Rheumatic Fever & Rheumatic Heart Disease

-Radin :) A*B Production Rheumatic Fever (RF) : Acute, immunologically-mediated, multisystem inflammatory following group A streptococcal pharyngitis (GAS) after interval of few weeks. Rheumatic heart disease (RHD) : Cardiac manifestation of RF (serious complication) a/w inflammation of valves, myocardium or pericardium. - A complication of acute RF which occurs decades later.

Rheumatic Fever (RF)

Etiology of RF Rheumatic fever follows a GROUP A -HEMOLYTIC STREPTOCOCCAL infection, usually pharyngitis. *cultures of RF patients are sterile Evidence include; 1. Epidemiology : outbreaks of streptococcal pharyngitis are followed by cases of RF. 2. Patient history : recurrent attacks & exacerbations of RF follow streptococcal infections 3. Serology : elevated levels of anti-streptococcal antibodies (>200 titer) Incidence of RF Parallels with epid of streptococcal pharyngitis (ONLY WHEN THERES GAS THROAT INF. THERES RF) - 3% - epidemics of exudative streptococcal pharyngitis in closed community (school, army) - 0.3% - civilian population with sporadic streptococcal throat infection - 50% - past history of RF - 1st attack between 5-15 years (childhood disease) * 2 prophylaxis is important!

RF RHD
Why is it so? 1. RF reversible, RHD not reversible. 2. RF involve multisystem, RHD only on heart valve Rheumatic Fever VS Rheumatic Heart Disease Feature Onset Age Pathology Aschoff bodies Diagnosis Prognosis Rheumatic fever can reoccur whenever the individual experience new GABH streptococcal infection, if not on prophylactic medicines Good prognosis for older age group & if no carditis during initial attack Bad prognosis for younger children & those with carditis with valvar lesion. Rheumatic Fever (RF) Acute Children (5-15 years) Carditis, arthritis, chorea Pathognomonic Johns criteria Rheumatic Heart Disease (RHD) Chronic Adults Valvular disease (MS, MR) Not seen Not applicable

Why not all patients that have GAS throat infection will have RF? Due to MICROORGANISM VARIABLES and HOST VARIABLES Microorganism Variables : only certain strains can produce immunologically active Ag Host Variables: some host produce large amount ofAbs after infection, but others dont.

Pathogenesis Pharyngitis by Group A Streptococcal (GAS) Body produces antibodies against GAS Antibodies cross react with human tissues due to antigenic similarity between streptococcal components & human connective tissue (molecular mimicry) [ amino acid seq similar between GAS & human tissue] Immunologically mediated inflammation & damage (autoimmune) - at site of antigenic *similarity like heart, joint, brain and connective tissue After latency period [1-3 weeks], antibody induced immunological damage to heart valves, joints, subcutaneous tissue & basal ganglia of brain. Elavated titers to one/more of three antistreptococcal antibodies (streptolysin O, hyaluronidase and streptokinase) * Similarity ; 1. Hyaluronic acid In GAS capsule and connective tissue of joints - Ab against GAS capsule start to attack joints arthritis 2. M protein In GAS cell wall and myocardium - Ab against GAS cell wall will attack heart carditis RF : Clinical Occurs 10 days to 6 weeks after pharyngitis Of genetic susceptibility Peak incidence : 5-15 years Pharyngeal culture may be negative, but anti streptolysin O (ASO) titer will be high. Arthritis : large joints, migratory Acute carditis : pericardial friction rubs, weak heart sounds, tachycardia and arrhythmias

Morphology : Acute RF *no need biopsy!

1. 2. Inflammatory infiltrates in a wide range of tissues : synovium, joints, skin, heart. Focal fibrinoid necrosis Mixed inflammatory reaction (diffuse/localized) fibrosis (chronic RHD)

Lesion characteristic of acute RF; 1. Aschoff body consist of a focus of fibrinoid necrosis (represent site of antigen-antibody reaction) Surrounded by activated histiocytes and lymphocytes. 2. Anitsckow cells The histiocytes. May be mononuclear and multinuclear 3. Foci found in pericardium, myocardium or in the valves. 4. Ultimately heal by fibrosis.

Morphology : Acute RF : Carditis - in heart

Pancarditis (endo- myo- pericarditis) - involve all layers Multiple foci of inflammation w/i connective tissue of the heart - Aschoff body Diffuse interstitial inflammatory infiltrates (may lead to generalized dilation of cardiac chambers)

Pericardial involvement Fibrinous pericarditis, Sometimes a/w serous/serosanguinous effusion Endocardium Mostly mitral and aortic valve Valve edematous & thickened with foci of fibrinoid necrosis (Aschoff nodules UNCOMMON) Verrucous endocarditis (small vegetations along lines of valve closure) * Acute changes may resolve completely or progress to scarring & chronic valvular deformities depends on immunity status of the patient. RF : Involvement of Other Organ 1. Arthritis : large joint Self limited No chronic deformities Skin Skin nodules Erythema marginatum 3. Lung (uncommon) Chronic interstitial inflammation Fibrinous pleuritis

2.

Chronic Rheumatic Heart Disease (CHD)

Irreversible deformity of one or more cardiac valves (previous acute valvulitis). Left side of heart > right Reduction of diameter (stenosis) or improper closure (regurgitation), or both. May lead to cardiac failure (overload) May predispose to infective endocarditis

Chronic Rheumatic Carditis : Clinical

Manifestation after years or decades after the initial episode of rheumatic fever Signs and symptoms depend on which valve(s) it involves: Cardiac murmurs Hypertrophy Dilation Congestive heart failure Arrhythmia Thromboembolic complications Infective endocarditis

Mitral valve (Chronic Rheumatic Mitral Valvulitis)

Most commonly and severely (65-70% of patients) Stenosis > regurgitation Females > males Stenosis; - Leaflets are thick, rigid & interadherent - Dilatation & hypertrophy of left atrium - Mural thrombi may present systemic emboli - Lungs firm & heavy (chronic passive congestion) - Right heart may be affected later
nd

Aortic valve ( Chronic Aortic Valvulitis)

2 most commonly (25% of the patients) *associated with mitral valvulitis Males > Females Stenosis : - Valve cusps are thickened, firm and interadherent (rigid triangular channel) - Left ventricular hypertrophy - Subsequent left ventricular failure and dilation * scarring of valve leaflets convert valve into stiff, thickened structure. * the orifice becomes stenotic *distortion and fixation of valve orifice fishmouth or buttonhole *shrinkage of valve leaflets causes mitral insufficiency Regurgitation; Retraction of leaflets

Complication of RHD
1. 2. 3. Depends on which cardiac valves or valves are involved Cardiac murmurs, cardiac hypertrophy and dilatation. Arrhythmias May develop heart failure due to mitral stenosis, mitral incompetence or mixes mitral valve disease Right-sided heart valves only affected after right-sided pressure rises due to left sided valve disease. Infective endocarditis. Left atrial thrombus formation

4. 5.

Treatment - valvuloplasty or valve replacement with lifelong Penicillin or Bicillin injection once in a lifetime to prevent further infection

Regurgitation; Retracted leaflets Left ventricular hypertrophy and dilatation. Tricuspid valve - only 10% of the patients and always associated with mitral and aortic lesion. Pulmonary valve is rarely affected

Mortality/Morbidity
RHD is the major cause of morbidity from RF, and the major cause of mitral insufficiency and stenosis in the world. Variables that correlate with severity of valve disease are the number of previous attacks of RF, the length of time between the onset of disease and start of therapy, antibiotic prophylaxis

Clinical Features Arthritis

- Flitting & fleeting migration polyarthritis, involving major joints - Commonly involved joints - knee, ankle, elbow, wrist - Occur in 80%, involved joints are exquisitely tender - In children <5 years, arthritis usually mild, but carditis more prominent - Arthritis do not progress to chronic disease

Other features( inor features m (

Fever (up to 38.5 C) Arthralgia Pallor Anorexia Loss of weight

Differential Diagnosis
Juvenile Rheumatoid Arthritis Septic arthritis Sickle-cell arthropathy Kawasaki disease Myocarditis Scarlet fever Leukemia

Laboratory Findings Sydenham Chorea

- Occur in 5-10% of cases - Mainly in girls of 1-15 years - May appear 6-12 years after the attack of rheumatic fever - Clinically manifest as - clumsiness, emotional lability or grimacing of face - Clinical signs - pronator sign, jack in the box sign, milking sign of hands. High ESR Anemia, leucocytosis Elevated C-reactive protein ASO titre > 200 Todd units - diagnostic! rd (Peak value attained at 3 weeks, then comes down to normal th by 6 weeks) 5. Anti-DNAase B test 6. Throat culture - GABH streptococci nd rd 7. ECG - prolonged PR interval, 2 or 3 degree blocks, ST depression, T inversion 8. Echo cardiography - valve edema, mitral regurgitation, LA & LV dilatation, pericardial effusion, decreased contractility. 1. 2. 3. 4.

Erythema Marginatum
- Occur in <5% of cases - Unique, transient, serpiginous-looking lesion of 1-2 inches in size - Pale center with red irregular margin - More on trunks & limbs & non-itchy - Worsen with application of heat - Often associated with chronic carditis

Diagnosis
Rheumatic fever is mainly a clinical diagnosis No single diagnostic sign or specific laboratory test available for diagnosis Diagnosis based on MODIFIED JONES CRITERIA

Subcutaneous nodules
- Occur in 10%. - Painless, pea-sized, palpable nodules - Mainly over extensor surfaces of joints, spine, scapulae & scalp - Associated with strong seropositivity - Always associated with severe carditis

Minor Manifestation Supporting Evidence of Streptococcal Infection Clinical Laboratory - Previous rheumatic Acute phase reactants : Increased Titer of Anti- Carditis fever or rheumatic - Erythrocyte Streptococcal Antibodies ASO - Polyarthritis heart disease sedimentation rate (anti-streptolysin O) - Chorea - Erythema Marginatum - Arthralgia - C-reactive protein Others; - Subcutaneous - Fever - Leukocytosis - Positive Throat Culture for Group A Streptococcus Nodules - Prolonged P-R interval - Recent Scarlet Fever The presence of TWO MAJOR CRITERIA, or of ONE MAJOR AND TWO MINOR CRITERIA, indicates a high probability of acute rheumatic fever, if supported by evidence of Group A streptococcal infection -Recommendations of the American Heart Association-

Major manifestation