Rheumatic FeverRheumatic Fever

Assessment of CVS & Assessment of CVS & MurmursMurmurs

Rheumatic Fever Rheumatic Fever Definition:Definition:

Rheumatic fever is a systemic disease of Rheumatic fever is a systemic disease of childhood, often recurrent that follows childhood, often recurrent that follows Group A Group A beta hemolytic streptococcal Pharyngitisbeta hemolytic streptococcal Pharyngitis * * infectioninfection

It is a delayed Multisystem, Autoimmune, non-It is a delayed Multisystem, Autoimmune, non-suppurative sequelae to URTI with suppurative sequelae to URTI with GABH GABH streptococci.streptococci.

It is a diffuse inflammatory disease of connective It is a diffuse inflammatory disease of connective tissue, primarily involving tissue, primarily involving heart, blood vessels, heart, blood vessels, joints, subcut. tissue and CNSjoints, subcut. tissue and CNS

Acute:Acute: Fever, Inflammed Skin, joint & heart Fever, Inflammed Skin, joint & heart ChronicChronic: Scarring of heart valves (mitral) : Scarring of heart valves (mitral)

dysfunction.dysfunction.

Introduction:Introduction:

““The most important consequence of The most important consequence of rheumatic fever is rheumatic fever is recurrent recurrent

autoimmune inflammationautoimmune inflammation of heart of heart valves due to valves due to ‘GABH Strep’‘GABH Strep’ causing causing scarring of valves leading to severe scarring of valves leading to severe cardiac dysfunction decades later” cardiac dysfunction decades later”

RHD – Mitral Stenosis.RHD – Mitral Stenosis.

EpidemiologyEpidemiology

Ages Ages 5-18 yrs5-18 yrs are most susceptibleare most susceptible Rare Rare <<3 yrs3 yrs M:F equally except Sydenham’s M:F equally except Sydenham’s

chorea which is more common in girlschorea which is more common in girls Common in Common in 3rd world countries3rd world countries Environmental factors--Environmental factors--over over

crowding, poor sanitation, crowding, poor sanitation, poverty,poverty,

Etiology:Etiology:1.1. Genetic SusceptibilityGenetic Susceptibility

2.2. Environmental factorEnvironmental factor – GABH strep – GABH strep..

3.3. AutoimmunityAutoimmunity – Autoantibodies ? . – Autoantibodies ? .

Pathogenesis & Pathogenesis & PathologyPathology Delayed immune response to infection Delayed immune response to infection

with with group.A beta hemolytic streptococci group.A beta hemolytic streptococci of throat onlyof throat only..

After a latent period of After a latent period of 1-3 weeks,1-3 weeks, antibody induced immunological damage antibody induced immunological damage (A(Ashcoff nodulesshcoff nodules ) ) resulting in-resulting in-

--PancarditisPancarditis in the heart in the heart

--Arthritis Arthritis in thein the joints joints

--Ashcoff nodulesAshcoff nodules inin the subcutaneous the subcutaneous tissuetissue

--Basal gangliar lesions resulting in Basal gangliar lesions resulting in choreachorea

Strains that produces rheumatic fever - Strains that produces rheumatic fever - M types l, 3, 5, 6,18 & 24M types l, 3, 5, 6,18 & 24

Pharyngitis-Pharyngitis- produced by GABHS can produced by GABHS can lead to- lead to- acute rheumatic fever , acute rheumatic fever , rheumatic heart disease & rheumatic heart disease & post post strept. Glomerulonepritisstrept. Glomerulonepritis

Skin infection-Skin infection- produced by GABHS produced by GABHS leads to leads to post streptococcal glomerulo post streptococcal glomerulo nephritisnephritis only. It will not result in only. It will not result in Rh.Fever or carditis as skin lipid Rh.Fever or carditis as skin lipid cholesterol inhibit antigenicitycholesterol inhibit antigenicity

Group A Beta Hemolytic Streptococcus

Clinical Features:Clinical Features: Fever 2-3 weeks following pharyngitisFever 2-3 weeks following pharyngitis Migratory polyarthritis of large jointsMigratory polyarthritis of large joints Pericardial friction rub Pericardial friction rub Weak heart soundsWeak heart sounds Tachycardia, arrhythmiasTachycardia, arrhythmias Increased vulnerability to reactivation Increased vulnerability to reactivation

with subsequent pharyngitis.with subsequent pharyngitis. Cumulative cardiac damage over Cumulative cardiac damage over

decadesdecades

1.Arthritis Fleeting migratory polyarthritis, Fleeting migratory polyarthritis,

involving major joints (joints-knee, involving major joints (joints-knee, ankle, elbow & wrist )ankle, elbow & wrist )

Occur in 80% of casesOccur in 80% of cases Involved joints are exquisitely tenderInvolved joints are exquisitely tender In children below 5 yrs arthritis usually In children below 5 yrs arthritis usually

mild but carditis more prominentmild but carditis more prominent Arthritis do not progress to chronic Arthritis do not progress to chronic

diseasedisease

2.Carditis Manifest as Manifest as pancarditispancarditis(endocarditis, (endocarditis,

myocarditis and pericarditis) myocarditis and pericarditis) Occur in 40-50% of casesOccur in 40-50% of cases Carditis is the only manifestation of Carditis is the only manifestation of

rheumatic fever that leaves a sequelae rheumatic fever that leaves a sequelae & permanent damage to the organ& permanent damage to the organ

Valvulitis occur in acute phaseValvulitis occur in acute phase Chronic phase- fibrosis,calcification & Chronic phase- fibrosis,calcification &

stenosis of heart valves stenosis of heart valves (fishmouth valves)(fishmouth valves)

3.Sydenham Chorea3.Sydenham Chorea Occur in 5-10% of casesOccur in 5-10% of cases Mainly in girls of 1-15 yrs ageMainly in girls of 1-15 yrs age May appear even 6/12 after the attack May appear even 6/12 after the attack

of rheumatic feverof rheumatic fever Clinically manifest as-clumsiness, Clinically manifest as-clumsiness,

deterioration of handwriting,emotional deterioration of handwriting,emotional lability or grimacing of facelability or grimacing of face

4.Erythema Marginatum4.Erythema Marginatum Occur in <5% of cases.Occur in <5% of cases. Unique,transient,serpiginous-looking Unique,transient,serpiginous-looking

lesions of 1-2 inches in sizelesions of 1-2 inches in size Pale center with red irregular marginPale center with red irregular margin More on trunks & limbs & non-itchyMore on trunks & limbs & non-itchy Worsens with application of heatWorsens with application of heat Often associated with chronic Often associated with chronic

carditiscarditis

Erythema marginatumErythema marginatum

5.Subcutaneous nodules

5.Subcutaneous nodules

Occur in 10% of casesOccur in 10% of cases Painless,pea-sized,palpable nodulesPainless,pea-sized,palpable nodules Mainly over extensor surfaces of Mainly over extensor surfaces of

joints,spine,scapulae & scalpjoints,spine,scapulae & scalp Associated with strong seropositivityAssociated with strong seropositivity Always associated with severe Always associated with severe

carditiscarditis

Rheumatic Fever: Rheumatic Fever: Clinical Clinical FeaturesFeatures

PolyarthritisPolyarthritis – w/ low grade fever, large joints, – w/ low grade fever, large joints, (~ 80 % )(~ 80 % )

migratory - affects 1 at a time, no permanent migratory - affects 1 at a time, no permanent dysfx.dysfx.

CarditisCarditis - pericarditis, cardiomeagly, or valvulitis - pericarditis, cardiomeagly, or valvulitis ( ~ 50%)( ~ 50%)

(valvulitis is the (valvulitis is the most seriousmost serious manifestation.) manifestation.)

Chorea Chorea – late occurrence, 3 - 4 months after – late occurrence, 3 - 4 months after ( ~ 10%)( ~ 10%)

infection, self-limiting, resolves in 1- 3 infection, self-limiting, resolves in 1- 3 months.months.

Erythema MarginatumErythema Marginatum – “classic” truncal rash, – “classic” truncal rash, ( ~ 5 %)( ~ 5 %)

migratory - appears & disappears within migratory - appears & disappears within hours.hours.

(pink rash – irregular red edges – clear center) (pink rash – irregular red edges – clear center)

Subcutaneous NodulesSubcutaneous Nodules – occurs late ( months – occurs late ( months (~ (~ 10 %)10 %)

after infection), painless small nodules over after infection), painless small nodules over bony bony

prominences - elbows, knees, spine.prominences - elbows, knees, spine.

Other features (Minor features)

Other features (Minor features)

Fever-(upto 38.3 degree Fever-(upto 38.3 degree centigrade)centigrade)

ArthralgiaArthralgia PallorPallor AnorexiaAnorexia Loss of weightLoss of weight

Laboratory Laboratory Investigations:Investigations:

No No specificspecific laboratory investigations* laboratory investigations* Throat culture-GABH streptococci - Cultures Throat culture-GABH streptococci - Cultures

are usually negative.are usually negative. High ESRHigh ESR Anemia, leucocytosisAnemia, leucocytosis Elevated C-reactive protienElevated C-reactive protien ASO titre >200 Todd units. (Peak value ASO titre >200 Todd units. (Peak value

attained at 3 weeks, then comes down to attained at 3 weeks, then comes down to normal by 6 weeks)normal by 6 weeks)

High Anti-DNAse B titresHigh Anti-DNAse B titres High Acute phase reactants –High Acute phase reactants –

Laboratory Findings Laboratory Findings (Contd)(Contd)

ECG-ECG- Prolonged PR interval, 2nd or Prolonged PR interval, 2nd or 3rd degree blocks,ST depression, T 3rd degree blocks,ST depression, T inversioninversion

2D Echo cardiography-2D Echo cardiography- valve valve edema,mitral regurgitation, LA & LV edema,mitral regurgitation, LA & LV dilatation,pericardial dilatation,pericardial effusion,decreased contractilityeffusion,decreased contractility

DiagnosisDiagnosis Evidence of recent streptococcal infection can Evidence of recent streptococcal infection can

include:include: Increased antistreptolysin O ( ASO ) or other Increased antistreptolysin O ( ASO ) or other

streptococcal antibodies (anti-DNAse B)streptococcal antibodies (anti-DNAse B) Positive throat culture for Group A beta-hemolytic Positive throat culture for Group A beta-hemolytic

streptococcistreptococci Recent scarlet feverRecent scarlet fever

Rheumatic fever is mainly a clinical diagnosisRheumatic fever is mainly a clinical diagnosis No single diagnostic sign or specific No single diagnostic sign or specific

laboratory test available for diagnosislaboratory test available for diagnosis Diagnosis based on Diagnosis based on MODIFIED JONES MODIFIED JONES

CRITERIACRITERIA

Jones clinical Criteria of Jones clinical Criteria of Diagnosis:Diagnosis:

Major CriteriaMajor Criteria Migratory Migratory

PolyarthritisPolyarthritis CarditisCarditis Subcutaneous nodulesSubcutaneous nodules Erythema marginatumErythema marginatum Sydenham ChoreaSydenham Chorea

Minor CriteriaMinor Criteria Nonspecific symptomsNonspecific symptoms FeverFever ArthralgiaArthralgia High ESR / CRPHigh ESR / CRP Prolonged PR IntervalProlonged PR Interval

Positive: 2 Major or 1 major + 2 minor Following Group-A strep. pharyngitis.

Jones Criteria (Revised) for Guidance in theDiagnosis of Rheumatic Fever*

Major Manifestation MinorManifestations

Supporting Evidence of Streptococal Infection

Clinical LaboratoryCarditisPolyarthritis

ChoreaErythema Marginatum

Subcutaneous Nodules

Previousrheumaticfever orrheumaticheart diseaseArthralgiaFever

Acute phasereactants:Erythrocytesedimentationrate, C-reactiveprotein,leukocytosis Prolonged P-R interval

Increased Titer of Anti-Streptococcal Antibodies ASO (anti-streptolysin O),othersPositive Throat Culture for Group A StreptococcusRecent Scarlet Fever

*The presence of two major criteria, or of one major and two minor criteria,indicates a high probability of acute rheumatic fever, if supported by evidence ofGroup A streptococcal nfection.

Differential DiagnosisDifferential Diagnosis

Juvenile rheumatiod arthritisJuvenile rheumatiod arthritis Septic arthritisSeptic arthritis Sickle-cell arthropathySickle-cell arthropathy Kawasaki diseaseKawasaki disease MyocarditisMyocarditis Scarlet feverScarlet fever LeukemiaLeukemia

Heart DiseaseHeart Disease Rheumatic Heart Disease – usually Rheumatic Heart Disease – usually

occurs years after initial attack. occurs years after initial attack. Mitral valve is more commonly Mitral valve is more commonly involved than aortic valve. Classically, involved than aortic valve. Classically, pts have mitral stenosis as a result of pts have mitral stenosis as a result of calcification.calcification.

TreatmentTreatment Step IStep I - - PreventionPrevention (eradication of streptococci)(eradication of streptococci)

Step IIStep II - Anti inflammatory treatment- Anti inflammatory treatment (aspirin,steroids)(aspirin,steroids)

Step IIIStep III-- Supportive management & Supportive management & management of complicationsmanagement of complications

Step IVStep IV-- Secondary prevention Secondary prevention (prevention of (prevention of recurrent attacks)recurrent attacks)

Primary ProphylaxisPrimary Prophylaxis Timely diagnosis of GAS pharyngitis Timely diagnosis of GAS pharyngitis

and appropriate treatment. and appropriate treatment. Treatment of choice is still Penicillin Treatment of choice is still Penicillin

as all GAS is susceptible.as all GAS is susceptible. Treatment administered within 10 days Treatment administered within 10 days

of onset of illness has been shown to of onset of illness has been shown to prevent ARF. prevent ARF.

Alternatives – amoxicillin, Alternatives – amoxicillin, erythromycin, 1st generation erythromycin, 1st generation cephalosporincephalosporin

STEP I: Primary Prevention of Rheumatic Fever (Treatment of Streptococcal Tonsillopharyngitis)

Agent Dose Mode Duration

Benzathine penicillin G 600 000 U for patients Intramuscular Once

27 kg (60 lb) 1 200 000 U for patients >27 kg

or Penicillin V Children: 250 mg 2-3 times daily Oral 10 d (phenoxymethyl penicillin) Adolescents and adults:

500 mg 2-3 times daily

For individuals allergic to penicillin

Erythromycin: 20-40 mg/kg/d 2-4 times daily Oral 10 d Estolate (maximum 1 g/d)

or Ethylsuccinate 40 mg/kg/d 2-4 times daily Oral 10 d

(maximum 1 g/d)

Arthritis only Aspirin 75-100mg/kg/day,give as 4divided doses for 6weeks(Attain a blood level 20-30 mg/dl)

Carditis Prednisolone 2-2.5mg/kg/day, give as twodivided doses for 2weeksTaper over 2 weeks &while tapering addAspirin 75 mg/kg/dayfor 2 weeks.Continue aspirin alone100 mg/kg/day foranother 4 weeks

Step II: Anti inflammatory treatmentClinical condition Drugs

Bed rest Bed rest Treatment of congestive cardiac Treatment of congestive cardiac

failure: failure: --digitalis,diureticsdigitalis,diuretics Treatment of chorea:Treatment of chorea:

- -diazepam or haloperidoldiazepam or haloperidol Rest to joints & supportive splintingRest to joints & supportive splinting

3.Step III: Supportive management & management of complications

Secondary ProphylaxisSecondary Prophylaxis

Patients diagnosed with ARF need to Patients diagnosed with ARF need to undergo secondary prophylaxis to undergo secondary prophylaxis to prevent relapses. prevent relapses.

Prophylaxis regimens include oral Prophylaxis regimens include oral Penicillin BID, Pen G IM monthly , or Penicillin BID, Pen G IM monthly , or oral erythromycin BID.oral erythromycin BID.

STEP IV : Secondary Prevention of Rheumatic Fever (Prevention of Recurrent Attacks)

Agent Dose Mode

Benzathine penicillin G 1 200 000 U every 4 weeks* Intramuscular

orPenicillin V 250 mg twice daily Oral

orSulfadiazine 0.5 g once daily for patients 27 kg Oral

1.0 g once daily for patients >27 kg

For individuals allergic to penicillin and sulfadiazine

Erythromycin 250 mg twice daily Oral

*In high-risk situations, administration every 3 weeks is justified and recommended

Duration of Secondary Rheumatic Fever Prophylaxis

Category Duration

Rheumatic fever with carditis and At least 10 y since last residual heart disease episode and at least until (persistent valvar disease*) age 40 y, sometimes lifelong

prophylaxis

Rheumatic fever with carditis 10 y or well into adulthood, but no residual heart disease whichever is longer (no valvar disease*)

Rheumatic fever without carditis 5 y or until age 21 y,

whichever is longer

*Clinical or echocardiographic evidence.

Duration of treatmentDuration of treatmentRheumatic Fever without carditisRheumatic Fever without carditis 5yrs or until 21yo – whichever is longer5yrs or until 21yo – whichever is longer

Rheumatic Fever with carditis but no Rheumatic Fever with carditis but no valvular diseasevalvular disease

10yrs or “well into adulthood” – 10yrs or “well into adulthood” – whichever is longerwhichever is longer

Rheumatic Fever with carditis and Rheumatic Fever with carditis and persistent valvular diseasepersistent valvular disease

At least 10yrs since last episode and at At least 10yrs since last episode and at least until 40yo; sometimes lifelongleast until 40yo; sometimes lifelong

PrognosisPrognosis Rheumatic fever can recur whenever Rheumatic fever can recur whenever

the individual experience new GABH the individual experience new GABH streptococcal infection,if not on streptococcal infection,if not on prophylactic medicinesprophylactic medicines

Good prognosis for older age group & Good prognosis for older age group & if no carditis during the initial attackif no carditis during the initial attack

Bad prognosis for younger children & Bad prognosis for younger children & those with carditis with valvar lesionsthose with carditis with valvar lesions