Objective: To evaluate the incidence of Borrelia burgdorferi infection in humans with erythema migrans (EM) in 2 southeastern states. Design: Prospective case series. Setting: Family medicine practice at academic center. Patients: Twenty-three patients with solitary EM lesions meeting Centers for Disease Control and Prevention (CDC) criteria for Lyme disease. Interventions: Patients underwent clinical and serologic evaluation for evidence of B burgdorferi infection. All lesions underwent photography, biopsy, culture and histopathologic and polymerase chain reaction analysis for B burgdorferi infection. Patients were treated with doxycycline hyclate and followed up clinically and serologically. Main Outcome Measures: Disappearance of EM lesions and associated clinical symptoms in response to antibiotic therapy; short-term and follow-up serologic assays for diagnostic antibody; growth of spirochetes from tissue biopsy specimens in Barbour- Stoenner-Kelly II media; special histopathologic stains of tissue for spirochetes; and polymerase chain reaction assays of tissue biopsy specimens for established DNA sequences of B burgdorferi. Results: The EM lesions ranged from 5 to 20 cm (average, 9.6 cm). Five patients (22%) had mild systemic symptoms. All lesions and associated symptoms resolved with antibiotic therapy. Overall, 7 patients (30%) had some evidence of B burgdorferi infection. Cultures from 1 patient (4%) yielded spirochetes, characterized as Borrelia garinii, a European strain not known to occur in the United States; 3 patients (13%) demonstrated spirochetallike forms on Special histologic stains; 55 patients (22%) had positive polymerase chain reaction findings with primers for flagellin DNA sequences; and 2 patients (9%) were seropositive for B burgdorferi infection using recommended 2-step CDC methods. No late clinical sequelae were observed after treatment. Conclusions: The EM lesions we observed are consistent with early Lyme disease occurring elsewhere, but laboratory confirmation of B burgdorferi infection is lacking in at least 16 cases (70%) analyzed using available methods. Genetically variable strains of B burgdorferi, alternative Borrelia species, or novel, uncharacterized infectious agents may account for most of the observed EM lesions.
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