kardio teaching demam rematik
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Rheumatic Fever :
What you should know ?
Teddy Ontoseno
Division of Cardiology
Department of Child Health Dr Sutomo HospitalAirlangga University, Surabaya
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Philosophical - Practical consideration
Licks the joints and bites the heart.
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Epidemiology
* Ages 5-15 yrs
*
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R.F. can be presented in many ways:
a.Arthritiswithout cardiac involvement.
b. Rheumatic choreawithout arthritis
nor carditis.c. Carditiswith or without arthritis.
R.F.What Pediatrician should know ?
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R.F.What Pediatrician should know ?Pathogenesis
* Recent concept :abnormal humoral (acutephase) and cellular (chronic phase) immuneresponse occurs.
* Antigenic mimicry :there is certain aminoacid sequence that is similar btw GABHS andhuman tissue in individuals with genetic
predisposition.
Immunologically mediated inf lammatory
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Rheumatic
fever is a
classicexample of
molecular
mimicry
Rheumatic fever-pathogenesis
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Throat
Heart
Rheumatic Fever Pathogenesis:TissueDamage
The Recent Concept :
HUMORAL and
CELLULAR
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R.F.What Pediatrician should know ?
B. Rheumatogenic strains of
GABHS M types l, 3, 5,
6,18,19 & 24 have antigenic
domains similar to antigensin components of the human
heart
A. Only infections
GABHS of the pharynx
initiate or reactivate RF.
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1st Problem
* 50% of patients with pharyngitis will be treatedbut will not be infected with GABHS
* 30% of patients with pharyngitis will not be
treated but will be infected with GABHS
GABHS pharyngitis and non-GABHS pharyngitisSigns and symptoms overlap broadly
http://images.google.com/imgres?imgurl=www.vvh.org/health/graphics/streplg.gif&imgrefurl=http://www.vvh.org/health/topics/strep.htm&h=203&w=200&prev=/images%3Fq%3Dstrep%2Bthroat%26svnum%3D10%26hl%3Den%26lr%3D%26ie%3DUTF-8%26oe%3DUTF-8%26sa%3DG -
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How do we diagnose it?
* A laboratory test
* A clinical diagnosis and offer presumptive
treatment.
so diagnosis remains a clinical decision !
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Rationale Decission Making
The WHO Acute Respiratory Infections (ARI) :
* In the absence of laboratory diagnosis forchildren under 15 years of age, acute
GABHS pharyngitis should be suspected and
presumptively treated when pharyngeal
exudate plus enlarged and tender cervicallymph nodes are found.
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Acute Pharyngitis
To treat or not to treat?.
That is the million dollar question.
WellSo what is the mostimportant goal of treatment?
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Modified CentorScore & Management Approach( McIsaac - JAMA 2007)
Criteria Points
*Temperature >38 C 1
*Absence of Cough 1
*Swollen Tender Cervical Node 1
*Tonsillar Swelling / Exudate 1*Age: 3 - 14 years 1
1544 years 0
45 years or older -1
Total Score : ( )
Management Approach:
SCORE: 0 - 1 No Further Testing or ABX Therapy.
2 - 3 Culture All
>4 Treat Empirically .
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GABHS Pharyngitis:Treatment Options
Four reasons to treat a GABHS pharyngitiswith antibiotics :
* To prevent rheumatic fever
* To prevent peritonsillar abscess* To reduce symptoms there is a modest (~ 1
day) reduction in symptoms with early treatment
* To prevent transmission this is important in
pediatrics due to extensive exposures but not in
adults
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2nd Problem
RHEUMATIC FEVER, DIAGNOSIS
It is difficult to give a satisfactory
clinical picture of the disease,
because the modes of onset are sovaried and the symptoms so diverse.
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RF, Clinical Features:
* Acute Rheumatic Fever- Acute Inflammatory Phase
- HeartPancarditis(40-50%)
- SkinErythema Marginatum/ S.nodule (10%)
- CNSSydenham Chorea (15%)
- Migratory polyarthritis(75%)
* Chronic Rheumatic Fever- Deforming fibrotic valvular disease.
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RF, Clinical Features:
Polyarthritis low grade fever, large joints,( > 75%), migratory, painful, warm and swollen
asymmetrical, no permanent dysfunction
Carditis - pericarditis, cardiomegaly, or
valvulitis (~ 50%) (valvulitis is the most serious
manifestation.)
Chorealate occurrence, 3 - 4 months after ( ~
10%) infection, self-limiting, resolves in 1- 3
months.
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RF, Clinical Features:
Erythema Marginatumclassic truncalrash, ( ~ 10%) migratory - appears &disappears within hours. (pink rashirregular
red edgesclear center)
Subcutaneous Noduleslate occurs
(1 - 2%) ( months after infection), painless smallnodules over bony prominences - elbows,knees, spine.
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Major criteria of Jones
Help to remember :CAPOCHES
CarditisPolyarthritis
ChoreaErythemaMarginatum
Subcutannodule
http://www.emedicine.com/med/images/Large/1554ARF_MANIFESTATIONS.JPG -
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The Jones Criteria for RheumaticFever, Updated 2003
Major Criteria
Carditis
Migratory polyarthritis
Sydenham's chore Subcutaneous nodules
Erythema marginatum
Minor Criteria
Clinical
fever
Arthralgia
Laboratory Elevated acute phase
reactants
Prolonged PR intervalplusSupporting evidence of a recent group A streptococcal infection
positive throat culture or
rapid antigen detection test; and/ or elevated or
increasing streptococcal antibody test
(e.g., anti-streptolysin O, anti-deoxyribonuclease B, anti-hyaluronidase).
C diti f ARF
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Carditis of ARF :What Paediatrician should know ?
* Pancarditis (endocarditis most serious, always present)* 40 and 60% of patients with ARF
* Characterised by
-persistent tachycardia
-organic cardiac murmurs not previously present
(mitral regurgitation)
- pericardial friction rub
- cardiomegaly
- prolonged PR interval and evidence of heart failure
may be presentnonspecific
Mitral regurgitation
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Mitral regurgitationWhat Paediatrician should know ?
Apical, softer and blowing holosystolic murmur
Pure rheumatic MR due
to shortening of valvecusps and of papillary
muscles, chordae
tendineae that becomematted and adherent to
the valve.
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Chronic RHD:
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Chronic RHD:What Paediatrician should know ?
Rheumatic fever cause- chronic process of
valvular fibrosis
- commissures are fused
- the cusps are severelythickened
- calcification with
shortened,thickened chordaetendineae
Subcutaneous nodules
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Subcutaneous nodulesWhat Paediatrician should know ?
Rarely seen and whenpresent
Usually associated withsevere carditis.
Painless, firm, movable,measuring around 0.5 to2 cm.
Located over extensorsurfaces of the joints,particularly knees, wristsand elbows
Erythema Marginatum
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Erythema MarginatumWhat Pediatrician should know ?
erythematous lesions
with pale centers and
rounded or serpiginous
margins
Laboratory Investigations:
http://www.emedicine.com/med/images/Large/1567ARF_Erythema_marginatum.jpg -
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Laboratory Investigations:What Pediatrician should know ?
No specific laboratory investigations
1. Acute phase reactant
(CRP, SAA, SAP, Complements, CoagulationProteins)
2. Serologis and bacteriologis (ASO, Anti-
DNAse B titres, Culture)3. Electrocardiography, radiology,
echocardiograpphy
Differential diagnosis of rheumatic fever
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Differential diagnosis of rheumatic feverWhat Pediatrician should know ?
* Rheumatic fever and rheumatoid arthritis are
completely different diseases although both
are immmunologically mediated diseases.
* But remmember R.F. is more serious and
more important as it can be prevented.
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MANAGEMENT
Step 0 : Primordial preventionStep I :Primary prevention
(eradication of streptococci)
Step II :Anti inflammatory treatment(aspirin,steroids)
Step III: Supportive management &
management of complications
Step IV:Secondary prevention(prevention of recurrent attacks)
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Step 0:Primordial Prevention
* Primordial prevention of the disease- Immunization (?)
- Socio economic
- Nutrition
- Public education (school going age, parents,teachers, all personel involve with children, etc)
* Control spread of disease to others
- Reduce risk of cross-transmission of organisms
- Infection control policies
- Handwashing
- Overcrowding
- Availability to prompt medical care
STEP I: P i P ti f
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STEP I:Primary Prevention ofRheumatic Fever
* The most important way to prevent
rheumatic fever is by proper and
prompt treatment of GABHS throat.
* Identification & Eradication of
GABHS
Step II Id tifi ti d t t t
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Anti inflamatory* Definite CarditisNo cardiomegaly
Salicylates 100 mg/kg/day
-In one or two weeks, reduce to 75 mg/kg/day
-Continue for 6 - 8 weeks
-Shift to prednisone if cardiomegaly develops
* Severe CarditisCardiomegaly or CHF
Prednisone 1 - 2 mg/kg/day for 2 - 4 weeks
-Begin Salicylates in final weeks of prednisone
and continue for 68 weeks
Step II: Identification and treatmentof ARFand RHD
Step II : Identification and treatment
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Step II: Identification and treatmentof ARFand RHD
Antibiotic regimensANTIBIOTIC ERADICATION REGIMEN
Benzathine penicillin,
imBodyweight < 27 kg 600,000 IU x 1
Bodyweight < 27 kg 1.2 MIU x 1
Penicillin V, oral 100,000 IU/kg/day for 10 daysin 3 doses/day
Erythromycin 50 mg/kg/day
in 3 doses/day for 10 days
The roles for antibiotics
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The roles for antibioticsin Rheumatic Fever
(1) initially treat GABHS pharyngitis
(2) prevent recurrent streptococcal
pharyngitis, RF, and RHD
(3) provide prophylaxis against bacterial
endocarditis.
Supportive & management ofStep III:
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Bed rest
Treatment of congestive cardiac failure:
-digitalis,ace inhibitor, diuretics
Treatment of chorea:
-diazepam or haloperidol Rest to joints & supportive splinting
Supportive & managementofcomplications
Step III:
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VariableAfter 6
months
After 10
weeks
After 6
8
weeks
All
Activties
3 months or
longer
3 months4 weeks3 weeksOutdoor
3 months6 weeks3 weeks2 weeksIndoor
36 months6 weeks3 weeks2 weeksBed Rest
Carditis; withenlargementCarditis; NoenlargementMinimalCarditisArthritis
Bed rest in Rheumatic Fever
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Activity :
->Initially, on bed rest, a period of indoor activity
,permitted to return to school.
->Do not allow full activity directly.
->Patients with chorea may require a wheelchair.
Treatment of congestive cardiac failure:
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Treatment of congestive cardiac failure:
Recommendat ions of American Heart Ass ociat ion
Treatment of congestive cardiac failure:
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Treatment of congestive cardiac failure:
Recommendat ions of American Heart Ass ociat ion
Treatment of congestive cardiac failure:
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Treatment of congestive cardiac failure:
Recommendat ions of American Heart Ass ociat ion
Treatment of congestive cardiac failure:
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Treatment of congestive cardiac failure:
Recommendat ions of American Heart Ass ociat ion
Treatment of congestive cardiac failure:
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Treatment of congestive cardiac failure:Recommendat ions of American Heart Ass ociat ion
STEP IV : Secondary Prophylaxis of RF
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STEP IV:Secondary Prophylaxis of RF(Prevention of Recurrent Attacks)
Agent Dose Mode
Benzathine penicillin G 1 200 000 U every 4 weeks* Intramuscular
or
Penicillin V 250 mg twice daily Oral
or
Sulfadiazine 0.5 g once daily for patients 27 kg (60 lb Oral1.0 g once daily for patients >27 kg (60 lb)
For individuals allergic to penicillin and sulfadiazine
Erythromycin 250 mg twice daily Oral
*In high-risk situations, administration every 3 weeks is justified andrecommended
Recommendat ions of American Heart Ass ociat ion
F ti f S d P h l i
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Function of Secondary Prophylaxis
The regular administration of antibiotics
Prevents GABHS infections
(which can result in recurrent ARF)
Reduces the severity of RHD
Helps prevent death from severe RHD.
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Prevention of bacterial endocarditis
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What Paediatrician should know ?
* Patients who had RF without valve damagedo not need endocarditis prophylaxis.
* Do not use penicillin, ampicillin, or amoxicillinfor endocarditis prophylaxis in patients alreadyreceiving penicillin for secondary RF
prophylaxis (relative resistance of oralstreptococci to penicillin and aminopenicillins).
Prevention of bacterial endocarditis
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* Alternate drugs recommended by the
American Heart Association for these
patients include oral clindamycin
(children: 20 mg/kg; adults: 600 mg)
and
oral azithromycinor clarithromycin
(children: 15 mg/kg; adults: 500 mg)
Prevention of bacterial endocarditisWhat Paediatrician should know ?
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Surgical vs Non Surgical Care:
* Surgery for patients who remain symptomatic
despite medical management.
* Critical MS : valvotomy / valve replacement(
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Diet:
* Without restrictions except in patientswith CHF, who should follow a fluid-restricted and sodium-restricted diet.
* Potassium supplementation(mineralocorticoid effect of corticosteroid
and the diuretics)
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Patient Education:
->Timely evaluation and treatment ofpharyngitis in children.
->Secondary prophylaxis.
->Additional prophylactic antibiotics prior to
dental and surgical procedures.
Complications:
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Complications:
* CHF from valve insufficiency (acute RF) or
stenosis (chronic RF).
* Atrial arrhythmias
* Pulmonary edema
* Recurrent pulmonary emboli
* Infective endocarditis * Thrombus formation
* Systemic emboli.
Rheumatic Fever Prognosis
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Rheumatic Fever - Prognosis
Is good if recurrence is prevented by continuous
antibiotic prophylaxis-particularly if no carditis in theinitial attack.
Can recur if not on prophylactic medicines.
Good prognosis for older age group & if no carditis
during the initial attack.
Bad prognosis for younger children & those with
carditis with valvar lesions.
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Is It Possible to Prevent Rheumatic Fever ?
In the future
Primary prevention will have to wait
till a safe and effective GABHSvaccine becomes available.
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PRIORITY ISSUES TO BE COVERED
SOCIO ECONOMIC STATUS OF THE PEOPLE
EARLY DIAGNOSIS OF THE STREPTOCOCAL THROAT
CASE DETECTION OF ARF
PRIMARY PREVENTION (3 to 15 YEARS OF AGE).
SECONDARY CONTINOUS PROPHYLAXIS (3 to 21/35
years).
REFERRAL SYSTEM, FOLLOW UP AND ADHERENCE
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Rheumatic Fever
A post-infectious connective tissue disease
Follows GAS pharyngitis by 3 weeks (vs. nephritogenic strains ofGAS)
Injury by GAS antibodies cross-reacting with tissue
DxJONES criteria (major and minor)
TestsThroat Cx, ASO titer, CRP, ESR, EKG, +/- ECHO
RxPCN x10 days and high-dose ASA or steroids
2oProphylaxisdaily po PCN or monthly IM PCN
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Jones Modified Criteria
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Rheumatic Carditis Present in 50% cases
Sleeping tachycardia is an early sign
Mitral and aortic valves most commonly involved
Rheumatic Arthritis Most common manifestation Pain, swelling and erythema
Resolves within 1 week
Rheumatic Feverorgans
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gaffected
1. Heart muscle & valvesmyocarditis & endocarditis(pericarditis rare w/o the others)
2. Jointspolyarthritis
3. BrainSydenhams Chorea (milkmaids grip or better yet,
motor impersistance)
4. Skinerythema marginatum (serpiginous border) due to
vasculitis
5. Subcutaneous nodulesnon-tender, mobile and on extensor
surfaces
Rheumatic Fever: The Problem
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Rheumatic Fever:The Problem
#1 Cause of Acquiredheart disease in children.
( world-wide but not in USA )
- AHA: >3200 deaths in US, related to RF/RHD in 2004.
Sequelae of inadequately treatedstrep. pharyngitis.( strep throat )
Highly Uncommon- < 1% of untreated infections.
- Gp A beta-hemolytic - rheumatogenic strainsM proteins.
- 1/3rd
of cases follow inapparent strep infections. A Non-SuppurativeSystemic Inflammatory illness
occuring 1 - 2 wks following a Strep.Infection.
Pathogenesis - Autoimmune mediated.
Multiple systems affected. (Joints, Skin, CNS & Heart !)
Primarily affects: 515 year old age group.
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Rheumatic Fever: Clinical FeaturesPolyarthritis w/ low grade fever, large joints, ( > 75%)
migratory - often 1 at a time, w/ no permanent dysfx.
Carditis - pericarditis, cardiomegaly, or valvulitis ( ~ 50%)
(valvulitis is the most seriousmanifestation.)
Chorealate occurrence, 3 - 4 months after ( ~ 10%)
infection, self-limiting, resolves in 1- 3 months.
Erythema Marginatumclassic truncal rash, ( ~ 10%)
migratory - appears & disappears within hours.
(pink rashirregular red edgesclear center)
Subcutaneous Noduleslate occurs late (1 - 2%)
( months after infection), painless small nodules
over bony prominences - elbows, knees, spine.
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Rheumatic Fever: Jones Criteria*
(Reqs: 2 Major or1 Major & 2 Minor)
Major MinorPolyarthritis Arthralgia
Carditis Prolonged PR interval
Chorea Elevated CRP, ESR
Erythema marginatum Fever (1012 F)
Subcutaneous Nodules Elevated WBC
* with (+) evidence of a prior strep. infection
( incrd ASO or anti-DNAse AB)
or Hx of (+) C/S or Rapid Strep Test
Rheumatic Fever: Prevention
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Rheumatic Fever: Prevention
ANTIBIOTICS - 2 TYPES of USE:
PrimaryPrevention - Appropriate detection
& treatment of Strep. Pharyngitis.
SecondaryPrevention - Patients with Hx
of Rheumatic Fever require continuous
prophylactic antibiotics due to:
1) increased susceptibilityto recurrences
2)increased severityof recurrences, &
3) asymptomaticnature of Strep. Infections
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Rheumatic FeverPrimaryPrevention:
ANTIBIOTICS: Therapeutic Course
IM - Benzathine Penicillin Drug of Choice !0.6 MU IM 1Time (< 27 Kg or60 lbs)
1.2 MU IM 1Time ( >27 Kg or60 lbs)
PO - Phenoxymethyl Penicillin (Pen VK)
Children ( 40mg/kg/day ) 250 mg B-TID x10 days
Adolescent /Adult 500 mg B-TID x10 days
( See Strep.Pharyngitis for alternatives )
ANTI-INFLAMMATORY AGENT: ASA or CCS
SYMPTOMATIC TX: for CHF or Chorea
BEDREST: Limited physical activity
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( )
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Acute Pharyngitis (AP): Background
GaBHS *- most common Bacterialcause of AP.
Majority of AP cases are Viral. Age Relationship: GaBHS accounts for ONLY;
20 - 30 % of AP in children 5 - 15 yrs old
10 - 20 % in adoles./adults 15 - 35 yrs
5 - 10 % after 35 yrs
Seasonal: winter and early spring.
~ 75% of patients seen in primary care settings
receive ABX Rxs for AP. ( 6.7 million visits/yr )
Also causes Skin InfectionsImpetigo/Pyoderma
( * GaBHS = Gp A beta-hemolytic strep. )aka: strep pyogenes
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Nimishikavi S, Stead L Streptococcal PharyngitisImages in Clinical Medicine.
NEJM 2005: 352:e10.
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Acute Pharyngitis:Clinical Features
Suggest Bacterial Suggest Viral
( GaBHS )
Sudden Onset Sore throat Conjunctivitis
Pain on Swallowing Runny Nose
Fever ( 101-104 F) Cough
Headache DiarrheaN/V & Abdominal Pain Hoarseness
(+) Cervical Nodes
Pharyngeal / Tonsillar
Erythema & Exudates
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Strep. Pharyngitis: Diagnostic Options
Throat Culture- Gold Standard ( read at 24 & 48 hrs )
High Specificity & High Sensitivity
- True positives / Few Falsenegatives
Rapid Antigen Detection Test(RADT) - Detects GaBHS CHO.
High Specificity & but only Good Marginal Sensitivity.
- True positives / Many Falsenegatives
Strept Antibody test - detects ASO & anti-DNAse ABs.
- No immediate value in deciding treatment.
Recommended approach:
(+) C/S or RADT confirms presence of GaBHS = Treat !
In child or adoles.- (-) RADTneeds C/S confirmation.
In adults, (-) RADT doesnt require C/S confirmation.
No Method Identifies GaBHS Carriers with Viral AP
$$$$$$ - Lots of testing ???
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Strep. Pharyngitis:First Line Treatment Options
Child - Penicillin VK 250 mg B-TID x 10 daysAmoxicillin 20-40 mg/kg/day divd TID x 10 days
Benzathine Pen G 600,000 units IM 1X ( 60lbs)
Erythomycin 250mg QID / 500mg BID x 10 days
STREP. PHARYNGITIS:
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DOSE MAX/DAY
Cefixime 8 mg/kg/day div q1224h 400 mg
Cephalexin 25 - 50 mg/kg/day div B-QID 2000 mg
Cefadroxil 30 mg/kg/day div BID 2000 mg
Clindamycin 20-30 mg/kg/day div T-QID 1800 mg
Azithromycin 12 mg/kg/day QD X5 days 500 mg
(>2y/o)
Cefdinir 14 mg/kg/day div BID X5 days 600 mg
Cefpodoxime 10 mg/kg/day div BID X5 days 400 mg
STREP. PHARYNGITIS:AlternativeTreatment Options
Pedi
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STREP. PHARYNGITIS:AlternativeTreatment Options
Adults/ Adolescents >12 yoa or > 40Kg
DOSE MAX/DAY
Cefixime 400 mg QD 400 mg
Cephalexin 250-500 mg QID 2000 mg
Cefadroxil 1-2 gms/day div Q12-24hr 2000 mgClindamycin 300-450 mg T-QID 1800 mg
Azithromycin 500 mg day 1, then
250 mg QD X4 days
Cefdinir 300 mg BID X5 days 600 mgCefpodoxime 200400 mg BID X5 days 800 mg
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Antibiotics NOTRecommendedfor Strep. Pharyngitis:
Sulfonamides
Trimethoprim / Sulfamethoxazole
Fluoroquinolones
Tetracyclines / Doxycycline /
Minocycline
References
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References
Endocarditis:
-Wilson W et al. AHA GuidelinePrevention of Infective Endocarditis.(A guideline from the AHA Rheumatic Fever, Endocarditis, &
Kawasaki Disease Committee, Council on Cardiovascular Disease
in the Young, & Council on Clinical Cardiology, Council on
Cardiovascular Surgery & Anesthesia, & the Quality of Care &
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Circulation 2007;116:1736-54.
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by the American Heart Association. JAMA 1997; 277: 1794-1801.
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Rheumatic Fever:
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Endocarditis, & Kawasaki Disease of the Council on Cardiovascular
Disease in the Young. Amer Heart Ass. Circulation 1993;87:302-7.
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Streptococcal Pharyngitis:
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Clinical Infectious Diseases 2002; 35:113-25.
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Pharyngitis and Prevention of Rheumatic FeverA Statement for
Health Professionals. Pediatrics 1995;96:758-764.
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of Pharyngitis in children and adults. JAMA 2004;291:1587-95.
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Pediatrics 2004; 113: 1816-19.
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