Acute rheumatic fever (ARF) is a multisystem disease resulting from an autoimmune reaction to infection with group A streptococcus.

ARF is mainly a disease of children aged 5 - 14 years

The prevalence of RHD, peaks between 25 and

40 years.

There is no clear gender association for ARF

RHD more commonly affects females, twice as frequently as males.

Organism Factors

ARF is exclusively caused by infection of the upper respiratory tract with group A streptococci .

Classically, certain M-serotypes (types 1, 3, 5, 6, 14, 18, 19, 24, 27, and 29) in high-incidence regions

Familial clustering of cases and concordance in monozygotic twins—particularly for chorea—confirm that susceptibility to ARF is an inherited characteristic.

(HLA) class II alleles appear to be strongly associated with susceptibility.

High levels of circulating mannose-binding lectin and polymorphisms of transforming growth factor 1 gene.

Because of the similarity btw hyaluronic acid in GAS capsule and in the connective tissue of the joints, Ab produced against GAS capsule will start to attack the joints and causes arthritis.

M-protein in GAS cell wall and the myocardium are similar, thus Ab produced against GAS cell wall will attack heart and will cause carditis and so forth.

Similarly Ab against NAG in GAS will affect cardiac valve tissue causing valvular damage.

When a susceptible host encounters a group A streptococcus, an autoimmune reaction results, which leads to damage to human tissues as a result of cross-reactivity between epitopes on the organism and the host Cross-reactive epitopes are present in the streptococcal M protein and the N-acetylglucosamine of group A streptococcal carbohydrate and are immunologically similar to molecules in human myosin, tropomyosin, keratin, actin, laminin, vimentin, and N-acetylglucosamine. It is currently thought that the initial damage is due to cross-reactive antibodies attaching at the cardiac valve endothelium, allowing the entry of primed CD4+ T cells, leading to subsequent T cell-mediated inflammation.

There is a latent period of 3 weeks (1–5 weeks) between the streptococcal infection and the appearance of the clinical features of ARF.

The exceptions are chorea and indolent carditis, which may follow prolonged latent periods lasting up to 6 months.

The most common clinical presentation of ARF is polyarthritis and fever.

Polyarthritis is present in 60–75% of cases and carditis in 50–60%.

The prevalence of chorea in ARF varies <2% to 30%.

Erythema marginatum and subcutaneous nodules are now rare, being found in <5% of case

Up to 60% of patients with ARF progress to RHD.

The endocardium, pericardium, or myocardium may be affected.

Valvular damage is the hallmark of rheumatic carditis.

The mitral valve is almost always affected, sometimes together with the aortic valve; isolated aortic valve involvement is rare.

Early valvular damage leads to regurgitation.

Therefore the characteristic manifestation of

carditis in previously unaffected individuals is

MR, sometimes accompanied by AR .

First-degree AV block

Softening of the first heart sound

The typical arthritis is migratory, moving from one joint to another over a period of hours. ARF almost always affects the large joints—most commonly the knees, ankles, hips, and elbows—and is asymmetric.

Aseptic monoarthritis

The joint manifestations are highly responsive to salicylates and other nonsteroidal anti-inflammatory drugs (NSAIDs).

Follows a prolonged latent period after group A streptococcal infection, and is found mainly in females.

The choreiform movements affect particularly the head and the upper limbs .

Chorea eventually resolves completely usually within 6 weeks

The classic rash of ARF is erythema marginatum

Pink macules that clear centrally, leaving a

serpiginous, spreading edge. The rash is evanescent, appearing and disappearing before the examiner's eyes. It occurs usually on the trunk, sometimes on the limbs, but almost never on the face.

Subcutaneous nodules occur as painless, small (0.5–2 cm), mobile lumps beneath the skin overlying bony prominences, particularly of the hands, feet, elbows, occiput, and occasionally the vertebrae.

They are a delayed manifestation, appearing 3 weeks after the onset of disease, and are commonly associated with carditis.

Fever occurs in most cases of ARF, although rarely in cases of pure chorea.

Elevated acute-phase reactants are also present in most cases. ,C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are often dramatically elevated. Occasionally the peripheral leukocyte count is mildly elevated.

anti-streptolysin O (ASO) and anti-DNase B (ADB) titers.

Post-streptococcal reactive arthritis (PSRA) is (1) small-joint involvement that is often symmetric;

(2) a short latent period following streptococcal infection (usually <1 week);

(3) occasional causation by nongroup A -hemolytic streptococcal infection;

(4) slower responsiveness to salicylates; (5) the absence of other features of ARF,

particularly carditis.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a term that links a range of tic disorders and obsessive-compulsive symptoms with group A streptococcal infections. People with PANDAS are said not to be at risk of carditis, unlike patients with Sydenham's chorea. The diagnoses of PANDAS and PSRA should rarely be made in populations with a high incidence of ARF.

MAJOR CRITERIA

1. Carditis2. Arthritis3. Subcutaneous nodules4. Erythema marginatum5. Chorea

CLINICAL

1. Fever2. Arthralgia3. Previous h/o rheumatic fever

LABORATORY

1. Acute phase reactants2. PR prolongation

Evidence of recent streptococcal infection evidenced by

1. Increase in ASO2. Positive throat culture for streptococcal

infection3. Recent history of scarlet fever4. Rapid antigen test for group A streptococcus

2 major / 1 major and 2 minor in the presence of essential criteria.

DIAGNOSTIC CATEOGORIES CRITERIA

Primary episode of rheumatic fever Two major or one major and two minor manifestations plus evidence of preceding group A streptococcal infection

Recurrent attack of rheumatic fever in a patient without established rheumatic heart disease

Two major or one major and two minor manifestations plus evidence of preceding group A streptococcal infection

Recurrent attack of rheumatic fever in a patient with established rheumatic heart disease

Two minor manifestations plus evidence of preceding group A streptococcal infectionc

Rheumatic chorea Insidious onset rheumatic carditis

Other major manifestations or evidence of group A streptococcal infection not required

Chronic valve lesions of rheumatic heart disease (patients presenting for the first time with pure mitral stenosis or mixed mitral valve disease and/or aortic valve disease)

Do not require any other criteria to be diagnosed as having rheumatic heart disease

Recommended for all cases White blood cell count Erythrocyte sedimentation rate C-reactive protein Blood cultures if febrile Electrocardiogram Chest x-ray if clinical or echocardiographic evidence of carditis Echocardiogram (consider repeating after 1 month if negative) Throat swab (preferably before giving antibiotics)–culture for

group A streptococcus Anti-streptococcal serology: both anti-streptolysin O and anti-

DNase B titres, if available (repeat 10–14 days later if 1st test not confirmatory)

Tests for alternative diagnoses, depending on clinical features

Repeated blood cultures if possible endocarditis

Joint aspirate (microscopy and culture) for possible septic arthritis

Copper, ceruloplasmin, anti-nuclear antibody, drug screen for choreiform movements

Serology and auto-immune markers for arboviral, auto-immune or reactive arthritis

Penicillin is the drug of choice and can be given orally [as phenoxymethyl penicillin, 500 mg (250 mg for children< 27 kg) PO twice daily, or amoxicillin 50 mg/kg (max 1 g) daily, for 10 days] or as a single dose of 1.2 million units (600,000 units for children 27 kg) IM benzathine penicillin G.

Aspirin is the drug of choice. An initial dose of 80–100 mg/kg per day in children (4–8 g/d in adults) in 4–5 divided doses is often needed for the first few days up to 2 weeks.

When the acute symptoms are substantially resolved, the dose can be reduced to 60–70 mg/kg per day for a further 2–4 weeks.

Naproxen at a dose of 10–20 mg/kg per day has been reported to lead to good symptomatic response.

Cases of severe carditis (causing heart failure) with glucocorticoids in the belief that they may reduce the acute inflammation and result in more rapid resolution of failure.

Prednisone or prednisolone are recommended at doses of 1–2 mg/kg per day (maximum, 80 mg). Glucocorticoids are often only required for a few days or up to a maximum of 3 weeks

Carbamazepine

Sodium valproate

Intravenous Immunoglobulin (Ivig)

Primary Prevention Avoid overcrowded housing.

Mainstay of primary prevention for ARF remains primary prophylaxis (i.e., the timely and complete treatment of group A streptococcal sore throat with antibiotics

Oral penicillin V (250 mg) can be given twice-daily

Benzathine penicillin G (1.2 million units, or 600,000 units if <27 kg) delivered every 4 weeks.

Erythromycin (250 mg) twice daily.

Category of Patient Duration of Prophylaxis

Rheumatic fever without carditis For 5 years after the last attack or 21 years of age (whichever is longer

Rheumatic fever with carditis but no residual valvular disease

For 10 years after the last attack, or 21 years of age (whichever is longer

Rheumatic fever with persistent valvular disease, evident clinically or on echocardiography

For 10 years after the last attack, or 40 years of age (whichever is longer). Sometimes lifelong prophylaxis