammatory state. Also, there may be a role for angiogenesis in accelerating the joint damage begun by recurrent hemarthroses. Hemophilic joint disease can be diagnosed by MRI which provides information about the pathology of the synovium, articular cartilage and bone. However, it is expensive, and maybe cumbersome in young children who require sedation. Newer, cost-effective imaging tools such as ultrasonography need to be explored to facilitate diagnosis and monitoring of joint disease. Repeated bleeds into the joint could be prevented by reducing the number of bleeds by the prophylactic infusion of factor concentrates on a bi-weekly to alternate day schedule depending on the activity level and bleeding phenotype. However, the dose, schedule and timing of prophylaxis still remain unresolved despite some multi-center clinical studies proving its benefit in preserving joint function. Prohibitive costs and the need for venous access devices in delivering factor concentrates in younger children continue to complicate universal recommendations of prophylaxis. In those patients who fail or refuse prophylaxis, procedures such as isotopic synovectomy can provide relief from repeated joint bleeds, again the timing of which is not well-defined. Newer strategies to identify early joint disease through the use of serological markers are needed. Also, cost-effective imaging modalities are needed so that treatment strategies such as prophylaxis and isotopic synovectomy can be appropriately timed to reap maximum benefits. A combination of serological and imaging evidence of early joint disease might ultimately impact on the optimal management of hemophilic joint disease.
Acharya
Suchitra S
SS
Pediatric Hematology/Oncology, Weill Medical College of Cornell University, 525 East 68th Street, P-695, New York, NY 10021, USA. ssa2001@med.cornell.edu
D006467:Hemophilia A / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007592:Joint Diseases / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D008279:Magnetic Resonance Imaging