What are the signs, symptoms, and treatment options for Lyme disease?

Signs and Symptoms of Lyme Disease

Lyme disease presents with distinct clinical manifestations across three stages: early localized, early disseminated, and late disseminated disease, with erythema migrans (EM) being the classic sign in 70-80% of patients.

Early Localized Disease (Stage 1)

• Erythema migrans (EM): A gradually expanding annular lesion >5 cm in diameter, occurring at the site of the tick bite 1
• Accompanying symptoms may include:
  • Fever
  • Lymphadenopathy
  • Myalgias
  • Arthralgias
  • Headache
  • Fatigue
  • Symptoms resembling a "summer cold" or viral infection 2

Early Disseminated Disease (Stage 2)

Occurs weeks to months after infection if untreated:

Cutaneous Manifestations

• Multiple EM lesions (secondary lesions) appearing at sites distant from the tick bite 1, 3
• Borrelial lymphocytoma (rare, more common in Europe) 1, 4

Neurologic Manifestations (15% of untreated patients)

• Meningitis
• Cranial neuropathy (especially facial palsy)
• Radiculopathy
• Mononeuropathy multiplex 1

Cardiac Manifestations (8% of untreated patients)

• Atrioventricular heart block (most common)
• Myopericarditis
• Cardiomegaly 1, 5

Late Disseminated Disease (Stage 3)

Occurs months to years after infection if untreated:

Musculoskeletal Manifestations

• Recurrent large-joint arthritis (60% of untreated patients)
• Typically affects knees and other large joints 1, 5

Neurologic Manifestations (uncommon in the US)

• Peripheral neuropathy
• Encephalopathy
• Encephalomyelitis 1

Cutaneous Manifestations

• Acrodermatitis chronica atrophicans (primarily in Europe) 1, 4

Laboratory Diagnosis

Laboratory testing is necessary to confirm the diagnosis in patients without EM or in those with EM who have atypical presentations 1.

Recommended Testing Approach

• Two-tiered serologic testing:
  1. Enzyme-linked immunoassay (EIA/ELISA) or immunofluorescence assay (IFA)
  2. If positive or equivocal, followed by Western immunoblot 1

Test Limitations

• Low sensitivity (30-40%) during early infection
• Higher sensitivity (70-100%) for disseminated disease
• High specificity (>95%) during all stages 1

Treatment Considerations

Treatment varies based on disease stage and manifestations:

Early Localized or Early Disseminated Disease (without neurologic involvement)

• Oral antibiotics for 14-21 days:
  • Doxycycline
  • Amoxicillin
  • Cefuroxime 1

Neurologic Involvement or Advanced Heart Block

• Parenteral antibiotics (ceftriaxone, cefotaxime, or penicillin G) for 14-28 days 1

Post-Treatment Lyme Disease Syndrome (PTLDS)

• Some patients experience persistent symptoms after appropriate treatment
• Not due to persistent infection; antibiotics not beneficial for these symptoms 6
• Focus should be on symptom management rather than prolonged antibiotic therapy 6

Common Pitfalls in Diagnosis and Management

1. Misdiagnosis: Relying solely on serologic testing in early disease when sensitivity is low
2. Overdiagnosis: Attributing nonspecific symptoms to "chronic Lyme disease" without objective evidence
3. Inappropriate treatment: Using prolonged or repeated courses of antibiotics for PTLDS, which shows no benefit and potential harm 6
4. Missing coinfections: Failing to consider babesiosis or anaplasmosis in patients with more severe symptoms or those who don't respond to treatment 1
5. Overlooking alternative diagnoses: Not considering other conditions that may mimic Lyme disease symptoms

Special Considerations

• Pregnant patients should receive the same treatment as non-pregnant patients, except doxycycline should be avoided 1
• Consider coinfection with Babesia microti or Anaplasma phagocytophilum in patients with more severe initial symptoms, especially high-grade fever persisting despite appropriate antibiotic therapy 1