Second edition

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nervous system involvement occurs in about 15 percent; the
percentage of patients who develop stage III disease is not
clear, but is probably low. Each of these stages is discussed in
turn, followed by a consideration of laboratory testing.
STAGE I
Erythema chronicum migrans appears anywhere from
3 days to a month after the tick bite. The rash is characterized
by a gradually enlarging, ring-like erythematous lesion,
which as it enlarges leaves a pale, indurated central portion,
thus creating an overall ‘bull’s-eye’ effect. Smaller,
‘satellite’ lesions may also occur. In general, the rash resolves
spontaneously in a matter of weeks.
STAGE II
Stage II typically follows stage I within weeks to months.
Cardiac involvement most frequently manifests with an
atrioventricular block; evidence of pericarditis or even
myocarditis may also be found. As noted earlier, polyarthralgia
may also occur. Nervous system involvement classically
manifests with the triad of meningitis, cranial neuritis, and
radiculoneuritis (Hansen and Lebech 1992; Pachner and
Steere 1985). The meningitis presents with headache, neck
stiffness, and malaise. Although cranial neuritis may affect
virtually any of the cranial nerves, by far the most common
manifestation is a unilateral or bilateral peripheral facial
palsy. When radiculitis occurs it is often accompanied by
significant pain. The occurrence of encephalitis is heralded
by somnolence and delirium, and, in a small minority,
seizures or chorea. In addition to this classic triad, one may
also find evidence of a mononeuritis multiplex, a primarily
sensory polyneuropathy, or, rarely, a myelitis. In general,
symptoms gradually remit over 3–18 months.
STAGE III
Stage III Lyme disease may appear anywhere from months
to up to a decade after stage I, and may be characterized by
a large-joint oligoarthritis or, in a minority, by a dementia.
The dementia tends to be quite mild and manifests with poor
short-term memory, poor concentration, mild somnolence,
fatigue, and either depression or irritability (Halperin et al.
1989; Logigian et al. 1990; Shadick et al. 1994); a peripheral
polyneuropathy may also be present and in a minority there
may also be focal signs such as ataxia, aphasia, or hemiplegia;
seizures have also been noted. In one very rare case, stage III
Lyme disease presented with a psychosis characterized by
delusions of persecution, auditory hallucinations, and stuporous
catatonia (Pfister et al. 1993). Although some
patients may show gradual progression, it appears that in
most cases the course is characterized by a stable chronicity.
LABORATORY TESTING
Serum should be tested for both IgG and IgM anti-Borrelia
antibodies: IgG antibodies are found in almost all patients
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with neurologic involvement, and IgM antibodies may be
found in those with stage I and stage II disease.
The CSF may display a lymphocytic pleocytosis, an elevated
protein, and oligoclonal bands; anti-Borrelia antibodies
may or may not be present. PCR assay is generally
less sensitive than testing for antibodies. Although the CSF
is typically clearly abnormal in stage II disease, findings
may be equivocal in stage III.
Magnetic resonance scanning in stage III may reveal
multifocal areas of demyelinization in the subcortical
and periventricular white matter, or multifocal areas of
cerebritis.
Course
This is as noted above.
Etiology
Erythema chronicum migrans represents a local reaction
to the infection; hematogenous spread then occurs to the
heart, joints, and nervous system. Various findings have
been reported in the nervous system, including a lymphocytic
vasculitis in stage II (Meurers et al. 1990), and, in
addition to a small-vessel vasculitis, multifocal areas of
either demyelinization or cerebritis in stage III (Kobayashi
et al. 1997; Oksi et al. 1996).
Differential diagnosis
In classic cases with a well-documented progression from
stage I to stage II and beyond, the diagnosis is fairly
straightforward. Unfortunately, however, as noted earlier,
up to one-quarter of patients do not have erythema chronicum
migrans, and those who do may not recall having it.
Consequently, diagnosis may rest on a high index of suspicion.
In this regard, however, prudence must be exercised
in evaluating the results of serum testing for anti-Borrelia
antibodies. Although the absence of IgG antibodies argues
strongly against the diagnosis, their presence cannot be
seen as strongly confirmatory: in some parts of North
America, 5 percent or more of inhabitants will be seropositive,
with absolutely no evidence of active disease.
Treatment
For stage II, intravenous ceftriaxone is recommended; in a
small minority, a Jarisch–Herxheimer-like reaction may
develop soon after the initiation of treatment, with
malaise, fever, and, in some, an exacerbation of the presenting
symptomatology. Treatment of stage III is a matter
of debate. Although some patients with marked dementia
and clearly positive CSF findings definitely respond to ceftriaxone
(Steinbach et al. 2005), it appears that patients