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Horizon BCBSNJ
Uniform Medical Policy ManualSection:Treatment
Policy Number:007
Effective Date: 01/14/2020
Original Policy Date:01/01/1992
Last Review Date:01/14/2020
Date Published to Web: 03/27/2019
Subject:
Intravenous Antibiotic Therapy for Lyme Disease

Description:
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IMPORTANT NOTE:

The purpose of this policy is to provide general information applicable to the administration of health benefits that Horizon Blue Cross Blue Shield of New Jersey and Horizon Healthcare of New Jersey, Inc. (collectively “Horizon BCBSNJ”) insures or administers. If the member’s contract benefits differ from the medical policy, the contract prevails. Although a service, supply or procedure may be medically necessary, it may be subject to limitations and/or exclusions under a member’s benefit plan. If a service, supply or procedure is not covered and the member proceeds to obtain the service, supply or procedure, the member may be responsible for the cost. Decisions regarding treatment and treatment plans are the responsibility of the physician. This policy is not intended to direct the course of clinical care a physician provides to a member, and it does not replace a physician’s independent professional clinical judgment or duty to exercise special knowledge and skill in the treatment of Horizon BCBSNJ members. Horizon BCBSNJ is not responsible for, does not provide, and does not hold itself out as a provider of medical care. The physician remains responsible for the quality and type of health care services provided to a Horizon BCBSNJ member.

Horizon BCBSNJ medical policies do not constitute medical advice, authorization, certification, approval, explanation of benefits, offer of coverage, contract or guarantee of payment.
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The administration of antibiotics via an intravenous infusion for the treatment of Lyme Disease.

[In the serodiagnosis of Lyme Disease, all testing should be initiated by enzyme-linked immunosorbent assay (ELISA), immunofluorescence assay (IFA) or antibody-capture enzyme immunoassay (EIA) as "screening" tests. These tests detect both IgM and IgG but do not necessarily differentiate between the two immunoglobulins. None of these antibody tests are standardized: results vary from lab to lab. False positive reactions have been reported in patients with syphilis, relapsing fever, juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), Parvovirus, Epstein-Barr virus (mononucleosis), Cytomegalovirus, subacute bacterial endocarditis, gingivitis, and periodontitis. Because these tests are generally sensitive, specimens negative by ELISA, IFA or EIA need not be tested further since the diagnosis of Lyme disease can virtually be excluded. However, specimens positive, minimally reactive, or equivocal by ELISA, IFA or EIA should be confirmed by Western blots because of their relatively low specificity. If signs or symptoms last 30 days or less, both IgM and IgG Western blots should be performed. If signs or symptoms last more than 30 days, only an IgG Western blot should be performed. Per the CDC, a positive IgM test result alone is not recommended for use in determining active disease in persons with illness lasting longer than 30 days because the likelihood of a false-positive test result for a current infection is high for these persons. Lyme disease can be confirmed if the ELISA/EIA/IFA and the Western Blot(s) are both positive. If early Lyme disease is suspected clinically despite a negative antibody titer, serological investigations (starting with ELISA, IFA or EIA) should be repeated approximately 2 to 4 weeks later since 60 percent of infected individuals may test negative at the early stage. Please note that antibiotic therapy may prevent an increase in specific antibodies and that seroconversion may even occur after antibiotic therapy.

The clinical findings and serological findings are dependent on disease duration or stage.
Early localized infection
  • a few days to a month after tick bite
  • erythema migrans in 50-70% of patients
  • fatigue/malaise/lethargy/headache/myalgias/arthralgias/regional or generalized lymphadenopathy
  • less than half of the patients have detectable specific antibodies, predominantly IgM.

Early disseminated disease
  • days to 10 months after tick bite
  • carditis - 8-10% of untreated patients
- conduction defects/mild cardiomyopathy
  • neurologic - approx. 10-12% of untreated patients
- meningitis/encephalitis/cranial neuropathy/peripheral neuropathy/myelitis
  • musculoskeletal - approx. 50% of untreated patients
- migratory polyarthritis &/or
  • polyarthralgias/fibromyalgia
  • the proportion rises to 70-90%, with a switch from IgM to IgG.
    However, in the early stage of the disease (localized or even disseminated), there may be an isolated IgM reactivity to ELISA, IFA or EIA, or in a minority of patients, there may only be an IgG response. Therefore, both IgM and IgG Western blots are recommended during the early stage.

Late/Chronic disease
  • months to years after tick bite
  • musculoskeletal - approx. 50% of untreated patients develop migratory polyarthritis
- approx. 10% of untreated patients develop chronic monoarthritis usually of the knee
- fibromyalgia
  • neurologic - chronic often subtle encephalopathy &/or peripheral neuropathy/ataxia/dementia/sleep disorder
  • skin - acrodermatitis chronica atrophicans
  • IgG antibody titers are usually high and may remain so for several years, even when treatment is successful. Elevated serum IgG alone indicates previous exposure to B. burgdorferi but not necessarily recent or active infection. IgG Western blot is usually sensitive and specific in this stage. There is no role for an IgM Western blot nor IgM-specific ELISA, IFA or EIA test because they have been shown to have a high number of false positives (low specificity) in patients whose symptoms have been present for more than one month.
    In no case should serologic reactivity be considered synonymous with active infection. Antibody tests (and Western blots) have been shown to remain positive for years after successful treatment.
IgM Western blot is considered positive if two of the following three bands are present: 21/22/23/24/25 kDa (OspC)*, 39 kDa (BmpA), and 41 kDa (Fla). IgG Western blot is considered positive if five of the following 10 bands are present: 18 kDa, 21/22/23/24/25 kDa (OspC)*, 28 kDa, 30 kDa, 39 kDa, (BmPH), 41 kDa (Fla) , 45 kDa, 58 kDa (not GroEL), 66 kDa, and 93 kDa.
    * The apparent molecular mass of OspC is dependent on the strain of B. burgdorferi being tested and thus, 21kDa, 22 kDa, 23 kDa, 24 kDa, and 25 kDa proteins referred to above are the same.

Although culture isolation of Borrelia burgdorferi is the “gold standard” for diagnosis, it is not a practical routine test at the present time since B. burgdorferi is very difficult to grow in the laboratory. Furthermore, most skin lesions in patients from endemic areas are easily identified on a clinical basis making culture techniques unnecessary. Positive culture rates of nearly 90% for secondary EM lesions, 50% for primary EM lesions, and 48% for large-volume (>9 ml) blood or plasma specimens for early Lyme disease have been reported. Isolation of B. burgdorferi from other sites (synovial fluid, CSF) are uncommon which is probably due to the small number of organisms present in these anatomic locations.

Spinal fluid analysis is mandatory in testing for neuroborreliosis (Lyme disease antibodies/ cell count & differential/ protein/ glucose/ Gram's stain/ VDRL). Expressing CSF and serum ELISA results as a ratio may help correct for passive diffusion of anti-Borrelia antibodies across the blood brain barrier and can also be used to support (but not confirm) a clinical diagnosis of neuroborreliosis. If the patient has cognitive dysfunction, neuropsychologic studies should be done. If there is peripheral nerve damage, EMG and nerve conduction velocity (NCV) studies are indicated; if there are sensory changes only, somatosensory evoked potentials (SSEP) are in order.

Magnetic Resonance Imaging (MRI) may be useful in looking for other abnormalities which may be confused with neuroborreliosis. Single-Photon Emission Computed Tomography (SPECT), a functional neuroimaging technique used to evaluate regional cerebral blood flow, may be useful to demonstrate whether a patient with suspected Lyme disease actually has encephalopathy and may be helpful to follow response to therapy. It has been reported to show improvement in perfusion abnormalities in patients with Lyme encephalopathy at 6 months after one-month course of ceftriaxone. Radiologic studies are not required in all patients and should only be used as an adjunct to other diagnostic tests when there is uncertainty as to the patient's diagnosis or response to therapy.

Neuropsychological testing indicated that cognitive impairment appeared to be similar in subjects with a short and with a long follow-up. This argues in favor of a static change occurring in the acute illness rather than a chronic progressive encephalopathy, as found in other chronic spirochete infections.

Polymerase Chain Reaction (PCR) testing of the CSF may be medically appropriate in patients with a short duration of neurologic symptoms (<14 days) during the window between exposure and the emergence of detectable levels of antibodies in the CSF. Furthermore, PCR testing of the CSF and synovial fluid may also be medically appropriate for patients suspected of Late/Chronic Lyme disease. Studies have shown that CSF PCR becomes negative shortly after treatment of patients with neuroborreliosis. If a patient has a persistently positive CSF PCR and ongoing symptoms, it would be reasonable to re-treat with IV antibiotics. PCR in synovial fluid of patients with Lyme arthritis may be predictive of ongoing infection in patients with persistent joint effusion after antibiotic therapy. A positive PCR test in synovial fluid suggests that a live spirochete is still present within the joint. The great problem with PCR is the risk of exogenous contamination causing false-positive results. On the other hand, inhibitory substances may cause false-negative reactions by interfering with polymerase activity. Additionally, PCR cannot distinguish between live and dead B. burgdorferi since it can amplify DNA from live and dead organisms. The significance of persistent PCR positivity in serum and urine is unknown. The importance of PCR in monitoring the efficacy of treatment has not yet been established.

According to the MMWR Weekly, February 11, 2005, “CDC and FDA have become aware of commercial laboratories that conduct testing for Lyme disease by using assays whose accuracy and clinical usefulness have not been adequately established. These tests include urine antigen tests, immunofluorescent staining for cell wall-deficient forms of B. burgdorferi, and lymphocyte transformation tests. In addition, some laboratories perform polymerase chain reaction tests for B. burgdorferi DNA on inappropriate specimens such as blood and urine or interpret Western blots using criteria that have not been validated and published in peer-reviewed scientific literature.” Furthermore, this article reminds health-care providers that “a diagnosis of Lyme disease should be made after evaluation of a patient’s clinical presentation and risk for exposure to infected ticks, and if indicated, after the use of validated laboratory tests.”

There are approximately 6,000 laboratories worldwide that have met the highest standards of excellence and have subsequently been awarded the College of American Pathologists (CAP) accreditation. A CAP accredited laboratory is one that is inspected by a private not-for-profit accrediting organization that has been approved by the Centers for Medicare & Medicaid Services (CMS) and its requirements deemed as equivalent to or more stringent than CMS’s regulatory requirements. Examples of such laboratories include, but are not limited to, Quest Diagnostics, LabCorp, Imugen, State University of New York at Stony Brook, and Mayo Clinic.

The diagnosis and management of patients with Lyme disease should be consistent with acceptable guidelines. These guidelines must be supported by scientific data published in peer-reviewed medical literature, and are consistent with recommendations from nationally recognized organizations including, but not limited, to the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the American Academy of Neurology, the American College of Rheumatology, the American College of Physicians and the Infectious Disease Society of America.

The International Lyme and Associated Diseases Society (ILADS) is an organization whose guidelines are different from those of the above-named organizations.]

Policy:
(NOTE: For Medicare Advantage, Medicaid and FIDE-SNP, please refer to the Coverage Sections below for coverage guidance.)


I. IV antibiotic therapy must be prescribed and monitored by the treating physician.

II. IV antibiotics in early localized infection are not considered medically necessary. The treatment of choice is a course of oral antibiotic therapy.

III. A 2- to 4-week course of intravenous (IV) antibiotic therapy is considered medically necessary in patients with early disseminated disease or late/chronic disease with neuroborreliosis with objective neurologic complications of documented Lyme disease when all of the following are met: (see the following for methods of documentation).
    A. Objective neurologic findings include:
      • Lymphocytic meningitis with documented cerebrospinal fluid (CSF) abnormalities
      • Cranial neuropathy, other than uncomplicated cranial nerve palsy, with documented CSF abnormalities
      • Encephalitis or encephalomyelitis with documented CSF abnormalities
      • Radiculopathy
      • Polyneuropathy.

    [INFORMATIONAL NOTE: Lyme disease may be documented either on the basis of serologic testing or by clinical findings of erythema migrans in early infection. Documentation of CSF abnormalities is required for suspected central nervous system (CNS) infection, as indicated above.]

    B. Serologic documentation of infection requires:
    • Positive or indeterminate enzyme-linked immunosorbent assay (ELISA), AND
    • Positive immunoblot blot by Centers for Disease Control and Prevention criteria.
    C. Polymerase chain reaction (PCR)‒based direct detection of B burgdorferi in CSF samples is considered medically necessary in patients with early disseminated disease or late/chronic disease and may replace serologic documentation of infection in patients with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies.
      D. Documented CSF abnormalities include ALL of the following:
      • Pleocytosis;
      • Evidence of intrathecal production of Borrelia burgdorferi antibodies in CSF; and
      • Increased protein levels.

      [INFORMATIONAL NOTE: As per the ISDA (Infectious Diseases Society of America) guidelines on Lyme Disease, the vast majority of patients with early neurologic Lyme disease are seropositive. Patients should have a total body skin examination to look for a concurrent erythema migrans lesion and should be questioned to determine whether one had been present within the preceding 1–2 months. For the small proportion of patients who have neurologic Lyme disease but are found to be seronegative by 2-tier testing, a convalescent-phase serum sample obtained ∼2 weeks after the acute-phase sample will usually yield positive results.]

      E. Antibiotics used are:
        • Ceftriaxone (Rocephin®), cefotaxime (Claforan®), or Penicillin G; or
        • Azithromycin (Zithromax®) in individuals with betalactam allergy or intolerance.
    IV. A single 2- to 4-week course of IV antibiotics is considered medically necessary in patients with early disseminated disease or late/chronic disease Lyme carditis, as evidenced by positive serologic findings (defined above) and associated with a high degree of atrioventricular block or a PR interval of greater than 0.3 second or clinical evidence of congestive heart failure. Documentation of Lyme carditis may include PCR-based direct detection of B burgdorferi in the blood when results of serologic studies are equivocal.

    V. A single 2- to 4-week course of IV antibiotic therapy is considered medically necessary in the small subset of patients with early disseminated disease or late/chronic disease with well-documented Lyme arthritis who have such severe arthritis that it requires the rapid response associated with IV antibiotics. Documentation of Lyme arthritis may include PCR-based direct detection of B. burgdorferi in the synovial tissue or fluid when results of serologic studies are equivocal.

    VI. For intravenous antibiotic therapy to be considered medically necessary, symptomatic pregnant women have to have failed oral antibiotics treatment course.


      [INFORMATIONAL NOTE: Based on recommendations published in peer-reviewed medical literature, co-infection with Babesia, Ehrlichia or Bartonella are generally treated and managed sufficiently with oral antibiotics. IV antibiotics are not routinely used solely based on the presence of co-infection with these organisms.]


    VII. Intravenous antibiotic therapy for early disseminated disease and late/chronic disease is considered medically necessary up to a maximum of four (4) week course of therapy. There are no clinical studies which demonstrate benefit in routinely administering IV antibiotics beyond 4 weeks. Furthermore, there are no clinical data to indicate that a second course longer than 4 weeks would be more beneficial than another 4 week course.
      [INFORMATIONAL NOTE: Based on recommendations published in peer-reviewed medical literature, there is no justification to extend IV antibiotic therapy beyond 4 weeks based solely on the presence of co-infection with Babesia, Ehrlichia or Bartonella.]

    Horizon Blue Cross Blue Shield of New Jersey ( Horizon BCBSNJ) may extend the course of treatment beyond four weeks when there is sufficient objective evidence of new or extending manifestations of the disease. The Medical Director will make this determination after receiving appropriate documentation from the treating physician which should include objective clinical and laboratory findings. Horizon BCBSNJ may require a consultation with an appropriate specialist.
      A. Continuation or extension of IV antibiotics beyond 4 weeks as a second course may be medically necessary in the following clinical situations:
        1. recurrent Lyme arthritis with active synovitis after a 4-week course of appropriate antibiotics (ceftriaxone, cefotaxime, penicillin G);
        2. recurrent neuroborreliosis, (neurologic involvement of Lyme disease) documented by CSF pleocytosis, CSF culture, or PCR of CSF, or neuropsychological studies.

      B. Re-treatment with a second separate course of IV antibiotics may be medically necessary for any of the following indications:
        1. clinical evidence of recurrent or new synovitis if other causes have been ruled out:
        2. clinical evidence of recurrent or new objective neurological physical findings in the absence of other explanations;
        3. laboratory evidence of persistent (non-improving) CSF pleocytosis if other causes have been ruled out. (If the spinal fluid showed a marked improvement but not complete resolution of the pleocytosis soon after completing therapy, another course of therapy may not be warranted.);
        4. laboratory evidence of persistently positive CSF and/or synovial fluid culture, i.e., positive after initial IV treatment;
        5. laboratory evidence of positive PCR in CSF and/or synovial fluid. (PCR of urine or serum is considered investigational.)

        [Examples of cases where extension of IV therapy or another course of IV therapy may be medically necessary since there is reasonable likelihood that the infection has not been eradicated: a patient has left knee arthritis and receives treatment only to develop neurologic disease or arthritis of another joint after termination of the treatment; a patient who has had treatment for established Lyme disease in the past and now develops new findings with increasing reactivity with Borrelia burgdorferi as indicated by expansion of the immunologic reactivity with new bands on Western blot. Please note that in order to determine expansion of the immunologic reactivity with new bands on Western blot, the specimens need to be run in parallel. This necessitates the laboratory storing the original specimen and retesting with new specimen.

        It is quite common for patients to have ongoing mild and slowly resolving non-specific findings after treatment. Further IV antibiotic therapy is not medically necessary in this case. Moreover, if the patient has received long-term and/or repeated treatment, in all likelihood there will no further response to additional treatment.]
    VIII. Intravenous antibiotic therapy is considered not medically necessary in the following situations:
      • Patients with symptoms consistent with chronic fatigue syndrome or fibromyalgia, in the absence of objective clinical or laboratory evidence for Lyme disease;
      • Patients with seronegative Lyme disease in the absence of CSF antibodies;
      • Initial therapy in patients with Lyme arthritis without coexisting neurologic symptoms;
      • Cranial nerve palsy (Bell palsy) without clinical evidence of meningitis;
      • Antibiotic-refractory Lyme arthritis (unresponsive to 2 courses of oral antibiotics or to 1 course of oral and 1 course of intravenous antibiotic therapy);
      • Patients with vague systemic symptoms without supporting serologic or CSF studies;
      • Patients with a positive ELISA test, unconfirmed by an immunoblot or Western blot test (see definition above);
      • Patients with an isolated positive serologic test in the setting of multiple negative serologic studies.
      • Patients with chronic (greater than or equal to 6 months) subjective symptoms ("post-Lyme syndrome") after receiving second intravenous antibiotic treatment regimen for documented Lyme disease.
      • Patients with mild cardiac involvement (such as 1st degree AV block with a PR interval of less than 300 milliseconds)
      • For Lyme disease prophylaxis
      [INFORMATIONAL NOTE: Controlled trials have found no clinical benefit from further antibiotic therapy for post-treatment.]

    IX. Services that are considered investigational include, but are not limited to, the following:
      • "Pulse" therapy (including, but not limited to, pulse therapy with Imipenem)
      • Hyperbaric oxygen therapy
      • IV magnesium or IV Bismuth
      • therapy with vancomycin
      • urine antigen tests
      • Polymerase Chain Reaction (PCR) other than CSF or synovial fluid
      • C6 peptide antibody assay
      • Genomic B. burgdorferi DNA test
      • Plasmid B. burgdorferi test
      • Urine Lyme disease dot blot assay.
      • Other diagnostic or monitoring testing, including but not limited to, C6 peptide ELISA or determination of levels of the B lymphocyte chemoattractant CXCL13

      Their clinical usefulness has not been validated or established based on data published in peer-reviewed medical literature.

    X. The supplies, cost of the drug and skilled nursing visits are eligible according to the provisions of the member's contract, if determined to be medically necessary.


    Medicare Coverage:
    There is no National Coverage Determination (NCD). In the absence of an NCD, coverage decisions are left to the discretion of Local Medicare Carriers. Novitas Solutions, Inc, the Local Medicare Carrier for jurisdiction JL, has not issued a determination for this service. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ Medical Policy.

    Medicaid Coverage:
    For members enrolled in Medicaid and NJ FamilyCare plans, Horizon BCBSNJ applies the above medical policy.

    FIDE-SNP Coverage:

    For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

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    Horizon BCBSNJ Medical Policy Development Process:

    This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

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    Index:
    Intravenous Antibiotic Therapy for Lyme Disease
    Antibiotic Therapy, IV for Lyme Disease
    ILADS (International Lyme and Associated Diseases Society)
    International Lyme and Associated Diseases Society (ILADS)
    IV Antibiotic Therapy for Lyme Disease
    Lyme Disease, IV Antibiotic Therapy
    Therapy, IV Antibiotic for Lyme Disease

    References:
    1. Schmidt BL. PCR in laboratory diagnosis of human Borrelia burgdorferi infections. Clinical Microbiology Review. 1997;10:185-201.

    2. Steere AC. Diagnosis and Treatment of Lyme Arthritis. Med Clin North America. 1997;81:179-94.

    3. Treatment of Lyme Disease. The Medical Letter. 2010;39:47-8.

    4. Halperin JJ, Logigian EL, Finkel MF, Pearl RA. Practice parameters for the diagnosis of patients with nervous system Lyme borreliosis (Lyme Disease). Neurology. 1996;46:619-27.

    5. Ledue TB, Collins MF, Craig W. New laboratory guidelines for serologic diagnosis of Lyme Disease: Evaluation of the two-test protocol. Journal of Clinical Microbiology. 1996;34:2243-50.

    6. Logigian EL, Johnson KA, Kijewski MF, et al. Reversible cerebral hypoperfusion in Lyme encephalopathy as demonstrated by quantitative single photon emission computed tomography (SPECT). VII International Congress on Lyme Borreliosis. 1996; Abstract #D612:134.

    7. Logigian EL, Kaplan EL, McHugh GL, Steere AC. Evaluation of IV ceftriaxone in the treatment of chronic Lyme neuroborreliosis. VII International Congress on Lyme Borreliosis. 1996; Abstract #D611:133.

    8. Recommendations for Test Performance and Interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. Morbidity and Mortality Weekly Report. August 11, 1995; 44(31):590-1.

    9. Benke TH, Gasse TH, Hittmair-Delazer M, Schmutzhard E. Lyme encephalopathy: Long-term neuropsychological deficits years after acute neuroborreliosis. Acta Neurol Scand. 1995;91:353-73.

    10. MetPath Clinical Laboratory. The 1995 Reference Manual.

    11. Pfister HW, Wilske B, Weber K. Lyme Borreliosis: Basic Science and Clinical Aspects. The Lancet. April 23, 1994; 343: 1013-16.

    12. Krupp LB, Masur D, Schwartz J, et al. Cognitive functioning in late Lyme borreliosis. Arch Neurol. 1991;48:1125-29.

    13. ECRI. Hotline Report: Treatment of Lyme Disease. 2001

    14. Practice Guidelines for the Treatment of Lyme Disease. Infectious Diseases Society of America. Clin Infect Dis 2000 Jul;31(Suppl 1):1-14.

    15. Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001 Jul 12;345(2):85-92.

    16. Donta ST. Treatment of patients with persistent symptoms and a history of Lyme disease. N Engl J Med 2001 Nov 8;345(19):1424; discussion 1425.

    17. Steere AC. Lyme Disease. N Engl J Med 2001 Jul 12;345(2):115-125.

    18. Centers for Disease Control. Notice to Readers: Caution Regarding Testing for Lyme Disease. MMWR 2005 Feb 11;54(05):125.

    19. Costello CM, Steere AC, Pinkerton RE, et al. A prospective study of tick bites in an endemic area for Lyme disease. J Infect Dis 1989 Jan;159(1):136-9.

    20. Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med 1990 Nov 22;323(21):1438-44.

    21. Shapiro ED, Gerber MA, Holabird NB, et al. A controlled trial of antimicrobial prophylaxis for Lyme disease after deer-tick bites. N Engl J Med 1992 Dec 17;327(25):1769-73.

    22. Dinerman H, Steere AC. Lyme disease associated with fibromyalgia. Ann Intern Med 1992 Aug 15;117(4):281-5.

    23. Agre F, Schwartz R. The value of early treatment of deer tick bites for the prevention of Lyme disease. Am J Dis Child 1993 Sep;147(9):945-7.

    24. Piesman J. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J Infect Dis 1993 May;167(5):1082-5.

    25. Asch ES, Bujak DI, Weiss M, et al. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994 Mar;21(3):454-61.

    26. Sigal LH. Persisting complaints attributed to chronic Lyme disease: possible mechanisms and implications for management. Am J Med 1994 Apr;96(4):365-74.

    27. Benke T, Gasse T, Hittmair-Delazer M, et al. Lyme encephalopathy: long-term neuropsychological deficits years after acute neuroborreliosis. Acta Neurol Scand 1995 May;91(5):353-7.

    28. Valesova H, Mailer J, Havlik J, et al. Long-term results in patients with Lyme arthritis following treatment with ceftriaxone. Infection 1996 Jan-Feb;24(1):98-102.

    29. Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med 1996 Oct 24;335(17):1270-4.

    30. Sood SK, Salzman MB, Johnson BJ, et al. Duration of tick attachment as a predictor of the risk of Lyme disease in an area in which Lyme disease is endemic. J Infect Dis 1997 Apr;175(4):996-9.

    31. Logigian EL, Johnson KA, Kijewski MF, et al. Reversible cerebral hypoperfusion in Lyme encephalopathy. Neurology 1997 Dec;49(6):1661-70.

    32. Steere AC, Sikand VK, Meurice F, et al. Vaccination against Lyme disease with recombinant Borrelia burgdorferi outer-surface lipoprotein A with adjuvant. Lyme Disease Vaccine Study Group. N Engl J Med 1998 Jul 23:339(4):209-15.

    33. Patel R, Grogg KL, Edwards WD, et al. Death from inappropriate therapy for Lyme disease. Clin Infect Dis 2000 Oct;31(4):1107-9.

    34. Seltzer EG, Gerber MA, Cartter ML, et al. Long-term outcomes of persons with Lyme disease. JAMA 2000 Feb 2;283(5):609-16.

    35. Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme disease. The Infectious Diseases Society of America. Clin Infect Dis 2000 Jul;31 Suppl 1:1-14.

    36. Nowakowski J, Schwartz I, Liveris D, et al. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin Infect Dis 2001 Dec 15;33(12):2023-7.

    37. Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med 2001 Jul 12;345(2):79-84.

    38. Murray T, Feder HM Jr. Management of tick bites and early Lyme disease: a survey of Connecticut physicians. Pediatrics 2001 Dec;108(6):1367-70.

    39. Klempner MS, Schmid CH, Hu L, et al. Intralaboratory reliability of serologic and urine testing for Lyme disease. Am J Med 2001 Feb 15;110(3):217-9.

    40. Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med 2002 Mar 19;136(6):421-8.

    41. Hayes EB, Piesman J. How can we prevent Lyme disease? N Engl J Med 2003 Jun 12;348(24):2424-30.

    42. Cameron D, Gaito A, Harris N, et al. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther 2004;2(1 Suppl):S1-13.

    43. ECRI. Health Technology Assessment Information Service (HTAIS). Custom Hotline Response: PVR (Polymerase Chain Reaction) Test for Diagnosis of Lyme Disease. Updated 10/25/2005.

    44. Jacobs DS, Oxley DK, DeMott WR. Laboratory Test Handbook. 5th Edition. Lexi-Comp, Inc. 2001.

    45. Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ 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 Nov 1;43(9):1089-134. Epub 2006 Oct 2. Accessed on 12/30/2019.

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

    47. 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. Neurology 2007;69(1):91-102.

    48. Centers for Disease Control and Prevention (CDC). Division of Vector-Borne Infectious Diseases. Lyme Disease Treatment. Last reviewed April 12, 2011. [Available at http://www.cdc.gov/lyme/Treatment/ (accessed 01/06/2014).]

    49. Centers for Disease Control and Prevention (CDC). Division of Vector-Borne Infectious Diseases. Lyme Disease Diagnosis and Testing. Last reviewed April 12, 2011. [Available at http://www.cdc.gov/lyme/diagnosistesting/index.html (accessed 01/06/2014).]

    50. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Lyme Disease. [Available at http://www.niaid.nih.gov/topics/lymedisease/understanding/pages/chronic.aspx (accessed 01/06/2014).]

    51. Feder HM, Johnson BJ, O'Connell S, et al. A Critical Appraisal of "Chronic Lyme Disease". N Engl J Med 2007 Oct;357(14):1422-30.

    52. Centers for Disease Control and Prevention (CDC). Lyme Disease: Two Step Laboratory Process. 2015; http://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html. Accessed January 15, 2016

    53. DeBiasi RL. A concise critical analysis of serologic testing for the diagnosis of lyme disease. Curr Infect Dis Rep. Dec 2014;16(12):450. PMID 25351855

    54. Steere AC. Lyme disease. N Engl J Med. Jul 12 2001;345(2):115-125. PMID 11450660

    55. 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; http://www.ncbi.nlm.nih.gov/books/NBK57026/. Accessed August 17, 2015.

    56. Situm M, Poje G, Grahovac B, et al. Diagnosis of Lyme borreliosis by polymerase chain reaction. Clin Dermatol. Mar-Apr 2002;20(2):147-155. PMID 11973049

    57. Oksi J, Marjamaki M, Nikoskelainen J, et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med. Jun 1999;31(3):225-232. PMID 10442678

    58. Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol. Feb 2007;49(1):13-21. PMID 17266710

    59. 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. PMID 24920219

    60. 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. Sep 2011;53(6):541-547. PMID 21865190

    61. Hsu VM, Patella SJ, Sigal LH. "Chronic Lyme disease" as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum. Nov 1993;36(11):1493-1500. PMID 8240427

    62. Steere AC, Taylor E, McHugh GL, et al. The overdiagnosis of Lyme disease. JAMA. Apr 14 1993;269(14):1812-1816. PMID 8459513

    63. 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. Sep 15 1993;119(6):518. PMID 8357119

    64. 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. Neurology. Jul 3 2007;69(1):91-102. PMID 17522387

    65. Nau R, Christen HJ, Eiffert H. Lyme disease--current state of knowledge. Dtsch Arztebl Int. Jan 2009;106(5):72-81; quiz 82, I. PMID 19562015

    66. 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. Mar 2014;58(5):663-671. PMID 24336823 symptoms and a history of Lyme disease. N Engl J Med. Jul 12 2001;345(2):85-92. PMID 11450676

    67. Kaplan RF, Trevino RP, Johnson GM, et al. Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology. Jun 24 2003;60(12):1916-1922. PMID 12821733

    68. Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. Jun 24 2003;60(12):1923-1930. PMID 12821734

    69. Oksi 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. Aug 2007;26(8):571-581. PMID 17587070

    70. Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. Mar 25 2008;70(13):992-1003. PMID 17928580

    71. Cameron D. Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-controlled clinical trial. Minerva Med. Oct 2008;99(5):489-496. PMID 18971914

    72. Dattwyler RJ, Luft BJ, Kunkel MJ, et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med. Jul 31 1997;337(5):289-294. PMID 9233865

    73. Eckman MH, Steere AC, Kalish RA, et al. Cost effectiveness of oral as compared with intravenous antibiotic therapy for patients with early Lyme disease or Lyme arthritis. N Engl J Med. Jul 31 1997;337(5):357-363. PMID 9233874

    74. 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. May 6 2003;138(9):697-704. PMID 12729423

    75. 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. Jul 1 2010;51(1):1-5. PMID 20504239

    76. Mygland A, Ljostad U, Fingerle V, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. Jan 2010;17(1):8-16, e11-14. PMID 19930447

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

    78. Fish AE, Pride YB, Pinto DS. Lyme Carditis. Infectious Disease Clinics of North America. 22 (2008) 275-288. Available at https://www.cdc.gov/lyme/resources/Fish2008-508.pdf

    Codes:
    (The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

    CPT*

    HCPCS
    0041U
    0042U
    87475
    87476
    96365

      96366
      96367
    96368
    96374
      96375
      96376
    J0456
      J0560
      J0561
      J0570
      J0580
      J0696
      J0698
    J0743
      J2510
      J2540
    J3370

    * CPT only copyright 2020 American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.

    _________________________________________________________________________________________

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    The Horizon BCBSNJ Medical Policy Manual is proprietary. It is to be used only as authorized by Horizon BCBSNJ and its affiliates. The contents of this Medical Policy are not to be copied, reproduced or circulated to other parties without the express written consent of Horizon BCBSNJ. The contents of this Medical Policy may be updated or changed without notice, unless otherwise required by law and/or regulation. However, benefit determinations are made in the context of medical policies existing at the time of the decision and are not subject to later revision as the result of a change in medical policy
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