This patient has an enlarging erythematous skin lesion with central clearing suggestive of erythema migrans and should be prescribed doxycycline. Erythema migrans is the most common presentation of Lyme disease, seen in up to 80% of patients, although an initial heterogenous patch of erythroderma is more common than the classic target-like appearance. Erythema migrans is often the only manifestation of early localized Lyme disease because fevers or constitutional symptoms are uncommon at this stage. Treatment of early stage Lyme disease with doxycycline prevents progression to later-stage cardiac, neurologic, or rheumatologic complications in more than 90% of patients. Amoxicillin or cefuroxime axetil could be alternative options for the treatment of Lyme disease; however, these agents have not been evaluated for the treatment of southern tick–associated rash illness (STARI). STARI also presents as erythema migrans and can be identical to Lyme disease. Therefore, in a patient presenting with erythema migrans, treatment with an oral antibiotic active against localized Lyme disease and STARI, such as doxycycline, would be most appropriate.

Babesiosis is a parasitic disease that is spread by the same tick as Lyme disease but does not cause erythema migrans. Although coinfection with Borrelia burgdorferi can occur, serologic testing is not recommended in the absence of signs or symptoms, which include fever, jaundice, and scleral icterus. Lyme disease and human granulocytic anaplasmosis coinfection has also been reported; however, doxycycline is active against the bacterium causing this infection as well.

Laboratory testing for Lyme disease is insensitive at the early stage of infection, with less than 50% of patients having detectable titers to B. burgdorferi. In addition, laboratory confirmation is not necessary when erythema migrans is present.