What is the treatment for a bullseye rash suspected to be erythema migrans associated with Lyme disease?

Treatment of Bullseye Rash (Erythema Migrans)

For a bullseye rash consistent with erythema migrans in Lyme disease endemic areas, initiate oral doxycycline 100 mg twice daily for 10 days immediately based on clinical diagnosis alone—do not wait for laboratory confirmation. 1

Diagnosis Approach

Make the diagnosis clinically without laboratory testing when the patient has potential tick exposure in an endemic area and a skin lesion compatible with erythema migrans. 1

• Serologic testing is not indicated for typical erythema migrans because antibody tests are usually negative in early disease. 1, 2
• Only order antibody testing if the rash is atypical or you're uncertain about the diagnosis, followed by convalescent serum 2-3 weeks later if the initial result is negative. 1

First-Line Treatment Options

The 2020 IDSA/AAN/ACR guidelines provide three equally effective first-line oral antibiotics: 1, 3

Adults:

• Doxycycline 100 mg twice daily for 10 days (preferred due to shorter duration and coverage of co-infection with Human Granulocytic Anaplasmosis) 1, 3, 4
• Amoxicillin 500 mg three times daily for 14 days 1, 3, 4
• Cefuroxime axetil 500 mg twice daily for 14 days 1, 3, 4

Children:

• Doxycycline 4.4 mg/kg/day in 2 divided doses (maximum 100 mg per dose) for 10-14 days if ≥8 years old 1, 4
• Amoxicillin 50 mg/kg/day in 3 divided doses (maximum 500 mg per dose) for 14 days if <8 years old 1, 4
• Cefuroxime axetil 30 mg/kg/day in 2 divided doses (maximum 500 mg per dose) for 14 days 1

Why Doxycycline is Preferred

Doxycycline offers two key advantages: 1, 3, 4

• Shorter treatment duration (10 days versus 14 days for beta-lactams) with equivalent efficacy 1
• Simultaneous coverage for HGA, which can co-occur with Lyme disease in endemic areas 1, 3

Second-Line Treatment

Use azithromycin only when patients cannot tolerate doxycycline AND beta-lactam antibiotics. 1, 3

• Azithromycin 500 mg daily for 7-10 days (7 days preferred in the United States) 1, 3
• Macrolides are less effective than first-line agents and should be reserved as last resort options. 1, 3, 4
• Patients on macrolides require close monitoring to ensure clinical resolution. 1

Critical Pitfalls to Avoid

Never use first-generation cephalosporins (e.g., cephalexin)—they are completely ineffective against Borrelia burgdorferi. 1, 3, 4

• If you cannot distinguish erythema migrans from bacterial cellulitis, use cefuroxime axetil or amoxicillin-clavulanate (500 mg three times daily in adults), which cover both conditions. 1
• Do not extend treatment beyond 10-14 days—longer courses provide no additional benefit. 1, 4
• Do not order laboratory testing for typical erythema migrans, as this delays treatment and early antibody tests are usually negative anyway. 1

Important Administration Details for Doxycycline

• Take with 8 ounces of fluid to prevent esophageal irritation 1, 4
• Take with food to minimize gastrointestinal side effects 1, 4
• Avoid sun exposure due to photosensitivity risk 1, 4
• Contraindicated in pregnancy, lactation, and children <8 years old 1, 4

Expected Outcomes

• Most patients respond promptly and completely to appropriate oral antibiotic therapy. 1, 3
• Less than 10% of patients fail to respond to initial treatment. 1
• Some patients experience mild Jarisch-Herxheimer-like reactions within the first 24 hours of treatment, which are transient and require no intervention. 1, 3
• Persistent subjective symptoms after treatment do not indicate treatment failure or require additional antibiotics. 1, 2

Special Consideration: Southern Tick-Associated Rash Illness (STARI)

In geographic regions where both Lyme disease and STARI are endemic, if you cannot distinguish between them clinically, treat with antibiotics directed at Lyme disease. 1