What are the clinical features and treatment options for Lyme disease?

Clinical Features of Lyme Disease

Early Localized Stage (Days to Weeks After Tick Bite)

Erythema migrans is the pathognomonic hallmark of Lyme disease, occurring in 70-80% of patients, typically 7-14 days after tick bite, and is the only manifestation sufficiently distinctive to allow clinical diagnosis without laboratory confirmation 1, 2.

Erythema Migrans Characteristics

• Appearance: Lesions are typically ≥5 cm in diameter and expand over days 1
• Morphology: Can be homogeneously erythematous (most common in U.S. cases), have central clearing, or display a target-like appearance 1, 3
• Location: Often occur at unusual sites for bacterial cellulitis (axilla, popliteal fossa, abdomen) 1
• Timing: Lesions present within 48 hours of tick detachment are likely hypersensitivity reactions, not erythema migrans—mark borders with ink and observe for 1-2 days to differentiate 1
• Variants: Vesicles or pustules at the center occur in ~5% of cases but without significant pruritus (unlike contact dermatitis); lesions are not scaly unless long-standing or treated with topical corticosteroids 1
• Secondary lesions: Multiple erythema migrans lesions indicate hematogenous dissemination 1

Associated Systemic Symptoms

• Constitutional symptoms: Fever (often low-grade), malaise, fatigue, headache, myalgia, and arthralgia resembling a "summer cold" or viral infection 2, 4, 5
• Asymptomatic infection: Some patients have no recognized illness 2

Early Disseminated Stage (Days to Months After Infection)

Neurologic Manifestations

• Cranial neuropathy: Seventh nerve palsy is most common; can be bilateral 1, 2
• Lymphocytic meningitis: Patients typically have prolonged illness duration (median 17 days), are less likely to be febrile than viral meningitis, and have <10% polymorphonuclear cells in CSF 1
• Radiculoneuritis: Painful radiculopathy affecting peripheral nerves 1, 2
• Key differentiating features: Presence of erythema migrans, cranial nerve palsy, or papilledema occurs in ~90% of pediatric Lyme meningitis cases (papilledema is uncommon in adults) 1

Cardiac Manifestations

• Atrioventricular heart block: Historically reported in 4-10% of untreated patients; can progress to complete heart block requiring temporary pacemaker 1, 2
• Myopericarditis: Less common cardiac involvement 2

Musculoskeletal Manifestations

• Migratory arthralgias and myalgias: Can occur with or without objective joint swelling 2

Late Disseminated Stage (Weeks to Years After Infection)

Lyme Arthritis

• Presentation: Intermittent swelling and pain of one or several large joints (especially knees), persisting for weeks to months 2, 5
• Prevalence: Occurs in 45-60% of untreated patients 6, 7
• Antibiotic-refractory arthritis: Approximately 10% develop persistent joint swelling despite appropriate antibiotic treatment 2

Late Neurologic Manifestations

• Chronic axonal polyneuropathy: Peripheral nerve involvement 2
• Encephalopathy: Cognitive dysfunction with objective findings 2

Dermatologic Manifestations

• Acrodermatitis chronica atrophicans: Chronic skin manifestation more common in Europe 1
• Borrelial lymphocytoma: Bluish-red nodule, typically on ear lobe or nipple 1

Diagnostic Considerations

Visual inspection of erythema migrans in the appropriate epidemiologic context is sufficient for diagnosis—serologic testing is too insensitive in the first 2 weeks to be helpful and should not delay treatment 1.

When Laboratory Support is Required

• Neurologic disease without erythema migrans: Manifestations are too nonspecific for purely clinical diagnosis 1
• Two-tier serologic testing: By convalescence, 65% of patients with confirmed erythema migrans develop positive IgM or IgG antibodies 3
• CSF analysis: Intrathecal antibody production or PCR can support diagnosis in neurologic cases 1

Critical Pitfalls to Avoid

• Do not treat tick bite hypersensitivity as Lyme disease: Reactions <5 cm, urticarial appearance, and resolution within 24-48 hours suggest hypersensitivity rather than infection 1
• Consider coinfection: Patients with high-grade fever persisting >48 hours despite appropriate antibiotics, or unexplained leukopenia, thrombocytopenia, or anemia should be evaluated for Babesia or Anaplasma coinfection 1
• Avoid first-generation cephalosporins: Cephalexin and similar agents are ineffective against Borrelia burgdorferi 1
• Do not use serologic testing to assess treatment response: Antibodies persist for months to years after successful treatment 8