Overview 

Have you ever heard about someone who developed heart problems because of a simple throat infection? Rheumatic fever refers to a rarely occurring abnormal inflammatory reaction by the body’s immune system after an infection with a bacteria known as group A streptococcus. This bacterial infection can be in the form of a throat or a skin infection that abnormally triggers the body’s immune system. The resulting abnormal immune reaction against this bacteria may involve multiple body systems including the heart, the joints, the brain, and the skin. Initial adequate treatment of the bacterial infection prevents the development of the abnormal immune reaction and subsequent development of rheumatic fever.^1,2 

A major long term complication of rheumatic fever is rheumatic heart disease, which results when the inflammatory reaction involves the heart and results in a number of heart problems we will discuss throughout the article. Rheumatic heart disease is considered to be the most common acquired heart disease in individuals under age 25 (i.e. in previously healthy individuals), and it is especially dominant in developing countries with poor health access.^1,3

Pathophysiology of Rheumatic Fever

Molecular mimicry

The abnormal immune response triggered in rheumatic fever against group A streptococcus bacterial infection is mainly due to a molecular similarity between antigens of this bacteria and self antigens, mainly “myosin” in the heart muscle and the heart valves. This similarity leads to a cross reaction between the two antigens, producing an abnormal immune reaction that underlies the development of rheumatic fever, mainly involving the heart in the form of cardiac myositis, and valvulitis. In addition these immune complexes can deposit in other parts of the body including the joints, other molecular similarities underlie the inflammation involving the brain and the skin.¹

Genetic susceptibility 

There is a genetic susceptibility for developing rheumatic fever, it is polygenic involving several genes coding for immune proteins associated with rheumatic fever. Rheumatic fever is considered a heritable disease given that frequent cases are observed in twins and in family members.⁴

Types of Rheumatic Heart Disease 

• Valvular heart disease: The damage to heart valves can be in form of valve stenosis or valve regurgitation 
  • Valve stenosis means narrowing of the valve restricting blood flow means abnormal return of the blood backward through the valve 
  • Valve problems can lead to heart failure or abnormal heart rhythm (such as atrial fibrillation)⁵
• Heart muscle disease (myocarditis)
• Heart sac disease (pericarditis) 

Mechanisms Leading to Valvular Damage

Inflammation involving the heart muscle and the heart valves leading to scarring, deformity, and abnormal functioning of the heart. The first episode of rheumatic fever may involve the heart, mostly heart valves resulting in inflammation of heart valves (valvulitis). However, the more damage occurs with time, after multiple episodes of rheumatic fever, progressive damage of heart valves results “Rheumatic valvular heart disease” which most commonly involves the left sided heart valves, mostly involving mitral valve of the heart causing abnormal functioning of the valves in form of abnormal backward flow of the blood through the valve (mitral regurgitation) or narrowing of the valve (mitral stenosis), the second most commonly affected heart valve is the aortic valve. When valvular damage is left untreated, it can result in heart failure or abnormal heart rhythm. Right side heart valves are less commonly affected (tricuspid and pulmonary valves).⁶ 

Mechanisms Leading to Heart Enlargement 

Rheumatic fever involving the heart muscle resulting in inflammation of the heart muscle is known as “rheumatic carditis”, which is characterized by the presence of Aschoff nodules.⁶ 

Heart enlargement may occur as a result of abnormal heart valve function, which allows blood to flow backward. This backward flow increases the volume of blood within the heart, eventually leading to its enlargement.⁴

Clinical Manifestations of Rheumatic Heart Disease

Rheumatic fever develops 2-3 weeks after a group A streptococcus bacterial infection. The clinical diagnosis is based on a criteria of symptoms called the Revised Jones Criteria. This criteria include major criteria and minor criteria used to predict diagnosis of rheumatic fever, in addition to a history of a group A streptococcus bacterial infection.⁷ For an initial episode, diagnosis requires two major criteria, or one major plus two minor criteria. The criteria can also be used for subsequent episodes, as patients with a history of rheumatic fever or rheumatic heart disease are at a risk for recurrent attacks if re-infected with group A streptococci.

Major criteria 

• Carditis (heart inflammation, typically diagnosed by echocardiogram)
• Arthritis (joint inflammation, manifested as swelling, redness, pain, and loss of function of affected joint)
• Chorea (abnormal uncontrolled dancing-like movement caused by brain involvement with rheumatic fever)
• Erythema marginatum (a type of skin rash)
• Subcutaneous nodules (painless small lumps under skin mostly over joints)

Minor criteria 

• Polyarthralgia (joint pain involving multiple joints)
• Fever (≥38.5° F)
• Laboratory test: Sedimentation rate (ESR) ≥60 mm and/or C-reactive protein (CRP) ≥3.0 mg/dl
• Prolonged PR interval seen on electrocardiogram (unless carditis is a major criterion)⁷

Rheumatic Heart Disease 

Several years may pass after a rheumatic fever episode until symptoms of heart damage develop.⁵ Rheumatic heart disease may result in a range of symptoms according to the part of the heart mostly involved by the disease, including:   

• Chest pain and discomfort 
• Abnormally felt heartbeats (irregular or rapid) 
• Shortness of breath 
• Weakness 
• Dizziness 
• Signs of heart failure (leg swelling, shortness of breathness especially with exertion and when laying flat)
• When listening with a stethoscope, abnormal sounds “murmur” are heard resulting from the abnormal flow of the blood through the valves 
• Friction rub sound heard on stethoscope in case of heart sac involvement (pericarditis)

Evaluation of Rheumatic Heart Disease  

• Electrocardiogram (ECG) to check for any heart rhythm abnormalities 
• Chest x-ray to check for heart enlargement and other signs of heart failure 
• Echocardiogram to check for valvular abnormality 

Treatment of Rheumatic Heart Disease 

No definitive cure present for rheumatic heart disease but surgery for damaged heart valves. Valve replacement may be indicated if heart valve involvement is severe. Medications to treat the symptoms of heart failure or abnormal heart rhythm may be indicated in patients according to their symptoms, as well as medication to reduce risk of clot formation may be needed.³

In addition:

• Daily antibiotics may be indicated to prevent recurrence of rheumatic fever and prevent added infection on the heart (infective endocarditis) 
• Controlling comorbidities like hypertension, diabetes, blood cholesterol reduce the risk of heart diseases 
• Maintaining a healthy lifestyle reduce the risk of additional complications 
• No smoking, less alcohol, maintaining active lifestyle, healthy balanced diet, and managing stress⁵

Long-Term Consequences of Rheumatic Heart Disease

• Heart failure 
• Arrhythmia
• Blood clot and embolic events (clots traveling through blood vessels to other parts of the body)
• Bacterial endocarditis 
• Need for valve surgery  

Rheumatic Heart Disease is Preventable

• At first, rheumatic fever itself can be prevented by effective treatment of the group A streptococcus bacterial infection with antibiotics
• Once rheumatic fever has developed, prevention of recurrent subsequent episodes is essential to prevent further damage, this can also be done by administration of antibiotics over a long period of time (typical regimen include intramuscular injection of benzathine penicillin G every 3-4 weeks for years. However, review with the specialist doctor is recommended)
• In low income countries with high incidence of rheumatic fever, improving standards of living and health care is important in reducing the risk of rheumatic fever³