Acute rheumatic fever

Index

1. Definition

2. Prevalance

3. Causes

4. Pathology

5. Clinical manifestation

6. Diagnosis

7. Differential diagnosis

8. Clinical course

9. Management

10. Prognosis

11. Prevention

DEFINITION

1. Rheumatic fever is the leading cause of acquired heart disease in children worldwide.

2. Initiated by a pharyngeal infection with group A beta-hemolytic streptococci (GAS)

3. latent period of approximately 2 to 3 weeks,

4. characterized by acute inflammation of the heart, joints, skin, subcutaneous tissue, and

central nervous system.

5. Pathologically, the inflammatory process causes damage to collagen fibrils and

connective tissue ground substance (i.e., fibrinoid degeneration),

6. connective tissue or collagen vascular disease.

Disease burden

1. incidence varies by socioeconomic development

2. annual incidence ranges between 8 and 51/1,00,000 among children and young people

3. Incidence remains high in the South Pacific, Australia and New Zealand

4. Not known in large parts of Africa and Asia because of the absence of regional data

True incidence of ARF

1. Needs systematic and active surveillance of children and young people in the community

2. Active disease specific surveillance is costly

3. SUBCLINICAL RHD detected by ECHO -> intermediate stage before development of

clinical disease

4. Also correlates with ARF incidence

5. Less costly, more feasible, repeatable, can be used as screening for locally representative

data and for targeted implementation of preventive programmes

Nomenclature of cardiac involvement in acute rheumatic fever and RHD 1. SUBCLINICAL CARDITIS - e/o valvular involvement by ECHO within 12 weeks of

onset of symptoms of ARF

2. SUBCLINICAL RHD - Rheumatic valvular HD detected on ECHO screening of

asymptomatic population

3. MISSED CLINICAL RHD – moderate and severe lesions detected incidentally but

evident on clinical examination

4. CLINICAL RHD – when symptomatic patients seek medical care.

Cause

1. Attributes of GABHS

2. GABHS M serotypes 1,3,5,6,14,18,19,24,27,29

a. Not associated with M 2,4,28

3. Only throat infection/ pharyngitis

4. Strains rich in M protein induce marked immune response and probably share

epitopes with human tissue

5. Recently, mucoid producing strains were found to be more rheumatogenic

Group A Streptococci: Cell wall Components of Clinical Interest

1. Capsule: Hyaluronic Acid: Non antigenic

2. Cell Wall:

I. Surface Protein:

i. M protein: Type Specific Antigen: Virulence factor

II. Group A carbohydrate: N acetyl glucosamine+ Rhamnose: Group specific

antigen: Lancefield classification

3. Mucopeptides: common to many bacteriae

I. N Acetyl glucosamine

II. N Acetyl muramic acid

PATHOGENESIS

• Incompletely understood

• An autoimmune response to pharyngeal infection with GAS in genetically predisposed

individuals, mediated through molecular mimicry

Conjunctivitis

Coryza

Hoarseness,

cough

Diarrhoea

Characteristic exanthems

Sudden onset

sore throat

Pain on swallowing

Fever

Tonsillo

Pharyngeal

exudates

Soft palate

petechiae

Red swollen

Uvula

Tender anterior

cervical nodes

• The theory of molecular mimicry holds that GAS pharyngitis triggers an

autoimmune response to epitopes in the organism that cross-react with similar

epitopes in the heart, brain, joints and skin, and repeated episodes of rheumatic

fever lead to RHD

• Inflammation leads to neovascularisation and healing by fibrosis, causing characteristic

valve lesions of RHD.

• Antibodies against GAS N-acetyl-beta-D-glucosamine cross react with neuronal cells in

basal ganglia causing excess release of dopamine -> chorea

• Accumulation of immune complexes cause transient, migratory joint manifestations

PATHOLOGY OF HUMAN TISSUE INVOLVEMENT

Skin, synovium, brain:

1. Inflammation is self limiting and heal without residua

2. Edema, inflammation and infiltration with predominant lymphocytes, few

neutrophils.

3. Perivascular inflammatory lesions

4. Subcutaneous nodules have central fibrinoid necrosis surrounded by inflammatory

reaction

CARDIAC INVOLVEMENT

1. The histopathologic findings in myocardium include the “pathognomonic” Aschoff

nodule

a. -found in the subendocardial or perivascular regions in the myocardium.

2. Little histopathologic damage to the myocardium, even in patients with florid clinical

carditis and heart failure.

3. Myocyte necrosis is uncommon, and the cellular infiltrate is confined to the interstitium.

4. This correlates with the lack of troponin leaks even in patients with frank rheumatic

myocarditis.

5. Progresses from exudative phase to fibrotic phase over 6 months

6. no marker is useful for active carditis

RISK FACTORS

1. People between 5 – 14 years

2. Incidence highest among children 10-14 years f/b 5-9 years

3. Poverty and social disadvantage- strongest predisposing factors

(OVERCROWDING)

4. Males = females (ARF) , Females > males (RHD)

5. Virulence of the strain and host susceptibility-important determinants

DIAGNOSIS OF ARF

1. MAJOR CRITERIA

2. MINOR CRITERIA

3. ESSENTIAL CRITERIA (e/o preceding GABHS infection)

Initial RF: 2 major / 1major + 2 minor

Recurrent RF: 2 Major/ 1 major + 2 minor / 3 minor

DIAGNOSIS

1. No single lab test or clinical feature is diagnostic

2. Most present with combination of FEVER, JOINT manifestations, and CARDIAC

involvement

3. Original JONES CRITERIA revised – to improve specificity

I. Risk stratification based on disease endemicity

II. Different implications of joint manifestations for different population

III. Acceptance of ECHO e/o carditis (SUBCLINICAL carditis)

IV. Diagnosing recurrent ARF

Essential criteria NOT required if:

• Chorea – Late presentation

• Indolent carditis – Late recognition

Risk stratification

• LOW RISK population

– Prevalence: ARF ≤ 2/100,000 school children.

- RHD < 1/1000 (all ages)

• Non-low risk: Considered as HIGH/MODERATE risk

• High sensitivity and High specificity

POSSIBLE” ARF

1. Clinical presentation may not fulfill the updated Jones criteria, but the clinician may still

have good reason to suspect ARF

2. High-incidence settings à use clinical judgement

3. AHA 2015 Guideline: “…. genuine uncertainty, it is reasonable to consider offering 12

months of secondary prophylaxis followed by reevaluation … include…. history and

physical examination in addition to a repeat echocardiogram.”

A retrospective study in North Queensland, Australia, investigated the impact of the

addition of subclinical carditis, monoarthritis, and low-grade fever (>37.5°C) to the 1992

revised Jones criteria

1. Of the 98 cases with a clinical diagnosis of ARF, only 71.4% met the revised Jones

criteria.

2. Modification of the criteria, as discussed above, increased the proportion of the cases

that satisfied diagnostic criteria to 91.8%.

3. Of the 28 people who did not meet the traditional Jones criteria, 12 (42%) developed

evidence of chronic RHD.

4. Addition of monoarthritis and subclinical carditis as major manifestations and low-grade

fever as a minor manifestation to the Jones criteria could increase sensitivity when

applied specifically to high-risk populations.

Carditis

1. major criteria

2. Most serious manifestation of ARF

3. May lead to RHD and complications like AF, Stroke, IE, CHF and death

4. 90-92% in <3years, 50% in 3-6, 32% in 14-17 and 15% in adults

5. Signs and symptoms depend upon involvement of pericardium, myocardium and heart

valves

6. Occurs in first 2 weeks of ARF

7. PAN-Carditis:

• Endocardium

• Myocardium

• Epicardium

8. Frequency:

• 60-90%

• Method of eval – clinical/echo doppler

• First attack - recurrent

9. Clinical Carditis

10. Subclinical Carditis (Echo Carditis)

11. Indolent Carditis

12. Recurrent Carditis

13. Symptoms

14. Tachycardia – out of proportion to fever

• 10C à 10bpm

15. Auscultation – Regurgitation murmurs

MR/TR/AR

• Echo-doppler: sub-clinical (echo carditis)

• 92 – 95% : MV involvement

• 70 – 75% : Isolated MV

• 20 – 25% : Aortic valve involvement (along with MV)

• 5 – 8 % : Isolated AV

• Involvement of TV : Rare (<10%)

• Always along with MV

• Involvement of all cardiac valves

• Reported, but extremely rare

• Severity of carditis – clinical:

• Cardiac murmurs

• Cardiomegaly

• CHF

• Pericardial rub

• Diagnostic/Therapeutic relevance

• Long term prognosis on valvular status & CRHD

CARDITIS THROUGH THE YEARS

2015 AHA Update to Jones Criteria for diagnosis of RF. Circ 2015

INDOLENT CARDITIS

• Evidence of Carditis:

» Insidious onset

» Slow progression (less aggressive)

» Milder forms (asymptomatic/Mild symptoms)

» Active inflammation

– Not recognised/late recognition during routine check-up for incidental illness

– Essential criteria NOT required – Late presentation

RECURRENT CARDITIS

• Established CRHD

• Recurrence of ARF – Carditis

– Onset of new cardiac murmur

– Pericarditis

– Onset of heart failure (worsening of valvular lesion)

• Signs of inflammation +

• Essential criteria is mandatory

• r/o SBE

ARF- PERCARDITIS

• 6 – 15% ARF

• Clinical diagnosis – symptoms

• Always associated with valvulitis – MR/AR

• Effusion – infrequent

• Tampondae – rare

• Indicates severe carditis

– Regression of valve disease less likely

ARF MYOCARDITIS

• No Evidence of myocarditis

– Cardiac biomarkers

– Systolic function – Echo

– Cardiac biopsy: No e/o cellular necrosis

– CE – due to severe valvular regurgitation, not due to myocarditis – surgical

correction of MR – reversal of CE

What do we do when abnormal Echo Doppler findings are picked up during screening/

health survey/ Epidemiological study: Guide lines

• Definite RHD

• Borderline RHD

• WHY : In endemic areas, even in absence of past ARF, echo features of RHD call for

secondary prophylaxis against rheumatic fever, as prevention of repeated attacks of ARF

can protect the individual from severe / continuing valve damage and is cost effective

Migratory Polyarthritis

• Earliest manifestation

• Sequential involvement of joint with inflammation resolving in one and beginning in

other

• May be additive

• If not treated, may involve 6-16 joints

• If persists for >4weeks, consider other diagnosis

• Co-relate with peak ASO titre

• 75% patient larger joint ( knee,ankle,wrist,elbow)

• Responds promptly to low dose of salicylates

• Joints are never deforming (exception- JACCOUD’s arthritis)

• Inverse relationship b/w severity of arthritis and cardiac involvement

JACCOUD’s arthritis or Arthropathy

• Chronic post rheumatic fever arthropathy

• After repeated attacks of ARF, recurrent inflammation of fibrous articular capsule

• Ulnar deviation of fourth and fifth fingers, flexion of MCP, hyper extension of PIP

• Correctable

• No true erosions on radiography

• RA factor negative

Differential Diagnosis:

• Post streptococcal reactive arthritis

• Septic arthritis

• Infective Endocarditis

• Lyme’s disease

• Leukaemia/lymphoma

• Viral arthropathy

• Sickle cell disease

Chorea

• 10-15% patient

• More common in females, even more after puberty

• Latent period is longer ( GAS infection to chorea) 6-8 weeks

• Involuntary, purposeless, jerky movements of hands, arms, shoulders, feet, legs, face and

trunk a/w hypotonia and weakness

• Interferes with voluntary activity and disappears during sleep

• May be unilateral (hemichorea)

Evaluation of chorea – MOTOR IMPERSISTENCE

• Demonstration of milkmaid grip- repetitive, irregular squeezes

• Spooning & pronation of hands

• Wormian darting movement of tongue upon pronation- involuntarily, intermittently

withdrawing the tongue when attempted to protrude for 30 seconds (JACK-IN-BOX)

• Emotional lability – inappropriate behaviour, personality changes, restlessness, outbursts

of laughter and crying

• May last for 1week to 2 years but usually 8-15 weeks

• When only manifestation – CRP, ESR, Ab titres are normal

• D/D – involuntary jerks of Tourette’s syndrome, PANDAS

Erythema marginatum

• Rare , only in 1% of patient

• Characteristics rash of ARF

• Evanascent, pink, extends centrifugally whole centre returns to normal, serpiginous

border

• Non pruritic

• Mainly on the trunk& extremities , not on face

• May become prominent after hot shower

Sub cutaneous nodules

• < 1 % of patient

• Along the extensor surface of tendon near bony prominence

• With prolonged active carditis rather than acute stages of ARF

• Firm, painless, app. 1cm, freely movable over subcutaneous tissue

• May persist for weeks

• Multiple crops are related to severity

Supporting evidence of antecedent group A streptococcal infection

• Positive throat culture or rapid streptococcal antigen test

• Elevated or increasing streptococcal antibody titre

Treatment

• Bed rest

• Monitoring for evidence of carditis

• ANTIBIOTIC THERAPY :

1. 10 days of oral penicillin or amoxicillin

2. Single intramuscular injection of benzathine

If allergic to penicillin give erythromycin( 10), azithromycin (5)

• Without secondary prophylaxis, recurrence is maximum in first five years and minimal beyond

15 years.

– < 5 years : 20%

– 5 – 10 years : 10%

– 10 – 15 years : 5%

– > 15 years : 2%

• Duration of secondary prophylaxis depends on:

– Presence of carditis during initial attack of RF

– Age of patient – infrequent > 45 yrs

– Severity of valve disease

– Duration after last episode of RF

RECURRENCE DESPITE PROPHYLAXIS

ANTI-INFLAMMATORY THERAPY

• Patient with typical migratory polyarthritis & carditis without cardiomegaly or CHF

• Aspirin 50-70mg/kg/day in 4 divided dose for 3-5 days

• f/b 50mg/kg/day for 3 week then half dose for another 2-4 week

• Patient with carditis & more than minimal cardiomegaly & or CHF

• Prednisone -2mg/kg/day in QID foe 2-3 wks f/b half dose for 2-3 wks

• Then tapering dose by 5mg/24hour every 2-3 days and along with this aspirin should be

started to prevent rebound inflammation

Sydenham chorea

• It occurs as isolated manifestation after acute phase

• Sedatives may be given

• Phenobarbitol is DOC

• Haloperidol or chlorpromazine

Complication

• Arthritis and chorea resolve completely without sequelae

Prevention

• Primary prevention : Prevention of initial attack, appropriate antibiotics should be given

before 9th day of symptoms of acute GAS pharyngitis.

• Secondary prevention- Prevention of acute GAS pharyngitis in patients at substantial

risk of ARF

Anti Streptococcal Vaccines

For mass primary prophylaxis against GABHS

• Target Antigen: M-Protein

• Type specific: N-Terminal region

• Protects against specific serotype

• Devoid of homology with human myocardial tissue

• Need polyvalent vaccine to cover all possible serological groups

• Carboxy terminal region( highly conserved): Protects against multiple serological groups

• Cross reaction with human tissue uncertain

Vaccine using Non M protein moieties

• Streptococcal C5a peptidase( similar antigen in several serotypes)

• Low risk of cross reactivity with human tissue

• Protects against several M serotypes

• Streptococcal extra cellular protease vaccine using strep. Pyrogenic exotoxin