ARTHRITIS & RHEUMATISM Vol. 42, No. 12, December 1999, pp 2705–2709 © 1999, American College of Rheumatology LACK OF BORRELIA BURGDORFERI DNA IN SYNOVIAL SAMPLES FROM PATIENTS WITH ANTIBIOTIC TREATMENT–RESISTANT LYME ARTHRITIS DAVID CARLSON, JESUS HERNANDEZ, BRADLEY J. BLOOM, JENIFER COBURN, JOHN M. AVERSA, and ALLEN C. STEERE Objective. To determine whether Borrelia burgdor- feri DNA may be detected in synovial tissue from patients with Lyme arthritis who have persistent syno- vial inflammation after antibiotic treatment. Methods. Synovial specimens obtained at syno- vectomy from 26 patients with antibiotic treatment– resistant Lyme arthritis and from 10 control subjects were tested for B burgdorferi DNA using 3 primer-probe sets that target genes encoding outer surface proteins A or B or a flagellar protein (P41) of the spirochete. Results. The 26 patients with Lyme arthritis, who had received antibiotic therapy for a mean total dura- tion of 8 weeks prior to synovectomy, and the 10 control subjects each had negative polymerase chain reaction (PCR) results in synovial samples. When the samples were spiked with 1–10 B burgdorferi, all but 1 had positive PCR results, suggesting that spirochetal DNA could have been detected in most of the unspiked samples if it had been present. Conclusion. These results indicate that synovial inflammation may persist in some patients with Lyme arthritis after the apparent eradication of the spirochete from the joint with antibiotic therapy. Arthritis is a common late manifestation of Lyme disease in the United States (1). Joint involvement in this infection ranges from joint pain to intermittent attacks of oligoarticular arthritis to chronic synovitis, usually affecting the knees. In most cases, Lyme arthritis can be treated successfully with antibiotic therapy (2). However, 10% of patients have arthritis for months or even several years after treatment, and we have termed this condition antibiotic treatment–resistant Lyme ar- thritis. The synovial lesion in these patients is similar to that seen in other forms of chronic inflammatory arthri- tis, including rheumatoid arthritis (3). A major question is whether persistent synovial inflammation in patients with treatment-resistant Lyme arthritis is due to either persistent spirochetal infection or immune-mediated phenomena. Although the spiro- chete has rarely been cultured from synovial fluid, Borrelia burgdorferi DNA can be readily detected by polymerase chain reaction (PCR) in the synovial fluid of untreated patients at any time in the illness (4,5). In our experience, however, PCR tests of joint fluid yield negative results after 2 months of oral antibiotics or 1 month of intravenous antibiotics (4), suggesting that synovial inflammation may persist in some patients after the apparent eradication of live spirochetes from the joint with antibiotic therapy. Two recent European studies found that B burg- dorferi DNA may be detected more readily in synovial tissue than in synovial fluid (6,7). In one study, in which a primer set was used that targeted the gene encoding the P41 flagellin protein of B burgdorferi, 10 of 11 patients had positive PCR results for B burgdorferi DNA in synovial tissue, but only 4 had positive results in synovial fluid (6). In the other study, in which nested PCR was done with 2 primer sets that targeted the genes for outer surface protein A (OspA) or integral mem- brane protein P66, 4 patients had negative PCR re- sults in synovial fluid, but positive results in synovial tissue (7). Supported by the NIH (grants AR-20358 and AR-07570), the Arthritis Foundation, the Mathers Foundation, the Lincoln Founda- tion of Fort Wayne, Indiana, the Lyme/Arthritis Research Foundation, and the Eshe Fund. David Carlson, BA, Jesus Hernandez, MD, Bradley J. Bloom, MD, Jenifer Coburn, PhD, Allen C. Steere, MD: Tufts University School of Medicine, New England Medical Center, Tupper Research Institute, Boston, Massachusetts; John M. Aversa, MD: the New Haven Orthopedic Group, New Haven, Connecticut. Address reprint requests to Allen C. Steere, MD, New England Medical Center, #406, 750 Washington Street, Boston, MA 02111. Submitted for publication March 31, 1999; accepted in revised form August 5, 1999. 2705