Rheumatic Fever Dr Sabika Iftikhar SR Pediatrics

Rheumatic Fever

1. Rheumatic Fever Dr. Sabika Iftikhar FCPS Pediatrics Senior Registrar Pediatrics

2. Introduction Acute Rheumatic Fever (RF) is a delayed inflammatory response following Group A Streptococcal (GAS) pharyngitis. Rheumatic Heart Disease (RHD) is a chronic condition resulting from RF, characterized by permanent damage to heart valves. 2/3 rd of patients with an acute episode of RF have a history of an upper respiratory tract infection several weeks before. Patients with acute RF almost always have serologic evidence of a recent GAS infection. Antimicrobial therapy that eliminates GAS from the pharynx also prevents initial episodes of acute RF and long term continuous antibiotic prophylaxis prevents recurrences of acute RF Not all serotypes of GAS can cause RF. When some GAS strains (e.g. M type 4) caused acute pharyngitis in a very susceptible rheumatic population, there were no recurrences of RF. Other serotypes in the same population led to frequent recurrences of acute RF Serotypes of GAS (M types 1, 3, 5, 6, 18, and 29) are more frequently isolated from patients with acute RF than are other serotypes.

3. Epidemiology Exceeds 50 per 100,000 children Rheumatic heart disease is the most common form of acquired heart disease in all age-groups Acute RF was associated with poverty and overcrowding (which facilitates the spread of infection) The dramatic decline in the incidence of acute RF and rheumatic heart disease in the industrialized countries is a shift in the prevalent strains of GAS causing pharyngitis from mostly rheumatogenic to non- rheumatogenic and antibiotic therapy of GAS pharyngitis preventing initial attacks and recurrences of the disease.

4. Pathogenesis Cytotoxicity Theory in Pathogenesis theory suggests that a GAS toxin, such as streptolysin O, directly affects mammalian cardiac cells. Streptolysin O has been shown to be cytotoxic in tissue culture. Drawback: this theory does not explain the 10-21 day latent period between GAS pharyngitis and the onset of acute RF. Immune-Mediated Pathogenesis An immune-mediated pathogenesis is suggested by the clinical similarity of RF to other immunopathogenic illnesses and the latent period. Molecular mimicry hypothesis: GAS components like M protein and cell wall carbohydrate share epitopes with mammalian tissues (heart valves, joints). This cross-reactivity leads to autoimmune responses damaging the heart and other tissues.

5. Clinical Manifestation and Diagnosis 5 Major criteria : Carditis, Polyarthritis, Chorea, Erythema marginatum, Subcutaneous nodules 4 Minor criteria : Arthralgia, Fever, Elevated acute phase reactants (ESR, CRP), Prolonged PR interval Evidences of preceding GAS infection must be present for a diagnosis. The Jones Criteria , used for diagnosing initial and recurrent attacks of acute RF. Criteria include: 2 major manifestations, or 1 major and 2 minor manifestations, plus evidence of preceding GAS infection.

6. Clinical Manifestation and Diagnosis ( conti ..) The 2015 revision of Jones criteria includes: Low-risk populations: Incidence ≤2 per 100,000 school-age children/year, RHD prevalence ≤1 per 1,000 population Moderate/high-risk populations: Higher incidence or prevalence rates They differ in: Major criterion of arthritis, minor criteria of arthralgia, definition of fever, and elevated inflammatory markers Diagnosis of acute RF can be made without strict adherence to the Jones Criteria in three circumstances: when chorea occurs as the only major manifestation of acute RF when indolent carditis is the only manifestation in patients who come to medical attention only months after the apparent onset of acute RF limited number of patients with recurrence of acute RF in particularly high-risk populations

7. Migratory Polyarthritis Arthritis occurs in approximately 75% of patients with acute RF. Joints involved: larger joints, such as - Knees - Ankles - Wrists - Elbows Involvement of the spine, small joints of the hands and feet, or hips is uncommon. Characteristics: Jo ints are hot, red, swollen, and tender, pain can precede objective findings and often disproportionate. Joint involvement in ARF is characteristically migratory . A severely inflamed joint can normalize within 1-3 days without treatment, while other large joints may become involved. Severe arthritis can persist for several weeks in untreated patients. Monoarticular arthritis is unusual unless anti-inflammatory therapy is initiated prematurely.

8. Migratory Polyarthritis ( conti ..) Response to Treatment A dramatic response to even low doses of salicylates is a characteristic feature of ARF arthritis. Absence of response suggests an alternative diagnosis. Treatment Options: - Salicylates (Aspirin) - NSAIDs (Naproxen, Ibuprofen) - Glucocorticoids (for severe cases) Synovial Fluid Characteristics : - 10,000-100,000 white blood cells/ μL with a predominance of neutrophils - Protein: approximately 4 g/dL - Normal glucose level - Good mucin clot formation There is often an inverse relationship between the severity of arthritis and the severity of cardiac involvement in ARF patients. Those with severe arthritis tend to have less severe cardiac manifestations and vice versa.

9. Carditis “Rheumatic carditis is characterized by pancarditis , involving inflammation of the myocardium, pericardium, and endocardium.” Major manifestations include: - Exudative pancarditis - Mild, transient cardiac involvement - Universal finding of endocarditis (valvulitis) Carditis in RHD can manifest as: - Pancarditis : Active inflammation of all three layers of the heart - Endocarditis (valvulitis): Universal in rheumatic carditis - Myocarditis: Variable and often accompanied by pericarditis Note: Myocarditis or pericarditis without endocarditis is rarely rheumatic.

10. Carditis ( conti …) RHD primarily affects the mitral and aortic valves: - Mitral Valvular Disease: Most common, often isolated - Combined Aortic and Mitral Valvular Disease: Less common - Isolated Aortic or Right-sided Valvular Involvement: Rare Valvular insufficiency is characteristic of both acute and convalescent stages of acute RF. Diagnosis : Echocardiography: Detects valvular damage, even in asymptomatic patients Essential for identifying subclinical carditis Helps in differentiating between pathological and physiological valve regurgitation Screening Methods: Auscultation and echocardiography

11. Chorea Sydenham chorea occurs in approximately 10–15% of patients with acute RF and presents as an isolated, frequently subtle, movement disorder. Characteristics : Emotional lability, incoordination, poor school performance, uncontrollable movements, and facial grimacing, all exacerbated by stress and disappearing with sleep. occasionally is unilateral (hemichorea) onset can be insidious rarely leads to permanent neurologic sequelae Diagnostic Criteria: Clinical findings Supportive evidence of Group A Streptococcus (GAS) antibodies

12. Erythema Marginatum rare (approximately 1% of patients with acute RF) characteristic rash consisting of erythematous, serpiginous, macular lesions with pale centers that are not pruritic occurs on the trunk and extremities, but not on the face can be accentuated by warming the skin

13. Subcutaneous Nodules rare (≤1% of patients with acute RF) firm nodules approximately 0.5-1 cm in diameter along the extensor surfaces of tendons near bony prominences.

14. Minor Criteria joint manifestations (only if arthritis is not used as a major criterion) polyarthralgia in low-risk populations monoarthralgia in moderate/high-risk populations fever, at least 38.5°C (in low-risk)and at least 38.0°C (in moderate/high-risk.

15. Treatment All patients with acute RF should be placed on bed rest and monitored closely for evidence of carditis. Antibiotic Therapy 10 days of orally administered penicillin or amoxicillin or a single IM injection of benzathine penicillin penicillin allergic, 10 days of erythromycin, 5 days of azithromycin, or 10 days of clindamycin is indicated. After initial course long-term antibiotic prophylaxis for secondary prevention should be instituted

16. Treatment ( conti …) Anti-inflammatory Agents: Salicylates Indications: Typical migratory polyarthritis, carditis without cardiomegaly or congestive heart failure Dosage: Aspirin 50-70 mg/kg/day in four divided doses for 3-5 days, then 50 mg/kg/day for 2-3 weeks, followed by half that dose for another 2-4 weeks Monitoring: Serum salicylate levels, signs of toxicity (tinnitus, hyperventilation) Corticosteroids ( reserved for severe cases due to potential side effects) Indications: Carditis with more than minimal cardiomegaly and/or congestive heart failure Dosage: Prednisone 2 mg/kg/day in four divided doses for 2-3 weeks, then half the dose for 2-3 weeks, followed by tapering by 5 mg/24 hr every 2-3 days Monitoring: Start aspirin at 50 mg/kg/day in four divided doses for 6 weeks during prednisone tapering to prevent rebound inflammation

17. Treatment ( conti …) Supportive Therapies for ARF Management Digoxin: Used for severe carditis, requires careful monitoring for cardiac toxicity Fluid and Salt Restriction: To manage congestive heart failure Diuretics: Help reduce fluid overload Oxygen Therapy: For patients with significant carditis and respiratory distress Chorea Sedatives may be helpful early in the course of chorea; phenobarbital (16-32 mg every 6-8 hours PO) is the drug of choice. If phenobarbital is ineffective, haloperidol (0.01-0.03 mg/kg/24 hr divided twice daily PO) or chlorpromazine (0.5 mg/kg every 4-6 hours PO) should be initiated.

18. Prevention Primary Prevention (Prevention of initial attacks): Identification and eradication of GAS causing acute pharyngitis Early antibiotic therapy before the ninth day of symptoms is highly effective Challenges: Approximately 30% of patients with acute RF do not recall a preceding episode of pharyngitis and did not seek therapy Secondary Prevention Approaches Continuous antibiotic prophylaxis for patients at substantial risk of recurrent acute RF Prophylaxis should begin immediately after completing a full course of antibiotic therapy for the initial episode Long-term prophylaxis is recommended for patients with carditis during the initial episode to prevent additional cardiac damage

19. Thank You