Borrelia burgdorferi

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Borrelia burgdorferi /
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Background

Epidemiology

North America

  • Transmitted by Ixodes scapularis (deer or black-legged tick), or Ixodes pacificus in the Pacific US
  • Reservoirs include deer and small mammals such as rodents
  • Lyme species are different outside of North America

Europe

  • Three main species of Borrelia exist in Europe: B. burgdorferi, B. afzelii, B. garinii
  • The vectors are Ixodes ricinus (in Europe and the Near East, and Ixodes persulcatus in Asia
  • The species have cross-reactivity with Lyme serology

Life Cycle

tick lifecycle

Pathophysiology

  • Tick bites host
  • Borrelia migrates from hidgut to mouth over ~36 hours, then gets regurgitated into the wound
  • Local multiplication followed by dissemination

Risk Factors

  • Hiking or camping in Vermont or other endemic area, with known or possible tick exposure

Clinical Manifestations

  • May not remember tick bite
  • There can be overlap between the three stages (early localized, early disseminated, late)

Early localized disease (7 days)

  • Presents within 1 month of exposure
  • Erythema migrans in 80%; appears 7-14 days after tick bite (range 3 to 32 days)
    • Expanding red or bluish-red patch ≥5 cm, with or without central clearing
    • Spreads over days
    • Can present atypically, without target appearance, with ulceration, or with vesicles
    • If appears immediately and rapidly; need to consider local irritation and allergy, rather than Lyme
  • Fever, fatigue, malaise, lethargy
  • Mild headache and neck stiffness
  • Myalgias and arthralgias
  • May have mildly elevated liver enzymes

Early disseminated disease (14-21 days)

  • Early disseminated (weeks to months), inflammatory phase
  • Can be a non-specific febrile illness with headaches, arthralgias and fatigue, but can also cause a number of other symptoms

Neuroborreliosis

Cardiac Lyme

  • AV conduction dysfunction, arrhythmia, and sometimes myocarditis or pericarditis, without other explanation
  • Resolves with treatment, so only ever needs temporary pacemaker

Late disease

  • Late or chronic (months to years), less inflammatory, usually within a single body site
  • Arthritis in 60% of untreated patients, now down to 15-20%
    • PCR of synovial fluid
  • Encephalomyelitis/encephalopathy next-most common
    • LP fairly benign, with slightly elevated protein
    • Diagnose with simultaneous serum/CSF antibodies
  • Peripheral neuropathy
  • Affects heart, nervous system and joints; arrhythmias, heart block and sometimes myopericarditis; recurrent arthritis affecting large joints (i.e., knees); peripheral neuropathy; central nervous system manifestations – meningitis; encephalopathy (i.e., behavior changes, sleep disturbance, headaches); and fatigue

Lyme arthritis

  • Recurrent attacks or persisting arthritis involving one or more large joints, without other explanation
  • Arthrocentesis shows 25,000 cells (range 500 to 110,000), mostly PMNs

Acrodermatitis chronica artophicans

  • Chronic red or bluish-red leions, usually on the extensor surgaces
  • Initially doughy, eventually atrophic
  • Can occur up to 8 years after infection

Late neuroborereliosis

  • Encephalopathy, encephalitis, and peripheral neuropathy

Complications

  • Carditis in 5% of untreated patients
    • Heart block
    • Cardiomyopathy
  • Neurologic involvement in 15% of untreated patients
    • Uni- or bilateral cranial nerve defects, especially CN VII
    • Meningitis and encephalitis
  • Migratory arthralgias in 60% of untreated patients
  • Conjunctivitis in 10% of untreated patients
  • Regional or generalized lymphadenopathy

Borrelial lymphocytoma

  • Painless bluish-red nodule, usually on the ear, nipple, or scrotum
  • More common in adults

Ocular manifestations

  • Conjunctivitis, uveitis, papillitis, episcleritis, keratitis

Coinfection

  • Can have thrombocytopenia and anemia if coinfected with Anaplasma or Babesia

Post-Lyme disease syndrome

  • Subjective symptoms that persist following treatment, without objective clinical findings of infection

Differential Diagnosis

Erythema Migrans

Borrelial Lymphocytoma

Lyme neuroborreliosis

Lyme carditis

Lyme arthritis

Acrodermatitis Chronic Atrophicans

Diagnosis

  • Treatment should be based on symptoms and compatible exposure history
    • If EM present, further testing is unhelpful outside of unusual cases
  • Usually done by serology, with EIA followed by reflexive Western blot
    • EIA should be positive by 4 to 6 weeks; if negative, Lyme is unlikely
      • Usually positive around 2 weeks
      • False negatives common early in clinical course
      • False positives with HIV, hepatitis C, and syphilis
      • Cross-reacts with European Lyme
    • Western blot split into IgM and IgG if positive or equivocal
      • IgM 4 weeks, IgG 8 weeks
      • IgM is prone to over-interpretation and false positives
      • Does NOT cross-react with European Lyme (in Ontario)
    • Serology is most helpful when the pretest probability is >20%
  • CSF antibodies is useful for neuroborreliosis, but persist years after treatment
  • PCR may be helpful in cases where patients are from populations with high seroprevalence
    • Pretty good for joint, less sensitive for CSF

Lyme Serology

EIA Western blot Interpretation Action
+ + Early disseminated or late disease
Previous exposure, treated or not 		Treat if compatible symptoms and history
+ – Early disease
Early disease, treated
European Lyme
False-positive 		If <8 weeks from exposure, repeat
If >8 weeks, look for other cause
Rule out HIV, hepatitis C, and syphilis
Assess for autoimmune diseases
Consider European Lyme
– – Very early Lyme <2 weeks
Negative 		Treat if erythema migrans

Management

Further Reading

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