II. Indications

  1. Endemic area with classic lyme symptoms and signs
  2. Endemic area with non-specific symptoms >2 weeks
  3. No test needed if highly endemic area and classic signs
    1. Treat empirically if high pretest probablity
    2. Erythema Migrans in endemic area is diagnostic
    3. Titers are insensitive for Lyme Disease in <2 weeks

III. Precautions

  1. Information based on IDSA and CDC guidelines
    1. IDSA: Infectious Disease Society of America
    2. IDSA is considered standard of care recommendations
    3. Tertiary centers (e.g. Mayo) follow these guidelines
  2. Other guidelines (e.g. ILADS) are not reviewed here
    1. ILADS: International Lyme and Associated Diseases
    2. ILADS guidelines are considered controversial

IV. Mechanism: Borrelia BurgdorferiAntibody

  1. Lyme IgM
    1. Present within 1-3 weeks after disease onset
    2. Peaks between 3 and 6 weeks
    3. Presence represents
      1. Early Lyme Disease
      2. Persists in prolonged Lyme Disease
      3. Reappears in Late Lyme Disease exacerbation
  2. Lyme Specific IgG
    1. Requires more than 3 weeks to develop
    2. Peaks months after disease onset

V. Efficacy: Test Sensitivity (two tiered testing)

  1. Timing in relation to Erythema Migrans rash
    1. Acute Erythema Migrans rash: 30-40% seropositive
    2. Two to four weeks after Erythema Migrans: 60-70% seropositive
    3. Six weeks after Erythema Migrans: 90% seropositive
  2. Timing in relation to Lyme phase
    1. Stage 1: Early localized
      1. Acute phase: 17% seropositive
      2. Convalescent: 53% seropositive
    2. Stage 2: Early disseminated
      1. Multiple Erythema Migrans lesions: 43% seropositive
      2. Cardiac or neurologic findings: 100% seropositive
    3. Stage 3: Late
      1. Arthritis or neurologic findings: 100% seropositive
  3. References
    1. Steere (2008) Clin Infect Dis 47(2): 188-95 [PubMed]

VI. Disadvantages

  1. Serology (ELISA) has False Positives, False Negatives
    1. Diagnosis should be clinical
    2. Test Lyme Titer to confirm diagnosis
    3. Test Specificity varies per timing of disease
      1. Early-Stage: 93%
      2. Late-Stage: 81%

VII. Causes: Lyme serology False Positives

  1. Infectious Mononucleosis (esp. Lyme IgM)
  2. Rheumatologic Conditions (esp. Lyme IgM)
  3. Prior Lyme Vaccine (LYMErix)
    1. Test Western Blot and ignore OspA band
  4. Cross reactivity with Treponema infection
    1. Syphilis
    2. Yaws
    3. Relapsing Fever

VIII. Causes: Lyme serology False Negatives

  1. Testing within first 2 weeks of symptoms
  2. Antibiotics early in course of lyme infection
    1. Inadequate antibiotic course can blunt seroconversion

IX. Protocol

  1. Tier 1: Obtain Lyme Serology (polyvalent ELISA)
    1. Initial test in all cases
    2. Move to tier 2 tests if positive or equivocal
  2. Tier 2: Immunoglobulin GWestern Blot Test
    1. Tests for IgM and IgG Immunoblots
    2. Confirms positive or equivocal Lyme Titer
      1. With Lyme Serology, Test Specificity: 99-100%
      2. IgG must be positive for symptoms >4 weeks
  3. Pitfalls
    1. Avoid using labs that do not follow CDC guidelines
    2. Avoid starting at Tier 2 (Western Blot)
      1. High False Positive Rate
      2. Faint positive bands in uninfected person is common
    3. Borrelia Burgdorferi PCR or culture not recommended
      1. Exception: Atypical dermatitis
    4. Avoid urine Antigen test (unreliable with high False Positive Rate)

X. Reference

Images: Related links to external sites (from Bing)

Related Studies