Blue Cross Blue Shield TN Lyme Testing Coverage

Coverage and Medical Necessity Criteria

inv-01: Serologic testing - Covered indications

Serologic testing using a two-tier testing strategy meets coverage criteria when specific conditions are met.

Covered when ALL of the following are met: 1) History of travel to a Lyme region (with or without known tick bite) AND 2) Compatible symptoms of Lyme disease; testing must use a two-tier strategy (sensitive EIA/IFA followed by immunoblot or FDA-cleared second EIA).

Policy II, items 1 and supporting two-tier sequence guidance.

Also covered for individuals with travel to a Lyme region presenting with any of the following disorders: a) Acute myocarditis/pericarditis of unknown cause; b) Meningitis, encephalitis, or myelitis; c) Painful radiculoneuritis; d) Mononeuropathy multiplex including confluent mononeuropathy multiplex; e) Acute cranial neuropathy.

Policy II, item 2 (a–e).

inv-02: Not Medically Necessary / Not Covered

Testing does NOT meet coverage criteria in the following explicit situations:

Not covered - Serology: a) Patients with erythema migrans (treat without testing); b) Screening of asymptomatic patients in endemic areas; c) Patients with non-specific symptoms only (eg, fatigue, myalgias/arthralgias); d) Patients with amyotrophic lateral sclerosis; e) Patients with relapsing-remitting multiple sclerosis; f) Patients with Parkinson's disease; g) Patients with dementia or cognitive decline, or new-onset seizures; h) Patients with psychiatric illness; i) Testing of the individual tick for diagnosis.

Policy II items 3a–b and Reimbursement Policy exclusions.

Not covered - PCR and repeat PCR: PCR-based direct detection of Borrelia burgdorferi is not covered; repeat PCR testing is not covered, including use to justify continuation of IV antibiotics beyond one month, to follow therapeutic response, or via urine samples.

Policy II items 4 and 6 (a–c).

Not covered - Other unvalidated tests: Other testing for Borrelia burgdorferi does not meet coverage criteria, including genotyping/phenotyping, CXCL13 level determination, urine antigen capture assays, panel immunoblot testing (Lyme ImmunoBlot, Dot Blot), CD57 assays, lymphocyte transformation tests, reverse Western blots, in-house immunoblot interpretation criteria, measurements of antibodies in joint fluid, and IgM/IgG tests without prior EIA/EIA/IFA.

Policy II item 7 and CDC list of non‑recommended/unvalidated tests.

inv-03: Repeat testing

Repeat serologic testing does NOT meet coverage criteria in certain circumstances.

Repeat serology not covered when: An individual previously tested positive for Lyme disease (positive results may not distinguish past from current infection).

Policy II, item 5.

inv-04: Covered with criteria (serology and CSF guidance)

Covered when clinical presentation and testing sequence meet guideline-based criteria:

Two-tier serology for suspected extracutaneous or late Lyme disease: Perform initial EIA/ELISA/IFA; if positive or equivocal, perform confirmatory immunoblot; interpret positive only if both EIA/IFA and immunoblot are positive.

Per two-tier algorithm guidance (CDC and guideline summaries).

When laboratory testing recommended: Patients with signs of early disseminated or late Lyme disease (eg, Lyme arthritis), neurologic involvement suggestive of neuroborreliosis (meningitis, radiculoneuritis, cranial neuropathies), or acute myocarditis/pericarditis in an appropriate epidemiologic setting.

IDEG and guideline recommendations (see policy guidance).

CSF testing for neuroborreliosis: If CSF testing is performed, obtain simultaneous CSF and serum for CSF:serum antibody index; do not rely on CSF serology alone; routine PCR/culture of CSF or serum is not recommended.

Guideline recommendations for CSF testing and simultaneous serum sample.

inv-05: Not medically necessary / unvalidated tests

Not recommended / unvalidated tests (generally considered not covered or clinically unestablished):

Unvalidated assays: Capture assays for antigens in urine, culture/immunofluorescence/cell sorting of cystic forms, lymphocyte transformation tests, quantitative CD57 lymphocyte assays, reverse Western blots, in‑house immunoblot interpretation criteria, measurements of antibodies in synovial (joint) fluid (when not recommended), IgM/IgG tests without a prior EIA/EIA/IFA, urinary antigen tests, novel culture techniques, and PCR on blood/serum/plasma (not validated).

CDC list of unvalidated tests and Red Book/AAP statements.

inv-06: Clinical diagnosis allowed without lab testing

Clinical diagnosis without lab testing:

Erythema migrans: Patients presenting with erythema migrans should be diagnosed and treated clinically without laboratory testing; for atypical lesions consider acute-phase serology and repeat convalescent testing if initial negative.

NICE and PHAC guidance and policy II regarding EM.

This policy identifies a range of unvalidated or non‑recommended tests for Lyme disease that generally do not meet coverage criteria. Examples include: urine antigen capture assays and other urinary-based antigen tests; panel immunoblot testing such as proprietary Lyme ImmunoBlot or Dot Blot assays; genotyping/phenotyping and novel culture techniques; lymphocyte transformation tests; quantitative CD57 lymphocyte assays; 'reverse Western blots' and in‑house criteria for immunoblot interpretation; and measurement of antibodies in synovial (joint) fluid. These assays are listed because their accuracy and clinical usefulness have not been adequately established by published scientific literature or public‑health guidance.

The policy specifically flags tests that public health authorities have labeled as unvalidated and advises that use of these assays may be considered clinically unestablished and therefore not recommended for coverage. Examples called out by the CDC and summarized here include capture assays for antigens in urine, lymphocyte transformation tests, quantitative CD57 assays, 'reverse Western blots', and immunoblot testing interpreted using in‑house criteria rather than standard methods.

The policy cites CDC guidance on laboratory tests that are not recommended and incorporates that list into its exclusions. The CDC examples include urine antigen capture assays, culture or cell‑sorting of purported cystic forms, lymphocyte transformation tests, CD57 assays, reverse Western blots, in‑house immunoblot interpretation criteria, measurements of antibodies in joint fluid, and standalone IgM or IgG tests performed without a prior EIA/EIA/IFA.

Serologic testing is not indicated for patients who present with erythema migrans; in such cases the guideline and this policy recommend clinical diagnosis and treatment without laboratory testing. The policy also states that serologic testing should not be used for population‑level screening of asymptomatic individuals in endemic areas because of low pre‑test probability and the resulting increased likelihood of false positives.

Routine testing is not medically necessary for asymptomatic patients after an Ixodes tick bite or for patients with only nonspecific symptoms (for example, fatigue, myalgias, or arthralgias) without other clinical or epidemiologic indicators. The policy also recommends against testing removed ticks to diagnose infection and advises clinicians to avoid routine Lyme testing for neurologic or psychiatric presentations unless there is additional clinical or epidemiologic support.

Polymerase chain reaction (PCR) testing for Borrelia burgdorferi has limited sensitivity and is not covered for routine direct detection in blood, serum, or urine. The policy notes PCR is generally not recommended except in specific circumstances (for example, PCR of synovial fluid when definitive evidence is needed for Lyme arthritis), and that repeat PCR testing — including to justify prolonged intravenous antibiotics, as a test‑of‑response, or using urine samples — does not meet coverage criteria.

Procedure and Proprietary Codes

Procedure CPT/HCPCS CodesCPT | HCPCS | mixed

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

Proprietary (PLA) CodesHCPCS | mixed

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

Applicable CPT/HCPCS Procedure CodesCPT

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

Proprietary / Reimbursement Policy CodesHCPCS

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.

Convalescent sample timing — recommended interval after acute sample

Recommended interval for convalescent sampleObtain convalescent serum 2 to 4 weeks after the acute (initial) sample

Alternate timing notedSome guidance references convalescent sampling at 2 to 3 weeks after the acute sample

Use case for convalescent sampleRecommended when initial testing is negative but clinical suspicion for early infection persists

Provider Responsibilities, Documentation, and Billing Guidance

Prior Authorization

Coding cited for potential prior authorization

Coding cited in the reimbursement section may be subject to coverage review or prior authorization. When submitting claims or authorization requests, include clinical documentation that supports medical necessity (see documentation callouts). Relevant procedure and proprietary codes cited in the policy include CPT/HCPCS and PLA/proprietary test codes — these are provided for reference and may require submission of supporting records.

86617 - Antibody; Borrelia burgdorferi (confirmatory, e.g., Western Blot or immunoblot)
86618 - Antibody; Borrelia burgdorferi (screening)
87475 - Infectious agent detection by nucleic acid; Borrelia burgdorferi, direct probe technique
87476 - Infectious agent detection by nucleic acid; Borrelia burgdorferi, amplified probe technique
0041U - Proprietary immunoblot IgM (IGeneX Lyme ImmunoBlot IgM)
0042U - Proprietary immunoblot IgG (IGeneX Lyme ImmunoBlots IgG)
0316U - Proprietary urine OspA antigen test (Galaxy Diagnostics Nanotrap)

Clinical Background and Epidemiology

Lyme disease is caused primarily by Borrelia burgdorferi in North America and is transmitted by Ixodes species ticks. Early localized infection commonly presents as erythema migrans accompanied by systemic, flu‑like symptoms; these early presentations are frequently diagnosed clinically because serologic testing is insensitive in this phase. Disseminated infection can involve the musculoskeletal, cardiac, and nervous systems; in suspected extracutaneous or late disease (for example, Lyme arthritis, meningitis, radiculoneuritis, cranial neuropathies, or acute Lyme myocarditis/pericarditis in an appropriate epidemiologic setting), guideline‑based serologic testing using a two‑tier algorithm is recommended.

Key Terms and Abbreviations

EIA — Enzyme immunoassay (first-tier serologic test)

DefinitionEnzyme immunoassay (EIA) — first-tier serologic test for Lyme disease (may be performed as EIA or ELISA)

Role in testing algorithmUsed as the initial screening test; if negative, no further testing of that specimen is recommended

When to followIf EIA is positive or equivocal, proceed to second-step immunoblot (Western blot) or FDA-cleared second EIA per modified two-tiered algorithms

EM — Erythema migrans (characteristic rash of early Lyme disease)

DefinitionErythema migrans (EM) — the characteristic expanding cutaneous rash of early localized Lyme disease

Clinical implicationPatients presenting with EM may be diagnosed and treated clinically without laboratory testing because serology is insensitive at this stage

OpenPayer

Lyme Disease Testing — Coverage Criteria (Serology, PCR, and Other Diagnostics)

Coverage and Medical Necessity Criteria

Procedure and Proprietary Codes

Provider Responsibilities, Documentation, and Billing Guidance

Clinical Background and Epidemiology

Key Terms and Abbreviations