Symptoms and Testing for Lyme Disease
When to Test Based on Clinical Presentation
If a patient presents with erythema migrans (EM) in an endemic area, no laboratory testing is required—treat immediately based on clinical diagnosis alone. 1
Key Symptoms That Warrant Testing
Early Localized Disease (First 30 Days):
- Erythema migrans rash (present in 70-80% of cases): gradually expanding annular lesion >5 cm diameter, appearing 7-14 days after tick bite 1, 2
- Fever, headache, myalgias, arthralgias 1
- Regional lymphadenopathy 2
- Fatigue and malaise 1
Early Disseminated Disease (Weeks to Months):
- Multiple EM lesions indicating spirochetemia 2
- Cranial nerve palsy (especially facial nerve/Bell's palsy) 1
- Meningitis symptoms: headache with prolonged duration (median 17 days vs. 2 days for viral meningitis), less likely to have fever 1
- Papilledema (in children with Lyme meningitis, ~90% have EM, cranial nerve palsy, or papilledema) 1
- Carditis 1
Late Disseminated Disease (Months to Years):
- Recurrent large-joint arthritis (especially knees, occurs in 45-60% of untreated patients) 1, 3
- Peripheral neuropathy, encephalopathy 1
- Acrodermatitis chronica atrophicans (chronic skin changes on extensor surfaces of hands/feet, more common in Europe) 2
Diagnostic Testing Algorithm
Step 1: Assess Pretest Probability
Exposure history is the single most crucial factor. 1, 4
- High pretest probability: EM present in endemic area → No testing needed, treat immediately 1
- Intermediate pretest probability: No EM but high clinical suspicion based on endemic exposure, season (May-October peak), and characteristic symptoms → Proceed to two-tiered serologic testing 1, 4
- Low pretest probability: No endemic exposure or travel history → Do not test (positive predictive value only 10% in non-endemic areas, false positives more likely than true positives) 1
Step 2: Two-Tiered Serologic Testing (When Indicated)
The recommended laboratory approach is two-tiered serologic testing: EIA/ELISA or IFA first, followed by reflexive Western immunoblot if positive or borderline. 1, 4
Critical Performance Characteristics:
- Sensitivity in early disease: 30-40% (due to antibody window period in first 2-4 weeks) 1, 4
- Sensitivity in disseminated disease: 70-100% 1, 4
- Specificity: >95% across all stages 1
Interpretation by Disease Stage:
- Early localized (<30 days): Serology often negative due to window period—do not rely on testing, diagnose clinically if EM present 1, 4
- Early disseminated/Late disease: Vast majority are seropositive; if initially negative, obtain convalescent sample 2 weeks later 1
Step 3: Specialized Testing (Select Cases Only)
For Neurologic Lyme Disease:
- CSF analysis: Look for pleocytosis with <10% polymorphonuclear cells (lower than viral meningitis) 1
- Intrathecal antibody production testing (requires demonstration of specific CNS production, not passive transfer from serum) 1
- CSF PCR for B. burgdorferi DNA (only if laboratory has excellent quality control; few labs perform this accurately) 1
- Positive CSF antibody is almost universal in Lyme meningitis 5
For Suspected Reinfection:
- Conduct acute and convalescent serologic testing to detect increase in EIA titer or number of antibody bands 1
Critical Pitfalls to Avoid
Do not order serologic testing in patients without endemic exposure—false positives will exceed true positives, leading to misdiagnosis and inappropriate treatment. 1, 4
Do not interpret negative serology as excluding Lyme disease in the first 2-4 weeks of illness—the antibody window period means early disease is often seronegative. 4
Do not interpret persistent positive antibodies as active infection—antibodies persist for months to years after successful treatment and cannot indicate active disease. 4
Do not perform Western immunoblot without first-tier EIA/IFA—this violates the two-tiered testing algorithm and increases false positives. 1
Do not use PCR of blood routinely—it lacks sensitivity and is not standardized, though it has utility for novel species like B. miyamotoi and B. mayonii. 1
In neurologic cases without EM, do not make a purely clinical diagnosis—neurologic manifestations are too nonspecific; laboratory support is required. 1