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Lyme Disease: Diagnosis and Intravenous (IV) Antibiotic Therapy
06.02.01l

Policy

​MEDICALLY NECESSARY

DIAGNOSIS
The following methods for the diagnosis of Lyme disease are considered medically necessary and, therefore, covered for documentation of infection:
  • Enzyme-linked immunosorbent assay (ELISA) ​performed concurrently or sequentially with a secondary ELISA
  • Western immunoblot ​performed after a positive or indeterminate ELISA result
  • Polymerase chain reaction (PCR)–based direct detection of Borrelia burgdorferi in blood samples in immunodeficient individuals
  • PCR-based direct detection of B. burgdorferi in cerebrospinal fluid (CSF) samples in individuals with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies
  • PCR-based direct detection of B. burgdorferi in blood samples in individuals with one of the Lyme carditis manifestations below when serological tests are equivocal
PCR TESTING FOR LYME ARTHRITIS
PCR-based direct detection of B. burgdorferi is considered medically necessary and, therefore, covered for testing of synovial fluid samples in seropositive individuals to inform therapeutic decisions for suspected Lyme arthritis.

THERAPY
Intravenous (IV) antibiotic therapy (up to 4 weeks) is considered medically necessary and, therefore, covered for the treatment of Lyme disease when one or more of the following diagnoses have been established:
  • For a diagnosis of neuroborreliosis as documented by the presence of at least one of the following objective neurologic complications:
    • Lymphocytic meningitis associated with CSF abnormalities including all of the following:
      • Pleocytosis
      • Increased levels of protein
      • Intrathecal production of B. burgdorferi antibodies in CSF
    • Bell palsy or other cranial neuropathy, or peripheral neuropathy, with documented CSF abnormalities (Note: a past medical history of Bell palsy is not sufficient) including all of the following:
      • Pleocytosis
      • Increased levels of protein
      • Intrathecal production of B. burgdorferi antibodies in CSF 
    • Encephalitis or encephalomyelitis with documented CSF abnormalities including all of the following:
      • Pleocytosis
      • Increased levels of protein
      • Intrathecal production of B. burgdorferi antibodies in CSF
    • Radiculopathy
    • Polyneuropathy
  • For a diagnosis of Lyme carditis, ​as documented by at least one of the following:
    • Atrioventricular (AV) block
    • PR interval greater than 0.3 seconds
    • Tachyarrhythmias
    • Myopericarditis demonstrated by EKG
  • For a diagnosis of severe Lyme arthritis that requires the rapid response of IV antibiotics, when serologic studies are equivocal
  • For a diagnosis of refractory Lyme arthritis that has failed to improve or has worsened after initial antimicrobial treatment, a second course of IV antibiotic treatment may be indicated.
NOT MEDICALLY NECESSARY

IV antibiotic therapy for Lyme disease is considered not medically necessary and, therefore, not covered in individuals who do not have any of the conditions listed above as covered, or who have any of the following, including, but not limited to:
  • Symptoms that are consistent with chronic fatigue syndrome or fibromyalgia in the absence of clinical findings suggestive of Lyme disease
  • Seronegative Lyme disease in the absence of CSF antibodies
  • Cranial nerve palsy (e.g., Bell palsy) without clinical evidence of meningitis
  • Vague systemic symptoms that are present without supporting serologic or CSF studies
  • A positive ELISA that is unconfirmed by a ​secondary ELISA or Western immunoblot test
  • An isolated positive serologic test in the setting of multiple negative serologic studies
  • Chronic (≥6 months) subjective symptoms ("post-Lyme syndrome") after receiving recommended antimicrobial treatment regimens for documented Lyme disease
IV antibiotic therapy for Lyme disease is considered not medically necessary and, therefore, not covered as initial therapy for Lyme arthritis in the absence of coexisting neurologic symptoms.

Repeat or prolonged courses (>4 weeks) of IV antibiotic therapy for Lyme disease are considered not medically necessary and, therefore, not covered for all disease entities except for a second course of IV antibiotics as warranted for refractory Lyme arthritis, where a second course may be medically necessary.

EXPERIMENTAL/INVESTIGATIONAL

The following methods for the diagnosis of Lyme disease are considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of these services cannot be established by review of the available published peer-reviewed literature:
  • PCR infectious agent detection, quantification​
  • PCR-based detection of B. burgdorferi in the following situations:
    • As a justification for IV antibiotic use beyond 4 weeks in individuals with persistent symptoms
    • As a technique to follow or measure therapeutic response
  • PCR-based direct detection of B. burgdorferi in urine samples
  • PCR-based genotyping or phenotyping analysis of B. burgdorferi
  • Lyme urine antigen test (LUAT)
  • Single-photon emission computed tomography (SPECT) scanning alone to diagnose Lyme disease encephalopathy
  • Determination of levels of the B lymphocyte chemoattractant CXCL13
  • Human natural killer-1 (HNK1), also known as Cluster of Differentiation (CD57) Profile
  • Standalone C6 peptide ELISA (i.e., unconfirmed by a Western immunoblot test)
  • Lyme ImmunoBlot IgM
  • Lyme ImmunoBlot IgG
  • ​iDart Lyme IgG ImmunoBlot kit
  • ​Urinary analysis of Borrelia ​outer surface protein A (OspA) antigen
REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to, records from the professional providers' office, hospital, nursing home, home health agencies, therapies, other health care professionals, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation must be made available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

DOCUMENTATION FOR IV ANTIBIOTICS

Documentation of CSF abnormalities is required for suspected CNS infection and neuroborreliosis. Documentation must include all of the following:
  • Evidence of pleocytosis
  • Evidence of intrathecal production of B. burgdorferi antibodies in CSF
  • Evidence of increased protein levels
PCR-based direct detection of B. burgdorferi in CSF samples may be considered medically necessary and may replace serologic documentation of infection in individuals with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies.

Serologic documentation of infection requires positive or indeterminate ELISA and positive Western immunoblot as recommended by the Centers for Disease Control and Prevention (CDC) criteria.

Guidelines

Oral antibiotic therapy is the usual treatment for Lyme disease. Intravenous (IV) antibiotic therapy is generally indicated only in individuals who have symptoms and laboratory findings consistent with central nervous system (CNS) or peripheral neurologic involvement, those who have heart block, or those who have been diagnosed with Lyme arthritis who have not responded to oral antibiotics.

REFRACTORY LYME ARTHRITIS THAT HAS FAILED TO IMPROVE OR HAS WORSENED AFTER INITIAL ANTIMICROBIAL TREATMENT

The slow resolution of inflammation after the initial course of antibiotic therapy should be taken into consideration before initiating retreatment with IV antimicrobial therapy.

POLYMERASE CHAIN REACTION (PCR)

The quantification technique has no clinical role at this time because treatment decisions are not based on the quantification of organisms present.

In direct probe techniques, nucleic acid is extracted from the specimen (e.g., isolate, tissue, cerebrospinal fluid [CSF], blood, synovial fluid) and the target sequence is detected by a reporter molecule, such as an oligonucleotide, deoxyribonucleic acid (DNA) fragment, or plasmid DNA. The reporter molecule has a label attached to generate a signal when hybridized to the target sequence in solution or immobilized on solid support. This technique is increasingly being replaced with amplification methods.

​

In amplified probe techniques, nucleic acid is extracted from the specimen (e.g., isolate, tissue, CSF, blood, synovial fluid) and then amplified using polymerase chain reaction (PCR). The specific organisms are differentiated through features of the melting curve analysis. However, due to the amplification steps, there is a high risk for exogenous contamination, resulting in false-positive results. Additionally, degradation of the DNA during sample transport, storage, and processing steps can result in false negatives. Standard PCR methods have demonstrated poor sensitivity in testing tissue and body fluids because the infectious agent resides in low number. Newer PCR methods have shown marked improvement in sensitivity, and it is likely that this will lead to more clinical uses of PCR to detect active infection.


BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, IV antibiotic therapy for Lyme disease is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met. However, services that are identified in this policy as experimental/investigational or not medically necessary are not eligible for coverage or reimbursement by the Company.

Description

Lyme disease is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi, which is transmitted by the bite of an infected Ixodes scapularis​ tick. Lyme disease is characterized by stages, with the initial stage of the disease presenting the most common clinical manifestation, a rash known as erythema migrans (EM). This rash is characterized by a red, raised, spreading lesion, with an area of clearing resembling a bull's eye. However, in some cases, EM may be overlooked or absent. Fever, malaise, fatigue, headache, muscle aches (myalgia), and joint aches (arthralgia) are also symptoms of early-stage Lyme disease.

A clinical finding of EM is indicative of Lyme disease. For individuals who do not present with EM and exhibit other nonspecific clinical manifestations consistent with Lyme disease, positive serologic assays are used for diagnosis. A confirmed history of ​I. scapularis exposure in an endemic area for Lyme disease may assist but does not establish the diagnosis.

The second stage of Lyme disease involves the dissemination of the spirochete to other body systems. Early manifestations of this dissemination may include lymphocytic meningitis, facial palsy, painful radiculoneuritis, atrioventricular nodal block, or migratory musculoskeletal pain. Latent Lyme disease symptoms are manifest months to years after infection by B. burgdorferi. These symptoms may include intermittent oligoarthritis (usually of the knee joint), chronic encephalopathy, spinal pain, or distal paresthesias.

Because of their nonspecific and overlapping symptoms, fibromyalgia and chronic fatigue syndrome may be confused with Lyme disease. However, neither fibromyalgia nor chronic fatigue syndrome has been shown to respond to antibiotic therapy.

The vaccine for Lyme disease is no longer available within the United States. It was discontinued by the manufacturer in 2002.

There is no formal definition of post-Lyme disease syndrome, and its pathogenesis is unclear. In untreated individuals, objective manifestations of latent Lyme disease, such as oligoarticular arthritis, may persist for several years. However, there is no evidence that persistent subjective symptoms after antibiotic treatment, sometimes called post-Lyme disease syndrome or chronic Lyme disease, is due to active infection. These symptoms may be related to various self-sustaining inflammatory mechanisms rather than persistent infection. It is recommended that Lyme disease should never be a diagnosis of exclusion to explain puzzling subjective symptoms, particularly when they are not accompanied by objective markers of organ damage and/or inflammation (Feder et al., 2007).

According to the Infectious Diseases Society of America guidelines, most early manifestations of Lyme disease are treated successfully with the appropriate oral antibiotics: doxycycline, amoxicillin, or cefuroxime axetil. Intravenous (IV) antibiotic therapy is usually reserved for individuals who present with neurologic and/or cardiac symptomatology. The various manifestations of Lyme disease that usually necessitate IV antibiotic therapy are discussed below.

CARDIAC MANIFESTATIONS OF LYME DISEASE

Lyme carditis in the early disseminated stage may appear as atrioventricular heart block, tachyarrhythmia, or myopericarditis. An individual may present with symptoms such as syncope, dyspnea, or chest pain. Continuous monitoring is advisable for symptomatic individuals. Oral and IV antibiotic therapy have been advocated, with IV therapy usually reserved for individuals who have high-degree atrioventricular block or a PR interval on electrocardiogram of greater than 0.3 seconds.

NEUROLOGIC MANIFESTATIONS OF LYME DISEASE

The term for central nervous system (CNS) Lyme disease is neuroborreliosis. Neurologic manifestations during the early disseminated stage of the disease may present as meningitis, cranial neuritis (frequently Bell palsy), radiculoneuritis, radiculoneuropathy or peripheral neuropathy, encephalopathy, mononeuritis multiplex, or a combination of these conditions. Symptoms are characterized by head and neck pain. The diagnosis of neuroborreliosis is determined by the combination of clinical findings with laboratory support provided by the following:
  • Lumbar puncture demonstrating cerebrospinal fluid (CSF) with pleocytosis and elevated protein.
  • Positive CSF enzyme-linked immunosorbent assay (ELISA) confirmed by Western immunoblot ​​​or secondary ELISA for antibodies to B. burgdorferi.
  • Matching serum samples for antibody production.
  • CSF polymerase chain reaction (PCR) for B. burgdorferi may be warranted if the above studies are not conclusive and the presentation is early in the course of disease.
Subacute encephalopathy can occur months to years after disease onset; symptoms include subtle changes in memory, mood, sleep, or cognition accompanied by fatigue. There are no abnormalities on electroencephalogram (EEG), magnetic resonance imaging (MRI), or CSF testing. The symptoms are nonspecific and similar to that of fibromyalgia and chronic fatigue syndrome. The diagnosis of Lyme encephalopathy is best validated with a mental status exam that may help differentiate it from chronic fatigue syndrome or depression. Treatment with IV antibiotics is generally not indicated for affected individuals unless CSF abnormalities are present.

Of greater concern, although rarely occurring, is the development of encephalomyelitis. The symptoms of encephalomyelitis are spastic paraparesis, ataxias, cranial neuropathy, cognitive impairment, and bladder dysfunction. IV antibiotic therapy is suggested when CSF testing is positive for pleocytosis and protein elevation.

LYME ARTHRITIS

A late manifestation of infection is Lyme arthritis. This is characterized by an elevated IgG response to B. burgdorferi and recurrent attacks of oligoarticular arthritis, usually affecting large joints such as the knee. Individuals may be effectively treated with a 30-day course of oral antibiotic therapy. However, caution must be taken to exclude CNS involvement, which would require IV antibiotic treatment. A second 4-week course of oral or IV antibiotic therapy may be prescribed for individuals whose arthritis has failed to improve or has worsened. The slow resolution of inflammatory symptoms after the initial treatment with antibiotics should be taken into consideration before initiating retreatment with antimicrobial agents. It is believed that the persistence of symptomatology in these individuals is not related to continued infection but is instead an immune response to the previous infection.

DIAGNOSTIC TESTS

SEROLOGIC TESTS
Specific IgM response in acute infection peaks between the third and sixth weeks of the disease process. Specific IgG response develops after months and includes antibodies to a variety of spirochete antigens; these antibodies may persist for months to years. In consideration of these findings, detection of IgG antibodies only indicates exposure, either past or present. Interpretation of serologic tests requires the correlation of the test results concurrently with the individual's signs and symptoms of Lyme disease.

When laboratory testing is indicated, the Centers for Disease Control and Prevention (CDC) recommends a two-step method testing for the serologic diagnosis of Lyme disease. ​​​This can be accomplished using the standard two-tiered (STT) testing ​​process, which consists of a US Food and Drug Administration (FDA)-approved enzyme immunoassay that, if positive or equivocal, is followed by an FDA-approved immunoblot test, commonly known as a "Western blot" test. In addition to the STT, a modified two-tiered (MTT) methodology can be used, where a second enzyme immunoassay (EIA) is tested in lieu of a Western blot. Results are considered positive only when both the EIA and Western blot are positive, or when both EIAs are positive.

Standardized Two-Tiered Testing: 

  • Step one: enzyme-linked immunosorbent assay (ELISA): The ELISA is a screening test for Lyme disease. Newly developed tests use recombinant or synthetic antigens for improved diagnostic sensitivity. The FDA has approved C6 ELISA when positive or equivocal results are supplemented by testing with a standardized Western blot procedure. The single-step enzyme immunoassay (EIA) using the C6 peptide, has not demonstrated improvements in specificity over the two-tiered testing approach (Branda et al., 2011). Lipsett et al. (2016) evaluated C6 EIA in 944 children, of whom 114 had Lyme disease. They found that s​tand-alone C6 EIA testing had lower specificity than two-tiered testing; specificity was increased to 98.6% with a supplemental immunoblot. A systematic review of diagnosis and treatment of Lyme disease also concluded that stand-alone C6 testing is not recommended over the two-tiered approach due to slightly lower specificity (Sanchez et al., 2016). An ELISA test by itself is not conclusive serologic evidence of Lyme disease. A negative ELISA needs no further testing. All of these tests must be corroborated with the Western immunoblot test and must be compared to objective clinical findings.
  • Step two: Western immunoblot: The Western immunoblot is used to identify individuals with positive or indeterminate ELISA results. This test identifies the specific antibody response to several clinically significant antigens of B. burgdorferi. According to CDC criteria, Western immunoblot is considered positive if two of the three most common IgM antibody bands are present, or if five of the 10 most frequent IgG antibody bands are present. Because of test variability, the Western immunoblot test is usually performed in an experienced and quality-controlled laboratory. Comparison titers should be performed on the same day using the same test kit.
Modified Two-Tiered Testing:

Like the STT method, a stand-alone EIA is not conclusive. Further, the sequence of MTT tests can be reversed or performed concurrently without change in performance. ​​​

  • VlsE1/pepC10 ELISA: One serologic test in the MTT methodology is intended for the qualitative, polyvalent detection of VlsE1 (variable major protein like sequence expressed) and pepC10 IgG/IgM antibodies. Both are outer membrane proteins found on the B. burgdorferi bacterium.
  • B. burgdorferi ELISA: Additional diagnostic tests in the MTT methodology are for polyclonal antibodies or separate IgG and IgM antibodies to B. burgdorferi​.
Since 1994, the recommended testing algorithm had been a two-step methodology as described above, using a sensitive EIA or immunofluorescence assay as a first test, followed by a Western immunoblot assay for specimens yielding positive or equivocal results. According to the report from the 1994 Second National Conference on Serologic Diagnosis of Lyme Disease, development of future tests should include blind testing against a comprehensive challenge panel, and new assays should be recommended only if their specificity, sensitivity, and precision equaled or surpassed the performance of tests used in the recommended two-test procedure. In July 2019, the FDA cleared several Lyme disease serologic assays, including ZEUS ELISA Borrelia VlsE1/pepC10 IgG/IgM Test System, ZEUS ELISA Borrelia burgdorferi IgG/IgM Test System, ZEUS ELISA Borrelia burgdorferi IgM Test System, and the ZEUS ELISA Borrelia burgdorferi IgG Test System, with new indications for use based on a modified two-test methodology. The modified methodology uses a second EIA in place of a Western immunoblot assay. Clearance by FDA of the new Lyme disease assays indicates that test performance has been evaluated and is “substantially equivalent to or better than” a legally marketed predicate test.

LYME IMMUNOBLOT IgG AND IgM
The Lyme ImmunoBlot tests were developed for clinical use by IGeneX as a qualitative assay that detects B. burgdorferi sensu lato specific IgG/IgM antibodies in human serum to the following B. burgdorferi species: B. burgdorferi B31, B. burgdorferi 297, B. californiensis, B. mayonii, B. spielmanii, B. afzelii, B. garinii, and B. valaisiana. Neither of these tests (Lyme ImmunoBlots IgM and Lyme ImmunoBlots IgG) have been validated and published in peer-reviewed scientific literature.

iDART LYME IgG IMMUNOBLOT KIT
The iDart Lyme IgG ImmunoBlot kit was developed by ID-FISH Technology as a qualitative assay for the detection of IgG antibodies to B. burgdorferi​. The test is to be used on samples from individuals who have a clinical history and signs and symptoms consistent with Lyme disease. The immunoblot strip contains two controls, Lyme screening antigen, and a number of other antigens. If the Lyme screening antigen and one band of at least at least two of six specific antigens are positive, then the test result is positive. This test kit has not been validated in published peer-reviewed scientific literature, but some data are available within the FDA 510(k) clearance. For the clearance, three cohorts of serum samples were obtained and tested, totaling 768 samples. The positive percent agreement with a standard two-tier test varied among cohorts, but maintained greater than 90% agreement, although with wide confidence intervals (CIs). The negative percent agreement with a standard two-tier test varied from 86% to 96% agreement, with narrower CIs. Additional research is needed to establish the iDart Lyme IgG ImmunoBlot as a clinically valid and useful technique for the diagnosis of Lyme disease.​

POLYMERASE CHAIN REACTION (PCR)
PCR testing detects the genetic material (deoxyribonucleic acid [DNA]) of the Lyme disease bacteria in samples taken from CSF, tissue, or synovial fluid. PCR-based direct detection of B. burgdorferi in CSF samples is typically used in individuals with a short duration (<14 days) of neurologic symptoms during the window between exposure and production of detectable antibodies. The detection of the Borrelia spirochete in the CSF is most successful within the first 2 weeks of infection.

However, PCR testing can be unreliable because it requires amplification of the B. burgdorferi DNA. This amplification places the sample at high risk for extrinsic contamination, which increases the likelihood of a false-positive result. Positive results in the absence of clear clinical indicators or positive serology are not definitive for diagnosis. In addition, PCR testing cannot distinguish between live, infectious spirochetes and noninfectious fragments of dead spirochetes. Finally, the risk of a false-positive result increases if a specimen being tested has low probability of infection. Because of these concerns, the major national laboratories usually contract with well-controlled laboratories to perform these tests.

B. burgdorferi was originally thought to be a single species; however, genotypic analysis has revealed that this group represents three distinct species and genomic groups. Borrelia PCR genotyping also provides information on which of these three major species are found in the specimen tested. Of these, the following have been isolated from individuals with Lyme disease: B. burgdorferi sensu lato, B. garinii, and B. afzelii. PCR-based technology has been used as one step in the genotypic analysis of these genospecies. The prevalence of these different genospecies may vary among populations and may be associated with different clinical manifestations. However, no data were found in the published literature with regard to whether or how knowledge of the genotype or phenotype of B. burgdorferi could be used to improve patient management and outcomes.

PCR-based detection is typically not performed in the urine due to the variable presence of endogenous polymerase inhibitors that affect test sensitivity. However, PCR-based direct detection of B. burgdorferi in the blood may be useful for documenting Lyme carditis when results of serologic studies are equivocal, and has the best detection rates for skin biopsy specimens from individuals with EM and for synovial tissue from individuals with Lyme arthritis. Whereas the most recent guidelines (Lantos et al., 2021) recommend serology testing over PCR testing for initial evaluation of possible Lyme arthritis, the guidelines recommend that PCR testing be used for treatment decision making on synovial fluid among individuals who are seropositive. Additionally, there is suggestion that PCR may be a preferred diagnostic method among individuals who are immunodeficient, as they are less likely to produce a robust immune response that would be detectable by serology. 

CEREBRAL SPINAL FLUID (CSF) EVALUATION
CSF evaluation may be performed in an individual with suspected Lyme disease if rarer neurologic symptoms such as encephalomyelitis, cranial neuropathy, and cognitive impairment are present.

Positive CSF findings include all of the following:
  • Pleocytosis
  • Increased protein levels
  • Intrathecal production of B. burgdorferi antibodies in CSF
    • Aside from the standard evaluation of CSF for pleocytosis, protein levels, and glucose levels, numerous tests are available to determine whether anti–B. burgdorferi antibodies are being produced in the CNS. Techniques include a variety of immunoassays, capture assays, and the ELISA test. It is imperative to simultaneously test the serum and CSF to determine whether the antibodies are being produced in the CNS or leaking across the blood–brain barrier. PCR testing can also be used to detect the presence of the spirochete in the CSF.
URINE TESTING
The Lyme urine antigen test (LUAT) is an antigen capture test. Current peer-reviewed literature does not support the utility of the LUAT in the detection of Lyme disease, and a positive value should be regarded as dubious. Also, the CDC and the FDA are aware of commercial laboratories that conduct testing for Lyme disease with assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, for which criteria have not been validated and published in peer-reviewed scientific literature.

Outer surface protein A (OspA) is a protein found on the outer membrane of Borrelia bacterial peptides. Limited evidence from a single cohort study (Magni et al., 2015) has shown that the shedding of Borrelia OspA in the urine is linked to active clinical manifestations (e.g., EM rash, arthritis), while the resolution of these symptoms after treatment is correlated with urinary conversion to OspA negative. Although preliminary evidence is promising for early-​stage Lyme diagnosis, additional research is needed to determine the diagnostic utility of urinary analysis in OspA. 

SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT)
SPECT scanning is a noninvasive radionuclide imaging technique that differs from other radiologic studies in that it provides information on perfusion (functional and metabolic activity) rather than anatomic structures. SPECT has been proposed for the diagnosis of encephalopathy secondary to B. burgdorferi infection; however, current peer-reviewed literature suggests that SPECT scanning alone is insufficient to diagnose Lyme encephalopathy.

T-CELL PROLIFERATIVE ASSAY
T-cell (T-lymphocyte) proliferation assays are difficult to perform and standardize, and their sensitivity is not well-defined. Therefore, they are not usually performed as diagnostic tests.

B LYMPHOCYTE CHEMOATTRACTANT CXCL13
Determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment has been reported to be elevated in acute neuroborreliosis; thus it is a potential marker for successful treatment. However, clinical studies and outcomes data are limited. Additional research is necessary to determine the true impact of this diagnostic technology.

HUMAN NATURAL KILLER-1 CELLS (HNK1), CLUSTER OF DIFFERENTIATION (CD)57
There have been only limited studies of HNK1 (also known as CD57) cell subsets in the context of bacterial or parasitic infections. Some individuals with reported chronic Lyme disease may have lower proportions of peripheral blood HNK1 (CD57) cells compared to those with acute disease and uninfected controls, and this phenotype was maintained for over 10 years in one individual with persistent infection. In contrast, no significant differences in numbers of peripheral blood HNK1 (CD57) cells were noted between individuals reported with "post-Lyme disease syndrome", individuals recovered from Lyme disease, and healthy control subjects. The suggestion that high frequencies of HNK1 (CD57) cells may be a biomarker of Lyme disease progression has not been adequately established, especially given the potential impact on HNK1 (CD57) cell phenotype of human cytomegalovirus (HCMV) and other infections. (Nielson et al., 2013). In addition, this available test has not been endorsed by the CDC or guidelines from major organizations as a diagnostic test for Lyme disease.

TREATMENT OF LYME DISEASE

ANTIBIOTIC THERAPY
Oral antibiotic therapy is the usual course of treatment for Lyme disease. IV antibiotic therapy is generally indicated only in individuals who have symptoms and laboratory findings consistent with CNS or peripheral neurologic involvement, those who have heart block, or those who have been diagnosed with Lyme arthritis who have not responded to oral antibiotics. IV antibiotic therapy consists of a single 2- to 4-week course of ceftriaxone or cefotaxime, both third-generation cephalosporins, penicillin, or chloramphenicol. With the exception of refractory Lyme arthritis, there are insufficient data to suggest that prolonged or repeated courses of IV antibiotics are effective. A repetitive course of IV antibiotic may be necessary for refractory Lyme arthritis. The lack of response should suggest an incorrect diagnosis or a slow resolution of symptoms, which is commonly seen in Lyme disease. In addition, some symptoms (such as Lyme arthritis) may persist after treatment, which could be attributed to various self-sustaining inflammatory mechanisms rather than persistent infection.

There is no current evidence to support the use of antibiotics beyond 4 weeks in individuals with chronic symptoms after standard, efficacious treatment for Lyme disease.

In a randomized, double-blinded, placebo-controlled trial, Berende et al. (2016) assessed longer term antibiotic therapy for persistent symptoms (musculoskeletal pain, arthritis, arthralgia, neuralgia, sensory disturbances, dysesthesia, neuropsychological disorders, or cognitive disorders, with or without persistent fatigue) attributed to Lyme disease. Researchers evaluated 281 participants who either had proven cases of symptomatic Lyme disease (symptoms temporally related to an EM rash) or were accompanied by B. burgdorferi IgG or IgM antibodies, as confirmed by immunoblot assay. All participants received open-label ceftriaxone intravenously daily for 14 days, followed by an investigative oral treatment course of either doxycycline (n=86), clarithromycin (n=96) or a placebo (n=98) for 12 weeks. The primary outcome of interest was health-related quality of life (measured by physical component summary score [PCS] of the RAND SF-36 (range between 15 and 61, higher scores indicating higher quality of life) at the end of the treatment (14 weeks). Secondary outcomes assessed were the physical and mental health aspects of health-related quality of life, assessed by subscales of RAND SF-36, and fatigue. SF-36 PCS did not significantly differ across three study groups (P=0.69). All of the secondary outcomes failed to differ significantly. This trial suggests that longer term antibiotic treatment (ceftriaxone followed by 12 weeks of either doxycycline or clarithromycin–hydroxychloroquine) did not have additional health-related quality of life benefits beyond those with shorter term treatment (ceftriaxone followed by placebo).

LYME DISEASE IMMUNIZATION VACCINE

Currently, there is no available vaccine against Lyme disease.​

References

Abrams Y. Complications of coinfection with Babesia and Lyme disease after splenectomy. J Am Board Fam Med. 2008;21(1):75-77.

American College of Physicians. Guidelines for laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med. 1997;127(12):1106-1108.

American College of Rheumatology. Appropriateness of parenteral antibiotic treatment for patients with presumed Lyme disease. A joint statement of the American College of Rheumatology and the Council of the Infectious Diseases Society of America. Ann Intern Med. 1993;119(6):518.

American Lyme Disease Foundation (ALDF). The laboratory diagnosis of Lyme disease II, The Banbury Center, Cold Spring Harbor. Emerging views on serodiagnosis. [ALDF website]. Original: 09/09/07. (Revised: 01/05/10). Available at: http://www.aldf.com/2nd-banbury-conference/. Accessed September 11, 2025. 

Aucott J, Morrison C, Munoz B, et al. Diagnostic challenges of early Lyme disease: Lessons from a community case series. BMC Infect Dis. 2009;9:79.

Auwaerter PG. Point: Antibiotic therapy is not the answer for patients with persisting symptoms attributable to lyme disease. Clin Infect Dis. 2007;45(2):143-148.

Baker, PJ. Limitations of antibody-based diagnostic tests for lyme disease. [American Lyme Disease Foundation Web site]. Available at: https://www.aldf.com/pdf/Limitations_of_Antibody_Based_Diagnostic_Tests.pdf. Accessed September 11, 2025.

Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016;374(13):1209-1220.

Branda JA, Body BA, Boyle J, et al. Advances in serodiagnostic testing for Lyme disease are at hand. Clin Infect Dis. 2018;66(7):1133. 

Branda JA, Linskey K, Kim YA, et al. Two-tiered antibody testing for Lyme disease with use of 2 enzyme immunoassays, a whole-cell sonicate enzyme immunoassay followed by a VlsE C6 peptide enzyme immunoassay. Clin Infect Dis. 2011; 53(6):541-547.

Bratton RL, Whiteside JW, Hovan MJ, et al. Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008;83(5):566-571.

British Infection Association. The epidemiology, prevention, investigation and treatment of Lyme borreliosis in United Kingdom patients: a position statement by the British Infection Association. J Infect 2011;62(5):329-338.

Buckingham SC. Tick-borne infections in children: epidemiology, clinical manifestations, and optimal management strategies. Paediatr Drugs. 2005;7(3):163-176.

Cameron D. Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-controlled clinical trial. Minerva Med. 2008;99(5):489-496.

Centers for Disease Control and Prevention (CDC). Learn about Lyme disease. [CDC website]. Updated 01/19/18. Available at: http://www.cdc.gov/lyme/. Accessed September 11, 2025.

Centers for Disease Control and Prevention (CDC). Lyme disease (Borrelia burgdorferi). Case definition. [CDC website]. 08/30/2021. Available at: Lyme Disease (Borrelia burgdorferi) 2022 Case Definition | CDC. Accessed September 11, 2025.

Centers for Disease Control and Prevention (CDC). Morbidity and Mortality Weekly Report (MMWR). Concerns regarding a new culture method for Borrelia burgdorferi not approved for the diagnosis of Lyme disease. [CDC Web site]. 04/18/ 2014. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6315a4.htm?s_cid=mm6315a4_w. Accessed September 11, 2025.

Columbia University Medical Center. Lyme and Tick-Borne Disease Research Center. Lyme diseases: spinal fluid and brain tests. [Columbia University Medical Center website]. Available at: http://www.columbia-lyme.org/patients/ld_spinal_fluid.html. Accessed September 11, 2025.

Dana A. Vector-borne infections in solid organ transplant recipients. Int J Dermatol. 2012;51(1):1-11. 

Dattwyler RJ, Luft BJ, Kunkel MJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med. 1997;337(5):289-294.

DeBiasi RL. A concise critical analysis of serologic testing for the diagnosis of lyme disease. Curr Infect Dis Rep. 2014;16(12):450.

Eckman MH, Steere AC, Kalish RA, Pauker SG. Cost effectiveness of oral as compared with intravenous antibiotic therapy for patients with early Lyme disease or Lyme arthritis. N Engl J Med. 1997;337(5):357-363.

Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.

Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of "chronic Lyme disease." N Engl J Med. 2007;357(14):1422-1430.

Halperin JJ, Shapiro ED, Logigian E, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology (AAN). Neurology. 2007;69(1):91-102.

Hsu VM, Patella SJ, Sigal LH. “Chronic Lyme disease” as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum. 1993;36(11):1493-1500.

Hu L. Diagnosis of Lyme disease. [UptoDate Web site]. 05/05/2025. Available at: http://www.uptodate.com/contents/diagnosis-of-lyme-disease?source=see_link#H4. [via subscription only]. Accessed September 11, 2025.

Hytonen J, Kortela E, Waris M, et al. CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation. J Neuroinflammation. 2014;11:103.

Infectious Diseases Society of America (IDSA). ​Summary practice guidelines for clinicians.​ Available at: https://www.idsociety.org/globalassets/idsa/practice-guidelines/lyme/idsa_aan_acr-lyme-disease-guideline---clinician-summary.pdf. Accessed September 11, 2025.

Institute of Medicine (US) Committee on Lyme Disease and Other Tick-Borne Diseases: The State of Science. Critical Needs and Gaps in Understanding: Prevention, Amelioration, and Resolution of Lyme and Other Tick-Borne Diseases: The Short-Term and Long-Term Outcomes: Workshop Report 2011. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21977545. Accessed September 11, 2025.

Kaplan RF, Trevino RP, Johnson GM, et al. Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology. 2003;60(12):1916-1922.

Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic therapy in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.

Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003;60(12):1923-1930.

Lantos PM, Auwaerter PG, Wormser GP. A systematic review of Borrelia burgdorferi morphologic variants does not support a role in chronic Lyme disease. Clin Infect Dis. 2014;58(5):663-671.

Lantos PM, Charini WA, Medoff G, et al. Final report of the Lyme disease review panel of the Infectious Diseases Society of America. Clin Infect Dis. 2010;51(1):1-5.

Lantos PM, Rumbaugh J, Bockenstedt LJ, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clinical Infect Dis. 2021;72(1):e1-e48.​

Lebech AM, Hansen K, Brandrup F, et al. Diagnostic value of PCR for detection of Borrelia burgdorferi DNA in clinical specimens from patients with erythema migrans and Lyme neuroborreliosis. Mol Diagn. 2000;5(2):139-150.

Lipsett SC, Branda JA, McAdam AJ, et al. Evaluation of the C6 Lyme Enzyme immunoassay for the diagnosis of lyme disease in children and adolescents. Clin Infect Dis. 2016;63(7):922-928.

Magni R, Espina BH, Shah K, et al. Application of nanotrap technology for high sensitivity measurement of urinary outer surface protein A carboxyl-terminus domain in early stage Lyme borreliosis. J Transl Med. 2015;13(346):1-22.

Marques A. Chronic Lyme disease: a review. Infect Dis Clin North Am. 2008;22(2):341-360.

Marques A, Brown MR, Fleisher TA. Natural killer cell counts are not different between patients with post-Lyme disease syndrome and controls. Clin Vaccine Immunol. 2009;16(8):1249-5010.

Mead P, Petersen J, Hinckley A. Updated CDC recommendation for serologic diagnosis of Lyme disease. MMWR Morb Mortal Wkly Rep. 2019;68:703. 

Mygland A, Ljostad U, Fingerle V, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010;17(1):8-16, e1-4.

National Institute of Allergy and Infectious Diseases (NIAID). Chronic lyme disease. [NIAID Web site]. 11/21/2018. Available at: https://www.niaid.nih.gov/diseases-conditions/chronic-lyme-disease. Accessed September 11, 2025.

Nau R, Christen HJ, Eiffert H. Lyme disease--current state of knowledge. Dtsch Arztebl Int. 2009;106(5):72-81.

Nielsen CM, White MJ, Goodier MR, et al. Functional Significance of CD57 expression of human NK cells and relevance to disease. Front Immunol. 2013;4:422.

Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. 1999;31(3):225-232.

Oski J, Nikoskelainen J, Hiekkanen H, et al. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. Eur J Clin Microbiol Infect Dis. 2007;26(8):571-581.

Pachner AR. Early disseminated Lyme disease: Lyme meningitis. Am J Med. 1995;98(4A):30S-43S.

Porwancher R, Landsberg L. Optimizing use of multi-antibody assays for Lyme disease diagnosis: A bioinformatic approach. PLoS ONE. 2021;16(9):e0253514.​
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Pritt BS, Mead PS, Johnson DK, et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis. 2016;16(5):556-564.

Ryan MF, Thorn C. Lyme carditis in an immunocompromised patient. Case Rep Emerg Med. 2013;2013:380734.

Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review. JAMA. 2016;315(16):1767-1777.

Sigal LH. Current recommendations for the treatment of Lyme disease. Drugs. 1992;43(5):683-699.

Sigal LH. Early disseminated Lyme disease: cardiac manifestations. Am J Med. 1995;98(4A):25S-29S.

Situm M, Poje G, Grahovac B, et al. Diagnosis of Lyme borreliosis by polymerase chain reaction. Clin Dermatol. 2002;20(2):147-155.

Steere AC. Diagnosis and treatment of Lyme arthritis. Med Clin North Am. 1997;81(1):179-194.

Steere AC. Lyme disease. N Engl J Med. 2001;345(2):115-125.

Steere AC, Taylor E, McHugh GL et al. The overdiagnosis of Lyme disease. JAMA.1993; 269(14):1812-1816.

Stricker RB, Burrascano J, Winger E. Longterm decrease in the CD57 lymphocyte subset in a patient with chronic Lyme disease. Ann Agric Environ Med. 2002; 9(1):111-113.

Talagrand-Reboul E, Raffetin A, Zachary P, et al. Immunoserological Diagnosis of Human Borrelioses: Current Knowledge and Perspectives. Front Cell Infect Microbiol. 2020;10:241.

Tugwell P, Dennis DT, Weinstein A, et al. Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med. 1997;127(12):1109-1123.

US Food and Drug Administration (FDA). Center for Devices and Radiological Health. [FDA Web site]. Available at: https://www.accessdata.fda.gov/cdrh_docs/reviews/K233367.pdf​. Accessed September 11, 2025.​

Wagemakers A, Visser MC, de Wever B, et al. Case report: persistently seronegative neuroborreliosis in an immunocompromised patient. BMC Infect Dis. 2018;18(1):362.

Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol. 2007;49(1):13-21.

Wormser GP. Clinical practice. Early Lyme disease. N Engl J Med. 2006;354(26):2794-2801.

Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43(9):1089-1134.

Wormser GP, Ramanathan R, Nowakowski J, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138(9):697-704.​​

Coding

CPT Procedure Code Number(s)

MEDICALLY NECESSARY


THE FOLLOWING CODES ARE USED TO REPRESENT SEROLOGIC TESTS FOR LYME DISEASE:​

86617

86618


THE FOLLOWING CODE IS USED TO REPRESENT POLYMERASE CHAIN REACTION (PCR) AMPLIFIED PROBE TECHNIQUE, FOR LYME DISEASE:

87476


THE FOLLOWING CODE IS USED TO REPRESENT POLYMERASE CHAIN REACTION (PCR) DIRECT PROBE TECHNIQUE, FOR LYME DISEASE:

87475


THE FOLLOWING CODES ARE USED FOR TREATMENT OF LYME DISEASE:

96365

96366

96367

96368

96601

96602


EXPERIMENTAL/INVESTIGATIONAL


THE FOLLOWING CODES ARE USED TO REPRESENT HNK1(CD57) PROFILE:

86356

86357


THE FOLLOWING CODE IS USED TO REPRESENT LYME URINE ANTIGEN TEST (LUAT):

81099


THE FOLLOWING CODES ARE USED TO REPRESENT LYME IMMUNOBLOT IgG AND IgM TEST:

0041U

0042U


THE FOLLOWING CODE IS USED TO REPRESENT LYME IMMUNOASSAY lgG TEST:

0580U


THE FOLLOWING CODE IS USED TO REPRESENT LYME URINE OspA PROTIEN EVALUATION:

0316U​

ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)

A69.20 Lyme disease, unspecified

A69.21 Meningitis due to Lyme disease

A69.22 Other neurologic disorders in Lyme disease

A69.23 Arthritis due to Lyme disease

A69.29 Other conditions associated with Lyme disease

HCPCS Level II Code Number(s)

S9494 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem (do not use this code with home infusion codes for hourly dosing schedules S9497-S9504)

S9497 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 3 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9500 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 24 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9501 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 12 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9502 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 8 hours, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9503 Home infusion therapy, antibiotic, antiviral, or antifungal; once every 6 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

S9504 Home infusion therapy, antibiotic, antiviral, or antifungal; once every 4 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem​

Revenue Code Number(s)
N/A


Coding and Billing Requirements

Policy History

Revisions From 06.02.01l:
​12/29/2025
This version of the policy will become effective 12/29/2025.​​ The intent of this policy remains unchanged.

The following criteria have been ​added​ to this policy as medically necessary:
  • ​PCR testing for diagnosis on Lyme disease among immunodeficient individuals
  • PCR testing of synovial fluid to inform therapeutic decisions for suspected Lyme arthritis​​
The following diagnostic test has been ​added​ to this policy as experimental/investigational:
  • iDart Lyme IgG ImmunoBlot kit
The following HCPCS codes have been added to this policy as medically necessary:
  • S9497 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 3 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
  • S9500 Home infusion therapy, antibiotic, ​antiviral, or antifungal therapy; once every 24 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
  • S9501 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 12 hours; administrative services, professional pharmacy services, care coordination, and ​all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
  • S9502 Home infusion therapy, antibiotic, antiviral, or antifungal therapy; once every 8 hours, administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem
  • S9503 Home infusion therapy, antibiotic, antiviral, or antifungal; once every 6 hours; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem​
The Company's coverage position of CPT code 87475 has changed from experimental/investigational to medically necessary.​
​
The following CPT code has been added to this policy as experimental/investigational:
  • 0580U

Revisions From 06.02.01k:
​11/13/2024
​This policy has been reissued in accordance with the Company's annual review process.​​
11/06/2023This version of the policy will become effective 11/06/2023. The intent of this policy remains unchanged; however the policy has been updated to reflect modified diagnostic testing paradigm.

​The following CPT cod​e has been added to this policy

Experimental/Investigational - 0316U

Revisions From 06.02.01j:
​02/24/2021
​The policy has been reviewed and reissued to communicate the Company’s continuing position on Lyme Disease diagnosis and intravenous antibiotic treatment.​
04/20/2020This version of the policy will become effective 04/20/2020. The intent of this policy remains unchanged, but the policy has been updated to reflect modified diagnostic testing paradigm.

Revisions From 06.02.01i:
06/05/2019The policy has been reviewed and reissued to communicate the Company’s continuing position on Lyme Disease diagnosis and intravenous antibiotic treatment.
05/21/2018This policy has undergone a routine review, and the following diagnosis and procedure codes have been added to the policy: 96365, 96366, 96367, 96368, 99601, 99602, 0041U, 0042U.

The following HCPCS codes have been added to the policy, S9494, S9504.

Policy language was added to include diagnostic services that are Medically Necessary, the intent of the policy remains unchanged.

Revisions From 06.02.01h:
01/01/2018This policy has been identified for the CPT code update, effective 01/01/2018.

The following CPT code has been termed from this policy: 87477

Effective 10/05/2017 this policy has been updated to the new policy template format.
12/29/2025
12/29/2025
06.02.01
Medical Policy Bulletin
Commercial
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