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Lab Management Guidelines V2.0.2021 Lyme Disease Testing MOL.CS.332.X v2.0.2021 Introduction Lyme Disease testing is addressed by this guideline. Procedures Addressed The inclusion of any procedure code in this table does not imply that the code is under management or requires prior authorization. Refer to the specific Health Plan's procedure code list for management requirements. Procedure addressed by this guideline Procedure code Borrelia burgdorferi antibody 86618 Borrelia antibody 86619 Borrelia burgdorferi, antibody detection of 0041U 5 recombinant protein groups, by immunoblot, IgM Borrelia burgdorferi, antibody detection of 0042U 12 recombinant protein groups, by immunoblot, IgG Borrelia burgdorferi antibody, confirmatory 86617 assay Borrelia burgdorferi, infectious agent 87475 detection by nucleic acid (DNA or RNA); direct probe technique Borrelia burgdorferi, Infectious agent 87476 detection by nucleic acid (DNA or RNA), amplified probe technique Borrelia group, tick-borne relapsing fever, 0043U antibody detection to 4 recombinant protein groups, by immunoblot, IgM Borrelia group, tick-borne relapsing fever, 0044U antibody detection to 4 recombinant protein groups, by immunoblot, IgG ©2021 eviCore healthcare. All Rights Reserved. 1 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 What Is Lyme Disease Definition Lyme disease (borreliosis) is caused by a Borrelia bacterial infection following a tick bite from the hard-backed Ixodes tick. It was named after the towns Lyme and Old Lyme in Connecticut after a 1975 investigation of 51 cases with a similar form of arthritis.1 Borrelia are part of the order spirochaetes, which are spiral-shaped bacteria. There are several subspecies, including B. burgdorferi, B. afezelii, B. garinii, B. spielmanii, and B. bavariensis. In the United States, the most common Lyme disease-causing organism is B. burgdorferi. Lyme disease incidence is significant, exceeding 30,000 new cases annually in the United States.2 There are some estimates greater than 300,000 when considering unreported cases.3 The incidence has increased as the geographic range of the ticks have expanded across the northeastern and upper mid-western states in the U.S., and most recently into Canada. It is expected that climate change will result in further northward expansion of the tick’s range. 4 However, the incidence may be confounded by high rates of misdiagnosis due to the systemic nature of Lyme Disease, and non-specific symptoms. One study found that 84.1% of a population referred to an Infectious Disease Clinic for Lyme disease were misdiagnosed.5 Lyme disease has three stages of infection: early localized, early disseminated, and late disseminated. Disseminated infection can affect multiple organs. While there is a broad spectrum of symptoms and severity, the first signs of infection are a characteristic skin rash with a bullseye appearance (called erythema migrans), fever, and non-specific symptoms like headache and lethargy. 6 There are several manifestations of Lyme disease that can occur through the three Lyme Disease Testing phases of infection: Neuroborreliosis most commonly manifests with painful meningoradiculitis and lymphocytic meningitis. This may also manifest as facial palsy in many cases, as well as multiple cranial neuropathies. 7 Neuroborreliosis is more common in Europe due to the prevalent Borellia subspecies, B. garinii, which is more frequently associated with neuroborreliosis than the other subspecies. 7 Lyme carditis, which may present as pericarditis, myocarditis, and/or conduction abnormalities Lyme arthritis manifests as migratory large joint arthritis and is a hallmark of late disseminated Lyme disease in the U.S.6 Fibromyalgia and chronic fatigue syndrome have been associated with chronic Lyme disease (CLD) or post-treatment Lyme disease syndrome (PTLDS). These conditions are characterized by unexplained subjective complaints with similar clinical symptoms as fibromyalgia and chronic fatigue syndrome. 8 ©2021 eviCore healthcare. All Rights Reserved. 2 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Test Information Introduction There are several diagnostic tests available for screening and confirmation of Lyme disease. They have variable sensitivity, specificity, and performance characteristics depending on the stage of the infection and testing matrix. Serologic tests include enzyme-linked immunosorbent assay (ELISA) to detect IgM or IgG antibodies, immunofluorescence assay (IFA), immunoblot, and confirmatory western blot. Molecular detection of Borrelia organisms is also available in bacterial isolates from culture, blood, and tissue biopsies. Borrelia Burgdorferi IgG or IgM Antibodies and Borrelia IgG or IgM Antibodies This test is performed by enzyme-linked immunosorbent assay (ELISA) or immunofluorescence assay (IFA). There are several commercially available kits. The assays use either whole-cell preparations of B. burgdorferi (for the specific test), Borrelia species, or recombinant antigens, such as C10 peptide, to bind to antibodies present in patient serum. Whole-cell sonicate preparations result in higher sensitivity due to the presence of multiple antigens, but some of the antigens cross-react with antigens from the host or other pathogens, leading to false positives. Overall, there is lower sensitivity in early stages of Lyme disease.9 Confirmatory Assay for Borrelia Burgdorferi Antibody This test is performed by western blot and has higher analytical specificity than ELISA. Patient serum is introduced in a separation gel or strip that has been prepared with antigen extracts and/or recombinant antigens native to B. burgdorferi and electrophoretically separated. Antibodies present in the patient’s serum bind to the Lyme Disease Testing corresponding antigen bands. The gel is then incubated with a chromogenic substrate to visualize the antigen-antibody complexes as “bands”. 9 Infectious Agent Detection by Nucleic Acid (DNA or RNA); Borrelia Burgdorferi, Direct Probe Technique In direct probe techniques, nucleic acid is extracted from the specimen (isolate, tissue, CSF, blood, synovial fluid, etc.) and the target sequence is detected by a reporter molecule, such as an oligonucleotide, DNA fragment, or plasmid DNA. The reporter molecule has a label attached to generate a signal when hybridized to the target sequence in solution or immobilized on solid support. This technique is increasingly being replaced with amplification methods. Infectious Agent Detection by Nucleic Acid (DNA or RNA); Borrelia Burgdorferi, Amplified Probe Technique In amplified probe techniques, nucleic acid is extracted from the specimen (isolate, tissue, CSF, blood, synovial fluid, etc.) and then amplified using polymerase chain ©2021 eviCore healthcare. All Rights Reserved. 3 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 reaction. The specific organisms are differentiated through features of the melting curve analysis. However, due to the amplification steps, there is a high risk for exogenous contamination, resulting in false-positive results. Additionally, degradation of the DNA during sample transport, storage, and processing steps can result in false negatives.10 Standard PCR methods have demonstrated poor sensitivity in testing tissue and body fluids because the infectious agent resides in low number. 11 Borrelia Burgdorferi, Antibody Detection of (4,5,12) Recombinant Protein Groups, by Immunoblot (IgM, IgG) The methodology is similar to the western blot, but is differentiated by using recombinant proteins derived from several species of Borrelia to prepare antigen strips, instead of whole blood lysates.12 Guidelines and Evidence Borrelia Burgdorferi IgG or IgM (CPT 86618) and Borrelia IgG or IgM (CPT 86619) The diagnosis of Lyme disease can be made clinically in patients with high pre-test probability, obviating the need for serologic testing. However, serologic testing takes on greater importance with later disseminated disease. 13 Testing for IgM antibodies is only recommended in the first 30 days of infection, after which IgG tests should be used.14 Serology should not be used for monitoring treatment, as antibodies can persist for several years post-infection. Negative serology does not rule out early infection within six weeks, as false negatives can occur. 1 In patients with an atypical presentation, or later disseminated disease, a two-tiered testing approach is recommended. The first tier consists of an ELISA or immunofluorescence assay, and if positive or equivocal, the same sample is tested by Lyme Disease Testing the second-tier western blot.15 Borrelia Burgdorferi Antibody, Confirmatory Assay (CPT 86617) Western blots require interpretation to determine if there are bands present, which is accomplished by skilled technologists or software. To avoid false positives due to variation in band interpretation, the CDC guidelines require that a specific number of bands be present to classify the result as positive: 6 “It is imperative to avoid interpreting fewer bands as a positive overall result or evidence of infection because antibodies to several antigens are cross-reactive with non-Borrelial antigens. For example, the 41-kDa band indicates reactive antibody against a B. burgdorferi flagellin protein. However, this antibody cross-reacts with other bacterial flagellar proteins and was found in 43% of healthy controls in 1 study, including many persons with little or no exposure risk for Lyme disease." The two-tiered approach to serology testing was recently updated by the CDC to allow FDA-approved enzyme immunoassays (EIA) to replace traditional western ©2021 eviCore healthcare. All Rights Reserved. 4 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 blot assays as the confirmatory test.16 The two-tiered EIA approach consists of the traditional whole-cell sonicate EIA followed by a C6 peptide EIA. Both tiers (ELISA and western blot or EIA) must be positive to classify the final result as positive. The two-tiered approach maximizes test sensitivity and specificity. Borrelia burgdorferi; Infectious Agent Detection by Nucleic Acid (DNA or RNA) (CPT 87475, 87476) Molecular detection of B. burgdorferi using PCR-based technology can identify the organism in cases of neuroborreliosis, synovial fluid in cases of Lyme arthritis, and rarely in skin biopsy specimens. Synovial fluid PCR testing for B. burgdorferi DNA is often positive prior to treatment, but it is not a reliable marker of spirochetal eradication after antibiotic therapy. 17 Intrathecal antibody production is more sensitive than PCR-based CSF detection in patients with suspected neuroborreliosis.18 However, PCR may be useful in patients with short duration of neurological symptoms in the early stage of the infection before emergence of detectable levels of antibodies in CSF. 6 o “Synovial fluid PCR is >75% sensitive for Lyme arthritis and might be useful in conjunction with other synovial fluid analyses to differentiate Lyme arthritis from other arthritides. Comparatively, PCR of CSF is substantially less sensitive, which limits its clinical utility. In 1 US study, PCR testing of CSF yielded positive results for only 38% of patients with early neuroborreliosis and was even less sensitive for late neuroborreliosis." Infectious Diseases Society of America clinical practice guidelines state the following regarding testing to be performed on CSF from patients suspected of having Lyme neuroborreliosis:19 o “When assessing patients for possible Lyme neuroborreliosis involving either the Lyme Disease Testing PNS or central nervous system (CNS), we recommend serum antibody testing rather than PCR or culture of either cerebrospinal fluid (CSF) or serum (strong recommendation, moderate-quality evidence).” o “If CSF testing is performed in patients with suspected Lyme neuroborreliosis involving the CNS, we (a) recommend obtaining simultaneous samples of CSF and serum for determination of the CSF:serum antibody index, carried out by a laboratory using validated methodology, (b) recommend against CSF serology without measurement of the CSF:serum antibody index, and (c) recommend against routine PCR or culture of CSF or serum (strong recommendation, moderate-quality evidence)” o Regarding diagnostic testing for Lyme arthritis, the guidelines state: “When assessing possible Lyme arthritis, we recommend serum antibody testing over PCR or culture of blood or synovial fluid/tissue (strong recommendation, moderate-quality evidence).” ©2021 eviCore healthcare. All Rights Reserved. 5 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 “In seropositive patients for whom the diagnosis of Lyme arthritis is being considered but treatment decisions require more definitive information, we recommend PCR applied to synovial fluid or tissue rather than Borrelia culture of those samples (strong recommendation, moderate-quality evidence)." A meta-analysis examining the overall accuracy of diagnostic tests for the detection of Lyme disease reviewed six studies that analyzed bacterial isolation by culture and detection of B. burgdorferi by PCR in blood and tissue biopsies. 1 o "Overall, the sensitivities of PCR studies conducted in North America were lower than those that employed a two-tiered serology diagnostic protocol. Due to the above limitations, bacterial isolation and PCR are not routinely used as diagnostic tools in clinical practise, although bacterial isolation is considered the gold standard to confirm diagnosis." A novel B. burgdorferi sensu lato genospecies, B. mayonii, was recently discovered using real-time PCR assay that targets the chromosomal oppA1 gene. In the first six patients detected with this infection, the two-tier algorithm was only positive in one patient. Until more is understood about the differences in detection rates by the two-tiered testing approach with this infection, PCR may have a role. 20 o "An important issue raised by identification of the novel B. burgdorferi sensu lato genospecies is whether existing Lyme borreliosis diagnostic tests can detect infection with this organism…The clinical range of illness must be better defined in additional patients to ensure that physicians can recognise the infection and distinguish it from other tick-borne infections. Many tick-borne pathogens have global distribution, therefore studies are needed to establish the geographic distribution of human beings and ticks infected with the novel B. burgdorferi sensu lato genospecies. Finally, clinicians should be aware of the potential role of oppA1 PCR for diagnosing infection with this novel pathogen." Lyme Disease Testing Borrelia Burgdorferi, Antibody Detection of (4,5,12) Recombinant Protein Groups, by Immunoblot (IgM, IgG): 0041U, 0042U, 0043U, 0044U Detection of B. burgdorferi and Tick-born relapsing fever antibodies by immunoblot using recombinant proteins is the latest addition of Lyme disease serology testing. There are not any independent studies evaluating the accuracy of this method. 12,21 Criteria Introduction This policy addresses laboratory testing for the diagnosis of Lyme disease. B. Burgdorferi Antibodies and Borrelia Antibodies (First-tier) Procedure codes: 86618 or 86619 ©2021 eviCore healthcare. All Rights Reserved. 6 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Medical Necessity Requirements o First-tier Lyme serology testing is indicated when all of the following circumstances are met: History of travel to, or residence in, a Lyme region, and Clinically compatible symptoms such as fever; redness, warmth and swelling in one or more joints. o Testing is not medically necessary when the classic erythema migrans (EM) rash is present. o IgM is only indicated for the first 30 days after infection. After 30 days, only IgG is indicated. Test Frequency Lyme serology testing is allowed up to 4 times per year for diagnosis of Lyme disease. Billing and Reimbursement First-tier Lyme serology will be considered medically necessary when billed with an ICD code from Table: Lyme Disease Testing Indications. Exceptions will be handled on a case-by-case basis. Because only IgG or IgM testing is indicated (not both) for initial screening, only one unit of CPT 86618 or CPT 86619 will be eligible for first-tier screening on a single date of service. B. Burgdorferi Antibody (Confirmatory, or Second-Tier) Lyme Disease Testing Procedure codes: 86617 or 86618 Medical Necessity Requirements The confirmatory or second-tier assay B. burgdorferi antibodies is indicated when the first-tier serology test is positive for either IgG or IgM antibodies. IgM is only indicated for the first 30 days after infection. After 30 days, only IgG is indicated. Once Lyme disease is confirmed, no further serology testing is indicated because serology should not be used for monitoring treatment as antibodies can persist for several years post-infection. Test Frequency Lyme confirmatory testing is allowed up to 4 times per year for diagnosis of Lyme disease. ©2021 eviCore healthcare. All Rights Reserved. 7 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Billing and Reimbursement Confirmatory testing (86617 or 86618) will only be reimbursable when first-tier Lyme serology testing was medically necessary and reimbursed. Because only IgG or IgM testing is indicated (not both) for confirmatory testing, only one unit of CPT 86617 or 86618 will be eligible for second-tier confirmation on a single date of service. As a result, when two-tier Lyme disease testing is medically necessary because first-tier testing was positive, no more than one unit of 86617 with 86618 or 86619, or two units of 86618 is reimbursable. Antibody testing that is not species-specific (billed with 86619) has no role in confirmatory testing, and is therefore not reimbursable for this purpose. B. Burgdorferi, Infectious Agent Detection by Nucleic Acid (DNA or RNA) Procedure codes: 87475, 87476 Medical Necessity Requirements Nucleic acid detection of B. burgdorferi through direct or amplified methods for the diagnosis of Lyme disease has not demonstrated value that exceeds the two-tier serology testing strategy, and is therefore determined to be not medically necessary. Nucleic acid detection of B. burgdorferi performed on synovial fluid to inform therapeutic decisions for seropositive patients in whom a diagnosis of Lyme arthritis is suspected will be considered for reimbursement on a case-by-case basis. B. Burgdorferi, Anitbody Detection of (4,5,12) Recombinant Protein Groups, by Immunoblot (IgM, IgG) Lyme Disease Testing Procedure codes: 0041U, 0042U, 0043U, 0044U Medical Necessity Requirements Antibody detection of B. burgdorferi using recombinant protein groups by Immunoblot has not been independently tested and validated for clinical use, and is therefore determined to be investigational and/or experimental. Diagnosis Codes Diagnosis codes in this section may be used to support or refute medical necessity as described in the above guidelines. Table: Lyme Disease Testing Indications Codes and descriptions ©2021 eviCore healthcare. All Rights Reserved. 8 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Code or Range Description A26.X Erysipeloid A41.8X Other specified sepsis A41.9 Sepsis, unspecified organism A68.X Relapsing fever A69.2X Lyme disease D69.2 Other nonthrombocytopenic purpura D69.3 Immune thrombocytopenic purpura D69.4X Other primary thrombocytopenia D69.5X Secondary thrombocytopenia D69.6X Thrombocytopenia, unspecified G36.X Other acute disseminated demyelination G37.X Other demyelinating diseases of the central nervous system G50-G59 Nerve, nerve root and plexus disorders G60-G65 Polyneuropathies and other disorders of the peripheral nervous system G72.3 Other and unspecified myopathies G72.4 Inflammatory and immune myopathies, not elsewhere classified G72.8 Other specified myopathies Lyme Disease Testing G72.9 Myopathy, unspecified G81.X Hemiplegia and hemiparesis G83.X Other paralytic syndromes G89-G99.X Other disorders of the nervous system H02.4X Ptosis of eyelid H15-H22 Disorders of sclera, cornea, iris and ciliary body H30-H36 Disorders of choroid and retina H43-H44.X Disorders of vitreous body and globe H46-H47.X Disorders of optic nerve and visual pathways H49.X Paralytic strabismus H53-H54.X Visual disturbances and blindness ©2021 eviCore healthcare. All Rights Reserved. 9 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Code or Range Description H55-H57.X Other disorders of eye and adnexa H81.X Disorders of vestibular function H90.X-H94.X Other disorders of ear I30-I52 Other forms of heart disease L08.X Other local infections of skin and subcutaneous tissue M06.4 Inflammatory polyarthropathy M12.X Other and unspecified arthropathy M13.X Other arthritis M14.X Arthropathies in other diseases classified elsewhere M25.4 Effusion of joint M25.5 Pain in joint M79.1X Myalgia M79.2 Neuralgia and neuritis, unspecified M79.6X Pain in limb, hand, foot, fingers, and toes M79.7 Fibromyalgia R20.X Disturbances of skin sensation R21 Rash and other nonspecific skin eruption R25-R29.X Symptoms and signs involving the Lyme Disease Testing nervous and musculoskeletal system R41.X Other symptoms and signs involving cognitive functions and awareness R42 Dizziness and giddiness R50.9 Fever, unspecified R51 Headache R52 Pain, unspecified R53.X Malaise and fatigue R55 Syncope and collapse R90.8X Other abnormal findings on diagnostic imaging of central nervous system R93.0 Abnormal findings on dx imaging of skull and head, NEC ©2021 eviCore healthcare. All Rights Reserved. 10 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Code or Range Description S00.06X Insect bite (nonvenomous) of scalp S00.26X Insect bite (nonvenomous) of eyelid and periocular area S00.36X Insect bite (nonvenomous) of nose S00.46X Insect bite (nonvenomous) of ear S00.56X Insect bite (nonvenomous) of lip and oral cavity S00.86X Insect bite (nonvenomous) of other part of head S00.96X Insect bite (nonvenomous) of unspecified part of head S10.16X Insect bite (nonvenomous) of throat S10.86X Insect bite of other specified part of neck S10.96X Insect bite of unspecified part of neck S20.16X Insect bite (nonvenomous) of breast S20.36X Insect bite (nonvenomous) of front wall of thorax S20.46X Insect bite (nonvenomous) of back wall of thorax S20.96X Insect bite (nonvenomous) of unspecified parts of thorax S30.86X Insect bite (nonvenomous) of abdomen, Lyme Disease Testing lower back, pelvis, and external genitals S40.86X Insect bite (nonvenomous) of upper arm S50.86X Insect bite (nonvenomous) of forearm S60.36X Insect bite (nonvenomous) of thumb S60.46X Insect bite (nonvenomous) of fingers S60.56X Insect bite (nonvenomous) of hand S60.86X Insect bite (nonvenomous) of wrist S70.26X Insect bite (nonvenomous) of hip S70.36X Insect bite (nonvenomous) of thigh S80.26X Insect bite (nonvenomous) of knee S80.86 Insect bite (nonvenomous) of lower leg S90.46X Insect bite (nonvenomous) of toe ©2021 eviCore healthcare. All Rights Reserved. 11 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 Code or Range Description S90.56X Insect bite (nonvenomous) of ankle S90.86X Insect bite (nonvenomous) of foot W57.XXXA Bitten or stung by nonvenomous insect and other nonvenomous arthropods, initial encounter W57.XXXD Bitten or stung by nonvenomous insect and other nonvenomous arthropods, subsequent encounter References Introduction These references are cited in this guideline. 1. Waddell LA, Greig J, Mascarenhas M, et al. The accuracy of diagnostic tests for Lyme disease in humans, a systematic review and meta-analysis of North American research. PLoS one. 2016;3(11):1-23. 2. Clark RP, Hu LT. Prevention of Lyme disease and other tick-borne infections. Infect Dis Clin North Am. 2008;22(3):381-96. 3. Hinckley AF, Connally NP, Meek JI, et al. Lyme disease testing by large commercial laboratories in the United States. Clin Infect Dis. 2014 Sep 1;59(5):676-81. 4. Brownstein JS, Holford TR, Fish D. Effect of climate change on lyme disease risk in North America. Ecohealth. 2005 Mar;2(1):38-46. doi: 10.1007/s10393-004-0139- Lyme Disease Testing x 5. Kobayashi T, Higgins Y, Samuels R, et al. Misdiagnosis of lyme disease with unnecessary antimicrobial treatment characterizes patients referred to an academic infectious diseases clinic. Open Forum Infect Dis. 2019 Jul 1;6(7):1-9. 6. Moore A, Nelson C, Molins C, Mead P, Schriefer M. Current guidelines, common clinical pitfalls, and future directions for laboratory diagnosis of Lyme disease, United States. Emerging Infectious Diseases. 2016 Jul; 22(7):1169-77. 7. Ross Russell AL, Dryden MS, Pinto AA, Lovette JK. Lyme disease: diagnosis and management. Pract Neurol. 2018;18:455-464. 8. Van Hout MC. The controversies, challenges and complexities of Lyme Disease: a narrative review. J Pharm Pharm Sci. 2018; 21: 429-436. 9. Lindsay LR, Bernat K, Dibernardo A. Laboratory diagnostics for Lyme disease. CCDR. 2014;40(11):209-17. 10. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of Lyme Borreliosis. Clin Micro Rev. 2005 Jul; 18(3):484-509. ©2021 eviCore healthcare. All Rights Reserved. 12 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
Lab Management Guidelines V2.0.2021 11. Schutzer SE, Body BA, Boyle J, et al. Direct diagnostic tests for Lyme disease. Clin Infect Dis. 2019; 68(6): 1052-1057. 12. Liu S, Cruz ID, Calalo Ramos C, et al. Pilot Study of Immunoblots with Recombinant Borrelia burgdorefi Antigens for Laboratory Diagnosis of Lyme Disease. Healthcare. 2018;99(6):1-15. 13. Fallon BA, Pavlicova M, Coffino SW, Brenner C. A comparison of Lyme disease serologic test results from 4 laboratories in patients with persistent symptoms after antibiotic treatment. Clin Infect Dis. 2014 Dec 15;59(12):1705-10. 14. Centers for Disease Control and Prevention. Two-Tiered Testing for Lyme Disease. Available at: https://www.cdc.gov/lyme/healthcare/clinician_twotier.html. 15. Centers for Disease Control and Prevention (CDC). Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme disease. MMWR. 1995 Aug 11;44(31):590-1. 16. Mead P, Petersen J, Hinckley A. Centers for Disease Control and Prevention (CDC). Updated CDC recommendation for serologic diagnosis of lyme disease. MMWR Morb Mortal Wkly Rep [Internet]. 2019 Aug 16;68(32):702-3. 17. Arvikar SL & Steere AC. Diagnosis and treatment of Lyme arthritis. Infect Dis Clin North Am. 2015;29(2):268-280. 18. Theel ES, Aguero-Rosenfeld ME, Pritt B, Adem PV, Wormser GP. Limitations and confusing aspects of diagnostic testing neurologic Lyme disease in the United States. J Clin Microbiol. 2019;57(1):e01406-18. 19. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical practice guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 guidelines for the prevention, diagnosis and treatment of Lyme disease. Clinical Infectious Diseases 2021;72(1):e1-e48. Lyme Disease Testing 20. Pritt BS, Mead PS, Hoang Jonson DK, et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis. 2016 May;16(5):556-564. 21. Shah JS, Liu S, Du Cruz I, et al. Line Immunoblot assay for tick-borne relapsing fever and findings in patient Sera from Austrailia, Ukraine and the USA. Healthcare. 2019;121(7):1-17. ©2021 eviCore healthcare. All Rights Reserved. 13 of 13 400 Buckwalter Place Boulevard, Bluffton, SC 29910 (800) 918-8924 www.eviCore.com
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