mp-359 - Medical Policies - Alabama
Intravenous Antibiotic Therapy and Associated Diagnostic Testing for Lyme Disease
Policy Number: MP-359
Latest Review Date: November 2019
Policy Grade: Effective October 26, 2015: Active policy but no longer scheduled for regular literature reviews and updates.
Treatment of Lyme disease (LD) consists of oral antibiotics, except for the following indications:
A 2- to 4-week course of IV antibiotic therapy may be considered medically necessary in members with neuroborreliosis with objective neurologic complications of documented LD (see the following for methods of documentation).
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
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.
Serologic documentation of infection requires:
Positive or indeterminate enzyme-linked immunosorbent assay (ELISA), AND
Positive immunoblot blot by Centers for Disease Control and Prevention (CDC) criteria.
Documented CSF abnormalities include ALL of the following:
Evidence of intrathecal production of Borrelia burgdorferi antibodies in CSF; and
Increased protein levels.
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi (by direct or amplified probe) in CSF samples may be considered medically necessary and may replace serologic documentation of infection in members with a short duration of neurologic symptoms (<14 days) during the window between exposure and production of detectable antibodies.
A single2- to 4-week course of IV antibiotics may be considered medically necessary in members with 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. Documentation of Lyme carditis may include PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal.
A single 2- to 4-week course of IV antibiotic therapy may be considered medically necessary in the small subset of members 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.
Intravenous antibiotic therapy is considered not medically necessary in the following situations:
Members with symptoms consistent with chronic fatigue syndrome or fibromyalgia, in the absence of objective clinical or laboratory evidence for Lyme disease;
Members with seronegative LD in the absence of CSF antibodies;
Initial therapy in patients with Lyme arthritis without coexisting neurologic symptoms;
Cranial nerve palsy (e.g. Bell’s 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);
Members with vague systemic symptoms without supporting serologic or CSF studies;
Members with a positive ELISA test, unconfirmed by an immunoblot or Western blot test (see definition above);
Members with an isolated positive serologic test in the setting of multiple negative serologic studies;
Members with chronic (> 6 months) subjective symptoms (“post-Lyme syndrome”) after receiving recommended treatment regimens for documented LD.
Repeat or prolonged courses (greater than 4 weeks) of intravenous antibiotic therapy is considered not medically necessary.
Repeat PCR-based direct detection of B. burgdorferi (by direct or amplified probe) is considered not medically necessary and investigational in the following situations:
As a justification for continuation of IV antibiotics beyond 1 month in patients with persistent symptoms
As a technique to follow therapeutic response
PCR-based direct detection of B. burgdorferi in urine samples is considered not medically necessary and investigational in all clinical situations.
Genotyping or phenotyping of B. burgdorferi is considered not medically necessary and investigational.
Determination of levels of the B lymphocyte chemoattractant CXCL 13 for diagnosis or monitoring treatment is considered not medically necessary and investigational.
Other diagnostic testing including but not limited to “stand alone” C6 peptide ELISA is considered not medically necessary and investigational.
DESCRIPTION OF PROCEDURE OR SERVICE
Lyme disease (LD) is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi and transmitted by the bite of an infected Ixodes scapularis (northeastern U.S.) or Ixodes pacificus (Pacific coast, most common in Northern California) tick. The disease is characterized by stages, beginning with localized infection of the skin (erythema migrans), followed by dissemination to many sites. Diagnostic testing for Lyme disease is challenging and there is the potential for overdiagnosis and overtreatment.
Manifestations of early disseminated disease may include lymphocytic meningitis, facial palsy, painful radiculoneuritis, atrioventricular (AV) block, or migratory musculoskeletal pain. Months to years later, the disease may be manifested by intermittent oligoarthritis, particularly involving the knee joint, chronic encephalopathy, spinal pain, or distal paresthesias. While most manifestations of LD can be adequately treated with oral antibiotics, intravenous (IV) antibiotics are indicated in some patients with neurologic involvement or atrioventricular block. The following paragraphs describe the various manifestations of Lyme disease, therapies, and the various laboratory tests used to support the diagnosis of LD.
Lymphocytic meningitis, characterized by head and neck pain, may occur during the acute disseminated stage of the disease. Analysis of the cerebrospinal fluid (CSF) is indispensable for the diagnosis of Lyme meningitis. If the patient has LD, the CSF will show a lymphocytic pleocytosis (lymphocyte count greater than normal) with increased levels of protein. Intrathecal production of antibodies directed at spirochetal antigens is typically present. A normal CSF analysis is strong evidence against Lyme meningitis. Usual treatment consists of 2 weeks of either oral (ambulatory setting) or IV (hospitalized patients) antibiotics.
Cranial neuritis, most frequently Bell’s palsy, may present early in the course of disseminated LD, occasionally before the development of antibodies, such that a LD etiology may be difficult to rule in or out. While Bell’s palsy typically resolves spontaneously with or without treatment with oral antibiotics, some physicians have recommended a lumbar puncture and a course of IV antibiotics if pleocytosis in the CSF is identified, primarily as a prophylactic measure to prevent further neurologic symptoms.
A subacute encephalopathy may occur months to years after disease onset, characterized by subtle disturbances in memory, mood, sleep, or cognition accompanied by fatigue. These symptoms may occur in the absence of abnormalities in the electroencephalogram (EEG), magnetic resonance imaging (MRI), or CSF. Also, the symptoms are nonspecific and overlap with fibromyalgia and chronic fatigue syndrome. Thus diagnosis of Lyme encephalopathy may be difficult and may best be made with a mental status exam or neuropsychological testing. Treatment with IV antibiotics is not indicated unless CSF abnormalities are identified.
Much rarer, but of greater concern, is the development of encephalomyelitis, characterized by spastic paraparesis, ataxias, cognitive impairment, bladder dysfunction, and cranial neuropathy. CSF examination reveals pleocytosis and elevated protein. Selective synthesis of anti-spirochetal antibodies can also be identified. A course of IV antibiotics with two weeks of ceftriaxone is suggested when CSF abnormalities are identified.
A variety of peripheral nervous system manifestations of LD have also been identified. Symptoms of peripheral neuropathy include paresthesias, or radicular pain with only minimal sensory signs. Patients typically exhibit electromyographic (EMG) or nerve conduction velocity abnormalities. CSF abnormalities are usually seen only in those patients with a coexistent encephalopathy.
Lyme carditis may appear during the early dissemination stage of the disease; symptoms include atrioventricular block, tachyarrhythmias, and myopericarditis. Antibiotics are typically given, although no evidence has demonstrated hastened resolution of symptoms. Both oral and IV regimens have been advocated. Intravenous regimens are used in patients with a high-degree atrioventricular block or a PR interval on the electrocardiogram more than 0.3 second. Patients with milder forms of carditis may be treated with oral antibiotics.
Lyme arthritis is a late manifestation of infection and is characterized by an elevated IgG response to B. burgdorferi and intermittent attacks of oligoarticular arthritis, primarily in the large joints such as the knee. Patients with Lyme arthritis may be successfully treated with a 30-day course of oral doxycycline or amoxicillin, but care must be taken to exclude simultaneous involvement, requiring IV antibiotic treatment. In the small subset of patients that do not respond to oral antibiotics, an additional 30-day course of oral or IV antibiotics may be recommended.
Fibromyalgia and Chronic Fatigue Syndrome
Fibromyalgia and chronic fatigue syndrome are the diseases most commonly confused with LD. Fibromyalgia is characterized by musculoskeletal complaints, multiple trigger points, difficulty in sleeping, generalized fatigue, headache, or neck pain. The joint pain associated with fibromyalgia is typically diffuse, in contrast to Lyme arthritis, which is characterized by marked joint swelling in one or more joints at a time, with few systemic symptoms. Chronic fatigue syndrome is characterized by multiple subjective complaints, such as overwhelming fatigue, difficulty in concentration, and diffuse muscle and joint pain. In contrast to LD, both of the above conditions lack joint inflammation, have normal neurological test results, or have test results suggesting anxiety or depression. Neither fibromyalgia nor chronic fatigue syndrome has been shown to respond to antibiotic therapy.
The optimum method of testing for Lyme disease depends on the stage of the disease. Diagnostic testing may not be necessary when a diagnosis can be made clinically in patients with a recent tick bite or exposure and the presence of the characteristic rash of erythema migrans. While diagnosis of Lyme disease is generally based on the clinical picture and demonstration of specific antibodies (see next), polymerase chain reaction (PCR) based technology can detect the spirochete in the central nervous system in cases of neuroborreliosis, in the synovial fluid of cases of Lyme arthritis, and rarely in skin biopsy specimens of those with atypical dermatologic manifestations. However, while PCR-based tests can identify organisms in skin biopsy specimens of patients with dermatologic manifestations (i.e., erythema migrans) this diagnosis is typically made clinically and antibiotic therapy is started empirically.
Similarly, diagnosis of Lyme arthritis is based on clinical and serologic studies without the need for synovial tissue or fluid. Finally, intrathecal antibody production is considered a more sensitive test than PCR-based cerebral spinal fluid (CSF) detection in patients with suspected neuroborreliosis. Polymerase chain reaction (PCR), may be clinically useful as a second approach 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. PCR-based detection is typically not performed in the urine due to the variable presence of endogenous polymerase inhibitors that affect test sensitivity.
The antibody response to infection with B. burgdorferi follows a typical pattern. During the first few weeks after the initial onset of infection, there is no antibody production. The specific IgM response characteristic of acute infection peaks between the third and sixth week. The specific IgG response develops only after months and includes antibodies to a variety of spirochetal antigens. IgG antibodies produced in response to LD may persist for months or years. Thus, detection of IgG antibodies only indicates exposure, either past or present. In LD endemic areas, underlying asymptomatic seropositivity may range from 5%–10%. Thus, as with any laboratory test, interpretation of serologic tests requires close correlation with the patients’ signs and symptoms. For example, patients with vague symptoms of LD, chronic fatigue syndrome, or fibromyalgia may undergo multiple serologic tests over many weeks to months to establish the diagnosis of LD. Inevitably, in this setting of repeat testing, one enzyme-linked immunosorbent assay (ELISA) or test, whether IgG or IgM, may be reported as weakly positive or indeterminate. These results most likely represent false positive test results in the uninfected patient who has had long-standing symptoms from a different condition and previously negative test results.
Currently, the Centers for Disease Control and Prevention (CDC) recommend a two-tiered method for the serologic diagnosis of LD: 1) an enzyme-linked immunosorbent assay (ELISA) or immunofluorescence assay, followed by 2) a confirmatory Western blot (including both IgM and IgG when signs or symptoms have been present ≤30 days; only IgG only if symptoms have been present >30 days). A negative ELISA or IFA may be followed by a later (e.g., in 4 to 6 weeks) convalescent serum test when symptoms have been present ≤30 days.
ELISA for B. Burgdorferi Antibodies
This ELISA test is a screening serologic test for Lyme disease. ELISA tests are available to detect IgM or IgG antibodies or both antibody types together. More recently developed tests using recombinant or synthetic antigens have improved diagnostic sensitivity. For example, the U.S. Food and Drug Administration‒approved C6 ELISA is highly sensitive to infection and is under study as an indicator of antibiotic therapy efficacy. A positive or indeterminate ELISA test result alone is inadequate serologic evidence of Lyme disease. All of these tests must be confirmed with a Western blot. Also, results must be correlated with the clinical picture.
This immunoblot test is used to confirm the serologic diagnosis of Lyme disease in patients with positive or indeterminate ELISA tests. In contrast with the standard ELISA test, the immunoblot investigates the specific antibody response to the different antigens of B. burgdorferi. Typically, several clinically significant antigens are tested. According to Centers for Disease Control and Prevention criteria, the test result is considered positive if 2 of the 3 most common IgM antibody bands to spirochetal antigens are present, or 5 of the 10 most frequent IgG antibody bands are present. Because Centers for Disease Control and Prevention criteria were developed for surveillance, they are conservative and may miss true Lyme disease cases. Some support the use of more liberal criteria for a positive result in clinical diagnosis; however, alternative criteria have not been well-validated. U.S. criteria for interpreting immunoblot results differ from those in Europe due to differences in prevalent Borrelia species causing disease.
Polymerase Chain Reaction (PCR)
In contrast to the previously discussed serologic tests, which indirectly assess prior or present exposure to B. burgdorferi, PCR directly tests for the presence of the spirochete. Because PCR technology involves amplification of DNA from a portion of B. burgdorferi, there is a high risk of exogenous contamination, resulting in false positive results. Positive results in the absence of clear clinical indicators or positive serology are not definitive for diagnosis. Also, the test cannot distinguish between live spirochetes or fragments of dead ones. The PCR technique has been studied using a variety of specimens. PCR has the best detection rates for skin biopsies from patients with erythema migrans (but may not be indicated with recent history of tick bite or exposure) and for synovial tissue (and synovial fluid, to a lesser extent) from patients with Lyme arthritis. CSF may be positive by PCR during the first two weeks of infection, but thereafter the detection rate is low. PCR is not recommended for urine or blood specimens. 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.
Borrelia PCR also provides information on which of the three major species pathogenic for humans has been found in the specimen tested (genotyping).
T-Cell Proliferative Assay
T-lymphocyte proliferation assays are not recommended as diagnostic tests because they are difficult to perform and standardize, and their sensitivity is not well characterized.
Evaluation of Cerebrospinal Fluid (CSF)
Aside from the standard evaluation of CSF for pleocytosis, protein levels, and glucose levels, various tests are available to determine whether anti-B. burgdorferi antibodies are being selectively produced within the central nervous system. Techniques include a variety of immunoassays. For example, intrathecal antibody production can be detected by the CSF/serum index of B. burgdorferi antibodies. CSF and serum samples diluted to match the total IgG concentration in CSF are run in parallel in an IgG ELISA. Excess Borrelia-specific antibody in CSF indicates a positive result. As noted, PCR can also be used to detect the spirochete in the CSF, most successfully within the first two weeks of infection.
Evaluation of the Chemoattractant CXCL13
CXCL13 is a B lymphocyte chemoattractant and has been reported to be elevated in acute neuroborreliosis, and a potential marker for successful treatment.
Treatment of Lyme Disease
As previously noted, treatment with IV antibiotics is generally indicated only in patients with symptoms and laboratory findings consistent with CNS or peripheral neurologic involvement, and in a small subset of patients with heart block or documented Lyme arthritis who have not responded to oral antibiotics. Typical IV therapy consists of a two- to four-week course of ceftriaxone or cefotaxime, or penicillin. No data suggest that prolonged or repeated courses of IV antibiotics are effective. Lack of effect should suggest an incorrect diagnosis or slow resolution of symptoms, which is commonly seen in LD. Also, some symptoms may persist after treatment, such as Lyme arthritis; this phenomenon may be related to various self-sustaining inflammatory mechanisms rather than persistent infection.
The most recent literature review was performed through August 5, 2019.
Summary of Evidence
Suspected Lyme Disease
For individuals who are suspected of having Lyme disease who receive genotyping or phenotyping of B. burgdorferi subspecies or who receive CXCL13 gene testing or C6 peptide assay testing, the evidence is limited. Relevant outcomes are change in disease status and morbid events. Polymerase chain reaction-based testing for B. burgdorferi genospecies is feasible. However, no evidence was identified that knowledge of the B. burgdorferi genotype or phenotype could be used to improve patient management and outcomes. Additional research is also needed to determine the diagnostic utility of CXCL13 and C6 peptide levels. The evidence is insufficient to determine the effects of the technology on health outcomes.
Confirmed Lyme Disease
For individuals with confirmed Lyme disease who receive prolonged or repeated courses of antibiotic therapy, the evidence includes randomized controlled trials (RCTs). Relevant outcomes are symptoms, change in disease status, morbid events, and health status measures. Oral antibiotics usually are adequate for treatment of Lyme disease, though in some persistent cases, a 2- to 4-week course of intravenous (IV) antibiotics may be appropriate. Evidence from RCTs has not shown a benefit to prolonged (>4 weeks) or repeat courses of oral or IV antibiotics. The evidence is sufficient to determine that the technology is unlikely to improve the net health outcome.
It is well established that optimum method of testing depends on the stage of the disease. Guidelines from the Centers for Disease Control and Prevention and other sources have support policy statements related to a tiered diagnostic testing strategy. Diagnostic testing may not be necessary when a diagnosis can be made clinically in patients with a recent tick bite or exposure and the presence of the characteristic rash of erythema migrans. When laboratory testing is indicated, 2-tiered serologic testing is recommended. Polymerase chain reaction (PCR), may be clinically useful as a second approach in patients with a short duration of neurologic symptoms (<14 days).
Practice Guidelines and Position Statements
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention has recommended a 2-tier process when testing blood for evidence of antibodies against the Lyme disease bacteria. Both steps can be done using the same blood sample. The first step uses a testing procedure called enzyme immunoassay or rarely, an indirect immunofluorescence assay. If this first step is negative, no further testing of the specimen is recommended. If the first step is positive or indeterminate (sometimes called “equivocal”) the second step should be performed. The second step uses an immunoblot test, commonly, a Western blot test. Results are considered positive only if the enzyme immunoassay or immunofluorescence assay and the immunoblot are both positive. The Centers for Disease Control and Prevention do not recommend skipping the first test and just doing the Western blot. Doing so will increase the frequency of false-positive results and may lead to misdiagnosis and improper treatment. New tests may be developed as alternatives to one or both steps of the 2-tier process. Before the Centers for Disease Control and Prevention recommend new tests, test performance must be demonstrated to be equal to or better than the results of the existing procedure, and they must be U.S. Food and Drug Administration approved.
Infectious Diseases Society of America et al
As of September 2018, updated guidelines from the Infectious Diseases Society of America and 12 other organizations are in development.
American College of Rheumatology et al
In 1993, the American College of Rheumatology and the Infectious Diseases Society of America (IDSA) published a position paper on intravenous (IV) antibiotic treatment for Lyme disease, which concluded that “empiric treatment of patients with nonspecific chronic fatigue or myalgia on the basis of positive serologic results alone will result in many more instances of antibiotic toxicity than cures of atypically symptomatic true Lyme disease.... In patients whose only evidence for Lyme disease is a positive immunologic test, the risks for empiric IV antibiotic treatment outweigh the benefits….” Other studies have also supported the use of oral, not IV, antibiotics in patients with Lyme disease without neurologic involvement.
National Institute for Health and Care Excellence
Guidance on Lyme disease from the National Institute for Health and Care Excellence (NICE)was published in 2018. NICE recommended that if “there is clinical suspicion of Lyme disease in people without erythema migrans,” “an enzyme-limked immunosorbent assay (ELISA) test for Lyme disease” should be offered. If the ELISA test is “positive pr equivocal,” an “immunoblot test” for Lyme disease should be performe. The NICE recommended oral antibiotics for the treatment of erythem migrans and/or nonfocal symptoms, and a 21-day course og IV antibiotics for Lyme disease affecting the central nervous or for Lyme carditis when the patients are hemodynamically unstable.
International Lyme and Associated Diseases Society
The International Lyme and Associated Diseases Society published guidelines in 2014 to address three clinical issues: the usefulness of antibiotic prophylaxis of tick bites, the effectiveness of erythema migrans treatment, and antibiotic retreatment in patients with persistent symptoms. The Society noted that the evidence on treatment of tick bites, erythema migrans rashes, and persistent manifestations is limited. Regarding the treatment of patients with persistent symptoms, the Society panel concluded that the evidence for retreatment is adequate to support retreatment, but is not strong enough to mandate treatment. The panel determined that there was no compelling evidence supporting withholding antibiotics from symptomatic patients, especially since there is a lack of alternative treatment options. Due to the number of clinical variables and the heterogeneity of the patient population, clinical judgment and patients’ values and goals should be considered when planning a treatment strategy.
U.S. Preventive Services Task Force Recommendations
Intravenous Antibiotic Therapy for Lyme Disease, Lyme Disease, Intravenous Antibiotic Therapy, B lymphocyte chemoattractant, C6 peptide ELISA, Chemoattractant CXCL13, CXCL 13, genotyping of B. burgdorferi, Lyme Disease, PCR based direct detection of B. burgdorferi in urine samples, phenotyping of B. burgdorferi, B. burgdorferi
APPROVED BY GOVERNING BODIES
The FDA has cleared multiple enzyme immunoassay, immunofluorescent assay and Western Blot IgG and IgM tests through the 510(k) process. There are also commercially available laboratory- developed tests for serologic testing for Lyme disease. Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments.
Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.
ITS: Home Policy provisions apply
FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan. FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
86617 Borrelia burgdorferi (Lyme disease) confirmatory test (e.g., Western blot or
87475 Infectious agent detection by nucleic acid; Borrelia burgdorferi, direct probe
87476 Infectious agent detection by nucleic acid; Borrelia burgdorferi, amplified probe
87477 Infectious agent detection by nucleic acid; Borrelia burgdorferi; quantification
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.
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. Mar 31 2016; 374(13):1209-1220.
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):541-7.
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 2011; 62(5):329-38.
Cameron D. Severity of Lyme disease with persistent symptoms. Insights from a double-blind placebo-controlled clinical trial. Minerva Med 2008; 99(5):489-96.
Centers for Disease Control and Prevention. Lyme disease: Two-step laboratory testing process. 2015; //www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html. Accessed September 12, 2017.
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 online at: www.ncbi.nlm.nih.gov/pubmed/21977545; www.ncbi.nlm.nih.gov/books/NBK57026/.
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):289–94.
DeBiasi RL. A concise critical analysis of serologic testing for the diagnosis of lyme disease. Curr Infect Dis Rep. Dec 2014; 16(12):450.
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 1997; 337(5):357-63.
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.
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.
Hsu VM, Patella SJ and Sigal LH. “Chronic Lyme disease” as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum 1993; 36(11):1493–500.
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 Disease Society of America. Lymr Guideline Update and Public Comment Period. 2018; Available at: www.idsociety.org/Lyme/.
- Kaplan RF, Trevino RP, Johnson GM, et al. Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology 2003; 60(12):1916-22.
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):1923-30.
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 2013.
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.
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. Jun 28 2016.
Lyme Disease Association (LDA). Official word on IDSA guidelines' removal from NGC. 2016; www.lymediseaseassociation.org/index.php/lda-news-a-updates/1456-official-word-on-idsa-guidelines-removal-from-ngc. Accessed September 12, 2017.
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 for Health and Clinical Excellence (NICE). Lyme disease (in development). 2016; www.nice.org.uk/guidance/indevelopment/gid-ng10007. Accessed September 12, 2017.
Nau R, Christen HJ, Eiffert H. Lyme disease--current state of knowledge. Dtsch Arztebl Int 2009; 106(5):72-81.
Oksi J, Marjamaki M, Nikoskelainen J, et al. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Ann Med 1999; 31(3):225-32.
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 2007; 26(8):571-81.
Sanchez E, Vannier E, Wormser GP, et al. Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and sabesiosis: a review. JAMA. Apr 26 2016; 315(16):1767-1777.
Situm M, Poje G, Grahovac B, et al. Diagnosis of Lyme borreliosis by polymerase chain reaction. Clin Dermatol 2002; 20(2):147-55.
Steere AC, Taylor E, McHugh GL, et al. The overdiagnosis of Lyme disease. JAMA 1993; 269(14): 1812–6.
Steere AC. Lyme disease. N Engl J Med 2001; 345(2):115-25.
Wilske B, Fingerle V and Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007; 49(1):13-21.
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):1089-134.
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.
Medical Policy Group, June 2009 (3)
Medical Policy Administration Committee, July 2009
Available for comment July 1-August 14, 2009
Medical Policy Group, January 2011 (3)
Medical Policy Administration Committee, January 2011
Available for comment January 11, 2011 through February 21, 2011
Medical Policy Group, March 2012 (3): Updates to Description, Policy, Key Points, References: Updated Guidelines and “Other Diagnostic Testing” as investigational
Medical Policy Administration Committee, March 2011
Available for comment March 28 through May 15, 2012
Medical Policy Group, October 2012 (3): Update to Description, Key Points and References
Medical Policy Panel, January 2014
Medical Policy Group, January 2014 (3): Update to Key Points and References; no change in policy statement
Medical Policy Panel, January 2015
Medical Policy Group, January 2015 (3): 2015 Updates – Key Points, Approved by Governing Bodies and References; no changes in policy statement.
Medical Policy Panel, October 2015
Medical Policy Group, October 2015 (6): Updates to Key Points, Key Words, Approved Governing Bodies, and References. Added “CSF abnormalities” to policy statement. Policy intent unchanged. Policy Retired.
Medical Policy Panel, October 2016
Medical Policy Group, November 2016 (3): 2016 Updates to Description, Key Points, & References; investigational indication clarification added to Policy statement but did not change policy statement intent.
Medical Policy Group, May 2017 (3): Verbiage clarification on CPT code 87476; no policy statement changes
Medical Policy Group, July 2017 (3): Verbiage clarification on policy statements related to “Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi” - adding “(by direct or amplified probe)”; no other changes
Medical Policy Panel, October 2017
Medical Policy Group, November 2017 (3): 2017 Minor updates to Description, Key Points & Approved by Governing Bodies. No new references added and no change to policy statement.
Medical Policy Group, December 2017: Annual Coding Update. Created Previous Coding section and moved deleted CPT code 87477 to this section.
Medical Policy Panel, October 2018
Medical Policy Group, December 2018 (2): 2018 Policy review; minor updates to Key Points (updated Practice Guidelines and Poistion Statements), added 2 References; no change to Policy Statement.
Medical Policy Panel, October 2019
Medical Policy Group, November 2019 (2): Updates to Key Points; no change in policy statement.
This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.
The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.
As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.
The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:
1. The technology must have final approval from the appropriate government regulatory bodies;
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
3. The technology must improve the net health outcome;
4. The technology must be as beneficial as any established alternatives;
5. The improvement must be attainable outside the investigational setting.
Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:
1. In accordance with generally accepted standards of medical practice; and
2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
3. Not primarily for the convenience of the patient, physician or other health care provider; and
4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.