Transcript Tic Talk

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Controversial
Suboptimal diagnostic testing
Transmitted by Ixodes ticks
◦ May also transmit Babesia and Anaplasma
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Variable disease presentation
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Cutaneous
Cardiac
Rheumatologic
Neurologic
Treatment is longer than for other spirochetal
illnesses
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1883 – Buchwald, degenerative skin d/o
1902 – Herxheimer, ACA
1909 – Afzelius, EM rash post tick bite described
1913 – Lipschutz, ECM rash described
1921 – Afzelius case reports, associates Ixodes
ticks
1930 Hellerstrom, links EM and lymphocytic
meningitis
1941 – Bannwarth, lymphocytic
meningoradiculitis
1946 – Svartz, PCN for ACA
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1948 – Lenhoff, spirochetes on EM
1950 – Hellerstrom, ECM with meningitis
treated with PCN
1955 – Binder, 355 cases of ECM treated with
PCN
1968 – Scrimenti, first case of EM in US
reported
1975 – Murray (Lyme resident) reports cases
in relatives and friends in area
1975 – Steere identifies cases as “Lyme
arthritis”
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1997 – Steere, defines more complete case
description (cardiac, rheum, neuro)
1980 – Steere, rx with PCN or tetracycline
1982 – Burgdorfer, discovers spirochetes in
blood, CSF, skin lesions of Lyme patients
1997 – genome sequenced
1999 – vaccine marketed
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Borrelia burgdorferi has has at least 132
functional genes (c/w about 22 for T
pallidum)
Most plasmids of any bacteria identified to
date
Antigenic variation/quorum sensing to evade
immune response
Dormancy? Cyst structures form in vitro
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Ixodes scapularis (east and midwest)
Ixodes pacificus (west)
Deer / blacklegged tick,
Ixodes scapularis
Western blacklegged tick
(Ixodes pacificus)
From left to right: The deer tick
(Ixodes scapularis) adult female,
adult male, nymph, and larva on a
centimeter scale.
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Most common tick-borne disease in US and Europe.
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Affects 50 nations worldwide
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Nymphal ticks are primarily responsible for Lyme
transmission to humans.
Tick must feed for ~ 48 hours and become engorged
before risk of transmission becomes substantial.
Risk of infection after a deer tick bite in a highly endemic
area is ~1.4%.
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Obtaining Lyme serology at the time of tick bite is not
recommended.
Prophylactic one time use of 200 mg doxy can be considered
if:
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20% or more of local ticks are Bb+ (this is generally true in East only)
The patient presents within 72 hours of Ixodes bite
The tick was attached for 36 hours or more.
No contraindication to doxy
Analysis of ticks to determine whether they are infected is not
recommended.
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Early local infection
◦ Skin - EM
◦ CNS
Early disseminated infection
◦ Skin
 Multifocal EM
 Lymphocytoma cutis (Europe)
◦ Heart
 Heart block
◦ Musculoskeletal
◦ Nervous System
◦ Ocular
 Conjunctivitis
Late stage infection
◦ Skin
◦ Musculoskeletal
 Oligoarticular arthritis
◦ Nervous system
◦ Eye
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uveitis
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EM:
◦ Erythema migrans appears 3-30 (usually 710) days after tick bite, commonly on thigh,
groin, axilla.
◦ EM recognized in 70% of patients with
objective evidence of B. burgdorferi infection.
◦ Early symptoms may include fever, malaise,
headache, myalgias, arthralgias, meningismus.
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Erythema migrans
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Clinical diagnosis – testing not indicated
Annular or macular
History of tick bite in only 25% of cases
Location: Skin/folds and creases
By definition at least 5 cm in size (controversial)
Lesions may grow 2-3 cm/day
Multiple EM reflective of disseminated disease
(hematogenous)
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Multiple EM 3-5 weeks after tick bite.
Cranial nerve palsies (especially facial nerve—
can be bilateral).
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Aseptic meningitis.
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Carditis 5% (AV block).
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Myalgias, arthralgias, headache, fatigue.
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Lyme Lymphocytoma
◦ May be associated with
EM lesion
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80% of untreated patients will develop
some manifestation of late disease
Arthritis (mono- or oligoarticular,
affecting large joints, especially the
knee).
Encephalitis/encephalopathy.
Polyradiculopathy.
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Early local infection (<30 days)
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Early disseminated infection (<3 mo)
◦ EM with CNS seeding (HA, stiff neck, cognitive
difficulties)
◦ Flu like syndrome with CNS seeding
◦ Aseptic meningitis
◦ Meningoencephalitis (acute cerebellar ataxia,
acute myelitis)
◦ Cranial nerve palsy (facial)
◦ Acute painful radiculoneuritis
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Late persistent infection (>3 mo)
◦ Encephalopathy
◦ Chronic axonal polyradiculoneuropathy
◦ Chronic encephalomyelitis
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4-10% of Lyme Disease patients develop
carditis
AV block
◦ 40% Wenkebach
◦ 50% complete
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Myocardial involvement
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Emerges in 60% of untreated EM within 6
months average
Intermittent attacks
Asymmetrical
Usually large joints especially the knees
May involve the TMJ
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No formal definition: persistent (predominantly neurologic)
subjective symptoms that date to initial Lyme disease illness
Most likely heterogeneous and multifactorial causes involved
◦ Persistent infection
◦ Post infectious immune/inflammatory syndrome
◦ Co infection
◦ Reinfection
◦ Fixed deficits
◦ Alternative diagnosis
◦ Hypochondriasis
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Most patients do not respond to antibiotics
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Medical Clinics of NA 2002;86(2)
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Erythema migrans is the only manifestation of
Lyme sufficiently diagnostic to be clinically
diagnosed without lab testing
Serology (ELISA)
◦ Only 30-40% of patients with EM have a positive
serology.
◦ IgM antibodies appear in 3-4 weeks, may persist
despite treatment.
◦ IgG antibodies appear in 6-8 weeks, usually remain
detectable for many years.
◦ 2-4 weeks after acute reaction 70-80% are positive
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Western blot
◦ Indicated for positive or equivocal ELISA.
◦ IgM is only diagnostic within the first month of illness.
Up-To-Date 2004
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False positive
◦ Other spirochete (syphilis)
◦ Cross reaction with other bacterial heat shock
protein (RMSF, Ehrlichia)
◦ RA
◦ SLE
◦ Mononucleosis
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IFA: At least as sensitive and specific as the
ELISA
Immune assays of CSF
◦ ELISA
TEST
SENSITIVITY
SPECIFICITY
ELISA/IFA (early)
59%
93%
ELISA/IFA (late)
95%
81%
ELISA/IFA + WB (early
+ late)
50-75%
99-100%
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Cultivation
◦ Barbour-Stoenner-Kelly (BSK) broth medium
◦ Sensitive for detection of early-phase infection (EM)
◦ Limited value for detection of infection during late
stages
◦ Very few places can do this
◦ Skin biopsy or blood taken within first 2-3 weeks of
infection
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Histology
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PCR
◦ Numbers of B. burgdorferi in tissues is low
◦ Very hard to find on specimens
◦ Silver stain
◦ Limited places are able to do this
◦ Urine PCR is available but there is insufficient
evidence of its accuracy, predictive value, or its
significance
◦ Unclear of benefit of this test
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Early localized
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Early disseminated
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Late disease
◦ Doxycycline 100 bid or amoxicillin 500 tid or Cefuroxime
500 mg po bid x 14-21 days.
◦ Isolated facial nerve palsy/mild carditis: doxy/amoxicillin.
◦ Meningitis/severe carditis: ceftriaxone 2gm qd x 14-28
days.
◦ Arthritis: doxycycline or amoxicillin or ceftrixaone or IV
PCN x 28 days.
◦ Recurrent arthritis: ceftriaxone.
◦ CNS disease: ceftriaxone or IV PCN.
◦ Facial palsy alone: oral meds may be enough
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Cardiac
◦ 1st degree AV block: oral meds
◦ High degree AV block: Ceftriaxone for 14-21 days
or IV PCN for 28 days