Laboratory testing for Lyme disease: possibilities and practicalities.

Lyme disease (LD) is a multisystem and multistage infection caused by three species of tick-borne spirochetes in the Borrelia burgdorferi sensu lato genogroup. These include B. burgdorferi sensu stricto (North America and Western Europe), Borrelia afzelii (Western Europe, Central Europe, and Russia), and Borrelia garinii (Europe, Russia, and northern Asia). LD has become the most common vector-borne disease in North America and Europe (5). In 1999, over 16,000 cases of human LD were reported in the United States by the Centers for Disease Control and Prevention (CDC), representing an overall incidence of 6.0 per 100,000 persons (9). Many cases go unreported in areas of endimicity; conversely, LD is probably overreported in some geographic areas where the disease is not known to be endemic. Like other spirochetal infections, the signs and symptoms of LD occur in stages and involve a variety of tissues and organs, including the skin, joints, heart, and nervous system. Early infection (stage 1) consists of primary erythema migrans (EM), an annular skin rash that begins days to weeks after a tick bite. Hematogenous dissemination of spirochetes over subsequent days to weeks (stage 2) can result in multiple skin lesions (secondary EM), as well as meningitis, radiculoneuritis, atrioventricular block, myocarditis, and oligoarticular arthritis. Persistent infection (stage 3) occurs months to years after the initial exposure and can be associated with acrodermatitis chronica atrophicans, varying degrees of encephalopathy and encephalomyelitis, and persistent arthritis. Of note, clinical manifestations of LD among patients in North America seem to differ somewhat from those residing in Europe and Asia. For example, acrodermatitis and severe encephalomyelitis due to LD are more common in Europe and Asia but are infrequent among patients in North America. These discrepancies can be explained, at least in part, by the different genospecies of Borrelia responsible for LD in various geographic areas and possibly by genetic differences among the affected populations (30). Recent reviews provide a comprehensive description of the clinical and epidemiologic aspects of LD (17, 21, 26). Since the initial description of Lyme arthritis 25 years ago, there have been tremendous gains in knowledge of the pathogenesis, epidemiology, diagnosis, and treatment of LD (29). The CDC has developed a case definition of LD for surveillance purposes that includes either physician-diagnosed EM along with solitary lesions with diameters of at least 5 cm or at least one late joint, neurologic, or cardiac manifestation along with laboratory confirmation (9). This definition is not intended to be 100% sensitive or specific for clinical diagnosis but is useful as a starting point for the development of a differential diagnosis and highlights the central role of laboratory testing, especially for extracutaneous LD. Laboratory tests have improved considerably over the above-mentioned time period, and clinicians now have available a wide, though somewhat bewildering, array of options for the direct detection of organisms in tissues, serologic detection of immune responses, and molecular detection of specific nucleic acid sequences and antigens. All of the various testing methodologies have their inherent advantages and limitations. It is extremely important to recognize that LD is a clinical diagnosis; any laboratory test used to supplement that evaluation should be ordered and interpreted in the context of careful investigation of the patient’s history and physical examination, i.e., after thoughtful assessment of the probability that a patient actually has a borrelial infection. This article reviews the various possibilities for LD testing and emphasizes some practicalities associated with the use of these tests given the present understanding of individual test performance.