Acute Rheumatic Fever (ARF)

Overview

Acute rheumatic fever (ARF) is an autoimmune disease that develops as a delayed, non-suppurative complication following an untreated infection with Group A Streptococcus (GAS) pharyngitis (strep throat). It most commonly affects children and adolescents aged 5–15.

🦠 Pathogenesis: Molecular Mimicry

ARF is an immune-mediated condition resulting from molecular mimicry. The immune system produces antibodies against GAS antigens, such as the M protein. These antibodies mistakenly cross-react with and attack host tissues due to similarities between the bacterial and human proteins. Specifically, these cross-reactive antibodies target cardiac proteins (e.g., myosin) and neuronal cell surface proteins (e.g., lysoganglioside in the basal ganglia).

The resulting inflammation and long-term morbidity are primarily related to damage in the heart (pancarditis), involving the endocardium, myocardium, and epicardium.

Pathological Hallmarks:

• Aschoff bodies: Cardiac interstitial granulomas found on histology, consisting of lymphocytes, macrophages, and scattered multinucleated giant cells.
• Anitschkow cells (Caterpillar cells): Plump macrophages with abundant cytoplasm and a characteristic central, slender chromatin ribbon.

Over subsequent years, the Aschoff bodies can be replaced by fibrous scar tissue, leading to chronic valvular damage.

📋 Clinical Presentation and Diagnosis

Manifestations of ARF typically begin 2–4 weeks after the GAS pharyngitis, which itself may have been mild or self-resolving. The most common initial symptoms are fever and arthritis.

Diagnosis is based on the Jones criteria, requiring evidence of a recent GAS infection plus a specific combination of major and minor clinical features.

Major Criteria

• Joints: Migratory polyarthritis of large joints (e.g., knees, ankles, elbows).
• ❤️ (Carditis): Inflammation of all layers of the heart (pancarditis), often manifesting as acute mitral valve regurgitation (new holosystolic murmur) or altered vital signs (e.g., tachycardia).
• Nodules: Small, firm, painless subcutaneous lesions over bony prominences (e.g., elbow).
• Erythema marginatum: Transient, nonpruritic, pink-red rash with sharp, annular, or serpiginous borders and central clearing on the trunk and extremities.
• Sydenham chorea: The longest latency (1–8 months), causing nonrhythmic, involuntary, rapid movements of the hands, feet, and face (e.g., grimacing).

Minor Criteria

• Fever
• Arthralgia (joint pain)
• Elevated inflammatory markers (ESR, CRP)
• Prolonged PR interval on ECG

Diagnostic Requirements:

Diagnosis generally requires two major criteria OR one major and two minor criteria, plus laboratory evidence of recent GAS infection (e.g., elevated anti-streptococcal antibodies like anti-streptolysin O or anti-DNAse B). Isolated indolent carditis or Sydenham chorea alone is also considered sufficient due to the high probability of ARF.

⚠️ Differential Diagnosis Considerations

The differential diagnosis depends on the primary presenting symptom:

Manifestation	Other Conditions to Consider	Key Distinguishing Features
Arthritis	Systemic Juvenile Idiopathic Arthritis	Arthritis persists for >6 weeks (not transient/migratory).
	Lyme disease	Rash is a targetoid bull's-eye lesion (Erythema migrans), and arthritis is usually monoarticular (e.g., knee only).
	Parvovirus B19 infection	Acute, symmetric arthritis of small joints (e.g., hands) with or without the characteristic "slapped-cheek" rash. Large joint arthritis is not seen.
Carditis	Infective Endocarditis	Typically presents with fever and a new murmur with signs of heart failure; migratory arthritis is absent, and a risk factor (e.g., congenital heart disease) is often present.

💊 Management and Prevention

Acute Management

The first-line treatment is a single intramuscular (IM) dose of benzathine penicillin G to eradicate any remaining GAS infection in the upper respiratory tract. Oral alternatives include amoxicillin or azithromycin (for penicillin allergy).

Additional management is symptomatic:

• NSAIDs for joint inflammation.
• Corticosteroids for severe chorea.
• Symptomatic management (e.g., ACE inhibitors, diuretics) for heart failure caused by carditis.

Secondary Prevention (Long-term Prophylaxis)

Patients with a history of ARF are at high risk for recurrence, which increases the risk of developing Rheumatic Heart Disease (RHD). Therefore, all patients require long-term antibiotic prophylaxis.

• Preferred Agent: Intramuscular benzathine penicillin G every 4 weeks.
• Duration: Ranges from 5 years to lifelong based on the severity and persistence of heart disease:

Severity	Duration of Therapy (following last attack)
Uncomplicated rheumatic fever	5 years or until age 21*
With carditis but no valvular disease	10 years or until age 21*
With carditis & valvular disease	10 years or until age 40*

^*: Whichever duration is longer.

Primary Prevention

Prevention of the initial ARF episode is achieved by prompt and appropriate treatment of GAS pharyngitis with antibiotics.

Feature	Streptococcal Pharyngitis Details
Symptoms	Sudden onset sore throat, fever, abdominal pain & headache; typically no cough, rhinorrhea, or congestion.
Examination	Tonsillar erythema & exudates, tender anterior cervical lymphadenopathy, palatal petechiae. No oropharyngeal vesicles or ulcers.
Treatment	Penicillin or amoxicillin. For penicillin allergy: cephalosporin (mild reactions) or azithromycin/clindamycin (anaphylaxis).

📈 Prognosis and Complications

Rheumatic Heart Disease (RHD) is the primary long-term complication, characterized by permanent valvular damage (e.g., mitral regurgitation/stenosis).

[Image of rheumatic heart disease mitral valve stenosis]

• RHD is usually identified 10-20 years after the initial ARF diagnosis.
• The mitral valve is the most commonly affected valve. It gradually thickens, fibroses, and calcifies, leading to heart failure symptoms.
• Calcification primarily affecting the valve commissures is characteristic of RHD.

Without carditis during the acute phase, full recovery is expected with adherence to prophylactic therapy.

With carditis, severe regurgitation or myocarditis can lead to cardiac dilation, heart failure, and death in a small percentage of patients.