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Disease Categories > Infectious Disease > Bacteria

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Borrelia burgdorferi - Lyme Disease

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

Epidemiology

Incidence – increased 40% from 2001 to 2002
Age – bimodal peaks (pediatric 5-14 years; elderly >60 years)
Sex – M:F; 1:1 except for the presentation of acrodermatitis chronica atrophicans (M<F)
Transmission – infected Ixodes tick bite

Organism

Borrelia burgdorferi is a member of the Spirochaetales family which also includes Treponema and Leptospira

Risk Factors

Exposure in regions where deer population is high during the spring or summer
Northeast or Midwest geographic location
- 12 U.S. states account for 95% of reported cases

Clinical Presentation

Centers for Disease Control (CDC) clinical case epidemiologic surveillance criteria for defining Lyme disease
- Erythema migrans (EM) ≥5 cm in diameter or
- Laboratory confirmation of infection and at least 1 late manifestation
  - Musculoskeletal manifestation – recurrent, brief attacks of objective joint swelling in 1 or more joints
  - Neurological manifestations
    - All or part of a triad
      - Lymphocytic meningitis – CSF pleocytosis with higher number of monocytes
      - Cranial neuritis
      - Radiculoneuritis – termed Garin-Bujadoux-Bannworth syndrome
      - Encephalomyelitis – requires demonstration of CSF antibody production
  - Cardiovascular manifestations – acute second or third degree arteriovenous (AV) heart block
Lyme disease stages
- Stage 1 early localized
  - Occurs within hours to several weeks after infection
  - Characterized by erythema migrans (EM) or lymphocytoma (rare in U.S.)
  - Manifestations
    - Regional adenopathy and/or minor constitutional symptoms
- Stage 2 early disseminated
  - Occurs weeks to months following the tick bite
  - Characterized by neurologic and cardiac involvement (manifested in 15% and 8% of patients, respectively)
  - Manifestations
    - Fever
    - Myalgias
    - Multiple EM lesions
    - Meningitis
    - Bells palsy
    - Guillain-Barré-like syndrome
    - Cardiac conduction abnormalities
    - Arthritis
- Stage 3 late disseminated
  - Occurs within a few weeks to 2 years following infection
  - Symptoms are more severe than early disseminated
  - Characterized by arthritis or central nervous system involvement
    - Occurs in 60% of individuals not effectively treated early in infection
    - Tends to be intermittent, lasting from several days to weeks
  - Manifestations
    - Memory loss
    - Fatigue
    - Polyneuropathy
Initial symptoms usually appear in late spring/early summer, when ticks are active
Late manifestations occur anytime

Diagnosis

Laboratory testing
- Diagnosis depends on clinical features, combined with available laboratory tests
  - C6 peptide antibodies or Borrelia antibodies by ELISA
- Refer to the Lyme Disease Testing algorithm
Current CDC recommendations for serologic diagnosis of Lyme disease
- Screen with a polyvalent ELISA test
- Confirm equivocal and positive results with Western Blot
- Refer to Lyme Disease Testing algorithm
Co- and triple-infections by parasites that cause babesiosis and granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis) may occur
- Serologic testing specific for these agents is recommended
- Co- and triple-infections by parasites that cause babesiosis and granulocytic anaplasmosis may occur; serological testing specific for these agents is recommended

Differential Diagnosis

Ehrlichia chaffeensis
Babesia microti
Rickettsia rickettsii
Parvovirus
Francisella tularensis
Colorado tick fever
Human granulocytic anaplasmosis

Treatment

Lyme disease, caught early, is easily treated
- Treatment prevents progression to chronic stage
- Severe, long-term effects occur in <10% of untreated patients
If known tick bite and erythema migrans present, proceed with treatment; testing is not necessary

Prevention

Avoid exposure to ticks
If exposure is unavoidable, use protective clothing and tick repellant; check for and remove ticks

Indications for Ordering

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

Test Name and Number	Recommended Use	Limitations	Follow Up
Borrelia burgdorferi Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot (Early Disease) 0050267 Method: Enzyme-Linked Immunosorbent Assay/Western Blot	Screen for Lyme disease <8 weeks after onset of disease If known tick bite and erythema migrans present, proceed with treatment – no testing necessary	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests
Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG & IgM by Western Blot 0051043 Method: Enzyme-Linked Immunosorbent Assay/Western Blot	Screen for Lyme disease <8 weeks after onset of disease If known tick bite and erythema migrans present, proceed with treatment – no testing necessary	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests
Borrelia burgdorferi Antibodies, IgG & IgM by Western Blot 0050254 Method: Western Blot	Confirm an equivocal or positive antibody test performed <8 weeks after appearance of erythema migrans If known tick bite and erythema migrans present, proceed with treatment – no testing necessary	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests	Retesting in 10-14 days may be helpful when serology test results are equivocal
Borrelia burgdorferi Antibody, IgG by Western Blot 0050255 Method: Western Blot	Confirm an equivocal or positive antibody test performed >8 weeks after appearance of erythema migrans If known tick bite and erythema migrans present, proceed with treatment – no testing necessary	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests
Borrelia species DNA Detection by PCR (Lyme Disease) 0055570 Method:	Diagnose Lyme disease in patient with negative serologic results but disease still strongly suspected, or with immune deficiency If known tick bite and erythema migrans present, proceed with treatment – no testing necessary	Negative result does not rule out presence of PCR inhibitors or B. burgdorferi DNA concentrations below detection level of assay No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests
Borrelia burgdorferi Antibody, IgG by Western Blot (CSF) 0055259 Method: Western Blot	Adjunct test for neuroborreliosis in patient with neurological symptoms >8 weeks after onset of disease	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests	Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier
Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA (CSF) 0051046 Method: Enzyme-Linked Immunosorbent Assay	Adjunct test for neuroborreliosis in patient with neurologic symptoms <8 weeks from onset of disease	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests	Detection of antibodies of B. burgdorferi in CSF may indicate central nervous system infection Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier For equivocal test results, repeat testing in 10-14 days may be helpful
Borrelia burgdorferi Antibodies, Total by ELISA (CSF) 0099483 Method: Enzyme-Linked Immunosorbent Assay	Screening test (confirmed by Western Blot) for neuroborreliosis in patient with neurologic symptoms <8 weeks from onset of disease	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests	Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection Consider possible contamination by blood or transfer of serum antibodies across blood-brain barrier 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: Western Blot	Confirm positive test for CSF antibodies	No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests	Detection of antibodies to B. burgdorferi in cerebrospinal fluid may indicate central nervous system infection Consider possible contamination by blood or transfer of serum antibodies across the blood-brain barrier

Additional Tests Available

Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Comments
Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA 0051044 Method: Enzyme-Linked Immunosorbent Assay
Borrelia burgdorferi Antibody, IgM by Western Blot 0050253 Method: Western Blot
Borrelia burgdorferi Total Antibodies, IgG and/or IgM by ELISA with Reflex to IgG by Western Blot (Late Disease) 0050268 Method: Enzyme-Linked Immunosorbent Assay/Western Blot
Borrelia burgdorferi Antibody, IgM by Western Blot (CSF) 0055258 Method: Western Blot
Borrelia hermsii Antibody Panel, IFA 0093170 Method: Immunofluorescence Assay
Lyme Antigen, Urine 0050219 Method: Lyme Dot-Blot Assay
Borrelia burgdorferi Antibodies, Total by ELISA 0050216 Method: Enzyme-Linked Immunosorbent Assay	Alternative first line screening test for Lyme disease If known tick bite and erythema migrans present, proceed with treatment – no testing necessary Up to 40% of patients with early disease are seronegative by ELISA at time they present with erythema migrans Serologic diagnosis often not established until advanced stage of disease No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests Retesting in 10-14 days may be helpful when serology test results are equivocal
Borrelia burgdorferi C6 Peptide Antibodies, Total by ELISA with Reflex to IgG by Western Blot 0051045 Method: Enzyme-Linked Immunosorbent Assay/Western Blot	Screen for Lyme disease >8 weeks after onset of disease If known tick bite and erythema migrans present, proceed with treatment – no testing necessary No objective tests for Lyme borreliosis exist that are 100% sensitive and 100% specific Diagnosis depends on clinical features, combined with available laboratory tests

Additional Information

Serological testing
- False-positive results from serologic tests may result from:
  - Other spirochetal disease (syphilis, periodontitis)
  - Autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis)
  - Other infections (subacute bacterial endocarditis, HIV, Acute EBV)

Guidelines

Evidence-based guidelines for the management of Lyme disease. International Lyme and Associated Diseases Society - Disease Specific Society. 2004. 13 pages. NGC:003481 (Link to NGC)

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, Krause PJ, Bakken JS, Strle F, Stanek G, Bockenstedt L, Fish D, Dumler JS, Nadelman RB. 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):1089-1134. (Link to PubMed)

General References

Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev. 2005;18(3):484-509. (Link to PubMed)

Bratton RL, Corey R. Tick-borne disease. Am Fam Physician. 2005;71(12):2323-2330. (Link to PubMed)

DePietropaolo DL, Powers JH, Gill JM, Foy AJ. Diagnosis of lyme disease. Am Fam Physician. 2005;72(2):297-304. (Link to PubMed)

Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT Jr. 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. (Link to PubMed)

Hoppa E, Bachur R. Lyme disease update. Curr Opin Pediatr. 2007;19(3):275-280. (Link to PubMed)

Shapiro ED. Lyme disease. Adv Exp Med Biol. 2008;609:185-195. (Link to PubMed)

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

Wilske B. Epidemiology and diagnosis of Lyme borreliosis. Ann Med. 2005;37(8):568-579. (Link to PubMed)

Reviewed by

Hillyard, David R., M.D. Medical Director, Molecular Infectious Diseases at ARUP Laboratories; Associate Professor, Pathology, University of Utah

Litwin, Christine, M.D. Medical Director, Immunology at ARUP Laboratories; Professor, Clinical Pathology, University of Utah

Comprehensive Review: July 2008
Last Update: July 2008