Lyme_Disease_Reimbursement_Policy

Coverage Summary

This policy Part 1 of 2 defines coverage for laboratory testing for Lyme disease and summarizes the recommended and not‑recommended tests. The primary covered diagnostic approach is 2‑tier serology (a sensitive EIA/IFA followed by a Western immunoblot or an FDA‑cleared second EIA) for patients with travel to a Lyme region and compatible symptoms, including certain acute neurologic or cardiac presentations.

Tests that are explicitly not covered include PCR/direct detection for routine use, urine antigen assays and other unvalidated urine tests, proprietary or panel immunoblot assays (e.g., IGeneX ImmunoBlot products), and testing of the removed tick for diagnosis of Lyme disease.

This part (1 of 2) covers the policy description, indications and limitations, background, guidelines, and applicable CPT/HCPCS codes (listed in the policy); coding and billing references are provided for laboratory reporting and claims processing. EFFECTIVE DATE: 7/1/2023.

Key policy highlights

Primary recommended diagnostic approach2-tier serology (EIA/IFA first, then immunoblot or FDA-cleared second EIA)

Direct detection generally not coveredPCR-based direct detection does not meet coverage criteria

Situations where serology is not coveredErythema migrans (treat clinically without testing), asymptomatic screening, nonspecific symptoms alone, listed neurologic/psychiatric diagnoses

Repeat testing / PCR limitationsRepeat serology or repeat PCR (including urine PCR) does not meet coverage criteria; PCR has low sensitivity

Procedure codes referencedCPT/HCPCS codes listed: 86617, 86618, 87475, 87476, 0041U, 0042U, 0316U

Proprietary tests notedThree proprietary/LDT assays listed (IGeneX ImmunoBlot IgM/IgG; Galaxy Diagnostics urine Nanotrap antigen test)

Medical-Necessity Criteria

Covered / Meets coverage criteria

Covered when ALL of the following are met:

ALL of the following

Serologic testing using a 2-tier testing strategy (sensitive EIA or IFA first, followed by Western immunoblot OR FDA-cleared second EIA) for patients with a history of travel to a Lyme region (with or without a history of a tick bite) with compatible symptoms of Lyme disease
ALL of the following
- ONE of
  - Acute myocarditis/pericarditis of unknown cause
  - Meningitis, encephalitis, or myelitis

Coding

Covered / referenced procedure codes for Lyme testing (general reference)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 (Proprietary test: Lyme ImmunoBlot IgM; IGeneX Inc.)
0042U	Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG (Proprietary test: Lyme ImmunoBlot IgG; IGeneX Inc.)
0316U	Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine (Proprietary test: Lyme Borrelia Nanotrap® Urine Antigen Test; Galaxy Diagnostics Inc.)

Applicable CPT/HCPCS Procedure CodesCPT

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
0042U	Borrelia burgdorferi, antibody detection of 12 recombinant protein groups, by immunoblot, IgG
0316U	Borrelia burgdorferi (Lyme disease), OspA protein evaluation, urine

Proprietary Tests / Lab Manufacturers (listed in Reimbursement Policy)mixed

0041U	Proprietary test: Lyme ImmunoBlot IgM; Lab/Manufacturer: IGeneX Inc.
0042U	Proprietary test: Lyme ImmunoBlots IgG; Lab/Manufacturer: IGeneX Inc.
0316U	Proprietary test: Lyme Borrelia Nanotrap® Urine Antigen Test; Lab/Manufacturer: Galaxy Diagnostics Inc.

Provider Actions & Billing Guidance

Documentation Required

Clinical indication and travel/exposure history required

Ensure documentation of a history of travel to a Lyme region or other epidemiologic exposure and the presence of compatible symptoms when ordering two-tier serologic testing; testing is contingent on clinical indication.

Denial Risk

Claims may be denied for testing in excluded situations

Do not order serologic testing for patients in the excluded situations listed below; claims for testing in these scenarios do not meet coverage criteria and may be denied.

Erythema migrans (EM) rash — treat clinically without testing
Asymptomatic screening of patients living in endemic areas

Background, Evidence & Definitions

Lyme disease is a multisystem infection caused predominantly in North America by Borrelia burgdorferi transmitted by Ixodes ticks; early disease commonly manifests with erythema migrans and nonspecific flu‑like symptoms and may disseminate to involve joints, heart, and the nervous system.

Diagnosis relies on clinical assessment plus laboratory testing when indicated. Serologic testing using the traditional two‑tier algorithm (EIA followed by immunoblot), termed STTT, is the established gold standard—sensitivity is limited in early localized disease but high in later stages.

A Modified Two‑Tiered Testing algorithm (MTTT, an EIA followed by a second EIA when FDA‑cleared) has FDA support and evidence of improved early sensitivity with high specificity.

Direct detection methods (e.g., PCR, urine antigen tests) have limited utility: PCR shows low sensitivity in many series and urine antigen assays and other novel tests are generally unvalidated and not recommended for routine diagnosis.

Evidence	Summary
Waddell 2016 pooled sensitivity/specificity
Overall sensitivity 82%, specificity 94.2%; early localized (Stage 1) sensitivity 54%, specificity 96.8%; Stage 3 sensitivity 94.7%, specificity 96.1%
MTTT vs STTT (Davis et al. 2020)
MTTT identified additional early infections (detected 25% more early infections); specificity 99.56%; detected some cases missed by STTT
PCR sensitivity (Nigrovic et al. 2019)
PCR sensitivity 41.8%, specificity 100% (low sensitivity)
Reference count (selected evidence citations in part)
Multiple guideline and scientific references cited (CDC, IDSA/AAN/ACR 2020, NICE, UpToDate, peer-reviewed literature) and applicable CPT/HCPCS codes listed

EIA — Enzyme immunoassay used as the first step in two‑tier serologic testing.

ELISA — Enzyme‑linked immunosorbent assay, a type of EIA commonly used for Lyme serology.

EM — Erythema migrans, the characteristic early skin lesion of Lyme disease; clinical diagnosis of EM should prompt treatment without serologic testing.

STTT — Standardized two‑tier testing: screening EIA/IFA followed by Western immunoblot; CDC‑recommended traditional algorithm.

MTTT — Modified two‑tier testing: screening EIA followed by a second FDA‑cleared EIA instead of immunoblot when applicable; FDA‑cleared MTTT assays improve early detection.

Revision History

7/1/2023adoptionLatest

EFFECTIVE DATE 7/1/2023 - Adopted Avalon policy recommendation (no specific clinical policy statement changes identified).

Not covered / Does not meet coverage criteria

The following situations DO NOT MEET COVERAGE CRITERIA:

ANY of the following

Serologic testing in patients with an erythema migrans (EM) rash; these patients should be treated without testing
Serologic testing for screening of asymptomatic patients living in endemic areas
Serologic testing for patients with non-specific symptoms only (e.g., fatigue, myalgias/arthralgias) due to low pre-test probability and false positive risk
Serologic testing in patients with amyotrophic lateral sclerosis
Serologic testing in patients with relapsing-remitting multiple sclerosis
Serologic testing in patients with Parkinson's disease
Serologic testing in patients with dementia or cognitive decline, or new-onset seizures
Serologic testing in patients with psychiatric illness
PCR-based direct detection of Borrelia burgdorferi (general statement): DOES NOT MEET COVERAGE CRITERIA
Repeat serologic testing in individuals who have tested positive previously (cannot distinguish past vs current infection)
ALL of the following
- As a justification for continuation of IV antibiotics beyond one month in patients with persistent symptoms
- As a technique to follow a therapeutic response
- Via urine sample
ALL of the following
- Genotyping and phenotyping
- Determination of levels of the B lymphocyte chemoattractant CXCL13
- Urine assays, including urinary-based antigen capture assays
- Panel immunoblot testing, such as Lyme ImmunoBlot IgM, Lyme ImmunoBlot IgG, and Lyme Dot Blot
Testing of the individual tick for diagnosis of Lyme disease