RSS Feeds
Guidelines for the Clinical Diagnosis of Lyme Disease
- Peter Tugwell, MD, MSc;
- Allen Steere, MD; and
- Arthur Weinstein, MD
- Ottawa General Hospital; Ottawa, Ontario K1H 8L6, Canada New England Medical Center; Boston, MA 02111 New York Medical College; Valhalla, NY 10595
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
IN RESPONSE:
Dr. Liegner and Ms. Kochevar and Dr. McCaulley raise the issue of the frequency and implications of false-negative results on laboratory tests in patients with true Lyme disease.
Liegner and Kochevar suggest that such patients may have negative ELISA results but positive or suspicious Western blots, claiming that this differs from the experience with HIV testing. In good laboratories with careful calibration of ELISA, this has not been the case. In these laboratories, ELISA almost always yields positive or indeterminate results in cases of true Lyme disease. Liegner and Kochevar state that the presence of one or two high specific bands may be a vital clue to diagnosis. The problem is that the bands are not completely specific. For example, approximately 25% of normal controls have the 23-kD band. Carefully designed studies with well-characterized patients and appropriate control groups have shown acceptable levels of diagnostic specificity only when multiple bands of specific molecular weights are required for diagnosis.
We disagree that withholding empirical treatment from seronegative patients with suspected Lyme disease will cause “incalculable, irreversible neurologic injury.” With attenuated antibody response, the disease itself is also attenuated and tends to respond rapidly to antibiotics at whatever stage therapy is given.
Dr. McCaulley refers to Shadick and colleagues' article. It is true that this study is unclear about which patients were asymptomatic and which were symptomatic, and it is difficult to distinguish between those with active disease and those with positive serologic results who no longer had active infections. This study included patients with several nonspecific symptoms, including those consistent with the chronic fatigue syndrome. This case–control study lacked the rigor of a longitudinal cohort design. Furthermore, the criteria for the ELISA and Western blot used differed from those proposed and evaluated in our papers and adopted by the Centers for Disease Control and Prevention.
For patients treated for possible Lyme disease, it is difficult to interpret the recurrence within 1 year of fatigue, headache, and difficulty with memory or concentration or the subsequent response to antibiotics. These cases may be relapsed Lyme disease, chronic fatigue syndrome that resolves spontaneously, or chronic fatigue syndrome that improves because of the placebo effect of treatment.
None of Nocton and colleagues' patients were seronegative. Nonetheless, their study and that by Mouristsen and colleagues were both cited by Dr. McCaulley as reporting positive PCR results in a subset of patients with Lyme disease who were seronegative. The PCR assay is extremely sensitive but must be formally tested in well-characterized patients with appropriate controls.
The centers with the most Lyme disease experience have not found that patients with late-stage Lyme disease are frequently seronegative or that vague symptoms are cured by additional antibiotics. On the other hand, patients with true Lyme disease, if given the appropriate antibiotics for the appropriate duration, respond well.
Drs. Blaauw and van der Linden raise concerns about the validity and generalizability of the guidelines. We are aware that several European studies evaluated the probability of Lyme disease in various patient groups. We believe that the biology of Lyme disease is sufficiently different that such studies may not apply to North America. Positive results on Lyme serology occur frequently in Europe without any clinical manifestations, but this is less common in the United States. We recommend that patients without clinical manifestations be neither tested nor treated for Lyme disease. Finally, we recognize that estimation of the prior probability of Lyme disease is difficult. Recurrent oligoarticular inflammatory arthritis is a more typical manifestation of Lyme disease in North American patients than in the European patients cited by Blaauw and van der Linden.
Peter Tugwell, MD, MSc
Ottawa General Hospital; Ottawa, Ontario K1H 8L6, Canada
- Copyright ©2004 by the American College of Physicians
