Borrelia burgdorferi - Lyme Disease

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Content

Lyme Disease Evaluation

Indications for Testing

  • Patient at risk for Lyme disease with clinical symptoms
    • Tick bite
    • Endemic area
  • No testing necessary, if patient presents with tick bite and erythema migrans – proceed with treatment

Laboratory Testing

  • Current two-step testing CDC recommendations for serologic diagnosis of Lyme disease
  • Borrelia burgdorferi or C6 peptide antibodies total by ELISA
    • Positive or indeterminate (if neurological symptoms present, see Neurologic Disease Evaluation below)
      • <4 weeks after disease onset
        • B. burgdorferi IgG and IgM antibodies by Western blot
          • Positive IgG and negative IgM – Lyme disease confirmed
          • Negative IgG and positive IgM – Lyme disease or false-positive IgM
            • Follow-up IgG Western Blot (within 30 days) recommended to help confirm Lyme disease and rule out false-positive IgM Western Blot
          • Negative IgG and IgM – consider other causes of false-positive ELISA result (syphilis, rheumatoid arthritis, acute EBV, HIV, subacute bacterial endocarditis, systemic lupus erythematosus, periodontitis)
            • If Lyme disease still suspected or patient immunocompromised – order Borrelia spp DNA by PCR
      • ≥4 weeks after disease onset
        • B. burgdorferi IgG antibodies by Western blot
          • Positive – Lyme disease confirmed
          • Negative – see negative IgG and IgM above
      • Consider coinfection with Babesia microti, Anaplasma phagocytophilum (HGA), or Ehrlichia chaffeensis
    • Negative
      • No further testing on initial sample; test convalescent sample
      • Endemic regions –  consider coinfection with Babesia microti, Anaplasma phagocytophilum, Ehrlichia chaffeensis

Neurologic Disease Evaluation

Indications for Testing

  • Meningoradiculitis, meningitis, cranial nerve deficits

Criteria for Diagnosis

Laboratory Testing

  • Acute neurological symptoms present
    • Full meningitis workup (CSF studies)
      • Lumbar fluid analysis; should also include testing for other bacterial and viral etiologies (eg, West Nile virus)
      • Cell count – lymphocytic pleocytosis is typical (>8 wbc/mm3)
      • Total protein, glucose, culture with gram stain
    • B. burgdorferi antibodies, total, by ELISA (CSF)
    • As an alternative, consider
      • B. burgdorferi total C6 peptide antibodies by ELISA (CSF)
      • B. burgdorferi IgG and IgM antibodies by Western blot (CSF)
      • Borrelia species DNA detection by PCR
    • If any of the Borrelia tests above are positive – CNS disease confirmed
  • Chronic neurological symptoms present
    • Full meningitis workup (CSF studies; see above)
    • B. burgdorferi IgG antibodies by Western blot (CSF)
    • Consider Borrelia spp by PCR
    • If either Borrelia test is positive – CNS disease confirmed

Differential Diagnosis

Tick-Borne Testing Algorithm

Lyme disease is the most common vector-borne disease in the U.S.

Epidemiology

  • Incidence – 20-100/100,000 in U.S.
  • Age – bimodal peaks
    • Pediatric – 5-14 years
    • Elderly – >60 years
  • Sex – M:F, equal
    • M<F with acrodermatitis chronica atrophicans
  • Transmission
    • Tick bite – Ixodes spp
      • Vector – Ixodes scapularis (formerly Ixodes dammini)
        • More commonly known as blacklegged or deer tick (in U.S.)

Organism

  • Borrelia burgdorferi is a member of the Spirochaetales family, which also includes Treponema and Leptospira
  • Borrelia miyamotoi – known to transmit several diseases, including Lyme disease, anaplasmosis, and babesiosis
    • Detected in Ixodes pacificus and Ixodes scapularis ticks, but only three confirmed cases have been identified in the U.S.

Risk Factors

  • Exposure during the spring or summer in regions where deer population is high
    • Infected Ixodes tick must feed on patient for 48-72 hours in order to transmit B. burgdorferi
  • Northeast or Midwest location

Clinical Presentation

  • Clinical case epidemiologic surveillance criteria for defining Lyme disease (see CDC 2011 case definition)
    • Erythema migrans ≥5 cm in diameter or laboratory confirmation of infection plus ≥1 of the following late manifestations
      • Musculoskeletal manifestation – recurrent, brief attacks of objective swelling in 1 or more joints
      • Neurological manifestations – all or some of the items listed below
        • Lymphocytic meningitis – cerebrospinal fluid (CSF) pleocytosis with higher number of monocytes
        • Cranial neuritis
        • Radiculoneuritis (Garin-Bujadoux-Bannwarth syndrome)
        • Encephalomyelitis – requires demonstration of CSF antibody production
      • Cardiovascular manifestations – acute second- or third-degree arteriovenous heart block
  • Presentation timeframe
    • Initial symptoms usually appear in late spring/early summer when ticks are active
    • Late manifestations may occur anytime

Prevention

  • Avoid tick exposure
    • If unavoidable, use protective clothing and tick repellant (DEET)
  • Check for and remove ticks

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG and IgM by Western Blot (Early Disease) 0050267
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Limitations

Diagnosis of Lyme disease should not be made on the basis of positive IgM results alone in patients with symptoms <4 weeks' duration; antibodies are usually undetectable during early localized stage

Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot 0051043
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot 0050254
Method: Qualitative Western Blot

Follow Up

Retesting in 10-14 days may be helpful when serology test results are equivocal

Borrelia burgdorferi Antibody, IgG by Western Blot 0050255
Method: Qualitative Western Blot

Borrelia Species by PCR (Lyme Disease) 0055570
Method: Qualitative Polymerase Chain Reaction

Limitations

Negative result does not rule out presence of PCR inhibitors or B. burgdorferi DNA concentrations below detection level of assay

Cell Count, CSF 0095018
Method: Cell Count/Differential

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

Glucose, CSF 0020515
Method: Enzymatic

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Borrelia burgdorferi (Lyme Disease) Reflexive Panel (CSF) 2007335
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA (CSF) 0051046
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Limitations

Blood contamination or transfer of serum antibodies across blood-brain barrier is possible

Follow Up

Detection of antibodies of B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

Retesting in 10-14 days may be helpful when serology test results are equivocal

Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot (CSF) 0055260
Method: Qualitative Western Blot

Limitations

Blood contamination or transfer of serum antibodies across blood-brain barrier is possible

Follow Up

Detection of antibodies to B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

Babesia microti Antibodies, IgG and IgM by IFA 0093048
Method: Semi-Quantitative Indirect Fluorescent Antibody

Anaplasma phagocytophilum (HGA) Antibodies, IgG and IgM 0097303
Method: Semi-Quantitative Indirect Fluorescent Antibody

Ehrlichia and Anaplasma Species by Real-Time PCR 2007862
Method: Qualitative Polymerase Chain Reaction

Limitations

E. ewingii and E. canis cannot be differentiated by this test

CD57+ NK Cells, Peripheral Blood by Flow Cytometry 2008912
Method: Flow Cytometry

Limitations

Significance of low CD57+NK values in diagnosing and monitoring chronic Lyme disease is not well established; use only in conjunction with other diagnostic tests specified in CDC Lyme Disease case definition

Additional Tests Available

Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA 0051044
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Borrelia burgdorferi Antibody, IgM by Western Blot 0050253
Method: Qualitative Western Blot

Borrelia burgdorferi Total Antibodies, IgG and/or IgM by ELISA with Reflex to IgG by Western Blot (Late Disease) 0050268
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Borrelia burgdorferi Antibody, IgM by Western Blot (CSF) 0055258
Method: Qualitative Western Blot

Borrelia burgdorferi Antibodies, Total by ELISA, CSF 0099483
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Comments

Screening test for acute neuroborreliosis in patient with neurologic symptoms <4 weeks from onset of disease

Results should be confirmed by Western Blot antibody testing

Detection of antibodies to B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

Retesting in 10-14 days may be helpful when serology test results are equivocal

Borrelia burgdorferi Antibody, IgG by Western Blot (CSF) 0055259
Method: Qualitative Western Blot

Comments

Adjunct test for diagnosis of neuroborreliosis in patient with neurological symptoms >4 weeks after onset of disease

Detection of antibodies to B. burgdorferi in CSF may indicate CNS infection; follow up with additional CSF studies

Borrelia hermsii Antibody Panel by IFA, Serum 0093170
Method: Semi-Quantitative Indirect Fluorescent Antibody

Borrelia burgdorferi Antibodies, Total by ELISA 0050216
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay

Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG by Western Blot 0051045
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Qualitative Western Blot

Ehrlichia chaffeensis Antibodies, IgG & IgM by IFA 0051002
Method: Semi-Quantitative Indirect Fluorescent Antibody

Guidelines

Halperin J, Shapiro E, Logigian E, Belman A, Dotevall L, Wormser G, Krupp L, Gronseth G, Bever C, Quality Standards Subcommittee of the American Academy of Neurology. 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. PubMed

Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I, European Federation of Neurological Societies. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010; 17(1): 8-16, e1-4. PubMed

Wormser G, Dattwyler R, Shapiro E, Halperin J, Steere A, Klempner M, Krause P, Bakken J, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler S, Nadelman R. 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. PubMed

General References

Bratton R, Whiteside J, Hovan M, Engle R, Edwards F. Diagnosis and treatment of Lyme disease. Mayo Clin Proc. 2008; 83(5): 566-71. PubMed

Dandache P, Nadelman R. Erythema migrans. Infect Dis Clin North Am. 2008; 22(2): 235-60, vi. PubMed

Feder H. Lyme disease in children. Infect Dis Clin North Am. 2008; 22(2): 315-26, vii. PubMed

Hu L. In the clinic. Lyme disease. Ann Intern Med. 2012; 157(3): ITC2-2 - ITC2-16. PubMed

Murray T, Shapiro E. Lyme disease. Clin Lab Med. 2010; 30(1): 311-28. PubMed

Stanek G, Wormser G, Gray J, Strle F. Lyme borreliosis. Lancet. 2012; 379(9814): 461-73. PubMed

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

Wright W, Riedel D, Talwani R, Gilliam B. Diagnosis and management of Lyme disease. Am Fam Physician. 2012; 85(11): 1086-93. PubMed

Medical Reviewers

Last Update: January 2016