There are three stages of infection with Lyme disease. After an incubation period of 1 to 30 days, stage one occurs when the spirochete migrates outward in the skin, resulting in the appearance of erythema chronicum migrans, the characteristic “bull’s eye” rash some infected people develop. This expanding rash has a clear center at the site of the bite surrounded by a red ring and may reach
a diameter of 50 cm. During this stage the spirochete may also spread to other sites by way of the lymph or blood. Other symptoms of the initial infection include fever and chills, headache, malaise, and lethargy. If the infection is undetected or untreated the disease becomes chronic, and cardiac and neurological involvement occur 2 to 3 months after the bite as part of the second stage of the disease. Symptoms of this stage of the infection include severe atrioventricular block, palpitations, syncope, stiff neck, photophobia, Bell’s palsy, fatigue, encephalitis, and radiculoneuritis (i.e., inflammation of spinal nerves, producing pain and increased sensation) that can last 6 months or longer. If untreated, approximately 70% of people infected with Lyme disease develop arthritis, primarily of large joints as part of the third stage of the disease within weeks to years after the initial infection. Arthritis associated with Lyme disease may be in the form of arthralgia or, in 10% of people, a chronic inflammatory synovitis. The third stage of the disease is thought to be the result of treatment failure, relapses caused by persistent infection, or possibly an autoimmune reaction to the spirochete.