Rb. Nadelman et al., THE CLINICAL SPECTRUM OF EARLY LYME BORRELIOSIS IN PATIENTS WITH CULTURE-CONFIRMED ERYTHEMA MIGRANS, The American journal of medicine, 100(5), 1996, pp. 502-508
BACKGROUND: The diagnosis of erythema migrans (EM), the characteristic
rash of early Lyme borreliosis, is based primarily on its clinical ap
pearance since it often occurs prior to the development of a specific
antibody response. Other skin disorders, however, may be confused with
EM. METHODS: Between June 1991 and September 1993, a prospective stud
y was conducted at the Lyme Disease Diagnostic Center of the Westchest
er County Medical Center to isolate Borrelia burgdorferi systematicall
y from patients with EM, and to characterize the clinical manifestatio
ns of patients with culture-documented infection. Skin biopsies and/or
needle aspirates of the advancing margin of primary lesions, and bloo
d specimens from adult patients were cultured for 6 burgdorferi in mod
ified Barbour-Stoenner-Kelly medium at 33 degrees C. RESULTS: B burgdo
rferi was recovered from 79 patients (49 [62%] males) ranging in age f
rom 16 to 76 years old (mean, 43 +/- 14 years old). Maximum EM diamete
r (mean, 16 +/- 10 cm; range, 6-73 cm) was a function of EM duration (
mean 6.7 +/- 6.4 days; range, 1-39 days) (correlation coefficient = 0.
7; P <0.001). Twenty (25%) patients had noted a tick bite at the site
of the primary lesion a mean of 10 days (range, 1-27 days) before onse
t. Multiple EM lesions (range, 2-70) were present in 14 (18%) patients
. Systemic symptoms were present at the time of culture in 54 patients
(68%) including fatigue (54%), arthralgia (44%), myalgia (44%), heada
che, (42%), fever and/or chills (39%), stiff neck (35%), and anorexia
(26%). Thirty-three patients (42%) had at least one objective finding
on physical examination in addition to EM, including 18 (23%) with loc
alized lymphadenopathy, 13 (16%) with fever (T greater than or equal t
o 37.8 degrees C), seven (9%) with tender neck flexion, six (8%) with
joint tenderness, and 1 each with joint swelling, nuchal rigidity, and
facial nerve palsy. No patient had new electrocardiogram evidence of
atrioventricular block. Liver function assays were abnormally elevated
in 37% of patients. Thirty-four percent of patients were seropositive
by enzyme-linked immunosorbent assay at presentation. Most others rap
idly seroconverted so that 69 of 78 evaluable patients (88%) were sero
positive at some point during the first month after diagnosis. CONCLUS
IONS: We describe the largest group of culture-positive patients with
EM from the United States to date. Although systemic symptoms were pre
sent in most patients, objective evidence of advanced disease was unco
mmon. Our patients with culture-confirmed EM were less sick than those
described in the days before culture confirmation was possible. The a
bility to isolate B burgdorferi from lesional skin of large numbers of
patients with EM should make culture-positive patients the standard b
y which to define manifestations of early Lyme borreliosis associated
with this rash. Microbiologic documentation of Lyme borreliosis will h
elp delineate the manifestations of this illness, and should form the
framework for research directed at pathophysiology, diagnosis, treatme
nt, and prevention.