What are the initial laboratory tests and treatment for suspected Lyme disease?

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From the Guidelines

The initial laboratory testing for suspected Lyme disease includes a two-tier approach with an enzyme immunoassay (EIA) or immunofluorescence assay (IFA) followed by Western blot confirmation if the first test is positive or equivocal. This approach is recommended because it improves specificity while maintaining sensitivity, reducing false positives that would occur with single-test approaches 1.

Key Points for Laboratory Testing:

  • The two-tier testing approach is used for laboratory diagnosis of Lyme disease in the United States.
  • The first tier uses a highly sensitive EIA or IFA.
  • If the result is positive or equivocal, it is followed by a highly specific Western immunoblot as the second-tier test.
  • Western immunoblot was included to increase specificity to >98%, reducing false-positive results produced by the first-tier EIA 1.

Treatment Recommendations:

  • Treatment for early localized Lyme disease (single erythema migrans rash) consists of doxycycline 100 mg twice daily for 10-14 days as first-line therapy for adults.
  • Alternative options include amoxicillin 500 mg three times daily for 14-21 days or cefuroxime axetil 500 mg twice daily for 14-21 days.
  • For children, amoxicillin 50 mg/kg/day divided into three doses (maximum 500 mg per dose) for 14-21 days is preferred, though doxycycline can be used for children of all ages.
  • For patients with early disseminated or late Lyme disease, treatment duration may extend to 14-28 days.
  • Importantly, antibiotic treatment should begin promptly when Lyme disease is suspected clinically, without waiting for laboratory confirmation, as early treatment prevents progression to later stages of disease 1.

Considerations:

  • Patients who have a lesion consistent with erythema migrans and live in or have traveled to Lyme-endemic areas can be given a diagnosis without laboratory testing 1.
  • The presence of erythema migrans, cranial nerve palsy, or papilledema is helpful in differentiating Lyme meningitis from viral meningitis 1.
  • Laboratory assays for the diagnosis of neuroborreliosis are of limited clinical value 1.

From the Research

Initial Laboratory Tests for Suspected Lyme Disease

  • The currently recommended approach for laboratory support of the diagnosis of Lyme disease is a standard two-tiered (STT) algorithm comprised of an enzyme-linked immunoassay (EIA) or immunofluorescence assay (IFA), followed by Western blotting (WB) 2.
  • Modified two-tiered (MTT) algorithms have been shown to improve the sensitivity of the testing in early disease while maintaining high specificity 2.
  • The two-test protocol relies on a sensitive screening test, which is followed by specific immunoglobulin M (IgM) and/or IgG immunoblotting (IB), depending on the date of disease onset 3.

Treatment for Suspected Lyme Disease

  • There is no direct information on treatment for suspected Lyme disease in the provided studies, however, it is mentioned that a reduction in the clinical sensitivity of the two-test protocol was associated with a lack of antibody response or seroconversion in LD patients treated with antibiotics 3.

Serologic Tests for Lyme Disease

  • Tests to determine serum antibody levels, such as the 2-tier sonicate immunoglobulin M (IgM) and immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and Western blot method, or the IgG of the variable major protein-like sequence-expressed (VlsE) sixth invariant region (C6) peptide ELISA method, are the major tests available for support of the diagnosis of Lyme disease 4.
  • Improved serologic testing for early Lyme disease may be achieved by the addition of multiple borrelial antigens that elicit IgM and IgG antibodies early in infection 5.

Laboratory Diagnosis of Lyme Borreliosis

  • Laboratory diagnosis of Lyme borreliosis is performed by direct detection of Borrelia burgdorferi in body fluids and tissue samples, or by serologic testing (indirect detection) 6.
  • Immunofluorescence, hemagglutination, ELISA tests with whole cell antigen should be considered as screening methods, while assays with selected fractions of B. burgdorferi antigens or tests using selected recombinant antigens should be considered as more specific 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Prospective study of serologic tests for lyme disease.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2008

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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