What are the manifestations and treatment options for Lyme disease?

Manifestations of Lyme Disease

Lyme disease presents with a wide spectrum of clinical manifestations that can be categorized into three stages: early localized, early disseminated, and late disease, with each stage having distinct clinical features.

Early Localized Stage (Days to Weeks After Infection)

• Erythema migrans (EM) - The pathognomonic skin rash occurs in 80% of patients, typically 7-14 days after the tick bite (range 3-30 days). It appears as an expanding red macule or papule that can grow to >20 cm in diameter, often with central clearing 1, 2
• Flu-like symptoms - Fever, malaise, fatigue, headache, myalgia, and arthralgia often accompany the rash 1, 2
• Some patients may have asymptomatic infection with no recognized illness 1

Early Disseminated Stage (Days to Months After Infection)

Cutaneous Manifestations

• Multiple erythema migrans lesions - Secondary skin lesions appearing days to weeks after initial infection, indicating hematogenous spread 1, 2
• Borrelial lymphocytoma - A rare cutaneous manifestation in Europe presenting as a solitary bluish-red swelling, commonly on the ear lobe in children or breast/nipple area in adults 1, 2

Neurologic Manifestations (Neuroborreliosis)

• Lymphocytic meningitis - Presenting with headache and neck stiffness 1
• Cranial neuropathy - Especially facial nerve palsy, which may be bilateral 1
• Radiculoneuritis - Motor or sensory radiculopathy, often presenting as shooting pains 1
• These three neurological manifestations together are known as Bannwarth syndrome in Europe 3

Cardiac Manifestations

• Atrioventricular heart block - Varying degrees of intermittent heart block, often occurring above the bundle of His 1
• Myopericarditis - Can occur in association with heart block 1
• Cardiac involvement is relatively rare (historically reported in 4-10% of untreated patients, but much lower in recent series) 1
• Not associated with severe congestive heart failure or valvular heart disease 1

Musculoskeletal Manifestations

• Migratory joint and muscle pains - With or without objective joint swelling 1

Late Disseminated Stage (Months to Years After Infection)

Musculoskeletal Manifestations

• Lyme arthritis - Intermittent swelling and pain of one or several large joints (especially knees), which can persist for weeks to months 1
• Approximately 10% of patients may develop persistent joint swelling even after appropriate antibiotic treatment 1

Neurologic Manifestations

• Chronic axonal polyneuropathy - Presenting with sensory disturbances 1
• Encephalopathy - Manifested by cognitive disorders, sleep disturbance, fatigue, and personality changes 1

Cutaneous Manifestations

• Acrodermatitis chronica atrophicans (ACA) - A late skin manifestation primarily seen in Europe, characterized by skin atrophy typically on the extensor surfaces of hands and feet 3, 2
• Due to skin atrophy, veins may become prominent, potentially leading to misdiagnosis as venous insufficiency 3

Post-Treatment Lyme Disease Syndrome

• Some patients experience persistent subjective symptoms (fatigue, arthralgia, myalgia) after appropriate antibiotic treatment 1
• The frequency of these symptoms decreases over time - from approximately 35% at 20 days post-treatment to 17% at 12 months 1
• These symptoms may be due to slow resolution of inflammation, residual damage, or other factors 1

Diagnostic Considerations

• Clinical diagnosis is primarily based on clinical findings, especially for early disease with erythema migrans 1
• Serologic testing (two-tier approach with ELISA followed by Western blot) is valuable for later-stage disease 1
• Antibodies often persist for months or years after successfully treated infection, so seropositivity alone cannot indicate active disease 1

Treatment Approach

• Early localized or early disseminated disease with erythema migrans: Oral antibiotics for 14 days

  • Doxycycline (100 mg twice daily)
  • Amoxicillin (500 mg three times daily)
  • Cefuroxime axetil (500 mg twice daily) 1

• Neurologic manifestations: Ceftriaxone 2g IV once daily for 14 days (range 10-28 days) 1

• Cardiac manifestations: Oral or parenteral antibiotics for 14 days (range 14-21 days); hospitalization and monitoring recommended for symptomatic patients or those with advanced heart block 1

• Lyme arthritis: Oral antibiotics for 28 days; persistent arthritis may require a second course or other approaches 1

Important Clinical Pitfalls

• Not all patients recall a tick bite (only about 25%) 3
• Coinfection with other tick-borne pathogens should be considered in patients with more severe initial symptoms, especially high-grade fever persisting >48 hours despite appropriate antibiotics 1
• Macrolide antibiotics are less effective and should only be used when patients cannot tolerate first-line agents 1
• Persistent symptoms after treatment do not necessarily indicate ongoing infection and may not benefit from additional antibiotics 1
• Lyme disease is rarely, if ever, fatal 1