Lyme disease laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2],Ilan Dock, B.S.

Overview

Laboratory blood tests are helpful if used correctly and performed with validated methods. Laboratory tests are not recommended for patients who do not have symptoms typical of Lyme disease. The Centers for Disease Control recommends a two-tier testing protocol for Lyme disease. Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. Currently, PCR is the only means to detect the presence of organism. Identification and testing of the individual tick after removal is generally not useful.

Laboratory Findings

• Lyme disease is diagnosed based on:

1. Signs and symptoms
2. A history of possible exposure to infected blacklegged ticks

• Laboratory blood tests are helpful if used correctly and performed with validated methods.
• Laboratory tests are not recommended for patients who do not have symptoms typical of Lyme disease.
• Just as it is important to correctly diagnose Lyme disease when a patient has it, it is important to avoid misdiagnosis and treatment of Lyme disease when the true cause of the illness is something else.

Serology

Two-step Laboratory Testing Process

• The serological laboratory tests most widely available and employed are the Western blot and ELISA.
• A two-tiered protocol is recommended by the Centers for Disease Control: the more sensitive ELISA is performed first, and if it is positive or equivocal, the more specific Western blot is run. The reliability of testing in diagnosis remains controversial, however studies show the Western blot IgM has a specificity of 94–96% for patients with clinical symptoms of early Lyme disease.
• The two steps of Lyme disease testing are designed to be done together. The CDC does not recommend skipping the first test and just doing the Western blot. Doing so will increase the frequency of false positive results and may lead to misdiagnosis and improper treatment.
• Erroneous test results have been widely reported in both early and late stages of the disease. These errors can be caused by several factors, including antibody cross-reactions from other infections including:
  • Epstein-Barr virus
  • Cytomegalovirus
  • Varicella zoster virus
  • Herpes simplex virus type 2
  • Rickettsial infections
  • Syphilis

The Two-tier Testing Decision Tree describes the steps required to properly test for Lyme disease. The first required test is the Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA). If this test yields negative results, the provider should consider an alternative diagnosis.  Or in cases where the patient has had symptoms for less than or equal to 30 days, the provider may treat the patient and follow up with a convalescent serum. If the first test yields positive or equivocal results, two options are available: 1) if the patient has had symptoms for less than or equal to 30 days, an IgM Western Blot is performed; 2) if the patient has had symptoms for more than 30 days, the IgG Western Blot is performed. The IgM should not be used if the patient has been ill for more than 30 days. - Source: CDC.gov

Polymerase chain reaction

• Polymerase chain reaction (PCR) tests for Lyme disease have also been developed to detect the genetic material (DNA) of the Lyme disease spirochete. PCR tests are rarely susceptible to false-positive results but can often show false-negative results, and the overall reliability of PCR in this role remains unclear.
• With the exception of PCR, there are not currently any practical means for the detection of the presence of the organism, as serologic studies only test for antibodies of Borrelia burgdorferi.
• Immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens: high titers of either antibody indicates disease, but lower titers can be misleading.
• The IgM antibodies may be present after the initial infection for a limited period but IgG antibodies may remain for years after the infection.
• Western blot, ELISA, and PCR can be performed by either blood tests via venipuncture or cerebral spinal fluid (CSF) via lumbar puncture.
• Though lumbar puncture is more definitive of diagnosis, antigen capture in the CSF is much more elusive. Reportedly, CSF yields positive results in only 10-30% of patients cultured.
• The diagnosis of neurologic infection by Borrelia burgdorferi should not be excluded solely on the basis of normal routine CSF or negative CSF antibody analyses.
• New techniques for clinical evaluation of Borrelia burgdorferi infection are under investigation, and includes:
  • Lymphocyte transformation tests
  • Focus floating microscopy
• New research indicates chemokine CXCL13 may also be a possible marker for neuroborreliosis.

Other Types of Laboratory Testing

• Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. These tests include:
  • Capture assays for antigens in urine
  • Culture, immunofluorescence staining, or cell sorting of cell wall-deficient or cystic forms of B. burgdorferi
  • Lymphocyte transformation tests
  • Quantitative CD57 lymphocyte assays
  • Reverse Western blots
  • In-house criteria for interpretation of immunoblots
  • Measurements of antibodies in joint fluid (synovial fluid)
  • IgM or IgG tests without a previous ELISA/EIA/IFA
• In general, the CDC does not recommend these tests.
• Patients are encouraged to ask their physicians whether their testing for Lyme disease was performed using validated methods and whether results were interpreted using appropriate guidelines.

Testing Ticks

• Patients who have removed a tick often wonder if they should have it tested.
• In general, the identification and testing of individual ticks is not useful in deciding if a person should get antibiotics following a tick bite because:
  • If the test shows that the tick contained disease-causing organisms, that does not necessarily mean that the patient was infected.
  • If the patient has been infected, symptoms will probably develop before results of the tick test are available, so appropriate treatment should not be withheld for availability of tick testing results.
  • Negative results can lead to false assurance. For example, the patient may have been unknowingly bitten by a different tick that was infected.

References

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