Pulling the Trigger on Lyme Arthritis

Abstract

The infectious disorders now collectively known as Lyme disease (Lyme borreliosis) began their long ascent to notoriety as a little noticed outbreak of oligoarthritis in Southeastern Connecticut during the mid 1970s [1, 2]. Local physicians mistakenly diagnosed many of these cases, mostly occurring in children, as juvenile rheumatoid arthritis. Two suspicious mothers called the “autoimmune” epidemic to the attention of rheumatologists at nearby Yale University, who made the critical observation that approximately one-quarter of the index case patients had developed a distinctive bull’s eye rash (erythema migrans) similar to one known to be transmitted in Northern Europe by the hard tick Ixodes ricinus. Further investigation implicated the deer tick, Ixodes scapularis, as the likely arthropod vector [3].These field studies prompted an intensive microbe hunt resulting in isolation, first from ticks [4] and then from a small number of skin, blood, and cerebrospinal fluid specimens [5, 6], of a spirochete subsequently determined to be a new Borrelia species [7]. Of the 20 or so species now known to comprise the Borrelia burfgdorferi sensu lato complex, Borrelia burgdorferi sensu stricto (ss), Borrelia afzelii, and Borrelia garinii ,p redominate as human pathogens [8]. B. burgdorferi ss is the only cause of Lyme disease in the United States. Surprisingly, B. burgdorferi ss, the member of the complex with the greatest proclivity to invade joints, has never been isolated from human joints, although spirochetal DNA can be amplified with polymerase chain reaction from synovial fluids. B. garinii, a common isolate in Europe, has earned a reputation for neurotropism because of its predilection for invasion of the central nervous system [8]. In nature, Lyme disease spirochetes persist asymptomatically in rodent reservoirs, such as the white-footed mouse Peromyscus leucopus [9]. Because humans are incidental and probably dead-end hosts for the bacterium, illness in humans may be an evolutionarily unintended outcome of the vector’s generalist feeding behavior [10].