Lyme disease, a systemic illness caused by the spirochete Borrelia burgdorferi, is the most common tick-borne disease in the United States. In 2011, 48 states reported 24 364 cases of Lyme disease using the Council of State and Territorial Epidemiologists (CTSE)/Centers for Disease Control and Prevention (CDC) surveillance case definition. Since the original discovery of Lyme arthritis in the mid 1970s the clinical spectrum of Lyme disease has expanded to include a wide variety of organ systems, primarily the skin, joints, nervous system, and heart. Protean symptoms, uncertainty in diagnosis due to lack of definitive testing methods, and public fear of late sequelae of disease often lead to overdiagnosis and overtreatment. Although optimal therapy of some of the clinical features of Lyme disease is unclear, better understanding of the natural history, epidemiology, and pathogenesis of Lyme disease helps in the often confusing and difficult decisions related to diagnosis and treatment.

B. burgdorferi has been isolated from blood, skin, cerebrospinal fluid (CSF) specimens, and (rarely) other specimens from infected patients although, with the exception of skin biopsy specimens, culture of B. burgdorferi from sites of infection is a low-yield procedure. B. burgdorferi displays phenotypic and genotypic diversity and has been classified into separate genospecies, five of which are pathogenic to humans: Borrelia burgdorferi sensu stricto, which includes all strains studied thus far from the United States and some European and Asian strains, and Borrelia garinii, Borrelia afzelii, Borrelia spielmanii, and Borrelia bavariensis, which are found in Europe and Asia. B. afzelii seems primarily associated with a chronic skin lesion, acrodermatitis chronica atrophicans, rare in the United States, and B. garinii is predominant among CSF isolates.