Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in cerebrospinal fluid in Lyme neuroborreliosis.

A polymerase chain reaction (PCR) assay that detects Borrelia burgdorferi DNA in cerebrospinal fluid (CSF) was evaluated as a diagnostic test for acute or chronic Lyme neuroborreliosis. In one laboratory, 102 samples were tested blindly, and 40 samples were retested in a second laboratory. In the first laboratory, B. burgdorferi DNA was detected in CSF samples in 6 (38%) of 16 patients with acute neuroborreliosis, 11 (25%) of 44 with chronic neuroborreliosis, and none of 42 samples from patients with other illnesses. There was a significant correlation between PCR results and the duration of previous intravenous antibiotic therapy. The overall frequency of positive results was similar in the second laboratory, but concordance between the laboratories and among primer-probe sets was limited because many samples were positive with only one primer-probe set. Thus, PCR testing can sometimes detect B. burgdorferi DNA in CSF in patients with acute or chronic neuroborreliosis, but with current methods, the sensitivity of the test is limited.

Infectious arthropathies and other rheumatologic manifestations of infectious diseases.

Infectious agents have been implicated in the pathogenesis of many rheumatologic diseases. In most of these diseases, including those in which specific organisms are known to play a role, the details of pathogenesis remain incompletely defined. Recent studies have aimed to isolate bacterial and viral pathogens from patients with rheumatic diseases, efforts have been made to further define the host immune response to infection, and there have been attempts to develop improved methods of diagnosis and treatment of infectious diseases affecting the musculoskeletal system. This review discusses recent studies on the association of infection with illnesses affecting the joints and musculoskeletal system, with an emphasis on the rheumatic diseases of childhood.

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis.

BACKGROUND: Borrelia burgdorferi is difficult to detect in synovial fluid, which limits our understanding of the pathogenesis of Lyme arthritis, particularly when arthritis persists despite antibiotic therapy. METHODS: Using the polymerase chain reaction (PCR), we attempted to detect B. burgdorferi DNA in joint-fluid samples obtained over a 17-year period. The samples were tested in two separate laboratories with four sets of primers and probes, three of which target plasmid DNA that encodes outer-surface protein A (OspA). RESULTS: B. burgdorferi DNA was detected in 75 of 88 patients with Lyme arthritis (85 percent) and in none of 64 control patients. Each of the three OspA primer-probe sets was sensitive, and the results were moderately concordant in the two laboratories (kappa = 0.54 to 0.73). Of 73 patients with Lyme arthritis that was untreated or treated with only short courses of oral antibiotics, 70 (96 percent) had positive PCR results. In contrast, of 19 patients who received either parenteral antibiotics or long courses of oral antibiotics (> or = 1 month), only 7 (37 percent) had positive tests (P < 0.001). None of these seven patients had received more than two months of oral antibiotic treatment or more than three weeks of intravenous antibiotic treatment. Of 10 patients with chronic arthritis (continuous joint inflammation for one year or more) despite multiple courses of antibiotics, 7 had consistently negative tests in samples obtained three months to two years after treatment. CONCLUSIONS: PCR testing can detect B. burgdorferi DNA in synovial fluid. This test may be able to show whether Lyme arthritis that persists after antibiotic treatment is due to persistence of the spirochete.

Human parvovirus B19-associated arthritis in children.

Human parvovirus B19 (HPV B19) infection has been associated with chronic joint complaints in adult patients. We now report 22 children with joint complaints associated with recent HPV B19 infection. These children had either erythema infectiosum or serologic evidence of recent infection. Twenty children had arthritis; two had arthralgias. Eleven children had associated constitutional symptoms. Laboratory findings were generally normal. The duration of joint symptoms was less than 4 months in 14 children; however, six children have had persistent arthritis for 2 to 13 months, which would fulfill criteria for the diagnosis of juvenile rheumatoid arthritis. Although HPV B19 is usually associated with acute arthritis of brief duration, in some children infection with HPV B19 may be associated with the development of chronic arthritis.

Sarcoidosis associated with nephrocalcinosis in young children.

Three patients with nonpulmonary sarcoidosis had chronic erythema nodosum within the first 2 years of life. Each subsequently had renal sarcoidosis and nephrocalcinosis; hypercalcemia was documented in each patient and hypercalciuria in two patients. Treatment with prednisone was not uniformly successful in normalizing creatinine clearance. Nephrocalcinosis may be more common than previously reported in patients with sarcoidosis.