Review

Appropriate laboratory testing in Lyme disease

Teny M. John, MD and Alan J. Taege, MD
Cleveland Clinic Journal of Medicine November 2019, 86 (11) 751-759; DOI: https://doi.org/10.3949/ccjm.86a.19029

Article Figures & Data

Figures

  • Figure 1
    Figure 1

    Ixodes scapularis is the vector of Lyme disease in the eastern United States. Infected nymphs account for most cases.

    From Sigal LH. Myths and facts about Lyme disease. Cleve Clin J Med 1997; 64(4):203–209. doi:10.3949/ccjm.64.4.203

  • Figure 2
    Figure 2

    Positive Western blot test (Borrelia B31 ViraStripe [Viramed Diagnostics]) in a patient who presented with rash and arthritis. This test uses purified specific antigens of strain B31 of Borrelia burgdorferi sensu stricto. Note that the patient has 3 of 3 IgM bands and 10 of 10 IgG bands (arrows).

  • Figure 3
    Figure 3

    Standard 2-tier testing for Lyme disease. Ig = immunoglobulin.

Tables

  • TABLE 1

    US states with the highest average incidence of Lyme disease, 2015–2017

    StateConfirmed cases per 100,000 persons
    1 Maine89.2
    2 Vermont86.7
    3 Pennsylvania66.7
    4 Rhode Island53.4
    5 New Hampshire51.9
    6 Connecticut41.8
    7 New Jersey40.5
    8 Delaware40.0
    9 Wisconsin26.6
    10 Minnesota23.4
    11 Maryland20.6
    12 Massachusetts16.6
    13 New York15.8
    14 Virginia12.3
    15 Washington, DC10.1

    • Data from reference 2.

  • TABLE 2

    Diagnostic testing methods in Lyme disease

    Direct methods
    Borrelia culture
    Polymerase chain reaction
    Indirect methods
    Immunofluorescent assay
    Enzyme-linked immunosorbent assay
    Western blot
  • TABLE 3

    Causes of false-positive enzyme-linked immunosorbent assay testing for Lyme disease

    Infections
    Bacterial infection
     Infective endocarditis
      Other borrelial disease (eg, relapsing fever)
      Other spirochetal infection (eg, syphilis, leptospirosis)
    Viral infection
      Epstein-Barr virus (polyclonal antibody production)
    Parasitic infection
      Malaria (polyclonal antibody production)
    Noninfectious causes
    Autoimmune conditions
      Systemic lupus erythematosus
      Rheumatoid arthritis
  • TABLE 4

    Interpretation of the Western blot test in the diagnosis of Lyme disease

    AntibodyAntigen (molecular mass)Positive test
    Immunoglobulin MOspC (24 kDa)a2 of 3 bands
    BmpA (39 kDa)
    Fla (41 kDa)
    Immunoglobulin GOspC (18, 21 kDa)b5 of 10 bands
    BmpA (28, 30, 39 kDa)
    Fla (41, 45, 58, 66, 93 kDa)

    • ↵a The apparent molecular mass of OspC depends on the strain of Borrelia burgdorferi being tested. The 24 and 21 kDa proteins are the same.

    • Based on information in reference 16.

  • TABLE 5

    Recommended tests in different stages of infection

    Stage of illnessClinical featuresPrimary testing recommendedAdditional testing
    Stage 1Early localized disease
    (< 4 weeks)
    Erythema migrans    		No serologic testing
    Stage 2Early disseminated disease
    Lymphocytic meningitis Facial palsy
    Radiculoneuropathy or carditis    		Two-tiered testing
    If initial test is negative, useacute and convalescent phase serology
    Stage 3Late Lyme disease (> 4 weeks)
    Lyme arthritis    		Two-tiered testingSynovial fluid polymerase chain reaction (PCR) if no improvement after 2 months of oral antibiotics
    Lyme neuroborreliosisCerebrospinal fluid (CSF) anti-bodies and 2-tiered testingCSF PCR or CSF culture
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