What is the diagnosis and treatment for a patient with suspected Lyme disease, presenting with fever, headache, and a characteristic bull's-eye rash, after spending time outdoors in wooded or rural areas?

Lyme Disease: Diagnosis and Treatment

Clinical Diagnosis

For patients presenting with a characteristic bull's-eye rash (erythema migrans) after outdoor exposure in endemic areas, clinical diagnosis alone is sufficient and treatment should be initiated immediately without waiting for laboratory confirmation. 1, 2

Key Diagnostic Features

• Erythema migrans is the hallmark of early Lyme disease, occurring in 50-80% of patients 2, 3
• The rash must be ≥5 cm in diameter and expands gradually over days to weeks (not hours) 4
• Typical onset is 7-14 days after tick bite (range 3-30 days) 1, 2, 4
• Associated symptoms include fever, headache, fatigue, myalgias, and arthralgias 1, 2

Critical Pitfall to Avoid

Do not confuse tick bite hypersensitivity reactions with erythema migrans. 4 Hypersensitivity reactions:

• Appear within 48 hours of tick removal (often while tick still attached) 4
• Resolve within 24-48 hours 4
• Are typically <5 cm in diameter 4
• Do not require antibiotic treatment 4

If uncertain, mark the rash borders with ink and observe for 1-2 days—true erythema migrans will expand while hypersensitivity reactions disappear 4

Laboratory Testing

When Laboratory Testing is Required

Laboratory confirmation is necessary for all manifestations except typical erythema migrans in endemic areas 1

Two-Tier Serologic Testing Protocol

The CDC-recommended approach consists of: 1, 5

1. Initial screening: Enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA)
2. Confirmatory test: Western immunoblot (performed reflexively if initial test is positive or equivocal)

Understanding Test Sensitivity by Disease Stage

Critical limitation: Two-tier testing has poor sensitivity (30-40%) during early localized disease due to the antibody window period 1

• Early disseminated disease: 70-100% sensitivity 1
• Late disseminated disease: 70-100% sensitivity 1
• Specificity remains high (>95%) at all stages 1

Clinical implication: Never withhold treatment for suspected early Lyme disease based on negative serology alone if erythema migrans is present 1

Treatment Recommendations

Early Localized Disease (Erythema Migrans)

First-line oral therapy: 1, 6, 5

• Doxycycline 100 mg twice daily for 10-14 days (preferred due to activity against coinfections like Anaplasma) 1, 4, 6
• Alternative: Amoxicillin 500 mg three to four times daily for 14 days 4, 7
• Alternative: Cefuroxime axetil (for patients who cannot tolerate doxycycline or amoxicillin) 6

Early Disseminated Disease

Neurologic manifestations (meningitis, cranial neuropathy, radiculoneuropathy): 1, 7

• Intravenous ceftriaxone 2 g daily for 14-21 days 1, 7
• Alternative: IV cefotaxime or IV penicillin G 7
• Exception: Isolated facial nerve palsy with normal CSF may be treated with oral doxycycline 7

Cardiac manifestations (high-grade AV block, myocarditis): 1

• Intravenous therapy with ceftriaxone or penicillin G for 14-21 days 7

Late Disseminated Disease

Lyme arthritis (intermittent large joint swelling, especially knee): 1, 2

• Oral doxycycline 100 mg twice daily for 28 days 1
• Alternative: Amoxicillin 500 mg four times daily for 28 days 1
• If persistent despite oral therapy, consider IV ceftriaxone 1

Late neurologic disease (encephalopathy, polyneuropathy): 1

• IV ceftriaxone 2 g daily for 14-28 days 1

Post-Treatment Considerations

Expected Recovery Timeline

• Subjective symptoms may persist for weeks to months after appropriate treatment due to slow resolution of inflammation, not persistent infection 2
• Approximately 35% have symptoms at day 20,24% at 3 months, and 17% at 12 months post-treatment 2

Post-Treatment Lyme Disease Syndrome

Prolonged antibiotic therapy beyond recommended regimens is NOT indicated and has not proven beneficial 1, 5, 8

• No reliable evidence supports survival of Borrelia in adequately treated patients 8
• Persistent symptoms may represent post-infectious sequelae or unrelated conditions (fibromyalgia, chronic fatigue) 7

Prevention Strategies

Personal Protective Measures

• Avoid tick-infested wooded, brushy, or grassy areas, especially during spring and summer 1
• Wear light-colored clothing to spot ticks easily 1
• Tuck pants into socks or boots 1
• Apply DEET-containing repellents to skin and permethrin to clothing 1
• Perform daily tick checks and prompt removal (transmission unlikely before 36 hours of attachment) 1, 6

Post-Exposure Prophylaxis

Single-dose doxycycline 200 mg orally may be considered in selected high-risk scenarios 6

• Must be given within 72 hours of tick removal
• Only for adult Ixodes scapularis ticks attached ≥36 hours in endemic areas

Environmental Modifications

• Remove leaf litter and brush around homes 1
• Clear trees to admit sunlight 1
• Consider deer exclusion fencing in high-risk residential areas 1

Geographic Risk Assessment

High-risk endemic areas in the United States: 1

• Northeastern states (coastal areas)
• Mid-Atlantic seaboard
• Upper north-central region (Great Lakes states)
• Northwestern California

Approximately 90% of cases occur in ~140 counties within these regions 1