ACUTE RHEUMATIC FEVER

ETIOLOGY 1. Immunologic Streptococcus Beta hemolytic group A 2. Predisposing factors - Family history - Socio economic status - Age 6 -15 years ( peak 8 years)

Pathogenesis pathway for ARF and RHD Lancet 2005; 366: 155–68

Clinical Manifestations

Clinical Manifestations MAYOR MANIFESTATION POLYARTHRITIS MIGRAN CARDITIS SYDENHAM’S CHOREA (St. VITUS’ DANCE) ERYTEMA MARGINATUM SUBCUTANEUS NODULE

Clinical Manifestations MINOR MANIFESTATION Fever Arthralgia Acute-phase reactant ↑ (LED & CRP, leukocyte) ECG showed: prolonged PR interval

Evidence of antecedent Group A Streptococcal infection Positive throat culture or rapid streptococcal antigen tests for group A : less reliable Streptococcal antibody tests : most reliable ASTO : 80% Anti-DNA se B Anti hyaluronidase

Diagnosis of Streptococcal Infection (cont’): Detection of recent streptococcal infection in 61 consecutive patients studied within 4 weeks of onset of acute rheumatic fever during 1994 and 1995. ADNB = anti-DNase B; AHT = antihyaluronidase; ASOT = antistreptolysin-O Titer

The Revised Jones Criteria 1992 Highly probable 2 mayor manifestations 1 mayor + 2 minor manifestations With proved evidence of GAS infection (culture or ASTO) Doubtful Without proved evidence of GAS infection

Exceptions Chorea may occur as the only manifestation of RF Indolent carditis may be the only manifestation Occasionally patients with RF recurrences may not fulfill the Jones criteria

Note * Rheumatic fever is a clinical syndrome for which no specific diagnostic test exist ! * No symptom, sign or lab test result is pathognomonic, although several combinations of them are diagnostic * Only carditis can cause permanent cardiac damage. Signs of mild carditis disappear rapidly in weeks but severe carditis may last for 2-6 months. Chorea and arthritis usually subside without permanent damage.

Echocardiography

Role of Echocardiography Prevalence of Rheumatic Valvular Abnormalities among Schoolchildren in Cambodia and Mozambique N Engl J Med 2007;357:470-6.

Management of RF Benzathin penicillin G 0.6 – 1.2 M units IM for eradication and prophylaxis Bed rest Acetosal for mild cases Prednison for severe cases Antiinflammatory agents not needed for isolated chorea

Prevention Ideally prophylaxis is indefinite Benzathin Penicillin (600,000-1,200,000 U) every 28 days, min till age 21-25 ys Sulfadiazine 0.5 g 1x daily (BW < 27 kg), 1 g 1X (BW >27 kg) Penicillin V 2 x 250 mg /day Erythromycin 2 X 250 mg /day

Recurrence Rate of RF with different regimen Taranta & Markowitz,1989

RHEUMATIC HEART DISEASE Affects Mitral valve 75 % Aortic valve 25 % Tricuspid valve rare Pulmonary valve never Stenosis and regurgitation usually occur together

2002–2003 WHO Criteria for The Diagnosis of ARF & RHD (Based on The Revised Jones Criteria) DIAGNOSTIC CATEGORIES CRITERIA Primary episode of RF 2 Mayor/1 Mayor+2 Minor manifestations + evidence of a preceding GAS infection Recurrent attack of RF in a patient without established RHD 2 Mayor/1 Mayor+2 Minor manifestations + evidence of a Recurrent attack of RF in a patient with established RHD 2 Minor plus evidence of a Rheumatic chorea Insidious onset of rheumatic carditis Other major manifestations or evidence of GAS infection not required Chronic valve lesions of RHD Do not require any other criteria to be diagnosed as having RHD

Thank You NO PAIN NO GAIN

Management of Chorea The signs and symptoms of chorea do not respond to anti-inflammatory agents In severe case: Neuroleptics Carbamazepine 7–10 mg/kg/day po tid Phenobarbital 3–5 mg/kg/day po bid Haloperidol 0.01–0.03 mg/kg/day po bid Valproic acid 15–20 mg/kg/day po tid

Clinical manifestations. Asymptomatic during childhood Clinical manifestations * Asymptomatic during childhood * Rare : fatigue, palpitation

Sign & Symptom of GAS Infection SIGNS/SYMPTOMS INFANT CHILDREN ADOLESCENT/ADULT ANTERIOR CERVICAL LYMPHADENITIS (PAIN) ++++ CONTACT SCARLATINIFORM RASHES + NOSE EXCORIATION TONSIL EXUDATE/PHARYNX THROAT CULTURE (+) FEVER ++ ACUTE ONSET ABDOMINAL PAIN CORYZA PHARYNX ERYTHEMATOUS HOARSENESS COUGH

ECG Normal in mild cases LVH or LV dominance, with or without LAH CXR LA and LV enlarged Pulmonary congestion pattern in CHF

INCIDENCE Annual specific incidence rate (temporal trend) of first attack of ARF Heart 2008;94;1534-1540

Changes of JONES Criteria

Potential Preventive Measures for Rheumatic Fever and Rheumatic Heart Disease

Bed rest and indoor ambulation ____________________________________ Arthritis Mild Moderate Severe Alone Carditis Carditis Carditis __________________________________________________________ Bed rest 1-2 wk 3-4 wk 4-6 wk as long as HF + Indoor ambulation 1-2 wk 3-4 wk 4-6 wk 2-3 mo _________________________________________________________ ESR: important for duration of restriction of activities. Full activity : ESR normal, except significant cardiac involvement _

Recommended anti-inflammatory agents _______________________________________________________________________________________ Arthritis Mild Moderate Severe alone carditis carditis carditis __________________________________________________ Prednisone 0 0 0 2-6 wk* Aspirin 1-2 wk 3-4 wk# 6-8 wk 2-4 mo ___________________________________________________ * Prednisone should be tapered and aspirin started during the final week # Aspirin may be reduced to 60 mg/kg/day Dosages Prednisone : 2mg/kg/day, in 4 divided doses Aspirin : 100 mg/kg/day, in 4-6 divided doses

Subcutaneous rheumatic nodules

Erythema marginatum

Subcutaneous Nodule

General Measures Arthritis Mild Carditis Moderate Carditis Severe Carditis Bed rest (Hospitalization) 1-2 weeks 2-3 weeks (up to 4 weeks) 4-6 weeks 2-4 months (CHF -) Indoor ambulation 2-3 months Outdoor activity 2 weeks 2-4 weeks 1-3 months 2- 3 months Full activity After 6-10 weeks After 3 (6-10) weeks After 3-6 months Variable These guidelines should be individualized by clinician(s) according to patient and family circumstances.

Suppression of The Inflammatory Process Arthritis Mild carditis Moderate carditis Severe carditis Prednisone 2-4 weeks 2-6 weeks Salicylates 1-2 weeks 6-8 weeks 2-4 months Prednisone:1–2mg/kg-day, to a maximum of 80mg/day given once daily, or in divided doses). After 2–3 weeks of therapy the dosage may be decreased by 20–25% each week. While reducing the steroid dosage, a period of overlap with aspirin is recommended to prevent rebound of disease activity Salicylates: 90-100 mg/kg/day/divided into 4-5 doses for 2 weeks 60–70mg/kg-day for 3–6 weeks

Suggested Duration of Secondary Prophylaxis Category of patient Duration of prophylaxis Patient without proven carditis For 5 years after the last attack, or until 18-21 years of age (whichever is longer) Patient with carditis (mild MR or healed carditis) For 10 years after the last attack, or until 21-25 years of age (whichever is longer) More severe valvular disease 10 years or until 40 years of age (whichever is longer), sometimes lifelong prophylaxis After valve surgery Lifelong

2002–2003 WHO Criteria for The Diagnosis of ARF & RHD (Based on The Revised Jones Criteria) DIAGNOSTIC CATEGORIES CRITERIA Primary episode of RF 2 Mayor/1 Mayor+2 Minor manifestations + evidence of a preceding GAS infection Recurrent attack of RF in a patient without established RHD 2 Mayor/1 Mayor+2 Minor manifestations + evidence of a Recurrent attack of RF in a patient with established RHD 2 Minor plus evidence of a Rheumatic chorea Insidious onset of rheumatic carditis Other major manifestations or evidence of GAS infection not required Chronic valve lesions of RHD Do not require any other criteria to be diagnosed as having RHD

Erythema marginatum

Group A beta hemolytic Streptococcus STRUCTURE Capsule: hyaluronic acid Cell Wall: outer, middle and inner layer Outer layer: proteins M, T and R M component is the most potent & antigenic Middle layer: specific carbohydrates eg N acetyl glucoamin Inner layer:peptidoglycan –responsible for cell wall rigidity Cytoplasm

IMMUNOPATHOGENESIS Of RF