Rheumatic Fever

Overview
  • Rheumatic Fever is a disease which affects multiple tissues but whose most serious clinical consequences arise from pathology of the heart valves. The disease follows pediatric cases of pharyngitis caused by Streptococcus pyogenes and affects roughly 3% of children not treated with antibiotics. Given the increasing use of antibiotics and improvements in hygiene, the disease is now rarely observed in developed countries although it is still relatively prevalent in developing countries.
Etiology
  • As mentioned, Rheumatic Fever is a potential complication of untreated pharyngeal infection with S. pyogenes. However, signs of the disease arise 2-3 weeks after the infection has cleared and are unlikely to be due to direct bacterial involvement. Rather, it is believed that the immune response to S. pyogenes may result in generation of antigen-specific antibodies that become misdirected toward structurally similar self-antigens, potentially resulting in the generation of auto-antibodies. Binding of auto-antibodies to self-antigens present in multiple tissues causes inflammation which is most clinically consequential in the heart.
Morphology
  • Overview
    • The pathology of rheumatic fever develops over time and possesses both acute and chronic phases. Acute disease is due to active inflammation whereas chronic disease is likely the result of prolonged wound healing responses. Inflammation occurs in multiple tissues, including the heart, joints, and skin, and manifests histologically as fibrinoid necrosis. However, the following discussion will largely focus on the histomorphology of the heart and its valves.
  • Acute Rheumatic Fever
    • Acute Rheumatic Fever is characterized by an inflammation of all three layers of the heart, including the endocardium, myocardium, and epicardium. Inflammation is centered around multiple foci termed "Aschoff bodies" which represent areas of fibrinoid necrosis surrounded by mononuclear cells. Because inflammation can affect all three cardiac layers, the heart valves and pericardium are involved as well. Inflammation tends to primarily affect the mitral valve and aortic valve, leading to their edematous thickening. Inflammation of the pericardium results in fibrinous acute pericarditis and can lead to a pericardial effusion.
  • Chronic Rheumatic Fever
    • Over many years, chronic inflammation and reactive healing of the valves results in their progressive fibrosis and scarring. The consequent structural deformation of the heart valves is the most feared complication of rheumatic fever. The mitral valve and the aortic valve are the most commonly affected and can result in stenosis or regurgitation as described below.
Clinical Consequences
  • Overview
    • Like the pathology, the clinical consequences of rheumatic fever develop along acute and chronic phases. The acute phase occurs 2-3 weeks after pharyngeal infection although in some patients pharyngitis may be subclinical. Chronic complications arise many years after the initial infection when the child has grown to adulthood.
  • Acute Rheumatic Fever
    • Acute Rheumatic Fever is characterized by arthralgia caused by a migrating arthritis of more than one joint (i.e. Migrating Polyarthritis). Subcutaneous nodules can appear along with a skin rash characterized by multiple pink macules with central clearing, termed "Erythema Marginatum". Cardiac inflammation can result in transient heart murmurs, tachycardia, as well as pericardial effusion, yielding a pericardial friction rub. Choreoform movements of the head and arms can occur during the acute phase and is termed "Sydenham's Chorea".
  • Chronic Rheumatic Heart Disease
    • Chronic Rheumatic Heart Disease is characterized by deformity of heart valves. The mitral valve is most commonly affected with a subset also developing pathology of the aortic valve as well. Involvement of the tricuspid valve is rare but can occur. Mitral disease can lead to mitral regurgitation or mitral stenosis. Aortic valve disease can lead to aortic regurgitation or aortic stenosis. Rare Tricuspid Valve disease typically leads to tricuspid stenosis. The pathophysiological and clinical sequelae of these valvular lesions are discussed on their own pages and are not unique to this particular etiopathogenesis.