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Laboratory Evaluation in the Diagnosis of Lyme Disease

Peter Tugwell, MD; David T. Dennis, MD; Arthur Weinstein, MD; George Wells, PhD; Beverley Shea, BScN; Graham Nichol, MD; Robert Hayward, MD; Robert Lightfoot, MD; Philip Baker, BSc; and Allen C. Steere, MD
[+] Article and Author Information

From the University of Ottawa, Ottawa, Ontario, Canada; Centers for Disease Control and Prevention, Fort Collins, Colorado; New York Medical College, Valhalla, New York; New England Medical Center, Boston, Massachusetts; and McMaster University Medical Centre, Hamilton, Ontario, Canada. Acknowledgment: The authors thank Diane Gagnon for support in preparing this manuscript. Requests for Reprints: Peter Tugwell, MD, Department of Medicine, Ottawa General Hospital, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. Current Author Addresses: Dr. Tugwell: Department of Medicine, University of Ottawa and Ottawa General Hospital, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(12):1109-1123. doi:10.7326/0003-4819-127-12-199712150-00011
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Purpose: To provide a quantitative and qualitative evaluation of the predictive value of the laboratory diagnosis of Lyme disease and to use the resultant data to formulate guidelines for clinical diagnosis.

Data Sources: A MEDLINE search of English-language articles or articles with English-language abstracts published from 1982 to 1996.

Data Extraction: Sensitivity, specificity, and likelihood ratios were calculated, and a random-effects model was used to combine the proportions from the eligible studies. Prespecified criteria were used to determine which studies were eligible for analysis.

Data Synthesis: Laboratory testing in general is not clinically useful if the pretest probability of Lyme disease is less than 0.20 or greater than 0.80. When the pretest probability is 0.20 to 0.80, sequential testing with enzyme-linked immunosorbent assay and Western blot is the most accurate method for ruling in or ruling out the possibility of Lyme disease.

Conclusions: Laboratory testing is recommended only in patients whose pretest probability of Lyme disease is 0.20 to 0.80. If the pretest probability is less than 0.20, testing will result in more false-positive results than true-positive results; a negative test result in this situation effectively rules out the disease.

Figures

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Figure 1.
Rates of Lyme disease cases in the United States in 1993 as reported by states to the Centers for Disease Control and Prevention.[28]

Shown by endemic county. Counties with rates less than 5 per 100 000 or with fewer than five cases reported are not highlighted. Rates in highly endemic counties ranged from 30 per 100 000 to more than 400 per 100 000 .

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Figure 2.
Scenario A: utility of enzyme-linked immunosorbent assay (ELISA) in patients with nonspecific myalgia.leftright

A nomogram is used to calculate the post-test probability from the pretest probability as follows. The nomogram expresses probability as a percentage, as modified from the method of Sackett and colleagues. For a patient with an 0.001 pretest probability of Lyme disease, the straight edge was anchored at 0.001 on the pretest column of the nomogram. Because the likelihood ratio (represented by the center line) for a positive ELISA result was 5.0 ( ), the straight edge was directed through the central column at 5. The post-test probability was then read as 0.004 from the post-test column of the nomogram. The post-test probability can also be calculated for pretest probabilities of 0.01 and 0.03. For a probability of 0.0001, the post-test probability cannot be calculated from this nomogram. For a patient with an 0.01 pretest probability of Lyme disease, the straight edge was anchored at 0.01 on the pretest column of the nomogram. Because the likelihood ratio for a positive ELISA result was 5.0, the straight edge was directed through the central column at 5. The post-test probability was then read as 0.04 from the post-test column of the nomogram. For a patient with an 0.03 pretest probability of Lyme disease, the straight edge was anchored at 0.03 on the pretest column of the nomogram. Because the likelihood ratio for a positive ELISA result was 5.0, the straight edge was directed through the central column at 5. The post-test probability was then read as 0.13 from the post-test column of the nomogram. For a negative ELISA result, the likelihood ratio is 0.06 ( ). The procedure is the same as that for a positive result. For a patient with an 0.03 pretest probability of Lyme disease, the straight edge was anchored at 0.03 on the pretest column of the nomogram and the straight edge was directed through the central column at 0.06. The post-test probability was then read as 0.0015. The 0.01 (moderate) and 0.001 (low) pretest probabilities reduce to less than 1 in 1000; these probabilities are so low that it is not important to have a precise estimate.

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Figure 3.
Scenario B: utility of enzyme-linked immunosorbent assay (ELISA) in patients with possible erythema migrans.

A nomogram is used to calculate the post-test probability from the pretest probability as follows. The nomogram expresses probability as a percentage, as modified from the method of Sackett and colleagues. For a patient with an 0.80 pretest probability of Lyme disease, the straight edge was anchored at 0.80 on the pretest column of the nomogram. Because the likelihood ratio (represented by the center line) for a positive ELISA result was 0.80, the straight edge was directed through the central column at 8. The post-test probability was then read as 0.98 from the post-test column of the nomogram. Conversely, because the likelihood ratio for a negative ELISA result was 0.44, the post-test probability was read as 0.63.

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Figure 4.
Scenario C: utility of enzyme-linked immunosorbent assay (ELISA) in patients who have arthritis and a 0.

50 pretest probability of Lyme disease. A nomogram is used to calculate the post-test probability from the pretest probability as follows. The nomogram expresses probability as a percentage, as modified from the method of Sackett and colleagues. The likelihood ratio (represented by the center line) was approximately 1000 for the clinical signs and symptoms present in the patient in scenario C. If the cutoff for a positive ELISA result is increased to at least 3 SDs above controls, the likelihood ratio increases to 19.5 and the post-test probability can then be read as 0.95. For a patient with an 0.50 pretest probability of Lyme disease, the straight edge was anchored at 0.50 on the pretest column of the nomogram. Because the likelihood ratio for a positive ELISA result was 5.0, the straight edge was directed through the central column at 5. The post-test probability was read as 0.83 from the post-test column of the nomogram. Conversely, because the likelihood ratio for a negative ELISA result was 0.06, the post-test probability was read as 0.06.

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Figure 5.
Utility of the Western blot for indeterminate enzyme-linked immunosorbent assay (ELISA) results.

A nomogram is used to calculate the post-test probability from the pretest probability as follows. The nomogram expresses probability as a percentage, as modified from the method of Sackett and colleagues. For a patient with an 0.50 pretest probability of Lyme disease, the straight edge was anchored at 0.50 on the pretest column of the nomogram. Because the likelihood ratio (represented by the center line) for a positive ELISA result was 0.20, the straight edge was directed through the central column at 0.20. The post-test probability was then read as 0.95. If the ELISA result is indeterminant, the likelihood ratio is 1.05 and the post-test probability is 0.51. If 0.51 is now the pretest probability and Western blot has a positive result, the likelihood ratio is 11.7. This yields a post-test probability of 0.92.

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