When is serologic testing for Lyme disease (Lyme borreliosis) indicated?

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Last updated: April 21, 2025View editorial policy

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From the Guidelines

Testing for Lyme disease is indicated when a patient presents with symptoms consistent with the infection and has a history of potential exposure to infected ticks, particularly in endemic areas, as recommended by the 2020 guidelines for the prevention, diagnosis, and treatment of Lyme disease 1.

Indications for Testing

  • Patients with the characteristic erythema migrans rash (a bull's-eye pattern expanding from the tick bite) should be considered for testing, especially in endemic areas.
  • Other indications include unexplained fever, fatigue, headache, muscle and joint aches, and swollen lymph nodes following potential tick exposure.
  • For later stages of infection, testing is warranted when patients develop neurological symptoms (such as facial palsy or meningitis), cardiac abnormalities (particularly heart block), or arthritis affecting large joints, especially the knee.

Diagnostic Approach

  • The standard testing approach involves a two-tier process: first, an enzyme immunoassay (EIA) or immunofluorescence assay (IFA), followed by a Western blot test if the first test is positive or equivocal, as recommended by the Infectious Diseases Society of America 1.
  • Testing is most reliable several weeks after infection when antibodies have had time to develop, as early testing may yield false negatives.

Considerations

  • In patients with a lesion consistent with erythema migrans and a history of potential exposure to infected ticks in endemic areas, clinical diagnosis rather than laboratory testing is recommended, according to the 2020 guidelines 1.
  • For patients with atypical skin lesions, antibody testing performed on an acute-phase serum sample (followed by a convalescent-phase serum sample if the initial result is negative) is suggested, rather than direct detection methods such as PCR or culture 1.
  • In endemic regions like the northeastern United States, testing should be considered more readily during tick season (spring through fall) when the risk of exposure is highest.

From the Research

Indications for Testing Lyme Disease

The following are indications for testing Lyme disease:

  • Residents of the coastal Northeast, northwest California, and the Great Lakes region are at highest risk 2
  • Children and those spending extended time outdoors in wooded areas are also at increased risk 2
  • Patients with a possible or confirmed recent tick bite and skin lesions suggestive of erythema migrans 3
  • Patients with symptoms such as fever, malaise, fatigue, headache, myalgias, and arthralgias, especially if they have recently spent time outdoors in areas where Lyme disease is common 2
  • Patients with neurologic manifestations (neuropathy or encephalopathy) 2
  • Patients with intermittent swelling and pain of one or more joints (especially knees) 2

Clinical Presentation and Diagnosis

Lyme disease can be diagnosed clinically, based on the presence of erythema migrans and other symptoms 2, 3

  • Serological tests are not useful in the early stages of the infection, but may be helpful in later stages 3, 4
  • Western blot and enzyme-linked immunosorbent assays can be used to assist in the diagnosis of Lyme disease, especially in cases where the clinical presentation is unclear 4

Treatment and Prophylaxis

Treatment with antibiotics such as doxycycline, amoxicillin, or cefuroxime axetil is usually effective in preventing the progression of Lyme disease 2, 3, 5, 6

  • Single-dose doxycycline (200 mg orally) can be used as prophylaxis in selected patients 2
  • Routine antibiotic prophylaxis is not justified after a tick bite, even in an endemic area, as the risk of infection is low 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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