Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia.

BACKGROUND: Effective ways to prevent arthropathy in severe hemophilia are unknown. METHODS: We randomly assigned young boys with severe hemophilia A to regular infusions of recombinant factor VIII (prophylaxis) or to an enhanced episodic infusion schedule of at least three doses totaling a minimum of 80 IU of factor VIII per kilogram of body weight at the time of a joint hemorrhage. The primary outcome was the incidence of bone or cartilage damage as detected in index joints (ankles, knees, and elbows) by radiography or magnetic resonance imaging (MRI). RESULTS: Sixty-five boys younger than 30 months of age were randomly assigned to prophylaxis (32 boys) or enhanced episodic therapy (33 boys). When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group were considered to have normal index-joint structure on MRI (P=0.006). The relative risk of MRI-detected joint damage with episodic therapy as compared with prophylaxis was 6.1 (95% confidence interval, 1.5 to 24.4). The mean annual numbers of joint and total hemorrhages were higher at study exit in the episodic-therapy group than in the prophylaxis group (P<0.001 for both comparisons). High titers of inhibitors of factor VIII developed in two boys who received prophylaxis; three boys in the episodic-therapy group had a life-threatening hemorrhage. Hospitalizations and infections associated with central-catheter placement did not differ significantly between the two groups. CONCLUSIONS: Prophylaxis with recombinant factor VIII can prevent joint damage and decrease the frequency of joint and other hemorrhages in young boys with severe hemophilia A. (ClinicalTrials.gov number, NCT00207597 [ClinicalTrials.gov].).

Arthritis associated with dermatologic conditions.

This article should alert radiologists to be on the lookout for clues in the clinical history for signs of joint disease or other multisystem involvement in patients with a skin disease. A skin rash may be the first indication of a serious disease that prompts a patient to seek medical attention. In this review, examples of joint-skin associations are shown, and a table is presented that includes a comprehensive list of these conditions. The classification system is partly anatomic and partly etiologic, including diseases of the epidermis, dermis, sebaceous glands and sweat glands, tumors, immunologic and collagen vascular diseases, infections, and environmental diseases.

Radiological evaluation of hemophilic arthropathy.

Hemophilia leads to recurrent bleeding episodes in joints resulting in a severe destructive arthropathy in many cases. Staging of hemophilic joint disease is important for identifying the site of bleeding and planning appropriate therapy. However, classification systems based on plain X-ray findings have been insensitive at detecting the earlier, possibly reversible, changes of synovial hyperplasia. They may also underestimate the severity of cartilage damage. Magnetic resonance imaging (MRI) has been shown to more accurately assess a hemophilic joint. Tentative hemophilic arthropathy scales based on MRI findings are being developed. Hopefully, use of these scales will result in more consistent assessment of hemophilic joints and facilitate development of more targeted treatment and thus prevent or delay the later, destructive changes in the articular cartilage and bone.

32P Radiosynoviorthesis in children with hemophilia.

BACKGROUND: This study was performed to prospectively evaluate the safety, efficacy, and cost of injecting P-colloid into joints of children with hemophilia and synovitis to decrease the rate of joint bleeding. PATIENTS AND METHODS: Eligibility included a diagnosis of hemophilia, history of more than six hemorrhages into a joint within a 6-month period, and evidence of synovitis by objective imaging. With written, informed consent, 0.25 to 1.0 mCi of P-colloid was injected into the problem joints. Safety was monitored by external beta-scanning and physical assessment. Efficacy was determined by analysis of the change in joint hemorrhage frequency from 6 months before and up to 96 months after the injection using a signed-rank test. Physical assessment and pain assessment were analyzed similarly using values obtained within 1 week before and 6 months after the radiosynoviorthesis. Cost was modeled using charges from the authors' institution in relation to existing alternative therapies. RESULTS: One hundred injections were given into 91 joints in 59 children. Seven children had high-titer neutralizing antibodies to factor VIII or IX. Nine children were infected with HIV. Joints injected included 44 ankles, 19 knees, 27 elbows, and 1 shoulder. Nine joints required reinjection. All children showed a significant decrease in bleeding rate (P < 0.0001) and pain (P = 0.03), with improved physical function (P = 0.02). In one child acute lymphocytic leukemia developed, but it was judged unrelated to the two P injections that he had received 3 and 10 months before the leukemia diagnosis. There were no cases of bleeding, infection, or inflammation caused by the injection. Cost was substantially less than medical and surgical alternatives. CONCLUSIONS: Radiosynoviorthesis is effective in limiting the frequency of joint hemorrhage, decreasing pain and improving function in children with hemophilia. However, long-term safety studies are needed.