II. Indications
- Endemic area with classic lyme symptoms and signs
- Endemic area with non-specific symptoms >2 weeks
- No test needed if highly endemic area and classic signs
- Treat empirically if high pretest probablity
- Erythema Migrans in endemic area is diagnostic
- Titers are insensitive for Lyme Disease in <2 weeks
III. Precautions
- Information based on IDSA and CDC guidelines
- IDSA: Infectious Disease Society of America
- IDSA is considered standard of care recommendations
- Tertiary centers (e.g. Mayo) follow these guidelines
- Other guidelines (e.g. ILADS) are not reviewed here
- ILADS: International Lyme and Associated Diseases
- ILADS guidelines are considered controversial
IV. Mechanism: Borrelia BurgdorferiAntibody
- Lyme IgM
- Present within 1-3 weeks after disease onset
- Peaks between 3 and 6 weeks
- Presence represents
- Early Lyme Disease
- Persists in prolonged Lyme Disease
- Reappears in Late Lyme Disease exacerbation
- Lyme Specific IgG
- Requires more than 3 weeks to develop
- Peaks months after disease onset
V. Efficacy: Test Sensitivity (two tiered testing)
- Timing in relation to Erythema Migrans rash
- Acute Erythema Migrans rash: 30-40% seropositive
- Two to four weeks after Erythema Migrans: 60-70% seropositive
- Six weeks after Erythema Migrans: 90% seropositive
- Timing in relation to Lyme phase
- Stage 1: Early localized
- Acute phase: 17% seropositive
- Convalescent: 53% seropositive
- Stage 2: Early disseminated
- Multiple Erythema Migrans lesions: 43% seropositive
- Cardiac or neurologic findings: 100% seropositive
- Stage 3: Late
- Arthritis or neurologic findings: 100% seropositive
- Stage 1: Early localized
- References
VI. Disadvantages
-
Serology (ELISA) has False Positives, False Negatives
- Diagnosis should be clinical
- Test Lyme Titer to confirm diagnosis
- Test Specificity varies per timing of disease
- Early-Stage: 93%
- Late-Stage: 81%
VII. Causes: Lyme serology False Positives
- Infectious Mononucleosis (esp. Lyme IgM)
- Rheumatologic Conditions (esp. Lyme IgM)
- Prior Lyme Vaccine (LYMErix)
- Test Western Blot and ignore OspA band
- Cross reactivity with Treponema infection
VIII. Causes: Lyme serology False Negatives
- Testing within first 2 weeks of symptoms
- Antibiotics early in course of lyme infection
- Inadequate antibiotic course can blunt seroconversion
IX. Protocol
- Tier 1: Obtain Lyme Serology (polyvalent ELISA)
- Initial test in all cases
- Move to tier 2 tests if positive or equivocal
- Tier 2: Immunoglobulin GWestern Blot Test
- Tests for IgM and IgG Immunoblots
- Confirms positive or equivocal Lyme Titer
- With Lyme Serology, Test Specificity: 99-100%
- IgG must be positive for symptoms >4 weeks
- Pitfalls
- Avoid using labs that do not follow CDC guidelines
- Avoid starting at Tier 2 (Western Blot)
- High False Positive Rate
- Faint positive bands in uninfected person is common
- Borrelia Burgdorferi PCR or culture not recommended
- Exception: Atypical dermatitis
- Avoid urine Antigen test (unreliable with high False Positive Rate)
X. Reference
- Steere in Mandell (2000) Infectious Disease, p. 2504-14
- (1995) MMWR Morb Mortal Wkly Rep 44:590 [PubMed]
- Klempner (2001) Am J Med 110:217-9 [PubMed]