Rheumatic fever (RF) is an autoinflammatory disease that is caused by the host response to an infection with group A β-hemolytic streptococcus. In this case report we describe a 15 years old boy with Down syndrome who had unusual presentation of acute rheumatic fever with a fulminant multisystemic which included heart failure secondary to pancarditis and adult respiratory distress syndrome. The final diagnosis was confirmed after cardiac biopsy that was performed during valve replacement surgery and demonstrated Aschoff bodies - a pathognomonic finding in acute rheumatic fever.