Lyme Disease

David C. Tompkins, M.D. Benjamin J. Luft, M.D.
State University of New York at Stony Brook

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Progressive infectious disease with many clinical manifestations, caused by the spirochete Borrelia burgdorferi
• Three stages:
  • Early localized
  • Early disseminated
  • Late persistent

• Erythema migrans in up to 85% of exposed persons
  • Appears 3–30 days (mostly 7–10 days) after exposure
  • Usually at the site of tick bite (knees, axilla, groin)
  • Red macule or papule, expands over days to weeks
  • Can appear as target lesion with central clearing, vesicular or necrotic areas
  • Can become multifocal
• Other common symptoms: arthralgias, myalgias, conjunctivitis, meningismus, regional lymphadenopathy
• Some patients asymptomatic

• Arthritis (60% of untreated patients)
  • Begins weeks to years after initial infection
  • Episodes of swelling and pain, primarily of large joints
  • Arthralgias, migratory arthritis, and chronic arthritis, usually of the knees
• Acute cardiac involvement (4% to 10% of untreated patients)
  • Most common: fluctuating atrioventricular (AV) block
  • Occasional: acute myopericarditis, mild left ventricular dysfunction
    • Duration usually brief (days to weeks)
• Acute neurologic abnormalities (10% to 15% of untreated patients)
  • Meningitis, meningoencephaitis, myelitis, cranial neuropathies, radiculitis

• Inflammatory joint disease for longer than 1 year (10% of untreated patients)
  • Primarily large joints (most often the knee)
  • May eventuate in joint destruction
• Chronic neurologic problems (5% of untreated patients)
  • Encephalopathy ranging from mild cognitive impairment to dementia
  • Chronic axonal polyneuropathy

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Differential Diagnosis

Early Localized Disease

• Erythema migrans
  • Allergy to tick saliva
  • Cellulitis
  • Southern tick-associated rash illness (STARI)

Early Disseminated Disease

• Arthritis
  • Bacterial arthritis (gonococcal, nongonococcal)
  • Crystalline arthropathy
  • Viral arthritis (hepatitis B, parvovirus)
• Cardiac involvement (AV block)
  • Ischemic heart disease
  • Fibrosis of conduction system
  • Medication
• Neurologic abnormalities
  • Cranial neuropathy
    • Herpes simplex virus
    • Varicella zoster virus
    • Idiopathic
  • Meningitis
    • Bacterial
    • Viral
    • Malignancy
    • Medications (NSAIDS, trimethoprim-sulfamethoxazole)
    • Sarcoid

Late Persistent Disease

• Arthritis
  • Osteoarthritis
  • Crystalline arthropathy
  • Mycobacterial and fungal infection

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Best Tests

• Characteristic clinical findings in a patient with tick exposure in an endemic area, plus positive serologic test results, confirm diagnosis
• Erythema migrans eliminates need for positive test results before treatment
• Serologic testing
  • Insensitive for several weeks from onset
  • Per CDC, perform ELISA or IFA first; if positive or equivocal, do Western blot on same serum
  • Western blot results
    • IgM positive if 2/3 bands reactive: 23 kd; 39 kd; 41 kd
    • IgG positive if 5/10 bands reactive: 18 kd; 23 kd; 28 kd; 30 kd; 39 kd; 41 kd; 45 kd; 58 kd; 66 kd; 93 kd
  • Tests do not detect titer rises

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Best Therapy

Antibiotic Therapy

• Early disease (local and disseminated)
  • Amoxicillin, 500 mg t.i.d. for 14–21 days
    • Preferred in children and pregnant women
    • Cost/21 days: $16
  • Doxycycline, 100 mg b.i.d. for 14–21 days
    • Cost/21 days: $29
  • Cefuroxime axetil, 500 mg b.i.d. for 14–21 days
    • Cost/21 days: $450
• Jarisch-Herxheimer reaction in 10% during first 24 hr of antibiotics: higher fever, redder rash, or greater pain
  • Treat with NSAID or aspirin

Treatment of Complications

• Neurologic
  • Facial palsies
    • Oral regimens (above) for 14–21 days; some experts suggest 30 days of antibiotic
    • Neurologic evaluation (CSF analysis)
  • Meningitis or encephalitis
    • Ceftriaxone, 2 g I.V., q.d., for 14–28 days
    • Penicillin, 18–24 million units I.V. divided 4–6 times/day for 14–28 days
  • Carditis
    • First-degree AV block: oral regimen (see early infections)
    • Second-degree AV block: see meningitis
  • Arthritis
    • Doxycycline, 100 mg p.o., b.i.d., for 30–60 days
      • Cost/mo: $42
    • Amoxicillin, 500 mg p.o., q.i.d., for 30–60 days
      • Cost/mo: $23
    • Ceftriaxone, 2 g I.V., q.d., for 14–28 days
    • Penicillin G, 20 million units I.V. in four divided doses daily for 14–28 days
    • Persistent symptoms after antibiotics: anti-inflammatory drugs or arthroscopic synovectomy

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Best References

Barbour AG, et al: Microbiol Rev 50:381, 1986 [PMID 3540570]

Massarotti EM, et al: Am J Med 92:396, 1992 [PMID 1313637]

MMWR Morb Mortal Wkly Rep 44:590, 1995 [PMID 7623762]

Seltzer EG, et al: JAMA 283:609, 2000 [PMID 10665700]

Steere AC, et al: J Infect Dis 154:295, 1986 [PMID 3722867]

The authors have no commercial relationships with manufacturers of products or providers of services discussed in this module.

August 2006