Rheumatic Fever: Causes, Symptoms, Diagnosis, Treatment and Prevention

~Introduction

Rheumatic fever (RF) is a serious inflammatory disease that can develop as a complication of untreated or inadequately treated group A streptococcal (GAS) throat infection, commonly known as strep throat. It primarily affects children between 5 and 15 years of age, although older adolescents and adults can also be affected. Despite being relatively rare in developed nations due to improved healthcare and widespread antibiotic use, rheumatic fever remains a major public health concern in developing countries, where access to medical care and antibiotics may be limited.

This disease is not merely an infection—it represents a misguided immune response, where the body’s immune system, while attacking the invading bacteria, mistakenly targets its own tissues, particularly the heart, joints, skin, and nervous system. If left untreated or if recurrent episodes occur, it can result in rheumatic heart disease (RHD), a chronic condition that damages the heart valves and is a leading cause of cardiovascular morbidity and mortality worldwide.

~Historical Background

Rheumatic fever has been recognized for centuries. In the 19th and early 20th centuries, it was one of the most common causes of death in children and young adults. With the advent of penicillin in the 1940s, the incidence dramatically declined in developed nations. However, in countries with limited healthcare resources, rheumatic fever remains prevalent, emphasizing the importance of primary prevention through proper treatment of streptococcal infections and community health education.

~Causes and Pathophysiology

The root cause of rheumatic fever lies in an infection with group A β-hemolytic Streptococcus (Streptococcus pyogenes). Not all individuals who experience a streptococcal throat infection develop rheumatic fever, suggesting that genetic susceptibility and immune factors play significant roles.

1. The Immune Mechanism

When the body encounters Streptococcus pyogenes, it produces antibodies to destroy the bacteria. However, some of the bacterial antigens closely resemble the body’s own tissues, especially those found in the heart, joints, and brain. This phenomenon, known as molecular mimicry, leads to the production of cross-reactive antibodies that mistakenly attack healthy tissues, triggering widespread inflammation.

2. Affected Organs

• Heart: The most serious involvement, leading to pancarditis (inflammation of all three layers—endocardium, myocardium, and pericardium).

• Joints: Cause of migratory polyarthritis, where inflammation moves from one joint to another.

• Skin: Formation of subcutaneous nodules and erythema marginatum.

• Nervous System: Leads to Sydenham’s chorea, characterized by involuntary movements.

~Epidemiology

Rheumatic fever remains endemic in many low- and middle-income countries, particularly in South Asia, sub-Saharan Africa, and the Pacific Islands. According to the World Health Organization (WHO), an estimated 30–40 million people worldwide suffer from rheumatic heart disease, and approximately 300,000 deaths occur annually due to its complications.

Contributing factors include:

• Overcrowding and poor sanitation

• Limited access to antibiotics

• Poor healthcare infrastructure

• Lack of awareness about the importance of treating sore throats

~Clinical Manifestations

The symptoms of rheumatic fever usually appear 2 to 4 weeks after a streptococcal throat infection. The presentation can vary depending on which organs are affected.

1. Major Clinical Features (Jones Criteria)

The Jones Criteria, first established in 1944 and later revised, are used to diagnose rheumatic fever. Major manifestations include:

a. Carditis

Inflammation of the heart is the most serious manifestation, occurring in up to 50–60% of patients.

• Symptoms: Chest pain, palpitations, shortness of breath, fatigue.

• Physical findings: Heart murmurs (due to valvular damage, especially mitral and aortic), pericardial rubs, or signs of heart failure.

• Long-term outcome: Can lead to rheumatic heart disease if scarring of the heart valves occurs.

b. Polyarthritis

Typically a migratory arthritis, meaning it moves from one large joint to another (knees, ankles, elbows, wrists).

• Each affected joint is swollen, red, and extremely painful.

• Arthritis usually responds well to aspirin.

c. Chorea (Sydenham’s Chorea)

A neurological manifestation occurring weeks or months after the initial infection.

• Characterized by rapid, involuntary movements of the face, hands, and feet.

• Emotional instability and muscle weakness are common.

• More common in females.

d. Erythema Marginatum

A distinctive, non-itchy rash with pink rings that appear mainly on the trunk and limbs.

• It is transient and often overlooked.

e. Subcutaneous Nodules

Small, firm, painless lumps found over joints or tendons, such as the elbows, knees, or spine.

• Usually appear in patients with carditis.

2. Minor Clinical Features

• Fever

• Arthralgia (joint pain without swelling)

• Elevated acute-phase reactants (ESR, CRP)

• Prolonged PR interval on ECG

A diagnosis of rheumatic fever requires two major criteria, or one major and two minor criteria, plus evidence of a preceding streptococcal infection (positive throat culture, rapid antigen test, or elevated antistreptolysin O titers).

~Diagnosis

Diagnosis of rheumatic fever is based on a combination of clinical evaluation, laboratory tests, and imaging studies.

1. Evidence of Recent Streptococcal Infection

• Throat culture for Streptococcus pyogenes

• Rapid antigen detection test (RADT)

• Elevated or rising ASO (antistreptolysin O) titers

• Anti-DNase B test

2. Blood Tests

• Elevated ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein) indicate inflammation.

• Leukocytosis (increased white blood cell count).

3. Electrocardiogram (ECG)

• Prolonged PR interval, indicating cardiac inflammation.

4. Echocardiography

• Detects evidence of valvulitis, especially mitral or aortic valve involvement.

• Assesses cardiac function and degree of valve regurgitation.

~Complications

If rheumatic fever is not treated effectively, it can lead to long-term and potentially fatal complications, primarily affecting the heart.

1. Rheumatic Heart Disease (RHD)

The most devastating consequence, resulting from scarring and deformity of the heart valves.

• Mitral valve is most commonly affected, leading to mitral stenosis or regurgitation.

• Can result in chronic heart failure, atrial fibrillation, and increased risk of stroke.

2. Chronic Heart Failure

Due to prolonged valve dysfunction and myocardial damage.

3. Recurrent Rheumatic Fever

Each recurrence increases the likelihood of progressive heart damage.

4. Infective Endocarditis

Damaged heart valves are more susceptible to bacterial infections.

~Treatment

The management of rheumatic fever aims to:

1. Eradicate the streptococcal infection.

2. Control inflammation.

3. Manage cardiac complications.

4. Prevent recurrences.

1. Eradication of Streptococcus

• Penicillin is the antibiotic of choice.

  • Benzathine penicillin G (single intramuscular injection).

  • If allergic: Erythromycin or Azithromycin.

2. Anti-inflammatory Therapy

• Aspirin is used to reduce fever, joint pain, and inflammation.

• In cases of carditis: Corticosteroids (Prednisolone) may be prescribed.

3. Management of Cardiac Failure

• Diuretics, ACE inhibitors, and digitalis may be needed for patients with congestive heart failure due to carditis.

4. Supportive Care

• Bed rest during the acute phase to minimize cardiac strain.

• Adequate nutrition and hydration.

~Prevention

Prevention of rheumatic fever is both possible and effective when streptococcal infections are identified and treated promptly.

1. Primary Prevention

• Early and appropriate treatment of strep throat with antibiotics.

• Public education on seeking medical help for sore throats.

2. Secondary Prevention

• Preventing recurrence in patients who have already had rheumatic fever.

• Long-term antibiotic prophylaxis with benzathine penicillin G every 3–4 weeks.

  • Duration depends on severity:

    • 5 years or until age 21 (whichever is longer) for patients without carditis.

    • 10 years or until age 40 for those with persistent carditis or RHD.

3. Community Measures

• Improving living conditions, reducing overcrowding, and promoting hygiene.

• School and community health screening programs to identify at-risk populations.

~Prognosis

The prognosis of rheumatic fever depends on:

• Severity of the initial attack.

• Presence and extent of cardiac involvement.

• Timeliness and effectiveness of treatment.

• Adherence to prophylaxis to prevent recurrences.

With early diagnosis and proper management, most patients recover fully. However, those with recurrent episodes or severe carditis may develop chronic rheumatic heart disease, which may require surgical intervention, such as valve repair or replacement.

~Global Burden and Socioeconomic Impact

Rheumatic fever and its sequelae, particularly rheumatic heart disease, place a significant burden on healthcare systems in low-income nations.

• Children and young adults are most affected, leading to loss of productivity and increased healthcare costs.

• Many patients require lifelong medical follow-up and expensive cardiac surgery, which is often unavailable in resource-poor settings.

International organizations like the World Health Organization (WHO) and World Heart Federation continue to promote global initiatives to eliminate rheumatic fever through early detection, antibiotic access, and community awareness.

~Recent Advances and Research

Recent research has focused on:

• Development of vaccines against Group A Streptococcus to prevent primary infection.

• Improved diagnostic tools to rapidly identify streptococcal pharyngitis.

• Understanding genetic susceptibility and immune mechanisms underlying autoimmune responses.

• Innovative community-based prevention strategies in high-risk areas.

While a safe and effective vaccine remains under development, the focus continues to be on strengthening public health systems, training healthcare workers, and ensuring affordable antibiotics.

~Conclusion

Rheumatic fever remains a preventable but persistent disease, particularly in regions where healthcare access is limited. Its long-term consequence—rheumatic heart disease—continues to affect millions, causing premature disability and death. However, with awareness, timely treatment of streptococcal throat infections, and consistent secondary prophylaxis, the global burden of this disease can be drastically reduced.

Combating rheumatic fever requires a combined effort from healthcare providers, policymakers, and communities. Education, prevention, and early intervention remain the most powerful tools in ensuring that this historic disease becomes a rarity of the past rather than a tragedy of the present.