Rheumatic fever (acute rheumatic fever or ARF) is an autoimmune disease that may occur after a group A streptococcal throat infection that causes inflammatory lesions in connective tissue, especially that of the heart, joints, blood vessels, and subcutaneous tissue. The disease has been described since the 1500s, but the association between a throat infection and rheumatic fever symptom development was not described until the 1880s. It was associated with scarlet fever (rash caused by streptococcal exotoxins) in the 1900s. Prior to the broad availability of penicillin, rheumatic fever was a leading cause of death in children and one of the leading causes of acquired heart disease in adults. The disease has many symptoms and can affect different parts of the body, including the heart, joints, skin, and brain. There is no simple diagnostic test for rheumatic fever, so the American Heart Association's modified Jones criteria (first published in 1944) are used to assist the physician in making the proper diagnosis.