CurrentCapital BluecrossPolicy AHS - G2143 - Lyme Disease Testing, 1 = Initial

Lyme Disease Testing

Defines coverage criteria and limitations for laboratory testing for Lyme disease (Borrelia burgdorferi) including serologic two-tier testing, modified two-tier testing (MTTT), nucleic acid detection, proprietary tests, and testing of ticks. Applies based on individual benefit coverage and references Medicare/Medicaid regulations.

Policy Summary

PayerCapital Bluecross

PolicyLyme Disease Testing

Policy CodePolicy AHS - G2143 - Lyme Disease Testing, 1 = Initial

Change TypeNo material change

Effective DateFeb 10, 2017

Next Review Date

Key ActionDocument presence of symptoms consistent with Lyme disease and travel/residence in an endemic region and follow the two-tier testing algorithm (EIA/IFA first, then immunoblot or FDA-cleared second EIA) to meet coverage criteria.

POLICY UPDATE CHANGES

No material clinical or coverage changes reported (has_material_change = false).

2-tier serologyPreferred diagnostic method

PCR/nucleic acidNot covered (direct detection)

Tick testingNot covered

MTTTAccepted alternative when FDA-cleared

Procedure codes listed

Coverage Summary

This policy defines coverage criteria and limitations for laboratory testing for Lyme disease (Borrelia burgdorferi), emphasizing that two-tier serology (sensitive EIA/IFA first, followed by western immunoblot or an FDA-cleared second EIA/MTTT) is the preferred diagnostic approach; it also states that nucleic acid/PCR-based testing and testing of ticks are not covered. Applicability of the criteria depends on an individual’s benefit coverage and applicable government (Medicare/Medicaid) policies and regulations.

Key statistics / highlights

Preferred diagnostic method2-tier serology (EIA/IFA first, then immunoblot or FDA-cleared second EIA)

Not covered (direct detection)PCR/nucleic acid detection does not meet coverage

Not coveredTesting of the individual tick

Accepted alternativeMTTT (FDA-cleared second EIA instead of immunoblot)

Procedure codes listed7 (86617, 86618, 87475, 87476, 0041U, 0042U, 0316U)

Medical-Necessity Criteria

Medically Necessary / Meets Coverage Criteria

Covered when ALL of the following are met:

ALL of the following

Individual has symptoms consistent with Lyme disease (e.g., erythema migrans, fever, arthralgia, myalgia, headache, neck stiffness, fatigue) AND a history of travel to or residence in a region endemic for Lyme disease (with or without a history of a tick bite).
Serologic testing is not recommended for patients without symptoms typical of Lyme disease because current assays do not reliably distinguish active from past infection.
Two-tier serologic testing strategy is used: an initial sensitive enzyme immunoassay (EIA) or immunofluorescence assay (IFA), followed by either a western immunoblot assay or an FDA-cleared second EIA (modified two-tier testing, MTTT).
MTTT (FDA-cleared second EIA) is an accepted alternative to traditional western blot second-tier testing; MTTT may improve sensitivity for early infection while maintaining comparable specificity.

Medically Necessary / Meets Coverage Criteria - Specific Presentations

Covered when ANY of the following specific clinical presentations are present in an individual with a history of travel to or residence in a Lyme-endemic region:

Provider Actions & Billing Guidance

Documentation Required

Document symptoms and epidemiologic exposure

Provider must document presence of symptoms consistent with Lyme disease and history of travel to or residence in a Lyme-endemic region to justify serologic testing; coverage depends on individual benefit coverage and applicable government policies.

86618
86617

Billing Rule

Follow two-tier testing algorithm for coverage

Perform EIA/IFA as first-tier; if positive or equivocal, perform confirmatory western immunoblot or FDA-cleared second EIA (MTTT) to meet coverage criteria.

86618
86617

Coding

Covered / Relevant CPT/HCPCS codes (mentioned)CPT|HCPCS|mixed

86617	Antibody; Borrelia burgdorferi (Lyme disease) confirmatory test (eg, 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 (IGeneX Lyme ImmunoBlot IgM)
0042U	Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG (IGeneX Lyme ImmunoBlots IgG)
0316U	Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine (Lyme Borrelia Nanotrap® Urine Antigen Test, Galaxy Diagnostics Inc)

Applicable CPT/HCPCS Procedure CodesCPT|HCPCS|HCPCS

86617	Antibody; Borrelia burgdorferi (Lyme disease) confirmatory test (eg, 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; Proprietary test: Lyme ImmunoBlot IgM; Lab/Manufacturer: IGeneX Inc.
0042U	Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG; Proprietary test: Lyme ImmunoBlots IgG; Lab/Manufacturer: IGeneX Inc.
0316U	Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine; Proprietary test: Lyme Borrelia Nanotrap® Urine Antigen Test; Lab/Manufacturer: Galaxy Diagnostics Inc

Background & Evidence

Lyme disease is a common, tick-transmitted multisystem infection in North America, predominantly caused by B. burgdorferi, with >63,000 reported cases to CDC in 2022 and an estimated ~476,000 Americans diagnosed/treated annually. Early localized infection typically presents with erythema migrans (70–80% of patients) and nonspecific flu-like symptoms; untreated infection can disseminate to cause cardiac (Lyme carditis), neurologic (neuroborreliosis, cranial neuropathies, meningitis, radiculoneuritis), and arthritic manifestations months to years after exposure.

Because direct detection methods have limited and stage-dependent utility, most laboratory confirmation relies on serology: the two-tier algorithm (EIA/IFA screening followed by immunoblot confirmatory testing) is the standard, with sensitivity ~50% in early localized disease but approaching ~100% in late disease. PCR and other direct-detection assays have limited sensitivity in blood and CSF and are not routinely recommended except in specific sample types (e.g., synovial fluid for Lyme arthritis) or early windows; proprietary and point-of-care assays (including single-step C6 ELISA, proprietary immunoblots, urine antigen tests, and novel POC multiplex assays) exist and may improve early detection but are variably validated and the CDC/guidelines currently endorse the two-step serologic process and require FDA clearance before recommending alternative tests.

Evidence summary

CDC reported cases (2022)Over 63,000 reported; ~476,000 Americans diagnosed/treated annually (estimate)

Serology sensitivity — early diseaseApproximately 50% sensitivity for early localized infection; approaches 100% in late disease (systematic review)

Revision History

2017-02-10policy_effective

Policy effective date

2025-07-01policy_reviewLatest

Last review

Policy Summary

PayerCapital Bluecross

PolicyLyme Disease Testing

Policy CodePolicy AHS - G2143 - Lyme Disease Testing, 1 = Initial

Change TypeNo material change

Effective DateFeb 10, 2017

Next Review Date

On This Page

ANY of the following

Acute myocarditis or pericarditis of unknown cause.
Meningitis, encephalitis, or myelitis.
Painful radiculoneuritis.
Mononeuropathy multiplex, including confluent mononeuropathy multiplex.
Acute cranial neuropathy.

Not Medically Necessary / Does Not Meet Coverage Criteria

Not covered when ANY of the following are present, or when ALL of the listed additional non-covered tests are requested:

ANY of the following

Screening of asymptomatic patients living in endemic areas.
Testing for individuals with amyotrophic lateral sclerosis (ALS).
Testing for individuals with relapsing-remitting multiple sclerosis (MS).
Testing for individuals with Parkinson's disease.
Testing for individuals with dementia, cognitive decline, or new-onset seizures.
Testing for individuals with psychiatric illness.
Repeat serologic testing for individuals who have previously tested positive for Lyme disease.

Additional non-covered tests

Detection of Borrelia burgdorferi by nucleic acid identification techniques (direct or amplified probe) including PCR-based methods.
All other testing for Borrelia burgdorferi not described as covered above (tests lacking published evidence of clinical benefit or validation).
Testing the individual tick for Borrelia burgdorferi to diagnose human infection.

Denial Risk

Testing without appropriate indications may be denied

Claims for serologic testing in asymptomatic patients, repeat serologic testing after prior positive, nucleic acid detection assays, tick testing, or other non-recommended tests risk denial as not meeting coverage criteria.

87475
87476
0316U

Documentation Required

Use procedure codes listed when reporting Lyme disease tests

Report Lyme disease laboratory testing using the applicable CPT/HCPCS codes listed in the policy.

86617
86618
87475
87476
0041U
0042U
0316U

Documentation Required

LDT reporting and validation expectations

Recognize that laboratory-developed tests are regulated under CLIA as high-complexity tests and must be validated and performed in-house by the lab; FDA clearance/approval may be absent for these tests.

MTTT vs STTT summaryMTTT improves early sensitivity and has comparable specificity to STTT; identifies additional early cases (studies: Davis et al., Sabin et al.)

References listedMultiple peer‑reviewed articles, CDC guidance, IDSA/AAN/ACR and NICE guidelines, manufacturer materials (total >39 references)

EIA: Enzyme immunoassay (first-tier serologic screening). STTT: Standardized two-tier testing — EIA/IFA followed by western immunoblot. MTTT: Modified two-tier testing — EIA followed by an FDA-cleared second EIA instead of immunoblot. LDT: Laboratory-developed test — tests developed and validated in-house and regulated by CMS under CLIA as high-complexity tests; LDTs are not necessarily FDA-cleared.

Laboratory-developed tests (LDTs) for Lyme disease are commonly created by clinical laboratories and must be validated and performed in-house. LDTs are regulated by CMS under CLIA '88 as high-complexity tests; as LDTs, they typically have not been cleared or approved by the FDA, and FDA clearance/approval is not currently required for clinical use.