Therapy for Lyme arthritis: strategies for the treatment of antibiotic-refractory arthritis.

Lyme arthritis, caused by the tick-borne spirochete Borrelia burgdorferi (1), typically causes intermittent or persistent arthritis in a few large joints, especially the knee, for several years (2). Treatment recommendations have changed over time. In the early 1980s, 3 intramuscular injections of benzathine penicillin or a 10-day course of high-dose intravenous (IV) penicillin cured only 35–55% of patients (3). In the late 1980s, treatment with IV ceftriaxone for 2 weeks was effective in 90% of patients (4,5); slightly better results were achieved with 4 weeks of therapy (6), but adverse events occurred more frequently. During the same period of time, a 4-week course of oral doxycycline or amoxicillin was also effective in 90% of patients with Lyme arthritis (7). However, joint swelling in some patients remained unresponsive to oral therapy and re-treatment with a 2-week course of IV ceftriaxone (7). To date, little information is available about therapy for such patients. One non–antibiotic-treated patient had resolution of joint swelling following hydroxychloroquine therapy (8). Sixteen of 20 patients with persistent arthritis despite antibiotic therapy experienced resolution after arthroscopic synovectomy (9). In 2000, an expert panel from the Infectious Diseases Society of America (IDSA) presented guidelines for the treatment of Lyme disease (10). The panel recommended initial treatment with oral doxycycline or amoxicillin for 4 weeks for patients with Lyme arthritis and no concomitant neurologic abnormalities. Results of a cost–benefit analysis suggested that such therapy is as effective as IV therapy, is safer than IV therapy, and is considerably less expensive (11). For patients in whom arthritis is persistent despite receiving 4 weeks of oral antibiotic therapy, the panel recommended re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of IV ceftriaxone. However, in a small percentage of patients, proliferative synovitis (12,13) persists for months to several years, even after 2 months of treatment with oral antibiotics, 1 month of treatment with IV antibiotics, or both, which we have termed antibiotic-refractory (or slowly resolving) Lyme arthritis.