Rheumatic fever & acute rheumatic heart disease Rheumatic fever & acute rheumatic heart disease
RHEUMATIC FEVER Rheumatology Research Center. Definition A multisystem disease resulting from an...
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Transcript of RHEUMATIC FEVER Rheumatology Research Center. Definition A multisystem disease resulting from an...
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
Microbe Immune systemActivation
Microbe Immune systemActivation
HEART
JOINT
BRAIN
SKIN
Microbe Immune systemActivation
HEART
JOINT
BRAIN
SKINGAS URTI (M1, , 5, 6, 18)
Microbe Immune systemActivation
HEART
JOINT
BRAIN
SKIN
- 3-6%- Familial clustering- Monozygotic twins
GAS URTI (M1, , 5, 6, 18)
Microbe Immune systemActivation
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)
Clinical PresentationClinical Presentation A children (5-15 Y) with fever & ArthritisA children (5-15 Y) with fever & Arthritis
Joint: 75%Joint: 75% Heart (carditis): 60%Heart (carditis): 60%
Skin:Skin:
Clinical PresentationClinical Presentation A children (5-15 Y) with fever & ArthritisA children (5-15 Y) with fever & Arthritis
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
Clinical PresentationClinical Presentation A children (5-15 Y) with fever & ArthritisA children (5-15 Y) with fever & Arthritis
Joint: 75%Joint: 75% Heart (carditis): 60%Heart (carditis): 60% Skin:Skin:
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
Clinical PresentationClinical Presentation A children (5-15 Y) with fever & ArthritisA children (5-15 Y) with fever & Arthritis
Joint: 75%Joint: 75% Heart (carditis): 60%Heart (carditis): 60% Skin:Skin:
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
Microbe Immune systemActivation
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
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
INFLAMMATION
Anti Inflammatory Factors
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
INFLAMMATION
Anti Inflammatory FactorsPYRIN
IL1
PATHOPHYSIOLOGYPATHOPHYSIOLOGY
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