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).