People with the Lyme disease rash rarely have problems after they are treated with antibiotics. In some cases, people become extremely tired after being treated for Lyme disease, but this problem doesn't tend to improve with additional antibiotics. The medical reason for this fatigue is uncertain. Many, and perhaps most, people with persistent symptoms have no clear evidence of active infection. Intensive antibiotic treatment (for example, intravenous treatment for prolonged periods) usually doesn't help.
About 10% of people with Lyme arthritis appear to have chronic (long-lasting) joint swelling despite taking antibiotics. Recent evidence suggests this is caused by an autoimmune effect, in which Lyme infection triggers the immune system to attack the body's own cells. This problem seems to follow Lyme disease primarily in people of certain genetic types. These people may respond to medications that suppress the immune system (similar to those used in rheumatoid arthritis) rather than to continued antibiotics.