Background and Design.-We report a series of 28 consecutive patients w
ith erythema migrans (EM) who underwent skin biopsies for culture of B
orrelia burgdorferi. Culture results, Lyme serologic findings, and cli
nical features in patients with only primary EM are compared with thos
e in patients with secondary EM. Results.-Culture preparations of skin
specimens obtained from six of 12 patients with only primary EM, and
from 14 of 16 patients with secondary EM were positive for B burgdorfe
ri. Seven patients with only primary EM were initially seronegative, a
nd only one patient had an annular lesion. A central crusted punctum w
as present in five of six primary EM lesions that were not culture pos
itive, but in none of nine culture-positive primary EM lesions. Patien
ts with secondary EM were all seropositive and had less cutaneous and
more constitutional symptoms than patients with only primary EM. Three
patients with secondary EM had abnormal liver enzyme profiles, one pa
tient had complete heart block, an d one patient had myocarditis simul
ating infarction. Less than one third of all patients recalled a tick
bite. An isomorphic nonresponse was seen in skin previously involved w
ith secondary EM in one patient who had a drug exanthem from amoxicill
in. Conclusions.-Borrelia burgdorferi can be reliably cultured from sk
in biopsy specimens of secondary EM. Culture preparation aids definiti
ve diagnosis of Lyme disease in patients with only primary EM who ofte
n lack constitutional symptoms, have nondiagnostic lesions, or are ser
onegative.