| Coverage Policy Manual | |
| Policy #: | 2010035 |
| Category: | Pharmacy |
| Initiated: | August 2010 |
| Last Review: | January 2024 |
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| Lyme Disease Intravenous Antibiotic Therapy and Associated Diagnostic Testing | |
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| Description: |
Lyme disease is a multisystem inflammatory disease caused by the spirochete Borrelia burgdorferi and transmitted by the bite of an infected Ixodes scapularis (northeastern region) or Ixodes pacificus (Pacific coast, most often in Northern California) tick. The disease is characterized by stages, beginning with localized infection of the skin (erythema migrans), followed by acute dissemination, and then late dissemination to many sites. 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 Lyme disease can be adequately treated with oral antibiotics, intravenous (IV) antibiotics are indicated in some individuals with disseminated Lyme disease. The following paragraphs describe the various manifestations of Lyme disease, therapies and the various laboratory tests that are used to support the diagnosis of Lyme disease.
Manifestations
Erythema migrans
Erythema migrans appears at the site of the tick bite and manifests generally between 7 to 14 days after the bite. The lesions typically expand slowly over the course of days or weeks, often with central clearing. If multiple lesions are present, it is considered a sign of early disseminated disease.
Neuroborreliosis
Lymphocytic meningitis, characterized by head and neck pain, may occur during the acute disseminated stage of the disease. In individuals with meningitis, the cerebrospinal fluid (CSF) will typically show a lymphocytic pleocytosis (lymphocyte count greater than normal) with increased levels of protein and normal glucose levels. Intrathecal production of antibodies directed at spirochetal antigens is also typically present. Other manifestations of early disseminated disease can include cranial neuritis (including unilateral or bilateral facial palsy) and peripheral nervous system manifestations. Cranial neuritis, most frequently Bell palsy, may present early in the course of disseminated Lyme disease, occasionally before the development of antibodies. Peripheral nervous system manifestations of Lyme disease include paresthesias or radicular pain with only minimal sensory signs. Individuals typically exhibit electromyographic or nerve conduction velocity abnormalities.
Neurological manifestations of late-stage dissemination can include mononeuropathy multiplex, encephalomyelitis, and subtle encephalopathy. A subacute encephalopathy is characterized by subtle disturbances in memory, mood, sleep, or cognition accompanied by fatigue. The symptoms are nonspecific and overlap with fibromyalgia and chronic fatigue syndrome. Much rarer, but of greater concern, is the development of encephalomyelitis, characterized by spastic paraparesis, ataxias, cognitive impairment, bladder dysfunction, and cranial neuropathy.
Lyme Carditis
Lyme carditis may appear during the early dissemination stage of the disease; symptoms include AV heart block, tachyarrhythmias, and myopericarditis. The most common abnormality is fluctuating degrees of AV block.
Lyme Arthritis
Lyme arthritis is a late manifestation of infection and is characterized by an elevated immunoglobulin G (IgG) response to B. burgdorferi and intermittent attacks of oligoarticular arthritis, primarily in the large joints such as the knee. However, both large and small joints may be affected.
Diagnostic Testing
Overview
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 individuals with a recent tick bite or exposure and the presence of the characteristic rash of erythema migrans, particularly in individuals presenting early before the development of a detectable serum antibody response. While diagnosis of Lyme disease is generally based on the clinical picture and demonstration of specific antibodies (see below), 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 (Steere, 2001; IOM, 2011). However, while PCR-based tests can identify organisms in skin biopsy specimens of individuals with dermatologic manifestations (i.e., erythema migrans), this diagnosis is typically made clinically, and antibiotic therapy is started empirically.
For Lyme neuroborreliosis, CSF examination may be useful in select individuals (Lantos, 2021). In individuals with suspected neuroborreliosis, evaluation allows for exclusion of bacterial or viral meningitis and can provide a more definitive diagnosis. However, direct detection of B. burgdorferi in CSF, by PCR or culture, is usually not possible in individuals with Lyme neuroborreliosis.
Similarly, the 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 CSF detection in individuals with suspected neuroborreliosis. PCR may be clinically useful as a second approach in individuals 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 (Situm, 2002). PCR-based detection is typically not performed with urine due to the variable presence of endogenous polymerase inhibitors that affect test sensitivity.
Fibromyalgia and chronic fatigue syndrome are the diseases most commonly confused with Lyme disease. 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 1 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 with Lyme disease, both of these conditions lack joint inflammation, have normal neurologic test results, or have test results suggesting anxiety or depression. Neither fibromyalgia nor chronic fatigue syndrome has been shown to respond to antibiotic therapy.
Serologic Tests
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 Immunoglobulin M (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 Lyme disease may persist for months or years. Thus detection of IgG antibodies only indicates exposure, either past or present. In Lyme-disease-endemic areas, underlying asymptomatic seropositivity may range up to 5–10%. Thus, as with any laboratory test, interpretation of serologic tests requires close correlation with the individuals’ signs and symptoms. For example, individuals with vague symptoms of Lyme disease, chronic fatigue syndrome, or fibromyalgia may undergo multiple serologic tests over many weeks to months to establish the diagnosis of Lyme disease. 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 individual 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 Lyme disease (Mead, 2019). This can be accomplished using the standard 2-tiered testing process, which uses a sensitive enzyme immunoassay (EIA) or immunofluorescence assay, followed by a western immunoblot assay for specimens yielding positive or equivocal results. Additionally, a modified 2-test methodology can be used, which uses a second EIA in place of the western immunoblot assay.
Enzyme-Linked Immunosorbent Assay for Borrelia burgdorferi Antibodies
This ELISA test is a screening serologic test for Lyme disease. ELISA tests are available to detect IgM or IgG antibodies or to detect 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 (FDA) 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 immunoblot or a second EIA. The overall predictive value is increased when correlated with the clinical picture.
Western Immunoblot
This immunoblot test is used to confirm the serologic diagnosis of Lyme disease in individuals with positive or indeterminate ELISA tests. In contrast to 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 CDC 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 the CDC 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. Criteria for interpreting immunoblot results are different in Europe than in the United States due to differences in the prevalence of different Borrelia species causing disease.
Nonserologic Tests
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 B. burgdorferi DNA. 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. In addition, 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 individuals with erythema migrans (but who may not be indicated with a recent history of tick bite or exposure) and for synovial tissue (and synovial fluid, to a lesser extent) from individuals with Lyme arthritis. CSF may be positive by PCR during the first two weeks of infection, but after 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 3 major species pathogenic for humans has been found in the specimen tested (genotyping).
T-Cell Proliferative Assay
T-lymphocyte proliferation assays, which detect responses of human mononuclear cells to borrelial antigens, are not recommended as diagnostic tests because they are difficult to perform and standardize, and their sensitivity is not well characterized.
Chemoattractant CXCL13
CXCL13 is a B-lymphocyte chemoattractant that has been reported to be elevated in acute neuroborreliosis and other inflammatory disorders in the central nervous system. It is being investigated as an adjunct in identifying infections and as a potential marker for successful treatment. The Centers for Disease Control and Prevention notes that standardized interpretation criteria is required before this test can be recommended (Lantos, 2021).
Borrelia Outer surface protein A
Antigen testing of urinary Borrelia Outer surface protein A (OspA) C-terminus peptide has been investigated using the Nanotrap® Antigen Test (Magni, 2015). This test employs Nanotrap particles to concentrate urinary OspA and uses a highly specific anti-OspA monoclonal antibody as a detector of the C-terminus peptides. Consistent with recommendations from the Centers for Disease Control and Prevention, the manufacturer of the Nanotrap® Antigen Test recommends using the Nanotrap® Antigen Test in conjunction with 2-tiered testing (ELISA with reflex to Western blot) for confirmation of a Lyme disease (Galaxy Advanced Microbial Diagnostics, 2022).
Treatment of Lyme Disease
Recommended treatment regimens are based on the stage and manifestations of Lyme disease (CDC, 2022). Most individuals can be treated with oral antibiotics, such as doxycycline, amoxicillin, or cefuroxime. Specific durations of therapy are dependent on the type of manifestations present. Treatment with IV antibiotics may be indicated in individuals with symptoms and laboratory findings consistent with central nervous system or peripheral neurologic involvement and in a small subset of individuals with heart block or documented Lyme arthritis who have not responded to oral antibiotics. Typical IV therapy consists of a 2- to 4-week course of ceftriaxone. 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 Lyme disease. In addition, 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.
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Policy/ Coverage: |
Effective January 10, 2024
Intravenous Antibiotic Therapy
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Treatment of Lyme disease consists of oral antibiotics, except for the following indications:
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Intravenous antibiotic therapy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, intravenous antibiotic therapy is considered investigational in the following situations:
Repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For contracts without primary coverage criteria, repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Repeat PCR-based direct detection of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations:
For members with contracts without primary coverage criteria, repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations:
PCR-based direct detection of B. burgdorferi in urine samples does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, PCR-based direct detection of B. burgdorferi in urine samples is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Genotyping or phenotyping of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genotyping or phenotyping of B. burgdorferi is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Determination of levels of the B lymphocyte chemoattractant CXCL13 or Outer surface protein A (OspA) antigen testing for diagnosis or monitoring treatment does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. (Effective, January 2011)
For members with contracts that do not have primary coverage criteria, determination of levels of the B lymphocyte chemoattractant CXCL13 or Outer surface protein A (OspA) antigen testing for diagnosis or monitoring treatment is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage. (Effective, January 2011)
Effective October 19, 2022 to January 9, 2024
Intravenous Antibiotic Therapy
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Treatment of Lyme disease consists of oral antibiotics, except for the following indications:
1. A 2 to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients with neuroborreliosis with one or more objective neurologic complications of documented Lyme disease (see the following for methods of documentation) (Wormser, 2006)
Objective neurologic findings include:
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 CNS infection, as indicated above (Halperin, 2007).
Serologic documentation of infection requires (Mead, 2019):
Documented CSF abnormalities include ALL of the following (Wormser, 2006):
2. A 2 to 4 week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients 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 (Wormser, 2006).
Documentation of Lyme carditis may include PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal.
3. A single 2- to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the small subset of patients with well-documented Lyme arthritis who have such severe arthritis that it requires the rapid response associated with IV antibiotics (Wormser, 2006).
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 (Lantos, 2010).
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Intravenous antibiotic therapy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, intravenous antibiotic therapy is considered investigational in the following situations:
Repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. For contracts without primary coverage criteria, repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Diagnostic Testing for Lyme Disease
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi in CSF and synovial fluid samples and when evaluating for lyme carditis, blood samples, meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes 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.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Repeat PCR-based direct detection of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations:
For members with contracts without primary coverage criteria, repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations:
PCR-based direct detection of B. burgdorferi in urine samples does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, PCR-based direct detection of B. burgdorferi in urine samples is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Genotyping or phenotyping of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genotyping or phenotyping of B. burgdorferi is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Determination of levels of the B lymphocyte chemoattractant CXCL13 or Outer surface protein A (OspA) antigen testing for diagnosis or monitoring treatment does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. (Effective, January 2011)
For members with contracts that do not have primary coverage criteria, determination of levels of the B lymphocyte chemoattractant CXCL13 or Outer surface protein A (OspA) antigen testing for diagnosis or monitoring treatment is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage. (Effective, January 2011)
Effective January 2020 to October 18, 2022
Intravenous Antibiotic Therapy
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Treatment of Lyme disease consists of oral antibiotics, except for the following indications:
1. A 2 to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients with neuroborreliosis with one or more objective neurologic complications of documented Lyme disease (see the following for methods of documentation) (Wormser, 2006)
Objective neurologic findings include:
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 CNS infection, as indicated above (Halperin, 2007).
Serologic documentation of infection requires (Mead, 2019):
Documented CSF abnormalities include ALL of the following (Wormser, 2006):
2. A 2 to 4 week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients 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 (Wormser, 2006).
Documentation of Lyme carditis may include PCR-based direct detection of B. burgdorferi in the blood when results of serologic studies are equivocal.
3. A single 2- to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the small subset of patients with well-documented Lyme arthritis who have such severe arthritis that it requires the rapid response associated with IV antibiotics (Wormser, 2006).
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 (Lantos, 2010).
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Intravenous antibiotic therapy does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, intravenous antibiotic therapy is considered investigational in the following situations:
Repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. For contracts without primary coverage criteria, repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Diagnostic Testing for Lyme Disease
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi in CSF and synovial fluid samples and when evaluating for lyme carditis, blood samples, meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes 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.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, polymerase chain reaction (PCR)-based direct detection of B. burgdorferi other than described above is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Repeat PCR-based direct detection of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations:
For members with contracts without primary coverage criteria, repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations:
PCR-based direct detection of B. burgdorferi in urine samples does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness.
For members with contracts without primary coverage criteria, PCR-based direct detection of B. burgdorferi in urine samples is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Genotyping or phenotyping of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, genotyping or phenotyping of B. burgdorferi is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. (Effective, January 2011)
For members with contracts that do not have primary coverage criteria, determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage. (Effective, January 2011)
Effective Prior to January 2020
Intravenous Antibiotic Therapy
Treatment of Lyme disease consists of oral antibiotics, except for the following indications:
1. A 2- to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients with neuroborreliosis with one or more objective neurologic complications of documented Lyme disease (see the following for methods of documentation).
Objective neurologic findings include:
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 CNS infection, as indicated above.
Serologic documentation of infection requires:
Documented CSF abnormalities include ALL of the following:
2. A 2- to 4-week course of IV antibiotics meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in patients 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.
3. A single 2- to 4-week course of IV antibiotic therapy meets primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes in the small subset of patients 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 does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, intravenous antibiotic therapy is considered investigational in the following situations:
Repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. For contracts without primary coverage criteria, repeat or prolonged courses (e.g., greater than 4 weeks) of IV antibiotic therapy is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Diagnostic Testing for Lyme Disease
Polymerase chain reaction (PCR)-based direct detection of B. burgdorferi in CSF and synovial fluid samples and when evaluating for lyme carditis, blood samples meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes 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.
Repeat PCR-based direct detection of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, repeat PCR-based direct detection of B. burgdorferi is considered investigational in the following situations:
PCR-based direct detection of B. burgdorferi in urine samples does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in the following situations. For contracts without primary coverage criteria, PCR-based direct detection of B. burgdorferi in urine samples is considered investigational. Investigational services are contract exclusions in most member benefit certificates of coverage.
Genotyping or phenotyping of B. burgdorferi does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. For contracts without primary coverage criteria, genotyping or phenotyping of B. burgdorferi is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment does not meet primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes. (Effective, January 2011)
For contracts that do not have primary coverage criteria, determination of levels of the B lymphocyte chemoattractant CXCL13 for diagnosis or monitoring treatment is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage. (Effective, January 2011)
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| Rationale: |
Direct Detection of Borrelia burgdorferi with Polymerase Chain Reaction (PCR) Technology
While diagnosis of Lyme disease is generally based on the clinical picture and demonstration of specific antibodies, PCR-based technology can detect the spirochete in the central nervous system (CSF) 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 (Steere, 2001). However, a PCR-based test is generally considered a second tier test, performed only when the results of serologic tests and clinical evaluation are equivocal. For example, 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 started empirically. A skin biopsy is rarely necessary. 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 CSF detection in patients with suspected neuroborreliosis, but a PCR-based technique may be useful in patients with a short duration of disease (i.e., less than 14 days) during the window between exposure and the emergence of detectable levels of antibodies in the CSF (Situm, 2002) . However, it should be noted that that the test cannot distinguish between live and dead organisms. PCR-based detection is typically not performed in the urine due to the variable presence of endogenous polymerase inhibitors that have an impact on the test's sensitivity.
PCR-based technology has been used as one step in the genotypic analysis of B.burgdorferi.B. burgdorferi was originally characterized as a single species (B. burgdorferi sensu lato), but genotypic analysis has revealed that this group represents 3 distinct species and genomic groups. Of these, the following have been isolated from patients with Lyme disease: B. burgdorferi sensu stricto, B. garinii, and B. afzelii. The prevalence of these different genospecies may vary among populations and may be associated with different clinical manifestations (Oksi, 1999). However, no data were found in the published literature regarding whether or how knowledge of the genotype or phenotype of B. burgdorferi could be used to improve patient management and outcomes. In the U.S., B. burgdorferi sensu stricto is the only human pathogenic species, but in Europe, all 3 species cause infection. Recently a new human pathogenic species, B. spielmanii, was found in a small number of European patients; therefore, criteria for interpreting immunoblot results are different in Europe than in the U.S. (Wilske, 2007).
Role of Intravenous (IV) Antibiotics
A diagnosis of Lyme disease requires appropriate epidemiologic data, supporting clinical observation (including exposure to ixodid ticks in an endemic area), and supporting laboratory findings. However, overdiagnosis and overtreatment of Lyme disease is common (Hsu, 1993) (Steere, 1993). Intravenous antibiotic therapy in patients with presumed Lyme disease would be inappropriate in the following situations: an incorrect diagnosis; a history of prolonged or repeated courses of IV antibiotics; and use of IV antibiotics when oral antibiotics are adequate. An incorrect diagnosis of Lyme disease includes those patients with positive serologies without characteristic signs or symptoms of Lyme disease, or those with non-specific symptoms and no known exposure to ticks in an endemic area, or those without supporting serologic evidence.
In 1993, the American College of Rheumatology published a position paper on 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 (Dattwyler, 1997) (Eckman, 1997) (Wormser, 2003).
Practice guidelines regarding the treatment of Lyme disease and including discussion of supportive evidence have been issued by the Infectious Diseases Society of America (IDSA) (Wormser, 2006). The IDSA also endorsed the American Academy of Neurology evidence-based practice parameter for the treatment of nervous system Lyme disease (Halperin, 2007). The IDSA guidelines recommend IV antibiotics only in the following situations (note: none of the recommendations suggest longer than a 1-month course of IV antibiotics):
In the particular case of cranial nerve palsy associated with Lyme disease (most commonly Bell’s palsy, also known as 7th nerve palsy) and without clinical evidence of meningitis, the evidence indicates that oral antibiotic therapy is satisfactory (Wormser, 2006) (Halperin, 2007). Cranial nerve palsy may, in fact, resolve without treatment, but treatment should be administered to avoid late complications of Lyme disease.
In addition, guidelines recommend symptomatic treatment for symptoms that persist after appropriate antibiotic therapy. For example, in a small number of patients with known prior infection, arthritis may persist despite negative B. burgdorferi DNA by PCR in synovial fluid or tissue. Such persistent arthritis is termed “antibiotic-refractory Lyme arthritis,” defined as “persistent synovitis for at least 2 months after completion of a course of intravenous ceftriaxone (or after completion of two 4-week courses of an oral antibiotic for patients unable to tolerate cephalosporins), in conjunction with negative results of PCR.” (Wormser, 2006) Symptomatic treatment, rather than additional antibiotic treatment, is recommended (Wormser, 2006).
The evidence generally does not support persistent B. burgdorferi infection in patients with well-documented infection who have received recommended antibiotic therapy (Halperin, 2007). Blinded, randomized controlled trials of extended antibiotic therapy versus placebo in such patients have shown no consistent differences in outcomes (summarized below). Therefore, prolonged courses of antibiotic therapy, which may be associated with adverse events, are not recommended.
Summary of Randomized Controlled Trials of Prolonged Antibiotic Therapy in Patients with Well-documented, Previously Treated Lyme Disease.
Klempner et al, 2001
Patients positive for IgG Abs to B. burgdorferi with persistent symptoms that interfered with patient function (N=78) were enrolled into one study and patients negative for IgG Abs to B. burgdorferi with persistent symptoms that interfered with patient function (N=51) were enrolled into a separate study. Patients were randomized to intravenous ceftriaxone daily for 30 days, oral doxycycline for 60 days or intravenous placebo and oral placebos. There was no significant difference in quality of life outcomes between the two groups. The studies were terminated after interim analysis indicated that it was highly unlikely that a significant difference in treatment efficacy would be observed.
Kaplan et al, 2003
This was the same trial as Klempner et al. Both treatment and control arms showed similar and not significantly different decreases in Medical Outcomes Study, cognitive, pain, and role functioning scales; and improved mood as assessed with the Beck Depression Inventory and Minnesota Multiphasic Personality Inventory.
Oksi et al, 2007
One hundred fifty-two consecutive patients with lyme borreliosis were treated with ceftriaxone intravenous for 21 days. After completion of the IV antibiotic phase, patients were randomized to receive either Amoxicillin or placebo twice daily for 100 days. Both treatment and control arms showed similar and not significantly different decreases in patient and investigator visual analogue scale (VAS) outcomes (VAS evaluation of symptoms, range 0-100, 0=no symptoms) at 12 mos. B. burgdorferi-specific antibodies declined similarly in both groups over 12 mos.
Fallon et al, 2008
Patients with well-documented lyme disease (N=37) with documented objective memory impairment were randomized to IV ceftriaxone or placebo daily for 70 days. The primary outcome of cognitive function across 6 domains was similarly improved in both groups at week 24, and was not significantly different between groups; improvement between groups was marginally significantly different at week 12.
Exploratory subgroup analyses suggested significantly better improvement in ceftriaxone-treated patients with more severe baseline pain and physical functioning.
Cameron, 2008
Eighty-six patients with symptoms of arthralgia, cardiac or neurologic involvement with or without fatigue after previous successful antibiotic treatment of Lyme disease were randomized to either oral amoxicillin 3 gm or placebo daily for 3 months. The study was conducted in a primary care internal medicine practice. 44% of enrolled patients were not evaluable at 6 months. Seventeen of these had poorer baseline quality of life and were lost due to treatment failure. SF-36 improvements for antibiotic vs. placebo arm were significant (46% vs. 18%, p=0.007) but text was not clear if analysis was of all or only evaluable patients. The SF-36 physical component improvement was not significantly different between treatment arms for evaluable patients. The SF-36 mental component significantly improved in antibiotic arm for evaluable patients.
Krupp et al, 2003
Krupp and colleagues published a randomized controlled trial of patients with persistent severe fatigue of 6 months or longer duration. Patients were randomized to either intravenous ceftriaxone daily for 28 days or IV placebo. The Ceftriaxone treatment arm showed no significant improvement in primary outcome of laboratory measure of persistent infection, no significant treatment effect on cognitive function and no difference in change in SF-36 scores. There was however a significant improvement in the secondary outcome of disabling fatigue.
2009-2010 Update
A literature update performed through November 2010 found no new evidence that would affect the policy statements, which remain unchanged. Specifically, no new trials of prolonged antibiotic therapy in patients with previously treated Lyme disease were found.
CXCL13 is a B lymphocyte chemoattractant that has been reported to be elevated in acute neuroborreliosis; thus it is a potential marker for successful treatment. However, data are limited. Additional research is necessary to determine diagnostic and treatment utility.
In November 2006, the Connecticut Attorney General initiated an antitrust investigation to determine whether the Infectious Diseases Society of America violated antitrust laws in the promulgation of their 2006 Lyme disease guidelines for assessing and treating Lyme disease. The investigation ended with an agreement under which the guidelines remained in effect while the Society convened a Review Panel to determine whether or not the 2006 guidelines were based on sound medical/scientific evidence or required revision. The final report of the Review Panel details the methodology, results, and conclusions of the review (Lantos, 2010). According to the report, “After multiple meetings, a public hearing, and extensive review of research and other information, the Review Panel concluded that the recommendations contained in the 2006 guidelines were medically and scientifically justified on the basis of all of the available evidence and that no changes to the guidelines were necessary.” The 2006 guidelines are currently being updated.
2012 Update
A search of the MEDLINE database through August 2012 did not reveal any new information that would prompt a change in the coverage statement.
A search of online site ClinicalTrials.gov in August 2012 identified no randomized controlled trials that addressed prolonged or repeated courses of intravenous antibiotics. Two randomized controlled trials were identified that will compare the effectiveness of oral doxycycline to intravenous ceftriaxone. One study will focus on patients with Lyme neuroborreliosis (NCT01635530) and the other will focus on patients with multiple erythema migrans (NCT01163994). Another randomized controlled trial, Persistent Lyme Empiric Antibiotic Study Europe (PLEASE), will compare outcomes after 12 weeks of treatment with 2 oral antibiotics (doxycycline or clarithromycin and hydroxychloroquine) or placebo after initial intravenous ceftriaxone. (NCT01207739) This study is expected to be completed in September 2013.
2013 Update
A literature search using the MEDLINE database through August 2013 did not reveal any new information that would prompt a change in the coverage statement.
2014 Update
A literature conducted through August 2014 did not reveal any new information that would prompt a change in the coverage statement.
2015 Update
A literature search conducted through December 2014 did not reveal any new information that would prompt a change in the coverage statement.
2016 Update
A literature search was conducted using the MEDLINE database through December 2015. There was no new literature identified that would prompt a change in the coverage statement.
2017 Update
A literature search conducted through January 2017 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
Lipsett and colleagues evaluated C6 EIA in 944 children of whom 114 (12%) had Lyme disease (Lipsett, 2016). They found stand-alone C6 EIA testing had lower specificity than 2-tiered testing (94.2% vs 98.8%); specificity was increased to 98.6% with a supplemental immunoblot. A 2016 systematic review of diagnosis and treatment of Lyme disease also concluded that “stand-alone” C6 testing is not recommended over the 2-tiered approach due to slightly lower specificity (Sanchez, 2016).
Section Summary: Chemokine CXCL13 and C6 peptide
Data on the determination of CXCL 13 levels in patients suspected of having Lyme disease is limited. Additional research is necessary to determine diagnostic and treatment utility. Stand-alone C6 testing is not recommended over the 2-tier approach.
Berende and colleagues reported on the role of intravenous or prolonged oral antibiotic therapy (Berende, 2016). 280 patients with persistent Lyme disease symptoms give IV ceftriaxone for 2 weeks. Experimental treatment of docycline or clarithromycin/hydroxyl-chloroquine for 12 weeks, Control treatment a placebo; results demonstrated SF-36 PCS did not differ between 3 study groups. event rates similar across 3 study groups, 4 serious ceftriaxone-related adverse events.
Summary of Evidence
For individuals who are suspected of having Lyme disease who receive genotyping or phenotyping of B. burgdorferi subspecies or are tested for determination of CXCL13 levels or C6 peptide assay, the evidence is limited. Relevant outcomes are test accuracy, change in disease status, and morbid events. Polymerase-chain reaction (PCR)-based testing for B. burgdorferi genospecies is feasible. However, no evidence was identified that knowledge of the genotype or phenotype of B. burgdorferi could be used to improve patient management and outcomes. Additional research is also needed to determine diagnostic utility of CXCL13 and C6 peptide levels. The evidence is insufficient to determine the effects of the technology on health outcomes.
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.
2018 Update
A literature search conducted using the MEDLINE database did not identify any new literature that would prompt a change in the coverage statement.
2019 Update
A literature search was conducted through December 2018. There was no new information identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
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, 2018). NICE recommended that if “there is clinical suspicion of Lyme disease in people without erythema migrans,” an “enzyme-linked immunosorbent assay (ELISA) test for Lyme disease” should be offered. If the ELISA test is “positive or equivocal,” an “immunoblot test” for Lyme disease should be performed. NICE recommended oral antibiotics for the treatment of erythema migrans and/or nonfocal symptoms, and a 21-day course of IV antibiotics for Lyme disease affecting the central nervous system or for Lyme carditis when the patients are hemodynamically unstable.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2020. No new literature was identified that would prompt a change in the coverage statement.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2022. No new literature was identified that would prompt a change in the coverage statement.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Magni et al published a cohort study evaluating antigen testing of urinary Borrelia OspA C-terminus peptide in early-stage Lyme borreliosis before and after treatment (Magni, 2015). A total of 268 urine samples from 168 patients were collected in a Lyme borreliosis endemic area. Results demonstrated that presence of OspA in the urine was linked to concurrent active symptoms (e.g., erythema migrans rash and arthritis), while resolution of these symptoms after therapy correlated with urinary conversion to OspA negative. Pre-treatment, 100% (n=24) of newly diagnosed patients with an erythema migrans rash were positive for urinary OspA and no asymptomatic patients had false-positive results. Among these 24 patients, serology results were positive in 12 patients, negative in 5 patients, equivocal in 3 patients, and non-determinate in 4 patients. Urinary OspA was positive in all patients who, during the course of antibiotic therapy, exhibited persistence of erythema migrans rash (n=10) or arthritis (n=6). Post-treatment, urinary OspA switched from detectable to undetectable following symptom resolution in 100% of patients (n=8). The lowest limit of detection for urinary OspA was 1.7 pg/mL (range, 1.7 to 30). Furthermore, when evaluating the correlation of urinary OspA to Centers for Disease Control serology criteria for early-stage Lyme borreliosis, the specificity of the test was 87.5 % (21 urinary OspA positive/24 serology positive).
Solheim et al conducted an RCT of 121 patients with European Lyme neuroborreliosis (Solheim, 2022). The active group received Doxycycline daily for 6 weeks while the comparator group received Doxycycline daily for 2 weeks followed by 4 weeks of placebo. At 6 months, the between-group difference in the primary outcome (Composite Clinical Score [0-64 points]) from baseline was 0.06 (95% CI, -1.2 to 1.2; p=.99) in the intention-to-treat population and -0.4 (95% CI, -1.4 to 0.7; p=.51) in the per-protocol population. Noninferiority of the treatment regimens was not established using the predetermined margin of 0.5 points.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement.
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American Collage 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. Association of Public Health Laboratories.(2021) Suggested Reporting Language, Interpretation and Guidance Regarding Lyme Disease Serologic Test Results. May 2021; https://www.aphl.org/aboutAPHL/publications/Documents/ID-2021-Lyme-Disease-Serologic-Testing-Reporting.pdf. Accessed December 27, 2021. Berende A, ter Hofstede HJ, Vos FJ, et al.(2016) Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. Mar 31 2016;374(13):1209-1220. PMID 27028911 Cameron D.(2008) 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 (CDC).(2022) Lyme Disease: Treatment. Updated March 1, 2022; https://www.cdc.gov/lyme/treatment/index.html. Accessed August 27, 2022. Centers for Disease Control and Prevention.(2021) Lyme Disease: Treatment. Updated August 23, 2021; https://www.cdc.gov/lyme/treatment/index.html. Accessed September 2, 2021. Dattwyler RJ, Luft BJ, Kunkel MJ et al.(1997) Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997; 337(5):289–94. Eckman MH, Steere AC, Kalish RA et al.(1997) 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.(2008) A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology 2008; 70(13):992-1003. Galaxy Advanced Microbial Diagnostics.(2022) Lyme Borrelia Nanotrap Antigen Test. https://www.galaxydx.com/nanotrap-urine-test-for-lyme-disease/. Accessed August 29, 2022. Halperin JJ, Shapiro ED, Logigian E et al.(2007) 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, Sigal LH.(1993) “Chronic Lyme disease” as the incorrect diagnosis in patients with fibromyalgia. Arthritis Rheum 1993; 36(11):1493–500. Institute of Medicine (IOM).(2011) 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. Washington, DC: National Academies Press; 2011. Kaplan RF, Trevino RP, Johnson GM et al.(2003) 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.(2001) 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.(2003) Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology 2003; 60(12):1923-30. Lantos PM, Charini WA, Medoff G et al.(2010) 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 LK, et al.(2021) 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. Clin Infect Dis. Jan 23 2021; 72(1): e1-e48. PMID 33417672 Lipsett SC, Branda JA, McAdam AJ, et al.(2016) Evaluation of the C6 Lyme Enzyme immunoassay for the diagnosis of lyme disease in children and adolescents. Clin Infect Dis. Oct 1 2016;63(7):922-928. PMID 27358358 Lyme Disease Association (LDA)(2016) Official word on IDSA guidelines' removal from NGC. 2016; https://www.lymediseaseassociation.org/index.php/lda-news-a-updates/1456-official-word-on-idsa-guidelines-removal-from-ngc. Magni R, Espina BH, Shah K, et al.(2015) 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. Nov 04 2015; 13: 346. PMID 26537892 Mead P, Petersen J, Hinckley A.(2019) Updated CDC Recommendation for Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep 2019;68:703. DOI: http://dx.doi.org/10.15585/mmwr.mm6832a4external icon. National Institute for Health and Care Excellence (NICE).(2018) Lyme disease [NG95]. 2018; https://www.nice.org.uk/guidance/NG95. Accessed September 14, 2018. National Institute for Health and Clinical Excellence (NICE).(2016) Lyme disease (in development). 2016; https://www.nice.org.uk/guidance/indevelopment/gid-ng10007. Nigrovic LE, Lewander DP, Balamuth F, et al.(2020) The Lyme Disease Polymerase Chain Reaction Test Has Low Sensitivity. Vector Borne Zoonotic Dis. Apr 2020; 20(4): 310-313. PMID 31821110 Oksi J, Marjamaki M, Nikoskelainen J et al.(1999) 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.(2007) 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.(2016) Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: JAMA. Apr 26 2016;315(16):1767-1777. PMID 27115378 Situm M, Poje G, Grahovac B et al.(2002) Diagnosis of Lyme borreliosis by polymerase chain reaction. Clin Dermatol 2002; 20(2):147-55. Solheim AM, Lorentzen AR, Dahlberg AO, et al.(2022) Six versus 2 weeks treatment with doxycycline in European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blinded, randomised and placebo-controlled trial. J Neurol Neurosurg Psychiatry. Jul 27 2022. PMID 35896378 Steere AC, Taylor E, McHugh GL et al.(1993) The overdiagnosis of Lyme disease. JAMA 1993; 269(14): 1812–6. Steere AC.(2001) Lyme disease. N Engl J Med 2001; 345(2):115-25. Wilske B, Fingerle V, Schulte-Spechtel U.(2007) Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol 2007; 49(1):13-21. Wormser GP, Dattwyler RJ, Shapiro ED et al.(2006) 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.(2003) Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2003; 138(9):697-704. Zannoli S, Fantini M, Semprini S, et al.(2020) Multicenter Evaluation of the C6 Lyme ELISA Kit for the Diagnosis of Lyme Disease. Microorganisms. Mar 24 2020; 8(3). PMID 32213811 |
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Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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