What are the symptoms and treatment options for Lyme disease?

Lyme Disease: Symptoms and Treatment

Clinical Manifestations by Stage

Lyme disease presents in three distinct stages with specific symptoms at each phase, and early recognition with appropriate antibiotic therapy leads to excellent outcomes. 1, 2

Early Localized Disease (Days to Weeks After Tick Bite)

• Erythema migrans (EM) is the hallmark skin lesion, occurring in 50-80% of patients 3, 4, 5

  • Can appear as the classic "bull's-eye" target lesion or as homogeneous erythema without central clearing 5, 6
  • Multiple EM lesions may occur with early dissemination 2, 6
  • Only 72.7% of the general public correctly identifies classic target EM, and just 20.5% recognize non-classic presentations 5

• Constitutional symptoms resembling a viral illness or "summer cold" 3, 4:

  • Fever, malaise, fatigue 1, 2
  • Headache 2
  • Myalgias and arthralgias 1, 2

Early Disseminated Disease (Days to Weeks Later)

• Neurologic manifestations 1, 7:

  • Cranial neuropathy (especially facial nerve palsy/Bell's palsy) 1, 7
  • Lymphocytic meningitis 1
  • Radiculoneuropathy (painful radiculitis affecting specific nerve roots) 1, 7
  • Mononeuropathy multiplex (multifocal nerve involvement) 1, 7
  • Rarely, encephalomyelitis 1

• Cardiac involvement 1, 2:

  • Atrioventricular heart block of varying degrees 1
  • Carditis 1, 2

• Multiple erythema migrans lesions 2, 6

Late Disseminated Disease (Weeks to Years After Onset)

• Musculoskeletal manifestations 1:

  • Intermittent or persistent mono- or oligoarticular arthritis 2, 6
  • Typically affects large joints, especially the knee 2

• Late neurologic disease 1:

  • Peripheral neuropathy (mild, diffuse "stocking-glove" pattern with intermittent paresthesias) 7
  • Encephalopathy 1
  • Cognitive dysfunction (though objective impairment is less common than subjective complaints) 1

• Acrodermatitis chronica atrophicans (primarily in European infections) 1

Diagnostic Approach

Diagnosis is primarily clinical in early disease, with serologic testing providing supportive information in later-stage disseminated disease. 1

When to Diagnose Clinically

• Treating patients with early disease based solely on objective signs (especially EM) and known tick exposure is appropriate without waiting for serologic confirmation 1
• The incubation period is typically 3-30 days after tick bite 4

Serologic Testing Recommendations

• Two-tier testing approach (ELISA followed by Western blot for equivocal or positive results) is the CDC-recommended standard 1, 7
• Testing is valuable for patients with endemic exposure and objective findings suggesting later-stage disseminated disease 1
• Critical caveat: Antibodies persist for months to years after successful treatment, so positive serology alone does not indicate active infection 1, 8
• Early antibiotic treatment can blunt or abrogate the antibody response 1
• Patients with early disseminated or late-stage disease usually demonstrate strong serologic reactivity with expanded IgG banding patterns 1

When NOT to Test

• Do NOT test for nonspecific neurologic symptoms without other clinical or epidemiologic support 7
• Isolated sensory symptoms without objective findings are not typical of Lyme neuroborreliosis and should prompt alternative diagnoses 7

Treatment Recommendations

Early Localized Disease (Erythema Migrans)

Oral antibiotics for 14 days (range 14-21 days) are the standard treatment: 1

• Doxycycline 100 mg twice daily (preferred) 1, 3, 2
• Amoxicillin 500 mg three times daily 1, 3
• Cefuroxime axetil as alternative 1, 2
• Macrolides (erythromycin) reserved only for patients intolerant of tetracyclines, penicillins, and cephalosporins due to lower efficacy 1, 2

Important: Doxycycline should be avoided in pregnant/lactating women and children <8 years of age 1

Early Neurologic Disease

• Meningitis or radiculopathy: Parenteral therapy for 14 days (range 10-28 days) 1

  • Ceftriaxone 2g IV daily 1
  • Cefotaxime or penicillin G IV as alternatives 1

• Isolated cranial nerve palsy: Oral regimen for 14-21 days (same as EM treatment) 1, 3

Cardiac Disease

• Advanced heart block or hospitalized patients: Initial parenteral therapy (ceftriaxone), then complete with oral regimen 1
• Outpatients with less severe cardiac involvement: Oral regimen for 14-21 days 1
• Temporary pacemaker may be required for advanced heart block; expert cardiology consultation recommended 1

Late Disease

• Arthritis without neurologic involvement: Oral regimen for 28 days 1

• Recurrent arthritis after oral therapy: Repeat oral or parenteral regimen for 14-28 days 1

• Antibiotic-refractory arthritis: Symptomatic therapy (NSAIDs, intra-articular corticosteroids, DMARDs like hydroxychloroquine); arthroscopic synovectomy may reduce inflammation duration 1

• Late neurologic disease (CNS or peripheral): IV ceftriaxone for 14-28 days 1, 7

  • Response is usually slow and may be incomplete 1

• Acrodermatitis chronica atrophicans: 21-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime axetil) 1

Tick Bite Prophylaxis

• Single dose doxycycline 200 mg may be offered when ALL of the following exist: 1
  • Attached tick identified as adult or nymphal Ixodes species
  • Tick estimated to have been attached ≥36 hours
  • Prophylaxis can be started within 72 hours of tick removal
  • Local Lyme disease rate ≥20%
  • Doxycycline not contraindicated

Post-Treatment Considerations

Expected Symptom Resolution

• Subjective symptoms (arthralgia, myalgia, fatigue) may persist temporarily due to slow resolution of inflammation, not persistent infection 1, 8
• At follow-up after EM treatment: 35% have symptoms at day 20,24% at 3 months, 17% at 12 months 1, 8

Post-Lyme Disease Syndrome

• Approximately 10% of treated patients experience persistent symptoms (fibromyalgia-like illness) unresponsive to prolonged antibiotics 4, 6
• Antibiotic therapy has not proven useful and is NOT recommended for patients with chronic subjective symptoms (≥6 months) after appropriate treatment 1
• Evaluate for alternative causes of symptoms; if none found, provide symptomatic therapy 1

Critical Pitfall to Avoid

• Do NOT misinterpret persistent positive serology as treatment failure or ongoing infection 1, 8
• Antibodies persist for months to years after successful treatment and should not guide re-treatment decisions 1, 8
• Neither positive serology nor previous Lyme disease confers protective immunity; reinfection can occur 1, 8

Coinfection Considerations

Consider coinfection with Babesia microti or Anaplasma phagocytophilum when: 1

• More severe initial symptoms than typical for Lyme disease alone 1
• High-grade fever persisting ≥48 hours despite appropriate Lyme treatment 1
• Unexplained leukopenia, thrombocytopenia, or anemia 1
• EM lesion resolved but viral-like symptoms persist or worsen 1

Treatments NOT Recommended

The following have no proven efficacy and should NOT be used: 1

• First-generation cephalosporins, fluoroquinolones, carbapenems 1
• Vancomycin, metronidazole, tinidazole 1
• Long-term antibiotic therapy or pulsed-dosing regimens 1
• Hyperbaric oxygen, ozone, fever therapy 1
• IV immunoglobulin, cholestyramine, IV hydrogen peroxide 1