COMMENTARY

PCR for Diagnosis of Lyme Disease: Is It Useful?

Christina A. Nelson, MD, MPH

Disclosures

June 11, 2012

Editorial Collaboration

Medscape &

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Hello. I am Dr. Christina Nelson, Medical Officer in the Bacterial Diseases Branch of CDC's Division of Vector-Borne Disease. I'm pleased to speak with you today as part of the CDC Expert Commentary Series on Medscape about the appropriate use of polymerase chain reaction assays (PCR) in the clinical diagnosis and management of Lyme disease.

PCR-based assays are being used more often in clinical settings, and they have several distinct advantages over serology. They detect the presence of infectious agents directly and can be highly sensitive. Unlike serology, they don't rely on the development of antibodies, which can take several weeks. Nevertheless, PCR testing has limitations as well. For example, DNA testing does not distinguish between living and dead organisms, and laboratory contamination with amplified DNA poses a risk for false-positive results. This leads to the question. is PCR useful for the diagnosis of Lyme disease? In general, the answer is no.

Borrelia burgdorferi, the spirochete that causes Lyme disease, concentrates in collagen-rich connective tissues. Although spirochetes initially disseminate from the site of an infected tick bite via the blood, the bloodborne phase is relatively brief and the concentration of spirochetes is quite low. In fact, PCR detects Borrelia DNA in the blood of fewer than half of patients in the early acute stage of disease when the erythema migrans rash is present. By the time symptoms of Lyme disease have been present for a month or more, spirochetes can no longer be found in blood. Similarly, PCR testing of cerebral spinal fluid (CSF) specimens is not clinically useful. PCR testing of CSF is positive in only about one third of US patients with early neuroborreliosis, and it is even less sensitive in patients with late neurologic disease. Urine is not a suitable sample for PCR testing at any stage of Lyme disease.

Borrelia burgdorferi can be detected by PCR in biopsy samples of infected skin, synovial tissue, or synovial fluid. These tissues are sometimes tested as part of a research study or to assess treatment response in a patient with previously confirmed Lyme arthritis. However, skin biopsy is not generally recommended because patients with erythema migrans can be reasonably diagnosed and treated on the basis of history and clinical signs alone. The utility of testing synovial fluid is not well established and should be considered only under special circumstances.

In view of these limitations, it is perhaps not surprising that there are no PCR-based assays for the diagnosis of Lyme disease currently cleared by the US Food and Drug Administration. Two-tiered serology remains the mainstay of laboratory testing for Lyme disease. For more information on 2-tiered testing for Lyme disease, please visit www.cdc.gov/Lyme. Remember that a diagnosis of Lyme disease should be made after evaluation of a patient's clinical presentation and risk for exposure to infected ticks, and, if indicated, after the use of validated laboratory tests. Thank you.

Related Resources

Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme borreliosis. Clin Microbiol Rev. 2005;18:484-509.

CDC. Notice to readers: Caution regarding testing for Lyme disease. MMWR, Morb Mortal Wkly Rep. 2005;54:125.

CDC. Notice to Readers Recommendations for Test Performance and Interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep.1995;44:590-591.

CDC: Two-Tiered Testing Decision Tree

CDC: Lyme Disease -- Understanding Test Results

Li X, McHugh GA, Damle N, Sikand VK, Glickstein L, Steere AC. Burden and Viability of Borrelia burgdorferi in skin and joints of patients with erythema migrans or Lyme arthritis. Arthritis Rheum. 2011;63:2238-2247.

Christina A. Nelson, MD, MPH , is a medical officer with the US Centers for Disease Control and Prevention, Division of Vector-Borne Diseases, in Fort Collins, Colorado. Her work involves epidemiologic research, prevention, and education related to Lyme disease, bartonellosis, and other infectious diseases. Dr. Nelson holds a medical degree from Case Western Reserve University School of Medicine and a master's degree in public health from the Colorado School of Public Health. She is board certified in both pediatrics and preventive medicine/public health.

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