Prevalence & incidence of ARF Prevalence & incidence of ARF & chronic RHD in india& chronic RHD in india

Dr Virbhan Balai

Acute Rheumatic FeverAcute Rheumatic FeverAn entirely preventable disease

The theory of molecular mimicryThe theory of molecular mimicry

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

Cunningham MW: Streptococcus and rheumatic fever. Curr Opin Rheumatol 24:408, 2012.

French physician Ernst-Charles Lasègue - 1884French physician Ernst-Charles Lasègue - 1884

“Pathologists have long known that rheumatic fever licks at the joints, but bites at the heart.”

Epidemiology Epidemiology Triad Triad 1. Agent: virulence

2. Host: Genetic susceptibility[3-5%]

3. Environment: Challenged socioeconomic

Hot spot

Kyrgyzstan Highest incidence of RF/RHD 543/100,000 population per year

(Modified from Parry E, Godfrey R, Mabey D, Gill G (Modified from Parry E, Godfrey R, Mabey D, Gill G [eds]: Principles of Medicine in Africa. 3rd ed. [eds]: Principles of Medicine in Africa. 3rd ed. Cambridge, Cambridge University Press, 2004, p Cambridge, Cambridge University Press, 2004, p 861.) 861.)

4 patterns RF in 150 years.◦ A- Preantibiotic fall in the

incidence of ARF of industrialized countries

◦ B-Persistent high incidence RF [Africa and south Asia].

◦C-Postantibiotic fall in the incidence of rheumatic fever in countries that instituted comprehensive programs for primary and secondary prevention of rheumatic fever, such as Cuba, Costa Rica, Martinique, and Guadeloupe.

◦D-Fall and rise in the incidence of rheumatic fever in the formerly Soviet Republics of Central Asia.

Agent Agent Group A beta-haemolytic

streptococcusA poisonous “GAS”

PathogenesisPathogenesis

2 Hit hypothesis2 Hit hypothesis

Hit -1:cross reaction Hit-2:T lymphocyte invasion

Epitopes on the cell wall of Streptococcus forms cross reacting antibodies to host antigens

The antigen and antibody complex at the target site invites T lymphocytes to come out of vessel and stimulates local epitheloid cell to become Anitkoff’s cell around the central Fibrinoid degeneration forming together called “Aschoff- Geipel bodies”

Targets of molecular Targets of molecular mimicrymimicry

Intracellular Extracellular

Cardiac myosinBrain tubulin

Laminin on the endothelial surface of the valve

Lysoganglioside and dopamine receptors in the brain

Susceptibility of hostSusceptibility of host 3-6% without primary

Rx X5 time if family Hx

positive Poor fellow No hygiene Lives in tight pack X6 time in monozygotic X3 times in children if

one parent + The heritability of

rheumatic fever is 60%

Family history is must in Rheumatic heart disease

PhotomicrographPhotomicrograph Aschoff nodule of acute

rheumatic fever. The nodule is composed of Anitschkow cells; these have clear nuclei with a central bar of chromatin, said to resemble a caterpillar. There is a central area of fibrin. This central necrosis is further surrounded by a mononuclear cell infiltrate. Myocardial fibres adjacent to the Aschoff body are undergoing Fibrinoid necrosis. (Sebire NJ, Ashworth M, Malone M, Jacques TS [eds]: Diagnostic Pediatric Surgical Pathology. Churchill Livingstone, United Kingdom, 2010.)

Potential barrier to Rx Potential barrier to Rx RF/RHDRF/RHDStreptococcal

pharyngitis- 2 to 3 Wk-no lab test + except throat culture

Rheumatic fever◦ 30% -asymptomatic

GAS pharyngitis ◦ 50% -asymptomatic

GAS pharyngitis in epidemic time

◦ Age :4-15 yrs◦ Juvenile(3-5 yrs) -India

Think of vaccine

ArthritisArthritisAlmost 100%Severe in young adults than in

teenagers (82%) and children (66%)MigratoryA few days to a week 2/3rd -polyarthritis resolves completelyIf joint swelling persists after 4 weeks,

it is necessary to consider other conditions

Poststreptococcal reactive Poststreptococcal reactive arthritisarthritisNot typical of rheumatic feverRecent streptococcal infectionshorter latent period responds less well to NSAID renal manifestationsNo carditisRx 2ndary prophylaxis with

pencillin

CarditisCarditis most serious CRHD Accidental detection with chorea The incidence of carditis during the initial attack of RF

◦ 40%-No echo◦ 91%-with echo

Varies with the age◦ 90% to 92% of children <3 years◦ 50% of children 3 to 6 years of age◦ 32% of teenagers aged 14 to 17 years◦ 15% of adults

Myocarditis in the absence of valvulitis is unlikely to be rheumatic in origin

ContdContdCHF - 5% to 10% during initial

attack and increases with repeated carditis

Transient apical mid-diastolic murmur (Carey-Coombs) may occur in association with the murmur of mitral regurgitation

WHF:Minimum Echocardiographic Criteria WHF:Minimum Echocardiographic Criteria for the Diagnosis of Pathologic Valvular for the Diagnosis of Pathologic Valvular Regurgitation Secondary to Rheumatic Regurgitation Secondary to Rheumatic Carditis Carditis

PATHOLOGIC MITRAL REGURGITATION (ALL FOUR DOPPLER CRITERIA MUST BE

MET)

PATHOLOGIC AORTIC REGURGITATION (ALL FOUR DOPPLER CRITERIA MUST BE

MET)

1. Seen on 2 views

1. Seen on 2 views

2. On at least 1 view jet length is ≥2 cm*

2. On at least 1 view jet length is ≥1 cm*

3. Peak velocity ≥3 meters/sec

3. Peak velocity ≥3 meters/sec

4. Pansystolic jet in at least 1 envelope

4. Pandiastolic jet in at least 1 envelope

Sydenham Chorea Sydenham Chorea

may be the only initial manifestationF>Mafter puberty-more6 to 8 weeks from pharyngitisChorea-involuntary, purposeless, jerky

movements of the hands, arms, shoulders, feet, legs, face, and trunk along with hypotonia and weakness,interfere voluntary activity and disappear during sleep

Hemichorea- completely unilateral jack-in-the-box tongue “the milking sign” Emotional lability last for a week to 2 years but

generally persists for 8 to 15 weeksSerological markers may be normal

because of long latency

PANDASPANDASsubgroup of children with tic or

obsessive-compulsive disorders that are triggered by GAS infection with no associated cardiac valve damage

if ever, make a diagnosis of PANDAS and should rather err on the side of diagnosis of rheumatic fever and implement secondary prophylaxis

Subcutaneous NodulesSubcutaneous NodulesDetected over the occiput, elbows,

knees, ankles, and Achilles tendonsOver olecranonFirm, painless, and freely movable

over the subcutaneous tissue. The nodules vary in size from 0.5 to 2 cm

1.5%In crops-carditis

Erythema MarginatumErythema Marginatumless common upper part of the arms or trunk but

not on the face not pathognomonic The rash

Evanescent, pink, and nonpruritic. It extends centrifugally whereas the skin at the center returns to normal—hence the name “erythema marginatum.” It has an irregular serpiginous border. The rash may also become more prominent after a hot shower. Erythema marginatum generally occurs only in patients with carditis and may develop early or later in the course of the disease.

1970-19901970-1990

1991-2011

In India, rheumatic fever is endemic and remains one of the major causes of cardiovascular disease, accounting for nearly 25-45% of the acquired heart disease. ROUTRAY SN2003

PRIMARY ATTACK RATE OF RF FOLLOWING STREPTOCOCCAL PHARYNGITIS ◦EPIDEMICS: 3%◦SPORADIC:0.3%

RF is a delayed autoimmune response to Group A streptococcal pharyngitis, and the clinical manifestation of the response and its severity in an individual is determined by host genetic susceptibility, the virulence of the infecting organism, and a conducive environment

AGENTAGENT Beta-haemolytic streptococci

can be divided into a number of serological groups on the basis of their cell-wall polysaccharide antigen

Serological group A (streptococcus pyogenes) can be further subdivided into more than 130 distinct M types.

The available evidence does not link streptococci in Non-group A types with the pathogenesis of rf and rhd

Group A streptococci are the most common bacterial cause of pharyngitis, with a peak incidence in children 5–15 years of age.

15–20% of sore throats are caused by group A streptococci.

A patient with a true infection is at risk of developing RF and of spreading the organism to close contacts, while this is not thought to be the case with carriers

Positive throat culture rate for Gr A streptococci are around 13.5% in Northern India in sore throat cases.

RHEUMATOGENIC STRAINSRHEUMATOGENIC STRAINSVery rich in M-

proteinHeavily

encapsulatedproduce striking

"mucoid" colonies on blood agar plates

Tropic primarily for the throat

M 1, 3, 5, 6, 18, 19 and 24

The site of infection must be pharyngeal

GAS virulence◦ (Extractable and

heterotypic antigen, the M protein)

◦ Capsule of hyaluronic acid("mucoid" appearance of GAS colonies)

◦ M protein and capsule, are primarily responsible for the striking resistance of virulent strains of GAS to phagocytosis

M protein and antigensM protein and antigens

M proteinM protein The streptococcal M-

protein extends from the surface of the streptococcal cell as an alpha–helical coiled dimer,

Shares structural homology with cardiac myosin and other alpha-helical coiled molecules, such as Tropomyosin, keratin and laminin(lines valve structure and is a target for poly reactive antibody)

Nonsuppurative sequel, such as RF and RHD, are seen only after group A streptococcal infection of the upper respiratory tract. Bramhanathan et al 2006

Exception: skin infection leading to RF described in some aborginal tribes of australia

Chronic streptococcal “carrier” states do not trigger the development of RF.

The role of group A streptococcus infection is complex and repeated infection is necessary to prime the immune response, quantitatively and qualitatively ,before the first episode of ARF occurs

HOST FACTORSAn inherited susceptibility to ARF and RHD is

supported by twin studies that have found a significantly increased concordance in monozygotic twins compared with dizygotic twins.

2 % OF ARF INFECTIONS HAVE BEEN FOUND TO BE FAMILIAL

Padmavathi 1962GAS pharyngitis is primarily a disease of

children 5 to 15 years of age

HOST FACTORSHOST FACTORSARF is a rare disease in the very young;

Only 5% of first episodes arise in children younger than age 5 years and the disease is almost unheard of in those younger than 2 years.

HOST FACTORSHOST FACTORS First episodes of ARF

are most common just before adolescence, wane by the end of the second decade, and are rare in adults older than age 35 years.

Recurrent episodes are especially frequent in adolescence and early adulthood, and occasional cases are seen in people older than age 45 years

HOST FACTORSHOST FACTORS In many populations, ARF and RHD are more

common in females than males◦ ?Innate susceptibility,◦ ? Increased exposure to group a

streptococcus because of greater involvement of women in child rearing,

◦ ?Or reduced access to preventive medical care for girls and women.

In populations exposed to rheumatogenic group A streptococci, the lifetime cumulative incidence of ARF is 3% to 6%.

HOST FACTORSHOST FACTORS

ENVIRONMENT FACTORSENVIRONMENT FACTORS

Direct and indirect results of environmental and health-system determinants onrheumatic fever and rheumatic heart disease

PATHOGENETIC PATHWAY FOR ARF AND RHD

Myosin is not present in cardiac valves, so how can an immune response

against myosin induce valvulitis?

The initial damage to the valve might be due to the presence of laminin,

another alpha-helical coiled-coil molecule present in the valvular

basement membrane and around endothelium, and which is recognised

by T cells

There is also evidence that antibodies to cardiac valve tissues cross-react

with N-acetyl glucosamine in group A carbohydrate.

An exaggerated antibody response to group A carbohydrate was noted in

patients with ARF, and titres remained raised in individuals with residual

mitral valve disease, providing further support for the notion that these

antibodies cause valve damage

THE IMMUNE RESPONSE

Immune complexes may produce nondestructive synovitis of the joints in patients with ARF and nondestructive reactions in the basal ganglia observed in Sydenham's chorea, whereas cell mediated autoimmune cytotoxic reactions may destroy heart valves.

Are spheroidal or fusiform distinct tiny structures or granulomas, 1-2 mm in size, occurring in the interstitium of the heart in RF.

Especially found in the vicinity of small blood vessels in the myocardium and endocardium and occasionally in the pericardium.

Lesions similar to the aschoff nodules may be found in the extracardiac tissues .

CLINICAL FEATURES AND DIAGNOSIS OF STREPTOCOCCAL SORE THROAT

CLINICAL ASPECTS

AROUND 20% OF SORETHROAT CASES

JONES CRITERIA AND ITS JONES CRITERIA AND ITS EVOLUTIONEVOLUTION

Every revision increased the specificity but decreased the sensitivity of the criteria,

2002–2003 WHO criteria for the diagnosis of rheumatic fever and rheumatic heart disease (based on the revised Jones criteria)

These revised WHO criteria facilitate the diagnosis of:

— A primary episode of RF— Recurrent attacks of RF in patients without

RHD— Recurrent attacks of RF in patients with

RHD— Rheumatic chorea— Insidious onset rheumatic carditis— Chronic RHD.

DEFINITIONSRecurrence: A new episode of rheumatic fever following

another GABHS infection; occurring after 8 week following stopping treatment

Rebound: Manifestations of rheumatic fever occurring within 4-6 wk of stopping treatment or while tapering drugs.

Relapse: Worsening of rheumatic fever while under treatment and often with carditis.

Sub clinical carditis: When clinical examination is normal but echocardiogram is abnormal. Around 30 percent of patients having chorea present as subclinical carditis.

Indolent carditis: It is a common entity in our country. Patient presents with persistent features of CHF, murmur and cardiomegaly.

JONES CRITERIAJONES CRITERIA INDIAN CONTEXTINDIAN CONTEXT

ROY PADMAVATHI

66% 55%

75%subside within 6 weeks 90% subside within 12 weeks <5% active after 6 months MORTALITY FROM ARF

◦GROVER: 7%◦SHARMA:1.2%

PROGRESSION TO RHD:India 5-20yrsWest 15-40yrs.

CARDITIS Most important manifestation Most often causes no symptoms of its own

and is most often diagnosed in the course of examination of a patient with arthritis or chorea.

In 93% carditis develops with in 3 months Rare to hear murmur after 6 months after

the onset of ARF

CARDITIS1. SLEEPING HR >

1002. NEW ONSET

MURMURS3. CHF4. CARDIOMEGALY5. PERICARDIAL

RUB6. S3

Incidence ◦ 33 to 55%( India)◦ 40-50% west)

Murmurs manifest in 85%by 2nd or 3 rd week.

In an RHD patient CCF should be suspected as a reccurence of carditis

MyocarditisMyocarditisDue to an acute hemodynamic overload on the

left ventricle from acute/ subacute mitral and/or aortic regurgitation.

Myocarditis (alone) in the absence of valvulitis is unlikely to be of rheumatic origin. It should always be associated with an apical systolic or basal diastolic murmur.

PERICARDITISPERICARDITIS Rheumatic pericarditis is relatively less common

clinically and is present in up to 15% patients. Since pericarditis neither results in tamponade nor

constriction and clears up without leaving a residue, its limited clinical significance lies in the fact that it provides clear cut evidence for the presence of active carditis as well as active RF.

Pericarditis does not occur in the absence of clinical findings indicative of valvulitis.

Simultaneous demonstration of valvular involvement generally considered essential.

CONGESTIVE HEART FAILURELeast common but most serious

manifestation.Occurs in5 to 10% of first attacks

of carditis.More common in children <6yrs

of age.

Malignant rheumatic Malignant rheumatic feverfeverSevere disease with multi valvular

lesions, gross cardiac enlargement, and congestive failure can occur in young patients, and such children show more symptoms of congestive failure than of rheumatic disease.

This severe disease may be due in large measure to a lack of rest during the initial carditis

The wide difference in the reported prevalence of carditisin the first attack could thus be related to clinicallyundiagnosed carditis in the first attack which becomesapparent after recurrences of acute RF

Arthritis and arthralgiaArthritis and arthralgia Most common and least specific 75% of pts with 1st attack of ARF. Occurs early in the course of the disease, as

the presenting complaint Incidence increases with age.(Often the only

major manifestation in adolescents, as well as in adults, where carditis and chorea become less common in older age groups.)

Inflamed joints are characteristically warm, red and swollen, and an aspirated sample of synovial fluid may reveal a high average leukocyte count

Important to differentiate from arthalgia( less specific)

Usually large joint Almost any joint can be affected

Tenderness in rheumatic arthritis may be out of proportion to the objective findings and severe enough to result in excruciating pain on touch.

“MIGRATORY” reflects the sequential involvement of joints, with each completing a cycle of inflammation and resolution, so that some joint inflammation may be resolving while others are beginning.

If untreated as many as 16 joints can be involved and atleast 6 in half of the patients

Resolves spontneously with in 3 weeks without sequelae( except jaccoud’s)

Inverse relation with carditis

Feinstein AR, Sterno EK, Spagnuolo M. The prognosis of acuterheumatic fever. Am Heart J 1964; 68: 817–834

severity Total no number % carditis

1 Red hot/ swollen

179 47 26

2 tender 30 12 403 Joint pains 25 24 964 No joint

symptoms29 29 100

JOCCOUD CHRONIC POSTRHEUMATIC ARTHRITISPeriarticular fibrosis of the

metacarpophalangeal joints. It usually occurs in patients with

severe RHD,but is not associated with evidence of RF

POST STREPTOCOCCAL REACTIVEARTHRITIS (PSRA)• Does not fulfill jones criteria• Latent period is shorter (1 week).• Arthritis is additive rather than migratory• Poor response to salicylates• Arthiritis persists for a mean period of two

months. • Evidence of recent GABS infection isMandatory• 6% develop mitral heart disease. Not associated with other major

manifestations of RF

Migratory arthritisMigratory arthritis RF ,

Gonococcemia Meningococcemia Viral arthritis Systemic lupus erythematosus Acute leukemia Whipple's disease

SYDENHAM’S CHOREAOccurs primarily in childrenRare after the age of 20Occurs primarily in femalesLess commonin postpubertal males.Prevalence of chorea in RF patients

varied from 5–36%

CHOREAConcomitant subclinical carditis

detected by echocardiography appears to be as high as 70%

Chorea is a uniquely delayed manifestation of RF, with a wide range in reported incidence between 5% and 35%, latency of 1 to 7 months, and choreiform manifestations that may last for months and occasionally years

CHOREAThere is a substantial risk of

subsequent RHD in these patients.Neurologic deficits typically resolve

within 2 years, but residual psychiatric disturbances occur in a small but significant number of patients in the subsequent decades

CHOREAA syndrome of pediatric autoimmune

neuropsychiatric disorders associated with streptococcal infections (PANDAS), in a fashion similar to poststreptococcal reactive arthritis, has a temporal relationship to GABHS infection but is not associated with other features of RF

Sub cutaneous nodulesSub cutaneous nodules Firm round painless. 0.5 to 2cms Overlying skin freely mobile Occurs in crops Located over bony prominences Lasting for 1 to 2 weeks Incidence: sanyal et al India: 2.3%combined with

erythema marginatum Subcutaneous nodules are almost always

associated with cardiac involvement and are found more commonly in patients with severe carditis

Subcutaneous nodulesSubcutaneous nodulesThey may also be found over the

scalp, especially theocciput, and the spinous processes of the vertebrae.

The number of nodules varies from one to a few dozen, but usually three or four.

They persist from days to 1–2 weeks to, rarely, more than a month

Erythema marginatumErythema marginatum Erythema marginatum occurs in up

to 15% of RF patients In view of the evanescent nature

may be easily missed. Appear first as a bright pink

macule or papule that spreads outward in a circular or seripiginous pattern.

The lesions are multiple, appearing on the trunk or proximal extremities, rarely on the distal extremities, and never on the face.

They are nonpruritic and nonpainful, blanch under pressure

Erythema marginatum usually occurs early in the course of a rheumatic attack.

It may, however, persist or recur for months or even years, continuing after other manifestations of the disease have subsided, and it is not influenced by anti-inflammatory therapy.

Nodules and erythema marginatum tend to occur together

The latent period between streptococcal infection and onset of RF is shortest in arthritis and erythema marginatum and longest in chorea with carditis and subcutaneous nodules in between.

Atleast 1/3 rd of cases of acute rheumatic fever may present with inapparent streptococcal infections

Arthralgia and fever are termed “minor” clinical manifestations of RF in the jones diagnostic criteria, because they lack diagnostic specificity

Elevated or rising streptococcal antibody titers.

It is recommended that acute serum be collected at the onset of

illness, and that the antibody titer be compared to a convalescent

serum collected 2-4 weeks later, to detect a rise in titer

1. The mitral valve is most often involved 2. Mitral regurgitation is the most common finding on color flow

imaging. 3. Mitral regurgitation in rheumatic carditis is related to

ventricular dilatation and/or restriction of leaflet mobility. 4. Rheumatic carditis does not result in congestive heart failure in

the absence of hemodynamically significant valve lesions. 5. In a quarter of patients with rheumatic carditis, valve nodules

were present that may represent echocardiographic equivalents of rheumatic verrucae

THE ECHOCARDIOGRAPHIC CRITERIA HAD SENSITIVITY OF 81% AND SPECIFICITY OF 93%.

THE EFFICACY OF ECHOCARDIOGRAPHIC CRITERIONS FOR THE DIAGNOSIS OF CARDITIS IN ACUTE RHEUMATIC FEVER .B. VIJAYALAKSHMIA1 C1, RAJAN O. VISHNUPRABHUA1, NARASIMHAN CHITRAA1,

Echocardiographic evidence Echocardiographic evidence of definite RHDof definite RHD ANY OF:

a) A mitral regurgitant jet at least 2 cm from the coaptation point of the valve leaflets, seen in two planes and persisting throughout systole plus thickened mitral valve leaflets and/or elbow or dog leg deformity of the anterior mitral valve leaflet.

b) An aortic regurgitant jet at least 1 cm from the coaptation point of the valve leaflets, seen in two planes plus thickened mitral valve leaflets and/or elbow or dog leg deformity of the anterior mitral valve leaflet.

c) Any significant mitral stenosis (defined as flow acceleration across the mitral valve with a mean pressure gradient greater than 4mmHg

Echocardiographic demonstration of valvular regurgitation is not a prerequisite for the diagnosis of rheumatic carditis and should not be considered a limitation where the facilities are not available.

Currently, data do not allow subclinical valvular regurgitation detected by echocardiography to be included in the Jones criteria, as evidenceof a major manifestation of carditis.

CARDIAC ENZYMESMarkers of myocardial damage in the

form of troponin I, myoglobin and CPK-MB were evaluated in patients with acute rheumatic carditis with and without cardiomegaly or congestive cardiac failure. The markers of myocardial damage remained normal inspite of clinically active carditis.

Gupta M, Kaplan EL,. Serum cardiac troponin I in acute rheumatic fever. Am J Cardiol 2002

NATURAL HISTORY OF MSNATURAL HISTORY OF MS In India, critical MS may be found in children

as young as 6 to 12 years old. ( UP TO 20%) In the asymptomatic or minimally

symptomatic patient, survival is greater than 80% at 10 years,

with 60% of patients having no progression of symptoms.

once significant limiting symptoms occur, there is a dismal 0% to 15% 10-year survival rate

Once there is severe pulmonary hypertension, mean survival drops to less than 3 years.

30 to 40% of patients with MS develop atrial fibrillation (AF).

Atrial fibrillation occurs more commonly in older patients and is associated with a poorer prognosis, with a 10-year survival rate of 25% compared with 46% in patients who remain in sinus rhythm.

The mortality of untreated patients with MS is due to

1.Progressive pulmonary and systemic congestion in 60% to 70%,

2.Systemic embolism in 20% to 30%, 3.Pulmonary embolism in 10%, 4. Infection in 1% to 5%. Serial hemodynamic and Doppler-

echocardiographic studies have reported annual loss of MV area ranging from 0.09 to 0.32 cm2.

Mitral regurgitation can be alone or with other lesions

As high as 70% of MR in initial attack can disappear over a period of time.

If AS is present with MV involvement it is likely to be rheumatic

AORTIC REGURGITATIONAORTIC REGURGITATIONAsymptomatic patients with

normal LV systolic function◦Progression to symptoms &/or LV

dysfn: 6%◦Progression to asymptomatic LV

dysfunction < than 3.5% per yearAsymptomatic patients with LV

dysfunction◦Progression to symptoms: more than

25% per year

ARF AND RHD INDIAN SCENARIO1. SCHOOL HEALTH SURVEYS2. HOSPITAL SURVEYS3. POPULATION DATA4. AUTOPSY SERIES

1970-19901970-1990

1991-2011

ICMR SCHOOL SURVEYSICMR SCHOOL SURVEYS

HOSPITAL BASED SURVEYS AUTHOR YEAR REGION TOTAL CARDIAC

CASES% RF/RHD

KUTUMBAIAH 1932-38 VIZAG 1155 39.5

RAMAN 1935-41 VIZAG 2076 35.6

SANJEEV 1941 MADRAS 616 46.8

VAKIL 1941-45 BOMBAY 1860 24.7

PADMAVATHI 1951-55 DELHI 2360 39.1

BENARJEE 1936-43 CALCUTTA 717 44.6

VAKIL 1946-55 BOMBAY 6825 29.7

MALHOTRA, GUPTA

1949-59 PUNJAB 5378 27.6

SEPAHA ET AL 1952-62 INDORE 61.38 13.5

JOSHI ETAL 1957-62 GUJARAT 1216 35.6

BHARGAVA 1945-1964 RAJASTHAN 3722 33.39

AGARWAL 1966-73 ALLAHABAD 2843 40.6

K S MATHUR 1947-61 AGRA 3309 35.1

Manifestations of RFManifestations of RFAUTHOR YEAR CARDITIS% ARTHRITIS

%ARTHRALGIA%

CHOREA% SC NODULES%

ERYTHEMA MARG%

ROY 1960 46 32 94 4 3 0

PADMAVATHI

1962 30.9 60.1 8.3 1.5 0

MAHAJAN 1972 77.1 33.9 45.7 77 18 0.3

SANYAL ET AL

1974 33.3 66.6 20 1.9 1.9

ARORA 42 30 42 2.6 6 0.2

GROVER 1ST

1988-1991 37.5 75 8.3 4 2

RECCURENCE 41 50 8.3 4 2

PERCENTAGE INCIDENCE OF VALVULAR INVOLVEMENT IN VARIOUS AUTOPSY REPORTS

AUTHOR &YEAR

MITRAL AORTIC MITRAL&AORTIC

MITRAL,AORTIC&TRICUSPID

MITRAL&TRICUSPID

TOTAL CASES

REDDY 1968

67.5 2.5 17.5 10 2.5 40

ROY AND TANDON 1972

22.9 3 31.8 25.1 16.6 66

KINARE1972

35.3 1.8 32.6 22.6 8 150

B N DATTA 37.3 1.5 27 22.6 11 252

Kinare et al Kinare et al RHEUMATIC HEART PATHOLOGY IN THE YOUNG: AUTOPSY SERIES1. 144 autopsy cases below the age of 18 years

were included.

2. Mitral stenosis was present in 80.23% cases. Pure mitral valve incompetence was noted in 12.79%.

3. Tricuspid lesions were minor in most of the cases, only in 7.50% had significant stenosis.

4. Multivalvular disease was noted in 75.69%, 5. Pulmonary vasculature was affected in 75% cases. 6. Calcification of valve was uncommon and was

present in 6% of mitral valve lesions and 2% of aortic valve lesions

Mitral Aortic Tricuspid Pulmonary vasculature

100% 63.89% 54.86% 75%

IMPORTANT FEATURES OF B N DATTA AUTOPSY SERIESMural thrombi: 13%Active pericarditis: 30%Aschoff bodies: 26%Bacterial endocarditis: 9%Organic TV disease: 34.2%When compared to the west:

young age of death and high rate of TV disease.

PADMAVATHIPADMAVATHI

Study Patients ARF RECURRENCE RATE/ PATIENT YEAR

PREVALANCE OF RHD %

UK-US 324 0.026 31.2Wood 156 0.004 NAMiller 47 0 NATompkins 115 0.001 26.1

Thomas 73 0.013 42.5SANYAL 65 0.006 35.4

Sujoy roySujoy roy Clinical and physiopathological findings in 108 patients

with mitral stenosis who were below the age of 20 years. History of at least one attack of rheumatic fever was

obtained in 71 (66%), and of more than one attack in 30(28%) patients.

Chorea and subcutaneous nodules appeared infrequently (3%), and erythema marginatum was conspicuously absent.

High prevalence of congestive heart-failure (45%) Low prevalence of atrial fibrillation (6%) The estimated mitral-valve area was less than 1 sq. Cm.

In most of the patients Isolated mitral stenosis in patients below the age of 20

with rheumatic heart-disease is common in india. Boys are affected oftener than girls

Sujoy roySujoy roy The frequency of atrial fibrillation was found to

increase with each decade, reaching 40% in patients over the age of 40.

Angina(12%) is due to functional impairment of the coronary flow caused by limitation of the cardiac output.

Absence of calcification in the mitral valve and of thrombi could be due to the youth of the patients.

Severe pulmonary hypertension with gross pulmonary vascular obstruction, fairly normal cardiac output

MS IN YOUNG( INDIAN ( INDIAN SCENARIO)SCENARIO) In developing countries, mitral stenosis is

severe enough to require commissurotomy before the age of 20 or even 15 years.

In1408 patients with rheumatic heart disease seen at the G B Pant Hospital, New Delhi, between 1967 and-1973

713 (51 %) had mitral stenosis 140 patients below age 20

<10 10-15 15-204 (2.8%) 55

(39.4%) 81 (57.8%)

ECHOCARDIOGRAPHY 2010 High prevalence of rheumatic heart

disease detected by echo in school children. PANWAR et al

1059 school children aged 6-15 years Careful cardiac auscultation and echo. The prevalence of lesions suggestive

of rheumatic heart disease by echo was 51 per 1,000 

AIIMSAIIMS2008-20102008-2010

BALLABHGARHCLINICAL RHD 0.8/1000

SUBCLINICAL RHD 20/1000

Heart 2011;97:201

2012

MANAGEMENT ASPECTSPRIMARY PREVENTION OF PRIMARY PREVENTION OF ARFARF

Treatment of GAS pharyngitis with a single intramuscular injection of 1.2 million units of benzathine penicillin G is the most reliable way to prevent primary attacks of ARF

Secondary prophylaxisSecondary prophylaxis Defined as the

continuous administration of specific antibiotics to patients with a previous attack of rheumatic fever, or documented RHD

Purpose is to prevent colonization or infection of the upper respiratory tract with group A beta-hemolytic streptococci and the development of recurrent attacks of rheumatic fever

After surgery or intervention secondary prophylaxis should be continued

IMPORTANCE of secondary prophylaxis1. Prevents reccurences2. Reduces new cardiac

damage,3. Facilitate resolution

of previous damage4. Reduces mortality

due to RHD.5. The risk of

reccurence is highest in first year after an index attack of RF

WHO GUIDELINES 2004

WHO GUIDELINES 2004

Because of the high infection rate in India, it has been suggested that penicillin should be given once every 3 rather than 4 weeks to maintain adequate blood levels during reinfection, and this has certainly resulted in a fall in the infection rate.

Secondary prophylaxisSecondary prophylaxis

RECURRENCE ON RECURRENCE ON PROPHYLAXISPROPHYLAXISSanyal 0.6/100 pt yearsPadmavathi 0.1/100 pt yearsWith out prophylaxis recurrence

rate around 11.6/100 pt years

EFFECT OF SECONDARY PROPHYLAXIS ON EFFECT OF SECONDARY PROPHYLAXIS ON RECCURENCE RATESRECCURENCE RATES

CATEGORY BENZATHINE PENICILLIN

ORAL PENICILLIN

SULFONAMIDES

STREPTOCOCCAL INFECTION

6.3 6.2 16

ARF RECCURENCE

0.45 2.6 3.2

VACCINE ??VACCINE ??ORPHAN STATUSFOCUS ON STRAINS IN DEVELOPED WORLDPAUCITY OF CLINICAL TRIALS COST

RHDAustralia (ARF/RHD writing group), National Heart Foundation of RHDAustralia (ARF/RHD writing group), National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand: Australia and the Cardiac Society of Australia and New Zealand: Australian Guideline for Prevention, Diagnosis and Management of Australian Guideline for Prevention, Diagnosis and Management of Acute Rheumatic Fever and Rheumatic Heart Disease. 2nd ed. Darwin, Acute Rheumatic Fever and Rheumatic Heart Disease. 2nd ed. Darwin, Australia, Menzies School of Health Research, 2012Australia, Menzies School of Health Research, 2012 Recommended for All Cases

White blood cell count ESR or CRP Throat swab before giving antibiotics for GAS culture Blood culture if febrile Antistreptococcal serology: both antistreptolysin O and anti-DNase B titers (repeated after 10-14 days if the first test is not confirmatory) Electrocardiogram Chest radiograph Echocardiogram

Tests for Alternative Diagnoses, Depending on Clinical Features

Repeated blood cultures with temperature spikes if infective endocarditis is suspected Joint aspiration for possible septic arthritis (microscopy and culture) Copper, ceruloplasmin, antinuclear antibody, and drug screen for choreiform movements Serology and autoimmune markers for arboviral, autoimmune, or reactive arthritis

Peripheral blood smear for sickle cell disease

Primary prophylaxisPrimary prophylaxisAntiobiotic Route doses

Benzathine benzylpenicillin Single IM injection 1.2 million units; 50% if <30 kg

Phenoxymethylpenicillin

(penicillin VK)

PO for 10 days 250-500 mg tid for 10 days

Erythromycin ethylsuccinatePO for 10 days Varies with the formulation

WHO Technical Report Series No. 923. Rheumatic Fever WHO Technical Report Series No. 923. Rheumatic Fever and Rheumatic Heart Disease: Report of a WHO Expert and Rheumatic Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1 November 2001. Geneva, Panel, Geneva 29 October-1 November 2001. Geneva, WHO, 2004. WHO, 2004.

Medication Route DosesBenzathine benzylpenicillin

Single intramuscular injection every 3-4 weeks

For adults and children ≥30 kg in weight: 1,200,000 units

    For children <30 kg in weight: 600,000 units

Penicillin V Oral 250 mg twice daily

Sulfonamide (e.g., sulfadiazine, sulfadoxine, sulfisoxazole)

Oral For adults and children ≥30 kg in weight: 1 g daily

WHO Technical Report Series No. 923. Rheumatic Fever WHO Technical Report Series No. 923. Rheumatic Fever and Rheumatic Heart Disease: Report of a WHO Expert and Rheumatic Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1 November 2001. Geneva, Panel, Geneva 29 October-1 November 2001. Geneva, WHO, 2004. WHO, 2004. No carditis: 5 years after the last

attack or until 18 years of age (whichever is longer)

Mild carditis (mild mitral regurgitation or healed carditis):10 years after the last attack or at least until 25 years of age (whichever is longer)

Severe valvular disease: Life-long After valve surgery: Life-long

IN INDIA Endemicity of carditis Erythema marginatum almost nonexistent Chorea and subcutaneous nodules infrequent Polyarthralgia >polyarthritis Young >Older Short interval - ARF to RHD Start at Young Rapid progression More PAH/CCF Rheumatic fever in < 50% High incidence of organic tricuspid valve disease

FUTURE PERSPECTIVES FUTURE PERSPECTIVES Overcoming barrier to transmission

◦Socioeconomic/Political/awarenessSpecial task force in highly endemicityIdentification of genetic

susceptibility(3-5%)Primary and 2ndary prophylaxis

reinforcementVery long acting penicillin(>3 months)VaccineUnderstanding molecular genetic

Rx for RFRx for RFPRIMODIAL PRIMARY SECONDARY TERTIARYAWARENESSSOCIOECONOMICPOLITICALVaccine

Rx pharyngitis Penicillin Surgery/PBMV

Socioecomical progress does not mean the extinct of Socioecomical progress does not mean the extinct of naturenature