RHEUMATIC FEVER

PROF. A K M MOHIBULLAH
MBBS; MD (CARDIOLOGY); FACP; FRCP; FACC

DIRECTOR AND PROFESSOR

NATIONAL INSTITUTE OF CARDIOVASCULAR DISEASES SHER-E-BANGLA NAGAR, DHAKA

INTRODUCTION
Acute rheumatic fever is a systemic disease of childhood, often recurrent that follows group A beta hemolytic (GABH) streptococcal infection. It is a delayed non-suppurative sequel to URTI with GABH streptococci. It is a diffuse inflammatory disease of connective tissue, primarily involving heart, blood vessels, joints, subcutaneous tissue and CNS.

PATHOGENESIS
Delayed immune response to infection with Group A beta hemolytic streptococci. After a latent period of 1-3 weeks, antibody induced immunological damage occur to

heart valves, joints, subcutaneous tissue and basal ganglia of brain.

Group A Beta Hemolytic Streptococcus

Strains producing rheumatic fever: M types l, 3, 5, 6, 18 & 24. Pharyngitis: Produced by GABHS can lead to- acute rheumatic fever, rheumatic heart Glomerulonephritis. disease & post-streptococcal

Skin infection: Produced by GABHS leads to post streptococcal glomerulonephritis only. It will not result in Rheumatic Fever or carditis as skin lipid cholesterol inhibit antigenicity.

Diagrammatic structure of the group A beta hemolytic streptococcus

Antigen of outer Capsule protein cell wall of GABHS Cell wall induces antibody Protein antigens response in victim which Group carbohydrate result in Peptidoglycan autoimmune damage to heart Cyto. membrane valves, subcutaneous Cytoplasm tissue, tendons, joints & basal ganglia of brain

Pathologic Lesions
Fibrinoid degeneration of connective tissue, inflammatory edema, inflammatory cell infiltration & proliferation of specific cells resulting in formation of Ashcoff nodules, resulting in-

-Pancarditis in the heart

-Arthritis in the joints -Ashcoff nodules in the subcutaneous tissue

-Basal gangliar lesions resulting in chorea.

Histology of Myocardium in Rheumatic Carditis (200X)

NATURAL HISTORY

Population

S.Infection

Manifestation

Long Term

Carditis(42%)

Residual RHD(66%)

Epidemic

3% Recurrence

Endemic

0.3% Recurrence
No carditis (58%) Residual RHD (8%)

Carditis (71%)

New Damage(38%) Residual RHD(60%)

Carditis
No Carditis (29%) New Damage(0%)

ARF

60% Recurrence

Carditis (7%)
No Carditis No Carditis (93%)

New Damage(46%)
Residual RHD(2%) New Damage(0%)

CLINICAL PRESENTATION

Arthritis
Flitting & fleeting involving major joints migratory polyarthritis,

Commonly involved joints: knee, ankle, elbow & wrist Occur in 80%, involved joints are exquisitely tender In children below 5 years, arthritis usually mild but carditis more prominent Arthritis do not progress to chronic disease.

Carditis
Manifests as pancarditis (endocarditis, myocarditis and pericarditis), occur in 40-50% of cases. Carditis is the only manifestation of rheumatic fever that leaves a sequel & permanent damage to the organ. Valvulitis occur in acute phase. Chronic phase- fibrosis, calcification & stenosis of heart valves (fish-mouth valves).

Rheumatic heart disease. Abnormal mitral valve. Thick, fused chordae.

Another view of thick and fused mitral valves in Rheumatic heart disease

Sydenham Chorea
Occurs in 5-10% of cases.

Mainly in girls of 1-15 yrs age.

May appear even 6/12 after the attack of rheumatic fever.

Clinically manifest as-clumsiness, deterioration of handwriting, emotional lability or grimacing of face

Clinical signs- pronator sign, jack-in-the-box sign, milking sign of hands.

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

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.

Other features (Minor features)

Fever (upto 101 degree F) Arthralgia

Pallor
Anorexia

Loss of weight.

Simplified schema for the diagnosis of acute rheumatic carditis

Criteria Valvulits First attacks Recurrences

New onset Change in murmur Apical systolic murmur New onset murmur Carey Coombs murmur Aortic regurgitation murmur Worsening cardiomegaly Worsening CHF Pericardial rubs pericardial effusion

Myocarditis Cardiomegaly CHF/gallop sounds

Unexplained tachycardia

Pericarditis Pericardial rubs Unexplained pericardial effusion

Miscellaneo us methods Conduction disturbances Echocardiographic imaging Nuclear imaging Morphologic evidence at surgery Histologic evidence at biopsy or pathology

LABORATORY INVESTIGATION

High ESR Anemia, leucocytosis Elevated C-reactive protein ASO titre >200 Todd units. (Peak value attained at 3 weeks, then comes down to normal by 6 weeks) Anti-DNAse B test

Throat culture: GABH streptococci.

ECG: Prolonged PR interval, 2nd or 3rd degree blocks, ST depression, T inversion. Echocardiography: Valve edema, mitral regurgitation, LA & LV dilatation, pericardial effusion, decreased contractility. Radionuclide imaging Endomyocardial biopsy.

DIAGNOSIS

Rheumatic fever is mainly diagnosis

a clinical

No single diagnostic sign or specific laboratory test available for diagnosis Diagnosis based on MODIFIED JONES

CRITERIA.

Jones Criteria (Revised) for Guidance in the Diagnosis of Rheumatic Fever*

Major Manifestation
Carditis Polyarthritis Chorea Erythema Marginatum Subcutaneous Nodules

Minor Manifestations
Clinical Previous rheumatic fever or rheumatic heart disease Arthralgia Fever Laboratory Acute phase reactants: Erythrocyte sedimentation rate, C-reactive protein, leukocytosis Prolonged PR interval

Supporting Evidence of Streptococal Infection

Increased Titer of AntiStreptococcal Antibodies ASO (anti-streptolysin O),

others
Positive Throat Culture for Group A Streptococcus 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 nfection.

Recommendations of the American Heart Association

Exceptions to Jones Criteria

1.

Chorea alone, if other causes have been excluded Insidious or late-onset carditis with no other explanation Patients with documented RHD or prior rheumatic fever, one major criterion, or of fever, arthralgia or high CRP suggests recurrence.

2.

3.

2002-2003 WHO CRITERIA FOR DIAGNOSING RHEUMATIC FEVER & RHEUMATIC HEART DISEASE (BASED ON REVISED JONES CRITERIA)
MAJOR MANIFESTATIONS:

Carditis
Polyarthritis Chorea Erythema marginatum Subcutaneous nodule MINOR MANIFESTATIONS: Clinical: Fever, polyarthralgia

Laboratory: Elevated acute phase reactants (ESR or leucocyte count)

ECG: Prolonged PR interval.

SUPPORTING EVIDENCE OF PRECEDING STREPTOCOCCAL INFECTION WITHIN THE LAST 45 DAYS:

Elevated or raising ASO or other streptococcal antibody titre, or

A positive throat culture, or Rapid antigen test for group A streptococci, or Recent scarlet fever.

DIAGNOSTIC CATEGORY
Primary episode of RF

CRITERIA
2 major or 1 major and 2 minor manifestations PLUS evidence of preceding group A streptococcal infection

Recurrent attack of RF without 2 major or 1 major and 2 minor established RHD manifestations PLUS evidence of preceding group A streptococcal infection Recurrent attack established RHD of RF with 2 minor manifestations PLUS evidence of preceding group A streptococcal infection

Rheumatic chorea
Insidious onset rheumatic carditis Chronic valve lesions of RHD

Other major manifestations or evidence of streptococcal infection not required

Do not require any other criteria

DIFFERENTIAL DIAGNOSIS

Rheumatiod arthritis Septic arthritis Sickle-cell arthropathy Myocarditis Leukemia.

TREATMENT

Step I - primary prevention (eradication of streptococci) Step II - anti inflammatory treatment (aspirin, steroids) Step III- supportive management & management of complications Step IV- secondary prevention (prevention of recurrent attacks)

STEP I: Primary Prevention of Rheumatic Fever

(Treatment of Streptococcal Tonsillopharyngitis)
Agent Benzathine penicillin G Dose Mode Duration Once 600 000 U for patients Intramuscular 27 kg (60 lb) 1 200 000 U for patients >27 kg

or
Penicillin V Children: 250 mg 2-3 times daily Oral (phenoxymethyl penicillin) Adolescents and adults: 500 mg 2-3 times daily For individuals allergic to penicillin Erythromycin: Estolate 20-40 mg/kg/d 2-4 times daily (maximum 1 g/d) Oral 10 d 10 d

or
Ethylsuccinate 40 mg/kg/d 2-4 times daily (maximum 1 g/d) Oral 10 d

Recommendations of American Heart Association

Step II: Anti inflammatory treatment

Clinical condition
Arthritis only

Drugs
Aspirin 75-100 mg/kg/day,give as 4 divided doses for 6 weeks (Attain a blood level 2030 mg/dl) Prednisolone 2-2.5 mg/kg/day, give as two divided doses for 2 weeks Taper over 2 weeks & while tapering add Aspirin 75 mg/kg/day for 2 weeks. Continue aspirin alone 100 mg/kg/day for another 4 weeks

Carditis

3.Step III: Supportive management & management of complications Bed rest Treatment of congestive cardiac failure: -digitalis, diuretics Treatment of chorea: -diazepam or haloperidol Rest to joints & supportive splinting.

STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)

Agent
Benzathine penicillin G

Dose
1 200 000 U every 4 weeks*

Mode
Intramuscular

or
Penicillin V 250 mg twice daily Oral

or
Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb 1.0 g once daily for patients >27 kg (60 lb) Oral

For individuals allergic to penicillin and sulfadiazine

Erythromycin 250 mg twice daily Oral

*In high-risk situations, administration every 3 weeks is justified and recommended

Recommendations of American Heart Association

Duration of Secondary Rheumatic Fever Prophylaxis

Category
Rheumatic fever with carditis and residual heart disease (persistent valvar disease*)

Duration
At least 10 y since last episode and at least until age 40 y, sometimes lifelong prophylaxis

Rheumatic fever with carditis but no residual heart disease (no valvar disease*)

10 y or well into adulthood, whichever is longer

Rheumatic fever without carditis

5 y or until age 21 y, whichever is longer

*Clinical or echocardiographic evidence.

Recommendations of American Heart Association

PROGNOSIS

Rheumatic fever can recur whenever the individual experience new GABH streptococcal infection, if not on prophylactic medicines. Good prognosis for older age group & if no carditis during the initial attack. Bad prognosis for younger children & those with carditis with valvular lesions.