Clinical Description
Lyme disease most often presents with a characteristic rash,
erythema migrans, accompanied by nonspecific symptoms such as
fever, malaise, fatigue, headache, myalgia, and arthralgia (5-7).
The incubation period from infection to onset of erythema migrans
is typically 7 to 14 days but may be as short as 3 days and as
long as 30 days. Erythema migrans is observed in 85% or more
of patients with early symptomatic infection (6); however, a
small proportion of infected individuals have no recognized illness
(asymptomatic infection determined by serological testing), or
manifest only non-specific symptoms suggesting viral illness,
such as fever, headache, fatigue, and myalgia.
Lyme disease
spirochetes disseminate from the site of inoculation by cutaneous,
lymphatic and blood-borne routes. The signs of early disseminated
infection usually occur days to weeks after the appearance of
a solitary erythema migrans lesion. In addition to multiple (secondary)
erythema migrans lesions, early disseminated infection may be
manifest as disease of the nervous system, the musculoskeletal
system, or the heart (5-7). Neurologic manifestations include
lymphocytic meningitis, cranial neuropathy (especially facial
nerve palsy), and radiculoneuritis. Musculoskeletal manifestations
may include migratory joint and muscle pains with or without
objective signs of joint swelling. Cardiac manifestations are
rare but may include transient atrioventricular blocks of varying
degree.
Borrelia
burgdorferi infection
in the untreated patient may progress to late disseminated disease
weeks to months after infection (5-7). The most common manifestation
of late disseminated Lyme disease is intermittent arthritis of
one or a few joints, usually large, weight-bearing joints such
as the knee. Less frequently, patients develop chronic axonal
polyneuropathy, or encephalopathy, the latter manifested by subtle
cognitive disorders, sleep disturbance, fatigue, and personality
changes. Infrequently, Lyme disease morbidity may be severe,
chronic and disabling, especially if the disease is treated late
(8, 9). An ill-defined post-Lyme disease syndrome occurs in some
persons following treatment for Lyme disease (10-12).
Lyme disease
is rarely, if ever, fatal.
Diagnosis
Persons with known endemic exposure and physician-diagnosed erythema
migrans should be treated for Lyme disease without serologic
testing. Erythema migrans should be clinically differentiated
from similar rashes that are not caused by B. burgdorferi
infection. In areas of low or no endemic risk, the likelihood
of Lyme disease in a patient with an erythema migrans-like rash
is low. Serologic testing may be useful when patients with endemic
exposures present with manifestations of disseminated Lyme disease
without erythema migrans. Negative test results are useful in
ruling out Lyme disease in patients with clinical findings compatible
with disseminated or late-stage infection (13). Since the proportion
of false positive results increases when the pretest probability
of Lyme disease is low, the use of testing to make a diagnosis
of Lyme disease in individuals without endemic exposure is not
recommended (13).
When serologic
testing is indicated, CDC recommends testing initially with a
sensitive first test, either an enzyme-linked immunosorbent assay
(EIA) or an indirect fluorescent antibody (IFA) test; followed
by testing with the more specific Western immunoblot (WB) test
to corroborate equivocal or positive results obtained with the
first test (14). Although antibiotic treatment in early localized
disease may blunt or abrogate the antibody response, patients
with early disseminated or late-stage disease almost always have
strong serological reactivity and demonstrate expanded WB IgG
banding patterns to diagnostic B. burgdorferi antigens
(15, 16).
Antibodies
often persist for months or years following successfully treated
or untreated infection. Thus seroreactivity alone cannot be used
as a marker of active disease. Neither positive serologic test
results nor a history of previous Lyme disease assure that an
individual has protective immunity. Repeated infection with B.
burgdorferi has been documented (17).
Borrelia
burgdorferi can
be cultured from 80% or more biopsy specimens taken from early
erythema migrans lesions (18). However, the diagnostic usefulness
of this procedure is limited because of the need for a special
bacteriologic medium (modified Barbour-Stoenner-Kelly medium)
and protracted observation of cultures. Polymerase chain reaction
(PCR) has been used to amplify genomic DNA of B. burgdorferi
in skin, blood, CSF, and synovial fluid (19, 20), but PCR
has not been standardized for routine diagnosis of Lyme disease.
Treatment
Lyme disease can usually be treated successfully with standard
antibiotic regimens (5, 6). Early and uncomplicated infection,
including infection presenting with isolated cranial nerve palsy,
almost always responds satisfactorily to treatment with orally
administered antibiotics. Parenteral antibiotics are generally
recommended for treating meningitis, later stage neurologic Lyme
disease, and complicated Lyme disease arthritis. Late, complicated
Lyme disease may respond slowly or incompletely, and more than
one antibiotic treatment course may sometimes be required to
eliminate active infection (8, 9). Refractory Lyme disease arthritis
is associated with the HLA-DR4 haplotype (21), and may require
antiinflammatory agents and surgical synovectomy for relief of
symptoms (8). A minority of patients have persistent or recurrent
symptoms following appropriate antibiotic therapy ("chronic
Lyme disease", "post-Lyme syndrome"). These symptoms
may be due to causes other than persisting infection (21, 22).
