Borrelia burgdorferi

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Borrelia burgdorferi

Background

Microbiology

Epidemiology

  • Most cases occur during June and July, when nymphal ticks are most active and people are outdoors
  • Infection is possible year-round, though, with ticks being active any time temperatures are above freezing

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 hindgut to mouth over ~36 hours, then gets regurgitated into the wound
    • May take as little as 24 hours
  • 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)
  • Requires minimum of 24 hours of tick attachment, but typically takes 36 hours or longer

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 Atrophicans

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

Late Neuroborreliosis

  • 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

Coinfections

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 erythema migrans is present, further testing is unhelpful outside of unusual cases and is not routinely recommended
  • The most commonly used test is serology from blood, with EIA followed by reflexive Western blot
  • 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

  • Typically done as a screening EIA followed by reflexive Western blot
    • In Ontario, the screening test is Borrelia Vls1/pepC10 IgM/IgG ELISA
    • The Western blot is done for IgM and IgG
  • 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
  • Serology is most helpful when the pretest probability is >20%
  • Serology remains elevated to months to years and should not be used to monitor response to treatment
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
  • Health Canada now recommends a modified two-tier EIA with combined IgM/IgG, with the screening EIA done with whole-cell lysate and the confirmatory EIA done with a recombinant protein
    • This approach has increased sensitivity at all stages (50-60% for early Lyme, around 100% for late Lyme including Lyme arthritis), and maintains
    • If you get a negative result when there is high pre-test probability for early Lyme, then submit a follow-up serology 3 to 6 weeks later
EIA 1 EIA 2 Interpretation
– N/A Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme
+/± +/± Positive; treat based on clinical syndrome, if appropriate
+/± – Negative; consider alternative diagnosis or resubmit in 3-6 weeks if compatible with early Lyme

Management

Erythema Migrans

Neurological Lyme Disease

  • Any of the following: ceftriaxone IV, cefotaxime IV, penicillin G IV, doxycycline PO
  • Duration of 14 to 21 days
  • If there is parenchymal involvement, which is rare and usually based on MRI
    • If present, prefer IV antibiotics and a 2 to 4 week course
  • In cases of facial nerve palsy, they may also receive corticosteroids within 72 hours

Lyme Carditis

Lyme Arthritis

  • Oral antibiotics for 28 days
  • If no response to oral antibiotics, can consider a course of ceftriaxone IV for 2 to 4 weeks

Post-Antibiotic Lyme Arthritis

  • Refer to rheumatologist for consideration of DMARDs, biologics, intraarticular steroid injections, or arthroscopic synovectomy

Borrelial Lymphocytoma

  • Oral antibiotics for 14 days

Acrodermatitis Chronica Atrophicans

  • Oral antibiotics for 21 to 28 days

Prevention

  • Routine personal protective measures to reduce tick exposure
  • DEET, picaridin, IR3535, oil of lemon eucalyptus, PMD, 2-undecanone, or permethrin
  • Remove ticks with clean fine-tipped tweezer inserted between the tick body and the skin
    • Do not cover, spray, or burn the tick
    • See tick removal for more information

Prophylaxis

  • Can be considered in children and adults within 72 hours of tick removal if all of the following criteria are met:
    • Ixodes tick is identified
      • Small, tear-drop shaped
      • Plain oval shield
      • Lack of festoons
    • Occurs in a highly endemic area
    • Tick was attached for ≥36 hours
      • You can get a sense by asking if the tick was flat or engorged
      • If definitely flat, almost certainly attached less than 36 hours
      • However, still looks flat at 24 hours
  • Use a single oral dose of doxycycline 4.4 mg/kg (max 200 mg) for children or 200 mg for adults

Further Reading

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