What is the appropriate evaluation and management—including diagnosis, antibiotic selection and duration, need for serologic testing, and prophylaxis—for a patient with possible early or late Lyme disease after a recent tick bite?

Evaluation and Management of Lyme Disease After Tick Bite

For a patient with a recent tick bite and possible Lyme disease, prophylaxis with a single 200 mg dose of doxycycline should be offered only if all four strict criteria are met: the tick is an identified engorged Ixodes scapularis, it was attached ≥36 hours, prophylaxis can start within 72 hours of removal, and the local tick infection rate is ≥20%; otherwise, observation is appropriate, and if erythema migrans develops, treat with doxycycline 100 mg twice daily, amoxicillin 500 mg three times daily, or cefuroxime axetil 500 mg twice daily for 14 days. 1

Post-Tick Bite Prophylaxis Decision Algorithm

Prophylaxis is NOT routinely recommended. Only consider single-dose doxycycline 200 mg when ALL four criteria are simultaneously met: 1

• Tick identification: Reliably identified as adult or nymphal Ixodes scapularis tick
• Attachment duration: Estimated ≥36 hours based on engorgement degree or known exposure time
• Timing: Prophylaxis can begin within 72 hours of tick removal
• Endemic area: Local Borrelia burgdorferi infection rate in ticks is ≥20%
• No contraindications: Doxycycline is not contraindicated (avoid in pregnancy, lactation, children <8 years)

If any criterion is not met, observation alone is recommended. 1 Patients should be instructed to monitor for symptoms and seek care if erythema migrans or systemic symptoms develop within 1 month. 1

Diagnosis of Early Lyme Disease

Clinical Diagnosis

Erythema migrans is a clinical diagnosis that does not require serologic confirmation in the United States. 2 The characteristic features include: 3, 4

• Expanding erythematous lesion developing 7-10 days (range: days to 1 month) after tick bite
• Central clearing may be absent in >50% of cases 4
• Multiple lesions occur in approximately 20% of current U.S. cases 4
• Associated symptoms: fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), fever/chills (39%) 4

Critical pitfall: Not all erythema migrans-like lesions are Lyme disease. Southern tick-associated rash illness (STARI) from Amblyomma americanum (lone star tick) can produce identical-appearing lesions but is not caused by B. burgdorferi. 5 Geographic location and tick identification are essential.

Serologic Testing Approach

Serologic testing should NOT be performed for patients with classic erythema migrans, as clinical diagnosis is sufficient and early antibody responses are often absent. 2 However, testing is indicated for patients with: 1, 2

• Suspected disseminated disease (neurologic, cardiac, arthritic manifestations)
• Atypical presentations without clear erythema migrans
• Endemic area patients with compatible symptoms but no rash

Two-tier testing algorithm: 1, 2

1. Initial screening: IgG and IgM ELISA/EIA
2. If positive or borderline: Confirmatory Western blot (IgG and IgM)
3. Timing considerations:
   • Antibodies develop approximately 2 weeks after symptom onset 2
   • Initial testing may be falsely negative in <4 weeks of illness 2
   • If symptoms <4 weeks and initial test negative with high clinical suspicion: repeat testing 2-4 weeks after symptom onset 2
   • During first 4 weeks: perform both IgM and IgG Western blot if ELISA positive 2

Important caveat: Early antibiotic treatment can blunt or abrogate antibody response, potentially causing false-negative serology. 2 Do not delay treatment while awaiting serologic results in patients with clinical erythema migrans.

Treatment of Early Lyme Disease

Erythema Migrans (Early Localized/Disseminated Without Neurologic or Cardiac Involvement)

First-line oral regimens for adults: 1, 6

• Doxycycline 100 mg twice daily for 14 days (range: 10-21 days) 1

  • Advantage: Also treats human granulocytic anaplasmosis (HGA), a potential coinfection 1
  • Contraindicated in pregnancy, lactation, children <8 years 1

• Amoxicillin 500 mg three times daily for 14-21 days 1

• Cefuroxime axetil 500 mg twice daily for 14-21 days 1, 6

Pediatric dosing: 1

• Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg/dose)
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg/dose)
• Doxycycline 4-8 mg/kg/day in 2 divided doses (maximum 100-200 mg/dose) for children ≥8 years 1

Alternative agents (only for intolerance to first-line agents): 1

• Azithromycin 500 mg daily for 7-10 days (less effective; reserve for true intolerance) 1
• Clarithromycin 500 mg twice daily for 14-21 days (if not pregnant) 1
• Erythromycin 500 mg four times daily for 14-21 days 1

Macrolides are NOT first-line therapy because they are less effective than other antimicrobials in clinical trials. 1 Patients treated with macrolides require close observation to ensure resolution. 1

Early Neurologic Lyme Disease

Meningitis or radiculopathy: 1

• Parenteral therapy required: Ceftriaxone 2 g IV daily for 14 days (range: 10-28 days) 1
• Alternative: Cefotaxime or penicillin G 1
• Pediatric: Ceftriaxone 50-75 mg/kg/day IV (maximum 2 g) 1

Cranial nerve palsy (including facial nerve palsy) without meningitis: 1

• Oral regimen is sufficient: Same as erythema migrans treatment for 14-21 days 1
• Lumbar puncture is indicated if severe/prolonged headache or nuchal rigidity present 1
• If CSF is normal or not performed (no meningeal signs), oral therapy alone is appropriate 1

Cardiac Lyme Disease

Oral or parenteral regimen for 14-21 days depending on severity of heart block. 1 Advanced atrioventricular block may require parenteral therapy and temporary pacing.

Late Lyme Disease

Lyme arthritis without neurologic involvement: 1

• Oral regimen for 28 days 1
• If recurrent after oral therapy: repeat oral or switch to parenteral for 14-28 days 1

Late neurologic disease (CNS or peripheral nervous system): 1

• Parenteral regimen for 14-28 days 1

Acrodermatitis chronica atrophicans: 1

• Oral regimen for 21 days (range: 14-28 days) 1

Agents NOT Recommended

The following are explicitly NOT recommended due to lack of efficacy, absence of supporting data, or potential harm: 1

• First-generation cephalosporins
• Fluoroquinolones
• Carbapenems
• Vancomycin
• Metronidazole/tinidazole
• Trimethoprim-sulfamethoxazole
• Benzathine penicillin G
• Long-term antibiotic therapy
• Combination antimicrobials
• Pulsed-dosing regimens

Ceftriaxone is NOT recommended for early Lyme disease without neurologic involvement or advanced heart block due to unnecessary adverse effects. 1

Coinfection Considerations

Consider coinfection with Anaplasma phagocytophilum (HGA) or Babesia microti in endemic areas when: 1

• High-grade fever persists ≥48 hours despite appropriate Lyme therapy 1
• Unexplained leukopenia, thrombocytopenia, or anemia present 1
• More severe initial symptoms than typical for Lyme disease alone 1
• Erythema migrans resolved but viral-like symptoms persist or worsen 1

Doxycycline treats both Lyme disease and HGA but NOT babesiosis. 1 Babesiosis requires atovaquone plus azithromycin or clindamycin plus quinine.

Post-Treatment Expectations and Follow-Up

Complete clinical response may be delayed beyond treatment duration. 1 This is normal and does not indicate treatment failure.

Post-treatment symptoms are common and expected: 7

• 35% have subjective symptoms at day 20
• 24% at 3 months
• 17% at 12 months
• These reflect slow resolution of inflammatory processes, NOT persistent infection 7

Antibodies persist for months to years after successful treatment. 7 Seroreactivity alone cannot be used as a marker of active disease or treatment failure. 7 Clinical response should be the primary determinant of treatment success, not serologic findings. 7

Post-Lyme disease syndrome: 1

• Evaluate for other potential causes of persistent symptoms
• If none found, provide symptomatic therapy
• Do NOT prescribe prolonged or repeated antibiotic courses 1, 8

Relapse with objective signs may occur with any regimen and may require a second course of treatment. 1 However, distinguish true relapse from: 7

• Post-treatment inflammatory symptoms (most common)
• Reinfection (possible; prior infection does not confer immunity) 7
• Alternative diagnoses (fibromyalgia, chronic fatigue syndrome)

Critical pitfall: Avoid misinterpreting persistent antibodies or post-treatment symptoms as ongoing infection requiring prolonged antibiotics. 7, 8 This leads to unnecessary treatment of noninfectious problems with potential for significant harm.