Position Statement

Growing attention to Lyme disease in the medical and lay press has led to increased serologic testing in patients with nonspecific symptoms (such as myalgia and chronic fatigue) without a history of classical clinical features of Lyme disease. Many patients with such nonspecific symptoms and a positive serologic test result are assumed to have Lyme disease and have been treated empirically with prolonged antibiotic therapy. A committee appointed by the American College of Rheumatology and the Council of the Infectious Diseases Society of America has examined the available evidence and has done a cost-effectiveness analysis of antibiotic therapy of such patients [1].

Important variables that affect the cost-effectiveness analysis include:

1. The sensitivity and specificity of currently used serologic tests.

2. The incidence and prevalence of Lyme disease in various geographic regions.

3. The prevalence of other conditions such as the chronic fatigue syndrome, fibromyalgia, and depressive disorders that commonly present with similar nonspecific symptoms.

4. The health costs incurred after treating Lyme disease and non-Lyme disease patients (for example, antibiotics, administration, physician costs, and costs of adverse events).

5. The effectiveness of antibiotic therapy in patients with chronic Lyme disease.

Testing for immunologic evidence of Lyme disease remains imperfect. The enzyme-linked immunosorbent assay is the most commonly used test for the detection of antibodies to Borrelia burgdorferi. Because Borrelia and other microorganisms, including Treponema, share antigens in common, false-positive test results can occur with enzyme-linked immunosorbent assay testing. In addition, false-positive results have been reported in other rheumatologic and neurologic conditions and in a small number of normal persons. Some laboratories use immunoblotting methods to improve specificity, although the use of this method has not been systematically assessed. For all tests available, the methods used in different laboratories have not been standardized, so substantial variability exists between laboratories. Fibromyalgia and other nonspecific rheumatic syndromes are much more common than Lyme disease. Therefore, positive Lyme disease serologic results in certain patients are more likely to represent false-positive results than proof of Lyme disease infection, with increasing uncertainty as one goes from an area of high-to-low endemicity for Lyme disease.

At this time, it is difficult to assess the natural history of asymptomatic seropositive persons. Because it is not possible to distinguish persons who are truly seropositive due to previous exposure to B. burgdorferi from false-positive results due to other causes, a positive serologic result is not definitive evidence for the diagnosis of Lyme disease in the absence of classical clinical symptoms. However, if highly specific serologic tests can be developed it will be imperative to do prospective longitudinal studies to evaluate the potential benefit of antibiotic therapy in persons who are seropositive but lack classical clinical features of Lyme disease. The accompanying cost-effectiveness analysis [1] indicates that empiric treatment with intravenous antibiotics of patients with nonspecific chronic fatigue or myalgia on the basis of positive serologic results alone will result in many more instances of antibiotic toxicity than cures of atypically symptomatic true Lyme disease. In addition, prolonged parenteral therapy can cost as much as $5000 per 2- to 4-week course.

Effective parenteral antibiotic regimens benefit patients with cutaneous, neurologic, cardiac, or joint features of Lyme disease. However, in patients whose only evidence for Lyme disease is a positive immunologic test, the risks for empiric, intravenous antibiotic treatment outweigh the benefits.