Rheumatic fever clinical features and diagnosis

RHEUMATIC FEVERRHEUMATIC FEVERClinical features Clinical features

and and diagnosisdiagnosis

DR . SUJIT SAHUDR . SUJIT SAHU

http://http://cardiologysearch.blogspot.in/cardiologysearch.blogspot.in/


INTRODUCTION INTRODUCTION HISTORICAL BACKROUND HISTORICAL BACKROUND EPIDEMIOLOGYEPIDEMIOLOGYPATHOGENESISPATHOGENESISPATHOLOGY PATHOLOGY CLINICAL FEATURESCLINICAL FEATURESDIAGNOSISDIAGNOSIS


INTRODUCTIONINTRODUCTION

Clinical syndrome Clinical syndrome

Acute , non-suppurative inflammatory Acute , non-suppurative inflammatory disease disease

following Group A Beta Hemolytic following Group A Beta Hemolytic Streptococcal sore throatStreptococcal sore throat

Classified as Connective tissue disease or Classified as Connective tissue disease or collagen vascular diseasecollagen vascular disease

affecting the Joints, heart , brain , skin and affecting the Joints, heart , brain , skin and subcutaneous tissuesubcutaneous tissue


HISTORICAL HISTORICAL BACKROUNDBACKROUND

1604 –1604 – Guilleaume (France)Guilleaume (France)

Thomas Syndenham (Eng)Thomas Syndenham (Eng)

--PolyarthritisPolyarthritis1605 -1605 - SydenhamSydenham - - St. Vitus Dance St. Vitus Dance 1761 -1761 - Morgani Morgani (Italy) – (Italy) – Heart valvesHeart valves1813 -1813 - W.C.wells W.C.wells – – Subcutaneous Subcutaneous

NodulesNodules 1818 -1818 - LaennecLaennec - - RHD (clinical)RHD (clinical)


HISTORICAL HISTORICAL BACKROUNDBACKROUND

1886 -1886 - CheadleCheadle - - Full syndromeFull syndrome 1904 -1904 - Aschoff Aschoff - - Aschoff NoduleAschoff Nodule1931 -1931 - Coburn Coburn - - Streptococcal Streptococcal

assocassoc..1944 -1944 - Jones Jones - - Criteria Criteria 1951 -1951 - WannamakerWannamaker (penicillin (penicillin

prophylaxis)prophylaxis)


EPIDEMIOLOGYEPIDEMIOLOGY


IndiaIndiaS PadmavatiS Padmavati

Director, National Heart Institute, New Director, National Heart Institute, New Delhi, IndiaDelhi, India

In 2000, in a school survey involving In 2000, in a school survey involving 3963 children from the district of 3963 children from the district of Kanpur, the prevalence of RHD was Kanpur, the prevalence of RHD was 4.54 per 1000 4.54 per 1000 (Urban 2.56 and Rural (Urban 2.56 and Rural 7.42). 7.42).

The prevalence of RF was 0.75 per The prevalence of RF was 0.75 per 1000 1000 (Rural 1.20, Urban 0.42) (Rural 1.20, Urban 0.42)


EPIDEMIOLOGYEPIDEMIOLOGY2000 - 20042000 - 2004

HOSPITAL BASED SURVEYSHOSPITAL BASED SURVEYS : : Agarwal et al (varanasi) : Decreasing Agarwal et al (varanasi) : Decreasing

(8.4% - RHD & 1.1% RF) (8.4% - RHD & 1.1% RF)

Despande et al (Mumbai): No changeDespande et al (Mumbai): No change

Mishra et al (cuttack) : No changeMishra et al (cuttack) : No change


EPIDEMIOLOGYEPIDEMIOLOGY

PREVELANCE :PREVELANCE :

2 million at present2 million at present

INCIDENCE :INCIDENCE :

50 000 new cases every year 50 000 new cases every year


PATHOGENESISPATHOGENESIS


STRUCTURE OF Group –A STRUCTURE OF Group –A Beta Hemolytic Beta Hemolytic StreptococcusStreptococcus


Group - A StreptococcusGroup - A Streptococcus Two highly conserved epitopes within M Two highly conserved epitopes within M

protein divide GAS protein divide GAS immunologically into immunologically into

Class I (throat) Class II (skin) strains.Class I (throat) Class II (skin) strains. All RF strains fall clearly into Class I throat All RF strains fall clearly into Class I throat

strains strains The site of infection must be pharyngealThe site of infection must be pharyngeal. .

Regardless of how virulent an invasive strain may be, Regardless of how virulent an invasive strain may be, ARF does not result when it is introduced extra-ARF does not result when it is introduced extra-pharyngeally, e.g. through skin lesions or wound pharyngeally, e.g. through skin lesions or wound infections infections


CROSS REACTIVITYCROSS REACTIVITY


CO-PATHOGENSCO-PATHOGENS

Burch et al & Pongpanich et al :Burch et al & Pongpanich et al :

(1970) (1976)(1970) (1976)

Serological evidence of Cox B Serological evidence of Cox B viruses in patients with rheumatic viruses in patients with rheumatic fever fever


GENETIC GENETIC PREDISPOSITIONPREDISPOSITION

Specific B - cell alloantigen Specific B - cell alloantigen HLA DR 3 - Indians HLA DR 3 - Indians Moari races in New Zealand & Moari races in New Zealand &

Samoans in Hawaii Samoans in Hawaii High concordance in twins High concordance in twins Increased risk in families with H/O Increased risk in families with H/O

RFRF


ENVIRONMENTENVIRONMENT Low socio-economic groupLow socio-economic group

Urban slumsUrban slums Poor accesibility to health carePoor accesibility to health care Over crowdingOver crowding Unclean environment Unclean environment

Mostly seen in developing Mostly seen in developing countriescountries


INTERACTIONINTERACTION


PATHOLOGYPATHOLOGY


INFLAMMATORY RESPONSEINFLAMMATORY RESPONSE

Edematous changeEdematous change

Cellular infiltrateCellular infiltrate

Fibrinoid necrosisFibrinoid necrosis

Aschoff body Aschoff body (seen only in heart)(seen only in heart)


Joints : Joints : serositisserositis

PericardiumPericardium

Skin (S/C nodule) : Skin (S/C nodule) : Fibrinoid Fibrinoid

Heart Heart degenerationdegeneration

Erythema Marginatum : Erythema Marginatum : VasculitisVasculitis

Chorea : Chorea : VasculitisVasculitis


GranulomaGranulomaCentral Central

fibrinoid fibrinoid necrosisnecrosis

Surrounded by Surrounded by lymphocytes, lymphocytes, Antischkow Antischkow cells and cells and Plasma cellsPlasma cells

ASCHOFF BODYASCHOFF BODY

Initial edemaInitial edema

Hyaline degenerationHyaline degeneration

Verrucae formation at the edge of leafletsVerrucae formation at the edge of leaflets

Prevents approximation Prevents approximation RegurgitationRegurgitation

Fibrosis & calcification Fibrosis & calcification StenosisStenosis


ORDER OF VALVE ORDER OF VALVE INVOLVEMENTINVOLVEMENT

MitralMitral

AorticAortic

Tricuspid Tricuspid

PulmonaryPulmonary


INTERNATIONAL SERIES BY INTERNATIONAL SERIES BY BONOWBONOW

PURE MS : PURE MS : 25 %25 %

PURE MR : PURE MR : 10 %10 %

MS / MR : MS / MR : 25 %25 %

AORTIC : AORTIC : 8 %8 %

ALL VALVES : ALL VALVES : 7 %7 %


CLINICAL FEATURESCLINICAL FEATURES


PERCENTAGE PERCENTAGE INVLOVEMENTINVLOVEMENT

(Indian Scenario)(Indian Scenario)ARTHRITISARTHRITIS : : 70 %70 %

ARTHALGIAARTHALGIA : : 90 %90 %CARDITISCARDITIS : : 70 %70 %CHOREACHOREA : : 08 %08 %S/C NODULES/C NODULE : : 02 %02 %ERYHTEMA MARGINATUMERYHTEMA MARGINATUM : : 01 % 01 %


LATENCYLATENCY

From onset of sore throat to onset From onset of sore throat to onset of initial attack of rheumatic fever of initial attack of rheumatic fever isis

1 – 5 weeks1 – 5 weeks

for recurrent attacksfor recurrent attacks

Median of 19 days & shorterMedian of 19 days & shorter


LATENCYLATENCY

Joint manifestations are Joint manifestations are firstfirst to occur to occur - heralding onset of disease- heralding onset of disease Carditis occurs within Carditis occurs within 2 weeks2 weeks - is apparent when patient is first seen- is apparent when patient is first seen Subcutaneous nodules appear Subcutaneous nodules appear 4 weeks4 weeks or or

more after onset of symptomsmore after onset of symptoms Chorea may appear Chorea may appear 2 to 6 months2 to 6 months later later

Erythema marginatum occurs both early & Erythema marginatum occurs both early & later later


MODE OF ONSETMODE OF ONSET

VariableVariable Abrupt onsetAbrupt onset with fever & acute polyarthritiswith fever & acute polyarthritis Insidious or sub clinical Insidious or sub clinical in mild indolent carditisin mild indolent carditis May present with CCFMay present with CCF

May present atypically with acute abdomen May present atypically with acute abdomen due to peritoneal inflammationdue to peritoneal inflammation


POLYARTHRITISPOLYARTHRITIS

Most common & Least specificMost common & Least specificsevere in adultssevere in adultsLarge joints ; asymetricalLarge joints ; asymetricalFlitting - Flitting - involves joints after jointsinvolves joints after jointsFleeting - Fleeting - Lasting for short timeLasting for short time3 days - 1 week 3 days - 1 week No residual damage No residual damage


POLYARTHRITISPOLYARTHRITIS

Responds dramatically to aspirinResponds dramatically to aspirin Severity inversely related to carditisSeverity inversely related to carditis

(Feinstein & Spagnuola et al – 1962)(Feinstein & Spagnuola et al – 1962)

JACCOUDS ARTHRITISJACCOUDS ARTHRITIS :: Small joints Small joints Produces residual damage Produces residual damage Seems to be related to RFSeems to be related to RF


PANCARDITISPANCARDITIS More severe in the youngMore severe in the young

Sub clinical to fulminant Sub clinical to fulminant

ENDOCARDITIS :ENDOCARDITIS : ARAR : 20 %: 20 %

MRMR : 75 %: 75 %

: due to - Valvulitis: due to - Valvulitis - MVP (anterior - MVP (anterior

leaflet)leaflet) - Annular - Annular

dysfunctiondysfunction


ENDOCARDITISENDOCARDITIS

Clinical Evidence of Clinical Evidence of Endocaritis :Endocaritis :

Apical holosystolic murmur Apical holosystolic murmur Carey coomb’s murmurCarey coomb’s murmur Early diastolic murmurEarly diastolic murmur


MYOCARDITISMYOCARDITIS

Clinical evidence of Myocarditis :Clinical evidence of Myocarditis :

Cardiomegaly Cardiomegaly

Clinical features of CHFClinical features of CHF

Gallop rhythm Gallop rhythm


PERICARDITISPERICARDITIS

Clinical evidence of Pericarditis :Clinical evidence of Pericarditis :Pericardial rubPericardial rub

Associated with endocarditisAssociated with endocarditis Indicates severe carditisIndicates severe carditis (High rheumatic activity)(High rheumatic activity)

No residual constriction No residual constriction


CHOREA CHOREA

Occurs 3 months later than other RF Occurs 3 months later than other RF features features - spontaneous resolution- spontaneous resolution

Duration : variable Duration : variable ( upto 6 months) ( upto 6 months) Often in prepuberal girlsOften in prepuberal girls Neuropsychiatric disorderNeuropsychiatric disorder Seen in 5 - 15 % casesSeen in 5 - 15 % cases


CHOREACHOREA

ST. VITUS DANCE ST. VITUS DANCE

25 - 30 % develop RHD particularly 25 - 30 % develop RHD particularly MSMS (Bland et al – 20 years follow up)(Bland et al – 20 years follow up)

Multiple purposeless movements of legs Multiple purposeless movements of legs and hands and hands

(also involves face)(also involves face)

on exertion & absent during sleepon exertion & absent during sleep


DD FOR CHOREADD FOR CHOREA

HABITUAL SPASMSHABITUAL SPASMS

WILSONS DISEASEWILSONS DISEASE

POST ENCEPHALITISPOST ENCEPHALITIS

HYSTERESIS HYSTERESIS


SUBCUTANEOUS SUBCUTANEOUS NODULENODULE

FIRM FIRM PAINLESS PAINLESS 0.5 – 3 cm IN SIZE 0.5 – 3 cm IN SIZE IN CROPS ( OVER EXTENSORS)IN CROPS ( OVER EXTENSORS)DISAPPEAR IN 12 WEEKS DISAPPEAR IN 12 WEEKS

ALWAYS ASSOCIATED WITH CARDITISALWAYS ASSOCIATED WITH CARDITIS


SUBCUTANEOUS SUBCUTANEOUS NODULENODULE

ERYTHEMA ERYTHEMA MARGINATUMMARGINATUM

Rare (< 1 %)Rare (< 1 %)

Bikini distributionBikini distribution

EvanescentEvanescent vanishingvanishing

Non pruritic Non pruritic


OTHER MANIFESTATIONSOTHER MANIFESTATIONS

EPISTAXISEPISTAXIS ABDOMINAL PAINABDOMINAL PAIN

- - Occurs in 5% cases Occurs in 5% cases

- Clinical importance - Clinical importance

Often appear hours or days before major Often appear hours or days before major manifestationsmanifestations

Acute abdomen [ appendicitis ] to be excluded Acute abdomen [ appendicitis ] to be excluded


FEVERFEVER

Relatively common But nonspecificRelatively common But nonspecific

Low grade; subside without treatment in 1-Low grade; subside without treatment in 1-2wk2wk

Associated with constitutional symptoms Associated with constitutional symptoms

Lab indices are high even after fever subsidesLab indices are high even after fever subsides Remission does not exclude rheumatic activityRemission does not exclude rheumatic activity


ECG CHANGESECG CHANGES

Seen in 2/5Seen in 2/5thth patients patients

[ Disciascio(1980)][ Disciascio(1980)]

PR interval ; PR interval ;

QT interval ;QT interval ;

AV blocksAV blocks

Does not correlate with organic murmurs, Does not correlate with organic murmurs,

prognosis or residual heart diseaseprognosis or residual heart disease

Nonspecific & occur in many other Nonspecific & occur in many other

infectioninfection


LAB INVESTIGATIONSLAB INVESTIGATIONS

Monitoring the Detecting the Monitoring the Detecting the antecedentantecedent

inflammatory activity infection with inflammatory activity infection with streptococcusstreptococcus

There is no single diagnostic testThere is no single diagnostic test


EVIDENCE OF STREPTOCOCAL EVIDENCE OF STREPTOCOCAL INFECTIONINFECTION

TH ROAT SWAB CULTURETH ROAT SWAB CULTURE : :

Only in Minority of casesOnly in Minority of cases

ASO TITREASO TITRE : : elevated from 7 - 10 days elevated from 7 - 10 days rise and fall rapidlyrise and fall rapidly >240 todd units (adults)>240 todd units (adults) >330 todd units (children)>330 todd units (children) Antibiotics/steroids/liver Antibiotics/steroids/liver

disease affect the titredisease affect the titre


EVIDENCE OF STREPTOCOCAL EVIDENCE OF STREPTOCOCAL INFECTIONINFECTION

ANTI-DNAase B TESTANTI-DNAase B TEST : :

## > 120 todd units (adults)> 120 todd units (adults)

# > 240 todd units (children) # > 240 todd units (children)

# used when ASO titre is not # used when ASO titre is not conclusive conclusive

# remains elevated for long time # remains elevated for long time

STREPTOZYME TESTSTREPTOZYME TEST : :

Detects antibodies against streptococcal Detects antibodies against streptococcal antigen antigen


RHEUMATIC ACTIVITY RHEUMATIC ACTIVITY DETECTIONDETECTION

Activity considered ended only when both Activity considered ended only when both ESR & CRP become normal ESR & CRP become normal

and remain so for 2 weeks after stopping and remain so for 2 weeks after stopping drugsdrugs

Fever & tachycardia subside long before Fever & tachycardia subside long before lab reactants declinelab reactants decline

Joint symptoms & active carditis do not Joint symptoms & active carditis do not occur after ESR & CRP declineoccur after ESR & CRP decline


RHEUMATIC ACTIVITY RHEUMATIC ACTIVITY DETECTIONDETECTION

CRP more specific than ESRCRP more specific than ESR

Usually lasts for 3 monthsUsually lasts for 3 months

Longer in patients with valvular Longer in patients with valvular involvementinvolvement

In 5% cases rheumatic activity persist In 5% cases rheumatic activity persist longer than longer than 6 months6 months

termed CHRONIC RHEUMATIC FEVERtermed CHRONIC RHEUMATIC FEVER


ECHOCARDIOGRAMECHOCARDIOGRAM

Abernathy et al : Abernathy et al :

echo allowed earlier diagnosis of echo allowed earlier diagnosis of carditiscarditis

Veasy et al :Veasy et al :

echo increased the sensitivity of echo increased the sensitivity of detecting carditis from 72% to 91% detecting carditis from 72% to 91%



Differentiates between innocent Differentiates between innocent murmur and Rheumatic MRmurmur and Rheumatic MR

Detects MVP due to Rheumatic feverDetects MVP due to Rheumatic fever

(Wu et al – JACC 1994)(Wu et al – JACC 1994)

- AML- AML

- Elongated chordae- Elongated chordae

- No myxomatous thickening- No myxomatous thickening



Cost effectiveness and the Cost effectiveness and the additional workload have to be additional workload have to be validatedvalidated

Vasan et al (Circ . 1994 ):Vasan et al (Circ . 1994 ): showed showed

no additional detection of carditis no additional detection of carditis by echo than by clinical detection by echo than by clinical detection


OTHER INVESTIGTIONSOTHER INVESTIGTIONS

Endomyocardial biopsyEndomyocardial biopsy – to establish – to establish the myocarditisthe myocarditis

not likely to provide additional not likely to provide additional informationsinformations

Radionuclide imaging- Radionuclide imaging- - - Gallium-67 imaging has better diagnostic Gallium-67 imaging has better diagnostic

characteristics than antimyosin scintigraphycharacteristics than antimyosin scintigraphy

- the results confirm that rheumatic carditis is - the results confirm that rheumatic carditis is infiltrative rather than degenerative in natureinfiltrative rather than degenerative in nature

- not suitable for routine investigation- not suitable for routine investigation


DUCKETT JONES DUCKETT JONES CRITERIACRITERIA

ORIGINAL (JAMA 1944)ORIGINAL (JAMA 1944)

MAJORMAJOR MINOR MINOR

Carditis Carditis erythema mariginatum erythema mariginatum ChoreaChorea fever / epistaxis / fever / epistaxis / ArthralgiaArthralgia abdominal pain abdominal pain S/C NoduleS/C Nodule WBC / ESR / CRP WBC / ESR / CRP Preexisting RFPreexisting RF



MODIFIEDMODIFIED :1956 - AHA :1956 - AHA Arthritis : Included as – major Arthritis : Included as – major

criteriacriteria Erythema marginatum: Included as – major criteriaErythema marginatum: Included as – major criteria

REVISEDREVISED : 1965 /84 - AHA : 1965 /84 - AHA Recent streptococcal infection is included as essential Recent streptococcal infection is included as essential

criteriacriteria

WHO : 1988 WHO : 1988

UPDATEDUPDATED : 1992 - AHA : 1992 - AHA WHO CRITERIA : 2003WHO CRITERIA : 2003



WHO CRITERIA FOR RF AND RHD- 2003WHO CRITERIA FOR RF AND RHD- 2003

MAJORMAJOR MINOR MINOR

CarditisCarditis ClinicalClinical Polyarthritis - FeverPolyarthritis - Fever ChoreaChorea - Arthralgia - Arthralgia S/C NodulesS/C Nodules LaboratoryLaboratory Ery. MarginatumEry. Marginatum - Leucocytosis - Leucocytosis

- Elevated : ESR /CRP- Elevated : ESR /CRP ECGECG - Increased PR - Increased PR

intervalinterval



Supporting evidence of antecedent Supporting evidence of antecedent streptococcal infection Within the streptococcal infection Within the last 45 dayslast 45 days - - positive Throat culture positive Throat culture

- Rapid streptococcal antigen test- Rapid streptococcal antigen test - Elevated or Rising ASO Titer- Elevated or Rising ASO Titer - Recent scarlet fever- Recent scarlet fever


Diagnostic categories: WHO Diagnostic categories: WHO 20032003

PRIMARY RF :PRIMARY RF : 2 major or 1 major and 2 minor + evidence of preceding 2 major or 1 major and 2 minor + evidence of preceding

Gr-A streptococcal infectionGr-A streptococcal infection

RECURRENT ATTACK OF RF WITHOUT RECURRENT ATTACK OF RF WITHOUT ESTABLISHED RHD ESTABLISHED RHD

2 major or 1 major and 2 minor + evidence of preceding 2 major or 1 major and 2 minor + evidence of preceding Gr-A streptococcal infectionGr-A streptococcal infection

RECURRENT ATTACK OF RF WITHRECURRENT ATTACK OF RF WITH ESTABLISHED RHDESTABLISHED RHD 2 minor + evidence of preceding Gr-A streptococcal 2 minor + evidence of preceding Gr-A streptococcal

infectioninfection



Rheumatic chorea Rheumatic chorea Insidious onset rheumatic carditisInsidious onset rheumatic carditis

Other major manifestations or evidence of Other major manifestations or evidence of Group-A streptococcal infection not Group-A streptococcal infection not requiredrequired



Chronic valve lesions of RHDChronic valve lesions of RHD

Patients presenting first time with Patients presenting first time with pure MS or mixed mitral valve pure MS or mixed mitral valve disease and /or aortic valve diseasedisease and /or aortic valve disease

Do not require any other criteria Do not require any other criteria for diagnosis as having RHDfor diagnosis as having RHD



Specificity – 97 %Specificity – 97 %

Sensitivity – 77 %Sensitivity – 77 %


BEYOND JONES CRITERIABEYOND JONES CRITERIA

Not a substitute for clinical judgmentNot a substitute for clinical judgmentNot meant to predict course or Not meant to predict course or

severityseverityUseful for initial diagnosis onlyUseful for initial diagnosis onlyExceptions : Exceptions :

- Chorea- Chorea

- Isolated indolent carditis- Isolated indolent carditis

- Recurrence with RHD- Recurrence with RHD


APPLYING JONES CRITERIAAPPLYING JONES CRITERIA

2 major criteria is stronger than 2 major criteria is stronger than One major and 2 minor One major and 2 minor

Arthalgia cannot be used as minor criteria Arthalgia cannot be used as minor criteria when arthritis is presentwhen arthritis is present

Prolonged PR cannot be used as a minor Prolonged PR cannot be used as a minor criteria when clinical carditis is present criteria when clinical carditis is present


APPLYING JONES CRITERIAAPPLYING JONES CRITERIA

Absence of evidence of an antecedent Absence of evidence of an antecedent Group-A Beta-hemolyticus Streptococci Group-A Beta-hemolyticus Streptococci is a warning that RF is unlikelyis a warning that RF is unlikely

Possibility of early suppression of full Possibility of early suppression of full clinical manifestations by drugs should clinical manifestations by drugs should be sought during history taking be sought during history taking


RECURRENCERECURRENCE

Cardiac status deteriorates with each new Cardiac status deteriorates with each new attackattack

Younger the patient - higher recurrence rateYounger the patient - higher recurrence rate

Recurrence decreases with passage of time – Recurrence decreases with passage of time – . . - - 50% within first year 50% within first year

- only 10% after 5 years- only 10% after 5 years Recurrence more in those with valvular lesionRecurrence more in those with valvular lesion

Increase antibody response associated with Increase antibody response associated with high recurrence ratehigh recurrence rate


RECURRENCERECURRENCE

Clinical manifestations in recurrence Clinical manifestations in recurrence tend to mimic those in preceding attacktend to mimic those in preceding attack

Recurrence distinguished from rebound Recurrence distinguished from rebound or exacerbation if interval of 3 months or exacerbation if interval of 3 months freedom of rheumatic activityfreedom of rheumatic activity

Valve stenosis at diagnosis indicates Valve stenosis at diagnosis indicates recurrencerecurrence


RHEUMATIC FEVERRHEUMATIC FEVER

Licks the Joint and Bites the Heart Licks the Joint and Bites the Heart


http://http://cardiologysearch.blogspot.incardiologysearch.blogspot.in//


THANK YOUTHANK YOU


Kindly send your suggestions to Kindly send your suggestions to improve this site improve this site

Visit us regularly for updatesVisit us regularly for updates

Send your articles/ ppt/pdf to Send your articles/ ppt/pdf to publish in this site . publish in this site .


Rheumatic fever clinical features and diagnosis

Health & Medicine

Transcript of Rheumatic fever clinical features and diagnosis