Long-term outcomes and management of patients with Lyme disease.

Abstract

ALTHOUGH LYME DISEASE WAS FIRST RECOGNIZED 25 years ago, serologic methods of diagnosis have not been well standardized, and there is significant variability between laboratories. In the absence of a criterion standard blood test, the diagnosis of Lyme disease is based on a characteristic clinical picture in the appropriate epidemiologic setting (often supported by serologic data). Because the initial IgM response to the causative spirochete Borrelia burgdorferi characteristically begins 1 to 2 weeks after infection, patients with early classic Lyme disease may be antibody-negative. Conversely, B burgdorferi expresses crossreactive antigens and false-positive test results may occur, even using the recommended 2-step system of enzyme-linked immunosorbent assay (ELISA) screening (high sensitivity) followed by Western immunoblot (high specificity). To further complicate the issue, all the currently licensed ELISA tests contain the OspA surface antigen and, therefore, are invalid for individuals who have received the Lyme disease vaccine (composed of purified OspA). For patients with classic presentations of Lyme disease, there is widespread agreement about the initial diagnosis and antibiotic management. However, without a serologic criterion standard, there is no valid way to address issues of asymptomatic or atypical infection for long-term outcomes. The situation is analogous to the early years of the acquired immunodeficiency syndrome, when the case definition was entirely clinical and only patients with the most classic presentations (eg, Pneumocystis carinii pneumonia or Kaposi sarcoma) were considered to represent acquired immunodeficiency syndrome cases. With the advent of reliable human immunodeficiency virus testing in 1985, the case definition was broadened to include a variety of additional presentations (eg, recurrent Candida or Mycobacterium aviumintracellulare infection), and studies of the epidemiology and natural history of the infection quickly followed. Uncertainty breeds strong disparate opinions. As long as Lyme disease is defined primarily by its clinical characteristics, legitimate disagreement will exist between those who acceptonly thenarrowcasedefinition, limited to thosepatients with well recognized Lyme disease manifestations, and those who believe that B burgdorferi also may be an important contributor to other, less well-defined illnesses, particularly when accompanied by positive (albeit imperfect) serologic test results. Physicians who accept less stringent criteria argue that the full spectrum of Lyme disease is not known and that the strict diagnostic criteria may recognize only the tip of the iceberg.Concernabout inadequatelydiagnosedor treatedB burgdorferi infection is heightened by comparisons to syphilis, another disease caused by a spirochete, in which subtle, proteansignsandsymptomsmayprogress insidiously ifnot treated effectively. For the highly motivated patient seeking a diagnostic label for persistent symptoms, it is not difficult to find a physician who, reasoning that the response to a course of antibiotics represents a diagnostic trial, is willing to treat for the unlikely possibility of Lyme disease. This “doctor’s dilemma” is addressed in this issue of THE JOURNAL by Seltzer and colleagues in their assessment of long-term outcomes of patients who were diagnosed as having Lyme disease and reported to the Connecticut Department of Public Health from 1984 to 1991. Their random subsample of 8764 patients with reported Lyme disease netted 678 enrollable study patients, the largest group of patients with Lyme disease followed up in a longitudinal study. It is reassuring that after a median follow-up of 51 months, patients with a diagnosis of Lyme disease that met the national surveillance case definition developed by the Centers for Disease Control and Prevention (CDC) had the same profile of symptoms and the same quality-of-life indicators as age-matched controls without Lyme disease. Thus, recognition and treatment of clear-cut Lyme disease resulted in a return to baseline with no measurable sequelae. On the other hand, patients who were reported to have Lyme disease but who did not meet the CDC’s case definition of Lyme disease had increased symptoms and worsening quality-of-life indicators. The implication is that many of these individuals really did not have Lyme disease and therefore did not respond to the treatment. Although this study used accepted epidemiologic methods and analyses, it is surprising that only 64.3% of cases reported to the state met the current CDC national surveillance definition of Lyme disease. Moreover, not all patients