RHEUMATIC FEVER Rheumatology Research Center. Definition A multisystem disease resulting from an autoimmune reaction to infection with group A streptococci

RHEUMATIC RHEUMATIC FEVERFEVER

RheumatologyRheumatology ResearchResearch CenterCenter

DefinitionDefinition

A A multisystem multisystem disease resulting disease resulting from an from an autoimmune autoimmune reaction to reaction to infectioninfection with group A with group A streptococcistreptococci

ARF & RHD is disease of ARF & RHD is disease of povertypoverty 15- 19 million15- 19 million people affected by people affected by

RHDRHD Prevalence of RHD in Prevalence of RHD in IranIran: 2/1000 : 2/1000

(5-14 y)(5-14 y) Sex : Sex : SimilarSimilar Age:Age: 5-14 Y 5-14 Y

ImportantImportant

Resolve completely except cardiac Resolve completely except cardiac valvular damage (valvular damage (RHDRHD))

Most common cause of heart disease Most common cause of heart disease in childrenin children

250000 death/ y250000 death/ yARF RHD Mortality & Morbidity

Microbe

PATHOGENESISPATHOGENESIS

Microbe Immune systemActivation

PATHOGENESISPATHOGENESIS



HEART

JOINT

BRAIN

SKIN


HEART

JOINT

BRAIN

SKINGAS URTI (M1, , 5, 6, 18)


HEART

JOINT

BRAIN

SKIN

- 3-6%- Familial clustering- Monozygotic twins

GAS URTI (M1, , 5, 6, 18)


HEART

JOINT

BRAIN

SKIN

3-6%Familial aggregationMonozygotic twine

GAS URTI (M1, , 5, 6, 18)

HLA class IITGF-1 and Ig genesTGF-1 and Ig genesHigh expression on B cells, D8-17High expression on B cells, D8-17

PATHOGENESISPATHOGENESISGroup A StreptococcusRheumatogenic Strains:

M1, , 5, 6, 18 mucoid phenotype

Susceptible HostHLA DR4, 2, 1, 3, 7

Dw10, DRw53

Immune ResponseCross-Reactive Humoral (Antibody)

and/or Cell- Mediated (T cell) Immunity

Target Tissue/ organInflammation of Heart, Joints, Brain, Connective Tissue

Acute Rheumatic Fever

Clinical Clinical PresentationPresentation

Clinical PresentationClinical Presentation

A children (5-15 Y) with: A children (5-15 Y) with: FeverFever PolyarthritisPolyarthritis

Clinical PresentationClinical Presentation

A children (5-15 Y) with fever & A children (5-15 Y) with fever & ArthritisArthritis Joint: 75%Joint: 75%

Polyarthritis Polyarthritis MigratoryMigratoryLarge jointLarge jointAsymmetric Asymmetric Sever and disablingSever and disablingDramatic response to ASADramatic response to ASA

Clinical PresentationClinical Presentation A children (5-15 Y) with fever & ArthritisA children (5-15 Y) with fever & Arthritis

Joint: 75%Joint: 75%

Heart (pancarditis): 60%Heart (pancarditis): 60%New murmur (New murmur (hallmark ) : MRhallmark ) : MR

PericarditisPericarditisFirst degree AV blockFirst degree AV block

Valvular Involvement(MR)

RHD (MS)


Joint: 75%Joint: 75% Heart (carditis): 60%Heart (carditis): 60%

Skin:Skin:


Joint: 75%Joint: 75% Heart (carditis): 60%Heart (carditis): 60% Skin:Skin:

Erythema marginatumErythema marginatum : : Classic rashClassic rash <5%<5% evanescent evanescent spare facespare face exacerbate with warmthexacerbate with warmth



Subcutaneous noduleSubcutaneous nodule <5% <5% Delayed manifestationDelayed manifestation Firm, non tenderFirm, non tender <2cm<2cm Last a few days up to 3 weeksLast a few days up to 3 weeks Associated with carditisAssociated with carditis



CNS (Sydenham’s choreaCNS (Sydenham’s chorea )) <2% - 30%<2% - 30% Mainly in femaleMainly in female Prolong latent period (up to 6 months)Prolong latent period (up to 6 months) Purposeless involuntary movementPurposeless involuntary movement Basal gangliaBasal ganglia Self limited (6 weeks)Self limited (6 weeks)

ORGAN DAMAGE

HEART

DIAGNOSISDIAGNOSIS

DIAGNOSISDIAGNOSIS Combination of typical clinical Combination of typical clinical

features together with evidence features together with evidence of the precipitating group A of the precipitating group A streptococcal infectionstreptococcal infection

2002-2003 WHO criteria (based on 2002-2003 WHO criteria (based on the 1992 the 1992 Revised Jones CriteriaRevised Jones Criteria))

Major criteria:Major criteria: CarditisCarditis PolyarthritisPolyarthritis ChoreaChorea Erythema marginatumErythema marginatum Subcutaneous nodulesSubcutaneous nodules

2002-2003 WHO criteria (based on 2002-2003 WHO criteria (based on the 1992 Revised Jones Criteria)the 1992 Revised Jones Criteria)

Major criteria:Major criteria: Minor criteria:Minor criteria:

FeverFever Polyarthralgia Polyarthralgia Elevated CRP or ESR or Elevated CRP or ESR or

Leukocyte countLeukocyte count Prolonged P-R intervalProlonged P-R interval

2002-2003 WHO criteria (based on 2002-2003 WHO criteria (based on the 1992 Revised Jones Criteria)the 1992 Revised Jones Criteria)

Supporting GAS:Supporting GAS: Positive throat culture or rapid antigen Positive throat culture or rapid antigen

testtest Elevated or rising:Elevated or rising:

ASOASO Children > 320 Todd unitsChildren > 320 Todd units Adult > 240 Todd unitsAdult > 240 Todd units

Anti-DNase BAnti-DNase B AntistreptokinaseAntistreptokinase AntihyaluronidaseAntihyaluronidase

Recent scarlet feverRecent scarlet fever

DIAGNOSISDIAGNOSIS First episode or recurrent attack First episode or recurrent attack

without RHD:without RHD: 2 major2 major + antecedent GAS + antecedent GAS 1 major +2 minor1 major +2 minor + antecedent GAS + antecedent GAS

Recurrent attack with RHDRecurrent attack with RHD 2 minor2 minor + antecedent GAS + antecedent GAS

Exception:Exception: ChoreaChorea Insidious onset rheumatic carditisInsidious onset rheumatic carditis Chronic valve lesionChronic valve lesion

TREATMENT


HEART

JOINT

BRAIN

SKIN

ANTIBIOTIC

ANTIINFLAMMATORY

Anti-inflammatory:Anti-inflammatory: Arthritis:Arthritis:

ASA: 80- 100mg/kg/d (2 w)ASA: 80- 100mg/kg/d (2 w) 60- 70 mg/kg/d (2-4w)60- 70 mg/kg/d (2-4w)

Carditis:Carditis: Prednisolone 1-2mg/kg d ( 3 w)Prednisolone 1-2mg/kg d ( 3 w)

Anti-inflammatory:Anti-inflammatory: Antibiotic:Antibiotic:

Benzathine penicillin 1.2 million Benzathine penicillin 1.2 million unitsunits

Oral penicillin: 500 mg bid 10 daysOral penicillin: 500 mg bid 10 days Erytromycin: 250 bid (penicillin Erytromycin: 250 bid (penicillin

allergy)allergy)

Anti-inflammatory:Anti-inflammatory: AntibioticAntibiotic Symptomatic Care:

Carditis: Bed rest, Diuretic, ACEI Chorea: Carbamazepine, Sodium

valproate, IVIG

Discharge from hospital within 1-Discharge from hospital within 1-2 weeks2 weeks

Normalization of acute phases Normalization of acute phases within 4-6 weekswithin 4-6 weeks

PreventionPrevention

Prevention Prevention

Antibiotic:Antibiotic: Benzathine Benzathine penicillinpenicillin every 3-4 every 3-4

weeksweeks Oral penicillin V 250mg po bidOral penicillin V 250mg po bid Erythromycin (250 mg) twice dailyErythromycin (250 mg) twice daily

Prevention Prevention

Antibiotic:Antibiotic: Benzathine penicillin every 3-4 Benzathine penicillin every 3-4

weeksweeks Erythromycin (250 mg) twice dailyErythromycin (250 mg) twice daily

Antibiotic prophylaxis against Antibiotic prophylaxis against endocarditisendocarditis

Duration of Antimicrobial Duration of Antimicrobial ProphylaxisProphylaxis

Without Carditis:Without Carditis: 5 Y, or 18 Y of age5 Y, or 18 Y of age

Mild Carditis (mild MR or healed Mild Carditis (mild MR or healed carditis)carditis) For 10 Y, or 25 years of age For 10 Y, or 25 years of age

More sever valvular disease: More sever valvular disease: LifelongLifelong

Valvular surgery: Valvular surgery: Lifelong Lifelong

INTERMITTENT INTERMITTENT

ARTHRITISARTHRITIS

1.1. FMFFMF

2.2. Palindromic rheumatismPalindromic rheumatism

3.3. Crystal-induced diseaseCrystal-induced disease

4.4. SLE, Behcet’s diseaseSLE, Behcet’s disease

FMFFMF

Familial Mediterranean FeverFamilial Mediterranean Fever

INTRODUCTIONINTRODUCTION

An An auto inflammatoryauto inflammatory and and inherited inherited disease.disease.

EPIDEMIOLOGYEPIDEMIOLOGY

Race: Race: Arab, Jewish, Armenian, Arab, Jewish, Armenian, TurkishTurkish

Age: Age: children - 20 Ychildren - 20 Y Sex:Sex: modest male predominance modest male predominance Inherited: Inherited: RecessiveRecessive Gene: Gene: MEFV (short arm of MEFV (short arm of

chromosome 16)chromosome 16) Pyrin:Pyrin: regulation of inflammation regulation of inflammation

and apoptosisand apoptosis

PATHOPHYSIOLOGYPATHOPHYSIOLOGY

INFLAMMATION


INFLAMMATION

Anti Inflammatory Factors


INFLAMMATION

Anti Inflammatory FactorsPYRIN

IL1


INFLAMMATION

Anti Inflammatory FactorsPYRIN

IL1

Clinical Manifestations Clinical Manifestations (Attacks)(Attacks) A children withA children with episodicepisodic Fever Fever ++

Serositis Serositis SynovitisSynovitis Skin rashSkin rash

Onset: Onset: AcuteAcute Trigger: Trigger: often unpredictableoften unpredictable Duration of attacks: Duration of attacks: 1- 3 days1- 3 days Frequency: Frequency: variesvaries

FeverFever

Nearly alwaysNearly always Some time only manifestation in Some time only manifestation in

childrenchildren

Abdominal painAbdominal pain

90%90% Mild to severMild to sever Acute abdomenAcute abdomen

Pleural involvementPleural involvement

UnilateralUnilateral Sharp chest painSharp chest pain

ArthritisArthritis

Acute Acute MonoarthritisMonoarthritis Knee, Ankle, HipKnee, Ankle, Hip Synovial fluid may appear septicSynovial fluid may appear septic Longer than serosal attack Longer than serosal attack ~ 5% chronic arthritis~ 5% chronic arthritis

SkinSkin

Erysipelas-like eryrhemaErysipelas-like eryrhema Dorsum of Foot, Ankle, lower legDorsum of Foot, Ankle, lower leg

OTHEROTHER

Myalgia (lasting a few weeks)Myalgia (lasting a few weeks) Testicular involvementTesticular involvement Vasculitis (Henoch- PAN)Vasculitis (Henoch- PAN)

COMPLICATIONCOMPLICATION

AMYLOIDOSISAMYLOIDOSIS

Most serious complicationMost serious complication Serum Amyloid ASerum Amyloid A Proteinuria (renal failure)Proteinuria (renal failure) Risk Factor:Risk Factor:

M694V homozygous M694V homozygous Family historyFamily history MaleMale Noncompliance with ColchicinNoncompliance with Colchicin

LAB TestLAB Test

ESRESR CRPCRP LeukocytosisLeukocytosis

DIAGNOSISDIAGNOSIS

High risk ethnic groupHigh risk ethnic group Typical symptomsTypical symptoms Therapeutic response to Therapeutic response to

colchicinecolchicine

Clinical judgment maintains a Clinical judgment maintains a central rolecentral role..

Differential DiagnosisDifferential Diagnosis

Other hereditary periodic fever Other hereditary periodic fever syndromessyndromes

Systemic onset JRASystemic onset JRA PorphyriaPorphyria Hereditary angioedemaHereditary angioedema

TREATMENTTREATMENT

Colchicin (choice)Colchicin (choice) Dose: 1.2-1.8 mg/dDose: 1.2-1.8 mg/d Daily prophylaxisDaily prophylaxis Decrease the frequency and Decrease the frequency and

IntensityIntensity Prevent the amyloidosisPrevent the amyloidosis

Documents

RHEUMATIC FEVER Rheumatology Research Center. Definition A multisystem disease resulting from an autoimmune reaction to infection with group A streptococci