BOSTON, Massachusetts—Patients with antibiotic-refractory Lyme arthritis continue to have synovial inflammation even after all evidence of the infection has cleared, and this inflammatory response may persist for years, according to data reported recently by Junghee J. Shin, PhD, Lisa J. Glickstein, PhD, and Allen C. Steere, MD, from Massachusetts General Hospital, in Boston.1
The researchers used cytometric bead array and flow cytometry techniques to measure chemokine and cytokine levels in 65 synovial fluid samples and in 7 synovial tissue samples from 52 patients with Lyme arthritis. Seventeen patients had antibiotic-responsive disease and 35 had antibiotic-refractory disease. Refractory disease was defined as persistent joint swelling for more than 3 months after the start of oral antibiotics used for more than 2 months, intravenous antibiotics used for more than 1 month, or both. Chemokine receptor expression in the synovial tissue samples was measured using immunohistochemistry.
Lyme infection eventually clears, but the malady lingers
"In the post-antibiotic period in patients with refractory arthritis, when [polymerase chain reaction] PCR results for [Borrelia burgdorferi] B. burgdorferi DNA were uniformly negative, the proinflammatory response remained high," the investigators report. The analysis showed that before or during antibiotic therapy, when most patients were still positive for B. burgdorferi DNA on PCR testing, the synovial fluid samples showed "exceptionally high" levels of Th1 chemoattractants and cytokines in samples from the antibiotic-refractory patients. These included significantly higher levels of chemokines CXCL9 and CXCL10 (both P <e;.001 vs patients with antibiotic-response Lyme arthritis). The antibiotic-refractory patients also had significantly higher synovial fluid levels of TNFα, interleukin-1β, interleukin-6, and interferon-γ.
Even after antibiotic treatment, when the synovial fluid and synovial tissue specimens were negative on PCR for B. burgdorferi DNA, the patients with antibiotic-refractory arthritis had high levels of proinflammatory chemokines and cytokines. "Thus even when antibiotic treatment reduces or completely clears the infection in these patients, the inflammatory response in synovium persists," the authors note.
Joint swelling and effusions decreased as a result of antibiotic treatment, but synovial hypertrophy became more apparent in the refractory patients. Joint swelling persisted for up to 53 months in these patients (median of 13 months after starting antibiotic therapy; range 4 to 53 months). Dr. Shin points out that many Lyme arthritis patients are treated with anti-inflammatory drugs after antibiotic therapy.
"In contrast to RA, but similar to findings in reactive arthritis, the inflammatory process in the synovium of patients with Lyme disease recedes and disappears within months to several years. Thus, without the stimulus of the infectious agent, even a putative infection-induced autoimmune response seems to right itself within months to several years, and synovial inflammation resolves," the authors conclude.
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Reference
1. Shin JJ, Glickstein LJ, Steere AC. High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory Lyme arthritis. Arthritis Rheum. 2007;56:1325-1335.