Lyme disease occurs when a tick injects spirochete-laden saliva into the bloodstream while feeding. After incubating for 3 to 32 days, the spirochetes migrate out to the skin, causing ECM. They then disseminate to other skin sites or organs via the bloodstream or lymph system. The spirochetes may survive for years in the joints, or they may trigger an inflammatory response in the host and then die.

Complications from Lyme disease include myocarditis, pericarditis, arrhythmias, heart block, meningitis, encephalitis, cranial or peripheral neuropathies, and arthritis.

Typically, Lyme disease has three stages. ECM occurs in about 75% of the cases and heralds stage one with a red macule or papule, commonly at the site of a tick bite. This lesion typically feels hot and itchy and may grow to more than 20 inches (50.8 cm) in diameter; it resembles a bull’s eye or target. Within a few days, more lesions may erupt and a migratory, ringlike rash, conjunctivitis, or diffuse urticaria occurs. In 3 to 4 weeks, lesions are replaced by small red blotches that persist for several more weeks. Malaise and fatigue are constant, but other findings are intermittent: headache, neck stiffness, fever, chills, achiness, and regional lymphadenopathy. Less common effects are meningeal irritation, mild encephalopathy, migrating musculoskeletal pain, hepatitis, and splenomegaly. A persistent sore throat and dry cough may appear several days before ECM.

Weeks to months later, the second stage (disseminated infection) begins, during which patients may develop additional symptoms depending on the system affected. Neurologic abnormalities—fluctuating meningoencephalitis with peripheral and cranial neuropathy—usually resolve after days or months. Facial palsy is especially noticeable. Cardiac abnormalities, such as a brief, fluctuating atrioventricular heart block, left ventricular dysfunction, or cardiomegaly may also develop. Cardiac involvement lasts only a few weeks but can be fatal.