RHEUMATIC FEVER

RHEUMATIC FEVER

INTRODUCTIONRF is an autoimmune inflammatory disease that occurs in children and young adults (5-15 years old)

Evidenced by its existence since 1600 when Sydenham described several of its classical features

Post group A streptococcal pharyngitis comprises a cascade ofArthritisChoreaDermal manifestationCarditis

In both developing and developed countries, pharyngitis is the most common infection caused by group A streptococci

Acute Rheumatic Fever occurs approximately 20 days after streptococcal throat infection

EPIDEMIOLOGYIn 2005, approximately 15.6 million people had suffered from RF (esp those from Sub-Saharan Africa and South Cental Asia)

Recent report suggested that among all the acquired heart diseases in the major hospitals in Malaysia, 20.6 % were cases of Rheumatic Heart Disease.

In developing countries, RF and rheumatic heart disease are estimated to affect nearly 20 million people.

Worldwide, there are 470,000 new cases of rheumatic fever and 233,000 deaths attributable to RF or rheumatic heart disease each year; most occur in developing countries and among indigenous groups. The mean incidence of ARF is 19 per 100,000.

In the United States and other developed countries, the incidence of ARF is much lower at 2 to 14 cases per 100,000; this is probably due to improved hygienic standards and routine use of antibiotics for acute pharyngitis.

A Study of 42 children with ARF admitted to HUSM between 1985 to 1989

Shows RF is seosonal low in MAY and AUGUSTAccording to the study, prevelance of 1.9-2.7 per 1000 students in Kelantam n Southern Thailand was diagnosed RF but only 0.002% admit to hospital.6

We can see that there is no single diagnostic tool or lab test exist. RF is dianosed basically by clinical criteria.Pericardial effusion only show clinically 7.1%(not clinically obvious),but echocardiography shows 68.6%.9

Low socioeconomic status: -poverty -malnutrition

Environment: -overcrowding -poor housing

Poor access to health care

Host genetic susceptibilty (only 3% develop RF)

Virulence of infecting organism

RISK FACTORS

Acute RF is a post infectious hypersensitivity reaction induced by host autoantibodies in response to group A Streptococcal infection.

GAS is a gram-positive, extracellular bacterial pathogen that typically colonizes the throat or skin. Rheumatogenic GAS strains are often encapsulated mucoid strains, rich in M proteins, and resistant to phagocytosis.

PATHOGENESIS

M proteins induce host autoantibodies production that cross react with glycoprotein antigen in heart, joints, and other tissues.

Molecular mimicry is the basis for the autoimmune response that leads to RF.Epitopes present in the streptococcal M protein are immunologically similar to molecules in cardiac myosin and other alpha-helical coiled coil molecules, such as tropomyosin, keratin and laminin.

These antigens induced production cytotoxic T- cells and antibodies which cross react with host tissues.

This explains the 2 to 3 week delay in symptom onset after the original infection, and the absence of streptococci in the lesions.

The chronic sequelae results from progressive fibrosis due to healing of the acute inflammatory lesions.

Genetic susceptibility is likely to influence the development of the pathogenic antibodies, as only a small minority of infected patients ever experience Rheumatic Fever( 3%).

An increase in class-II HLA antigens DR2 and DR4 has been found in black and white patients, respectively. Evidence suggests that elevated immune-complex levels in blood samples from patients with ARF are associated with HLA-B5.

16

Cross reaction with host tissue(autoimmune response)

Cardiac tissue

Joint

Brain

Skin

CLINICAL PRESENTATIONS

A latent period of ~3 weeks (15 weeks) between the precipitating group A streptococcal infection and the appearance of the clinical features of acute rheumatic fever

Symptoms (which result from inflammation in the heart, joints, skin or central nervous system) may include: FeverCardiac problems (may not have symptoms, or may result in shortness of breath and chest pain) Joint pain, joint swelling, redness or warmth Small, painless nodules beneath the skin Flat or slightly raised, painless rash with a ragged edgeEmotional instability, muscle weakness and quick, uncoordinated jerky movements that mainly affect the face, feet, and hands

Other clinical manifestations: Abdominal pain Nosebleeds

1. Heart involvement

The endocardium, pericardium, or myocardium may be affected pancarditis

Carditis is present in 50-60% of cases

Carditis is the most serious complicationof rheumatic fever

Carditis is most commonly revealed by a new or changed murmur and tachycardia that is out of proportion to the fever

a) Endocarditis

The mitral valve is almost always affected, sometimes together with the aortic valve

Isolated aortic valve involvement is rare

Fibrinoid necrosis and vegetations along the lines of closure of the heart valves

Early valvular damage leads to regurgitation murmur

Valvular regurgitation causes irregular endocardial thickening called MacCallum plaques

Recurrent episodes cause leaflet thickening, scarring, calcification, and valvular stenosis may develop Chronic rheumatic heart disease

Vegetations on the heart valve

b) Pericarditis

Fibrinous or serofibrinous pericardial exudate described as "bread-and-butter"pericarditis

Most commonly causes a friction rub or a small effusion on echocardiography

Occasionally cause pleuritic chest pain

Usually resolves without sequelae

Bread-and-butter pericarditis

c) Myocarditis

Myocardial inflammation may affect electrical conduction pathways, leading to P-R interval prolongation (first-degree AV block)

Prolonged P-R interval (>0.2ms) (>5 small squares)

Aschoff bodiesMicroscopic appearance of Aschoff body in myocardium of acute rheumatic carditisPathological Lesion

Aschoff bodies

Foci of fibrinoid necrosis

Scattered within the interstitium perivascularly

Surrounded primarily by T lymphocytes and occasionally plasma cell

Anitschkow cells - pathognomonic - macrophages - abundant amphophilic cytoplasm - round to ovoid nucleus with central slender wavy chromatin (Caterpillar cells) - Aschoff giant cells

2. Joint involvement

Polyarthritis is the most common symptom and is frequently the earliest manifestation of acute rheumatic fever (60-75%)

Inflammation, with hot, swollen, red and/or tender joints and involvement of more than one joint

The typical arthritis is migratory, moving from one joint to another over a period of hours

Almost always affects the large jointsmost commonly the knees, ankles, hips, and elbowsand is asymmetric

The pain is severe and usually disabling until anti-inflammatory medication is commenced

3. Chorea

Sydenham's chorea (St Vitus dance) commonly occurs in the absence of other manifestations, follows a prolonged latent period (1-6 months) after group A streptococcal infection

Found mainly in females

Definite sign of rheumatic fever (in the absence of a family history of Huntington chorea or findings consistent with SLE)

The choreiform movements affect particularly the head and the upper limbs

Eventually resolves completely, usually within 6 weeks

Antibody produced towards streptococcal cross reacts with basal ganglia (subthalamic & caudate nuclei)

4. Skin manifestations

Erythema marginatum

Begins as 1-cm to 3-cm diameter, pink-to-red nonpruritic macules or papules

Located on the trunk and proximal limbs but never on the face

The lesions spread outward to form a serpiginous ring with erythematous raised margins and central clearing

The rash may fade and reappear within hours and is exacerbated by heat

Occurs in 5-13% of patients with acute rheumatic fever

Erythema marginatum in acute rheumatic fever

ii) Subcutaneous nodule

An infrequent manifestation of rheumatic fever (0-8%)

Painless, small (0.52 cm), mobile lumps beneath the skin

Nodules appear over the extensor surfaces overlying bony prominences (particularly of the hands, feet, elbows, occiput, and occasionally the vertebrae)

Appearing 23 weeks after the onset of disease, last for just a few days up to 3 weeks

Commonly associated with severe rheumatic carditis

Subcutaneous nodules in acute rheumatic fever

More than 50% of all patients with ARF will developrheumatic heart disease, predominantly affecting the mitral (70%), aortic (40%), tricuspid (10%), and pulmonary (2%) valves. Incompetent lesions develop during attack and stenoses years later.

Acute attack last an average of 3 months

75% of cases, the acute attack lasts only 6 weeks.

90% of cases resolve in 12 weeks or less.

Fewer than 5% of patients have symptoms that persist for 6 months or more.

PROGNOSIS

DIAGNOSIS- REVISED JONES CRITERIASA criteria (proposed by T.D. Jones in 1944 andmodified in 1965) used to make the diagnosis of rheumatic fever.

Major CriteriaCardiac manifestation:

Carditis

All layers of cardiac tissue are affected (pericardium, epicardium, myocardium, endocardium)

Evidenced by cardiomegaly, cardiac failure, pericarditis, tachycardia, significant murmur(mitral regurgitation/mitral stenosis/aortic regurgitation)

Non- cardiac manifestation:

ii. Polyarthritisiii. Syndenhams Choreaiv. Erythema marginatumv. Subcutaneous nodules

Major Criteria

Minor Criteriai. Feverii. Arthralgiaiii. Previous rheumatic feveriv. Raised ESR/C-reactive proteinv. Leukocytosisvi. Prolonged PR interval

Supporting evidence of a preceding streptococcal infection within the last 45 daysi. Positive throat swab for group A streptococciii. Elevated Antistrepsolysin O Titre (ASOT>250U)iii. Elevated streptococcal antibodiesiv. Prolonged PR interval v. Positive rapid antigen test for group A streptococciiv. History of recent scarlet fever

2002-2003 WHO criteria for the diagnosis of RF & RHD (based on the revised Jones criteria)The disease presents with sudden onset of fever, joint pain, malaise and loss of appetite.

Diagnosis relies on the presence of: 2 or more major criteria or 1 major criteria plus 2 or more minor criteria.

Diagnostic categoriesCriteriaPrimary episode of RFTwo major or one major and two minor manifestation plus evidence of a preceding group A streptococcal infection.Recurrent attack of RF in a patient without established rheumatic heart diseaseTwo major or one major and two minor manifestation plus evidence of a preceding group A streptococcal infection.Recurrent attack of RF in a patient with established rheumatic heart diseaseTwo minor manifestation plus evidence of a preceding group A streptococcal infection.Rheumatic chorea.Insidious onset rheumatic carditisOther major manifestation or evidence of group A streptococcal infection not required Chronic valve lesions of RHD (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.

Blood Investigations: Throat culture confirmation of group A streptococcal infection.

Antibody titer test Antistreptolysin O titer (ASOT). Elevated titer is an evidence of previous streptococcal infection. Usually more elevated in pharyngeal infection than skin infection. Antistreptococcal DNAse B (ADB) test. Elevated regardless of the site of infection.

Non specific indicators of inflammation Erythrocyte sedimentation rate (ESR) and C Reactive protein (CRP) usually elevated and serve as minor manifestation of Jones Criteria. INVESTIGATIONS

Imaging Studies:

Chest radiograph - can reveal cardiomegaly in patient with carditis.

Echocardiogram - may demonstrate valvular regurgitation lesion.

Other test:

Electrocardiography prolong PR interval, count as minor manifestation in Jones Criteria.

MANAGEMENT

Can be divided into 4 approaches :

General treatment of the acute episodeTreatment of the group A streptococcal infectionCardiac managementPenicillin prophylaxis

General treatment of the acute episode

Bed restIs mandatory for all patient and it is important especially in those with carditis Until clinical syndrome has subsided (eg: no pyrexia, normal pulse rate, normal ESR, normal white cell count) and the duration may be up to 6 months in patient with severe carditis

Anti-inflammatory agentsAre used to control the arthritis, fever, and other acute symptomsSalicylates are the preferred agentsSteroids are also effective but should probably be reserved for patients in whom salicylates failNone of these anti-inflammatory agents has been shown to reduce the risk of subsequent rheumatic heart disease

Haloperidol or diazepam to treat chorea

2. Treatment of the group A streptococcal infection

Benzylpenicillin 0.6-1.2g IM stat then penicillin V 250mg/6h PO

For patients who are allergic to penicillin, administer erythromycin or a first-generation cephalosporin

3. Cardiac management

Bed rest or decreased physical activity is recommended until evidence of carditis has subsided

Corticosteroids may be given to minimize heart damage along with high-dose aspirin therapy

Carditis resulting in heart failure is treated with diuretics (to enhance urine output)or digoxin (to enhance pumping ability of the heart) according to the patient condition.

4. Penicillin prophylaxis

Is required to prevent additional streptococcal infections and is the critical step in management of ARF

Patients with a history of rheumatic fever are at a high risk of recurrent ARF, which may further the cardiac damage.IM benzathin penicillin monthly OR oral penicillin V 250mg bdDuration with carditis and valvular disease lifelong - without carditis until 21 years old or 5 years after the last episode

Thank You