CurrentMolina HealthcarePolicy G2143

Lyme Disease Testing — Coverage Criteria

Coverage and clinical guidance for laboratory testing for Lyme disease (Borrelia burgdorferi) including serologic two-tier and molecular methods, for Molina Healthcare members in North Carolina.

Policy Summary

PayerMolina Healthcare

PolicyLyme Disease Testing — Coverage Criteria

Policy CodePolicy G2143

Change TypeTechnical review — no material coverage changes

Effective DateJul 1, 2025

Next Review DateN/A

Key ActionOrder two-tier serologic testing (EIA/IFA then confirmatory immunoblot or FDA-cleared second EIA) only for patients with compatible symptoms and epidemiologic exposure; document clinical indications.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2-tier serologyrecommended testing strategy

Not coverednucleic acid detection techniques

Not coveredtesting the removed tick

63,000+reported to CDC (2022)

0coverage changes required

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Coverage Criteria for Lyme Disease Testing

Covered indications (serologic testing)

Covered when ALL of the following are met (two-tier serologic testing):

Primary criteria: Serologic testing using a 2-tier strategy (sensitive EIA or IFA first-step, followed by western immunoblot or an FDA-cleared second EIA) is covered for individuals with symptoms of Lyme disease and a history of travel to or residence in a Lyme-endemic region (with or without a known tick bite).

Supported by CDC two-step recommendation and policy statement.

Specific clinical presentations where testing meets criteria: Testing meets coverage for patients with a history of travel to an endemic region who present with acute myocarditis or pericarditis of unknown cause; meningitis, encephalitis, or myelitis; painful radiculoneuritis; mononeuropathy multiplex (including confluent mononeuropathy multiplex); or acute cranial neuropathy.

Each listed condition is sufficient when paired with travel/residence in an endemic area.

Not medically necessary / Not covered

Not covered (serologic testing and other methods) in the following situations:

Explicit noncovered scenarios: Serologic testing and other Borrelia detection methods do NOT meet coverage for: individuals with erythema migrans (EM); asymptomatic screening of persons living in endemic areas; individuals with only nonspecific symptoms (e.g., fatigue, myalgias/arthralgias); patients with amyotrophic lateral sclerosis, relapsing-remitting multiple sclerosis, Parkinson's disease, dementia/cognitive decline or new-onset seizures, or psychiatric illness; detection of Borrelia burgdorferi by nucleic acid identification techniques (direct or amplified probe); repeat serologic testing for individuals who previously tested positive; testing of a removed tick; and all other Borrelia tests not described as covered (including proprietary or unvalidated assays).

Policy lists these as DO NOT MEET COVERAGE CRITERIA.

Covered when guidelines-based indications and testing sequence are followed

Coverage aligns with clinical guidelines recommending testing only in appropriate clinical contexts and using two-tier algorithms.

Two-tier algorithm: Perform an initial EIA or IFA. If the first-step result is negative, no further testing is indicated. If the first-step result is positive or equivocal, perform a confirmatory immunoblot (western blot) or an FDA-cleared EIA second-tier test (modified two-tier testing when FDA-cleared).

CDC, AAP and guideline statements endorse this sequence and accept FDA-cleared EIA second-tier alternatives.

Clinical indications for testing: Test patients who have clinical syndromes compatible with Lyme disease and epidemiologic exposure (for example: neurologic syndromes such as meningitis, painful radiculoneuritis, mononeuropathy multiplex, acute cranial neuropathies; acute myocarditis/pericarditis in an appropriate setting; Lyme arthritis) as recommended by CDC/IDSA/AAP/NICE. Note: erythema migrans is diagnosed clinically and does not require laboratory testing.

Guidelines recommend testing only with compatible clinical presentation plus plausible geographic exposure.

CSF testing for neuroborreliosis: When CSF testing is performed for suspected Lyme neuroborreliosis involving the CNS, obtain simultaneous CSF and serum samples to determine the CSF:serum antibody index using validated methods; do not rely on routine CSF or serum PCR or culture for diagnosis.

The policy excludes testing of the removed tick and certain proprietary or non‑standard assays because these approaches lack sufficient validation and do not reliably inform clinical management. Specifically, testing the removed tick for Borrelia burgdorferi DOES NOT MEET COVERAGE CRITERIA, and urine‑based antigen tests and other proprietary assays that have not been widely validated (for example, some commercial urine tests and non‑FDA‑cleared antibody panels) are not covered due to insufficient published scientific evidence of clinical utility.

Routine testing of asymptomatic individuals after an Ixodes spp. tick bite is not supported and may be denied; the CDC explicitly recommends against testing asymptomatic patients following an Ixodes tick bite. The policy also does not cover routine screening of asymptomatic persons living in endemic areas or testing in the absence of clinical or epidemiologic evidence of disease.

A literature review accompanying the policy update identified no evidence requiring changes to the established coverage criteria. No modifications to coverage criteria were necessitated by the literature review, and existing exclusions and indications remain in effect.

Repeat serologic testing for individuals who previously tested positive is not medically necessary and DOES NOT MEET COVERAGE CRITERIA. The AAP and other guideline sources note that antibodies may persist for years after infection and repeat antibody testing does not distinguish cure from prior exposure, so serial serologies in previously seropositive individuals should not be used to assess treatment success.

The policy does not support routine Lyme testing as a workup for chronic neurologic disorders or other non‑specific presentations without supporting clinical or epidemiologic evidence. Examples explicitly listed as not meeting coverage include typical amyotrophic lateral sclerosis, relapsing‑remitting multiple sclerosis, Parkinson’s disease, dementia or cognitive decline, new‑onset seizures, psychiatric illness, and nonspecific MRI white matter changes; testing in these scenarios is recommended against and considered not medically necessary.

No additional not‑medically‑necessary conditions were added as a result of the most recent evidence review. The literature review did not identify new scenarios requiring denial or expansion of the existing not‑medically‑necessary list; current exclusions remain unchanged.

Procedure and Billing Codes

Applicable CPT/HCPCS procedure codesmixed

No codes listed

Applicable CPT/HCPCS/Proprietary procedure codesmixed

86617	Antibody; Borrelia burgdorferi (Lyme disease) confirmatory test (e.g., Western Blot or immunoblot)
86618	Antibody; Borrelia burgdorferi (Lyme disease)
87475	Infectious agent detection by nucleic acid (DNA or RNA); Borrelia burgdorferi, direct probe technique
87476	Infectious agent detection by nucleic acid (DNA or RNA); Borrelia burgdorferi, amplified probe technique
0041U	Borrelia burgdorferi, antibody detection of 5 recombinant protein groups, by immunoblot, IgM (Lyme ImmunoBlot IgM) - IGeneX Inc.
0042U	Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG (Lyme ImmunoBlots IgG) - IGeneX Inc.
0316U	Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine (Lyme Borrelia Nanotrap® Urine Antigen Test) - Galaxy Diagnostics Inc.

Provider Actions, Documentation, and Prior Authorization

Prior Authorization

Prior authorization requirements for Lyme disease testing remain unchanged following the most recent literature review. Providers should follow existing payer rules for prior authorization where applicable.

Prior authorization unchanged — no changes to prior authorization requirements following review.
Procedure codes may require prior authorization per payer rules (see Applicable CPT/HCPCS Procedure Codes).

Documentation Required

Documentation Requirements

Documentation must support the presence of signs or symptoms consistent with Lyme disease and epidemiologic exposure (residence in or travel to a Lyme-endemic region, with or without a reported tick bite) when ordering serologic testing.

Document clinical signs/symptoms (e.g., erythema migrans is a clinical diagnosis and testing is not indicated).
Document travel/residence in an endemic area or plausible tick exposure when ordering tests.

Background on Lyme Disease

Lyme disease is a tick‑borne multisystem infection in North America most commonly caused by Borrelia burgdorferi. Early disease often presents with erythema migrans and nonspecific systemic symptoms (fever, malaise, myalgias), while disseminated infection can affect the heart, joints, and nervous system. Because direct detection methods have limited sensitivity in routine clinical practice, laboratory confirmation primarily relies on serologic testing using a two‑tier strategy (initial EIA/IFA screening followed by confirmatory immunoblot or FDA‑cleared second‑tier EIA when indicated). Clinical diagnosis of classic erythema migrans should be made without laboratory testing.

Definitions and Testing Terminology

First-step serologic test — EIA or IFA.

DefinitionFirst-step serologic test = EIA (enzyme immunoassay) or IFA (immunofluorescence assay).

PurposeInitial screening for antibodies to Borrelia burgdorferi in blood; negative first-step requires no further testing.

When usedPerform as the first tier in the two-step diagnostic algorithm for patients with compatible symptoms and epidemiologic exposure.

NotesEIA/IFA results that are positive or equivocal require a confirmatory second-step test (immunoblot or FDA-cleared second EIA).

Second-step serologic test — Immunoblot (western blot) or FDA-cleared second EIA.

DefinitionSecond-step serologic test = immunoblot (commonly western blot) or an FDA-cleared second EIA used to confirm a positive or equivocal first-step result.

Revision History and Evidence Updates

07/01/2025policy_reviewLatest

Reviewed and updated background, guidelines and recommendations, and evidence-based references supporting the policy (no changes required to coverage criteria).

08/16/2019guideline_update_cdc

CDC published updated recommendations endorsing a two-step serologic testing process for Lyme disease (EIA/IFA followed by confirmatory testing).

2021

Policy Summary

PayerMolina Healthcare

PolicyLyme Disease Testing — Coverage Criteria

Policy CodePolicy G2143

Change TypeTechnical review — no material coverage changes

Effective DateJul 1, 2025

Next Review DateN/A

SourceLink

On This Page

CDC recommends paired samples and measurement of CSF:serum antibody index and advises against routine PCR/culture.

Claims for testing of asymptomatic individuals or for non-indicated uses (including routine screening after tick bite without symptoms) will be denied.

Note

Two-Tier Serologic Testing Requirement

Two-tier serologic testing is the required diagnostic pathway for covered Lyme disease serologic testing: a sensitive first-tier EIA or IFA, followed by a confirmatory western immunoblot or an FDA-cleared second EIA (modified two-tier testing) when the first-tier result is positive or equivocal.

First-tier: EIA (enzyme immunoassay) or IFA (immunofluorescence assay).
If first-tier is negative: no further testing of that specimen is recommended.
If first-tier is positive or equivocal: perform second-tier confirmatory testing using western immunoblot or FDA-cleared second EIA (modified two-tier algorithm).
Testing algorithms that deviate from the two-tier approach are not supported for coverage.

Documentation Required

Specimen Pairing and Test Sequence for Neuroborreliosis

When testing cerebrospinal fluid (CSF) for suspected Lyme neuroborreliosis, obtain simultaneous CSF and serum samples and measure the CSF:serum antibody index as part of validated laboratory methodology. Routine PCR or culture of CSF/serum is not recommended.

Obtain paired CSF and serum samples for CSF:serum antibody index determination.
Do not rely on CSF serology without measurement of CSF:serum antibody index.
Routine PCR or culture of CSF or serum is not recommended for diagnosis.

Note

Literature Review and Evidence Update

The literature review updated evidence-based scientific references and provided supporting guidance, but did not necessitate changes to coverage criteria. Providers should document clinical indications consistent with the cited guidance when ordering tests.

Updated references include CDC, IDSA/AAN/ACR, AAP, and recent peer-reviewed studies.
No modifications to coverage criteria were required based on the literature review.
Providers should reference current guidelines when determining the appropriateness of testing.

Denial Risk

Denial Risks / Noncovered Testing

Testing that does not meet clinical indications — including testing of asymptomatic individuals, testing solely for erythema migrans, repeat serologic testing after prior positive results, testing of removed ticks, or use of direct nucleic acid detection techniques for routine diagnosis — will be considered noncovered and may be denied.

Claims for serologic testing will be denied for screening of asymptomatic individuals, testing of erythema migrans cases, or other non-indicated uses.
Detection of B. burgdorferi by nucleic acid techniques (PCR/direct probe) does not meet coverage criteria for routine diagnosis.
Repeat serologic testing after a previous positive result does not meet coverage criteria.

PurposeConfirmatory testing to improve specificity after a positive or equivocal EIA/IFA first-step.

Usage constraintDo not perform immunoblot without a prior positive or equivocal EIA/IFA, as specificity is reduced if used alone.

Regulatory noteFDA-cleared EIA assays may be accepted as the second-tier alternative when cleared for this purpose.

Two-tier testing / Modified two-tier testing (MTTT) — definition of algorithm

DefinitionTwo-tier testing (standard): initial EIA or IFA screening; if negative, no further testing; if positive or equivocal, perform a confirmatory immunoblot (western blot).

Modified two-tier testing (MTTT)An FDA-cleared EIA may be used as the second-tier confirmatory test in place of immunoblot when cleared by FDA.

Key principleResults are considered positive only if both first- and second-tier tests meet positivity criteria.

ImplementationBoth steps can be performed on the same blood sample per CDC guidance.

CSF:serum antibody index — paired CSF and serum testing to assess intrathecal antibody production for suspected neuroborreliosis.

DefinitionCSF:serum antibody index = assessment using simultaneous cerebrospinal fluid and serum samples to determine intrathecal antibody production for suspected neuroborreliosis.

RecommendationObtain paired CSF and serum samples; laboratories should use validated methodology to calculate the CSF:serum antibody index.

Tests to avoidCDC recommends against CSF serology without measuring the CSF:serum antibody index and recommends against routine CSF or serum PCR/culture for Lyme disease.

Clinical contextUse when evaluating patients with suspected Lyme neuroborreliosis involving the central nervous system (e.g., meningitis, radiculoneuritis, cranial neuropathies).

IDSA/ACR/AAN Guidelines — reference to clinical practice guidelines for Lyme disease prevention, diagnosis, and treatment.

Documented guideline setIDSA, AAN, and ACR clinical practice guidelines: 2020 guidelines for prevention, diagnosis, and treatment of Lyme disease (Clinical Infectious Diseases 2021).

CDC roleCDC recommends the two-step serologic testing process (EIA/IFA first, then immunoblot or FDA-cleared EIA as second-tier when applicable).

Clinical applicationGuidelines support testing only in patients with compatible clinical syndromes and epidemiologic exposure; erythema migrans is diagnosed clinically without lab testing.

Reference examplesCDC 2-step recommendations and FDA clearance requirement for new tests; IDSA/AAN/ACR guidelines cited as primary clinical practice guidance in the policy.

guideline_publication_idsa_acr_aan

IDSA/ACR/AAN clinical practice guidelines for prevention, diagnosis, and treatment of Lyme disease were published to inform testing and management recommendations referenced by the policy.

07/10/2019guideline_update_nice

NICE updated Lyme disease guidance and quality standards, including recommendations to diagnose erythema migrans clinically without laboratory testing.