Forty-four percent of patients with erythema migrans had bloodstream infection with Lyme disease bacteria. Patients with bloodstream infection were more likely to have symptoms (and more severe symptoms) than those who did not. Specifically, those with bloodstream infection more commonly had chills or fever, headache, and stiff neck and were more likely to have enlarged lymph nodes. In addition, patients with bloodstream infection often had more than one erythema migrans red spot and were more likely to have bacteria that could be grown from a skin biopsy sample. Even so, no single symptom or combination of symptoms could reliably predict which patient had bloodstream infection since some patients had similar findings even when blood cultures were negative. The risk for bloodstream infection remained high for more than 2 weeks after the first red spot appeared.