What are the diagnostic tests for Lyme disease (Lyme borreliosis)?

From the Guidelines

Lyme disease testing should be performed using a two-step process, starting with an enzyme immunoassay (EIA) or immunofluorescence assay (IFA), followed by a Western blot test if the initial result is positive or equivocal, as recommended by the Infectious Diseases Society of America (IDSA) in 2021 1. This approach is supported by the most recent and highest quality study, which emphasizes the importance of proper interpretation of test results in the context of clinical symptoms and potential tick exposure in endemic areas.

• The two-step testing process increases accuracy by reducing false positives, with a specificity of >95% during all stages of the disease 1.
• Testing should be considered for patients with symptoms consistent with Lyme disease, such as erythema migrans rash, fever, fatigue, headache, and joint pain, and a history of potential tick exposure in endemic areas.
• It's essential to note that antibodies may not be detectable in early infection (first few weeks), potentially leading to false negatives if testing is done too early.
• In cases where a characteristic erythema migrans rash is present, treatment can begin without waiting for test results, as recommended by the IDSA in 2021 1.
• For suspected early Lyme disease, doxycycline (100mg twice daily for 10-14 days) is the standard treatment for adults, with alternative antibiotics including amoxicillin or cefuroxime for those who cannot take doxycycline.
• Testing for co-infections may be warranted, as ticks can transmit multiple pathogens simultaneously, and follow-up testing after treatment is generally not recommended, as antibodies can persist for months or years after successful treatment 1.

From the Research

Lyme Disease Testing

• Lyme disease is typically diagnosed clinically, with laboratory tests used as adjuncts to confirm the diagnosis 2, 3
• The most common laboratory tests used to diagnose Lyme disease include:
  • Enzyme-linked immunosorbent assays (ELISAs) with recombinant antigens 4
  • Western blot analyses with whole cells of Borrelia burgdorferi 5, 4
  • Polymerase chain reaction (PCR) assays, although these are not typically used for routine diagnosis 6
• The diagnosis of Lyme disease is based on a combination of clinical manifestations, such as erythema migrans, fever, and arthritis, and laboratory test results 2, 3
• The Western blot technique is used to analyze the humoral immune response in Lyme borreliosis and is used as a serodiagnostic confirmation test 5
• Interpretation criteria for blot positivity in early-stage borreliosis are primarily based on the presence of the 21 kDa band and the semiquantitatively recorded intensity of the 41 kDa band 5
• In the diagnosis of late-stage infection, blot positivity relies on the presence of the 94 kDa, 39 kDa, 31 kDa, 30 kDa and 21 kDa bands 5

Testing for Lyme Disease

• ELISAs with recombinant antigens can be used to detect IgM and IgG antibodies to Borrelia burgdorferi 4
• The most important immunodominant proteins of Borrelia burgdorferi include the 94 kDa, 60 kDa, 41 kDa, 34 kDa, 31 kDa, 30 kDa, 21 kDa, and 17/18 kDa proteins 5
• Antibodies against the 94 kDa, 31 kDa, and 21 kDa proteins are largely species-specific 5
• The early immune response in Lyme borreliosis is triggered mainly by the flagellin 5
• In the later stage, a wide range of immunogenic proteins is involved, with the 94 kDa antigen being the best marker for late immune response 5