12. Acute Rheumatic Fever by Dr Budi (24 Oktober 2013)

7/23/2019 12. Acute Rheumatic Fever by Dr Budi (24 Oktober 2013)

1/64

CURRENT CONCEPTS AND

MANAGEMENT OF ACUTERHEUMATIC FEVER

RAHMAT BUDI KUSWIYANTODEPARTMENT OF PEDIATRIC & CHILD HEALTH

FK UNPAD / HASAN SADIKIN HOSPITAL

BANDUNG


2/64


3/64


4/64

LICKS THE BRAIN (JOINT) BITES THE HEART

CHRONIC

LESIONS


5/64

Rheumatic Fever (RF) and Rheumatic Heart Disease(RHD) are non-suppurative complicationsof Group A

streptococcal (GAS) pharyngitis due to a delayed

immune response/Immunologically mediated

inflammatory RHD remains the most serious sequelae of RF and

causes considerable global morbidity and mortality

(Major public health problem)

Preventable and treatable

Definition


6/64

STRUCTURE

Capsule: hyaluronic acid

Cell Wall: outer, middle and inner layer

Outer layer: proteins M, T and R

M component is the most potent & antigenic

Middle layer:specific carbohydrates eg N acetyl glucoamin and rhamnose

Inner layer:peptidoglycanresponsible for cell wall rigidity

Cytoplasm

Group Abeta hemolytic Streptococcus = GAS


7/64

Aschoff bodies in myocardium

HISTOPATOLOGIS


8/64

Lancet 2005; 366: 15568

Pathogenesis pathway for ARF and RHD


9/64

Immunologically mediated inflammatory

Abnormal humoral (acute phase) & cellular (chronic phase) immune response occurs

Antigenic mimicry: certain amino acid sequence that is similar btw GAS & human tissue

in individual with genetic predisposition


10/64

EPIDEMIOLOGY

Worldwide; rare in developed countries: better livingconditions and control of streptococcal infections. Influxof immigrants from highly prevalent countries & newstrains of streptococci (new outbreaks)

Still major public health problems among children andyoung adults in developing countries

RF is the most frequent cause of heart disease in the 5-

to 30-year age group ARF & RHD are important causes of death in young

people

RHD causes 2540% of all cardiovascular disease


11/64

INCIDENCE

PHARYNGITIS

GAS

15-20%

RESOLVEDARF

0,3-3%

VIRAL

>80%

Worldwide: 12 million ARF & RHD (1994); Cause of 3 million CHF & readmission

Annualincidence: 1,0-150/100.000; Prevalence of RHD: 0,2 77,8/1000 children

The overall mean incidence rate of first attack of ARF was 551/100 000 population

(mean 19/100 000; 95 CI 9 to 30/100 000).

Low incidence rate of (10/100 000 per year : America and Western Europe

Higher incidence (>10/100 000): Eastern Europe, Middle East (highest), Asia & Australasia

Mortality rate/100.000: 0,5-8,2;South East Asia 7,6

Heart 2008;94;1534-1540


12/64

RISK FACTORS

Family History of ARF

Genetic predisposition

(HLA-DR1, HLA-DRW6, twin)Low socioeconomic

Age 6 -15 years (mostly 8 years)

Health System-related factors


13/64

Direct and indirect results of environmental and health-

system determinants on RF & RHD


14/64

Clinical Manifestations


15/64

Clinical Manifestations

MAYOR

MANIFEST

ATION

CARDITIS

POLYARTHRITIS MIGRAN

SYDENHAMS CHOREA (St. VITUS DANCE)

ERYTEMA MARGINATUM

SUBCUTANEUS NODULE
http://www.histopathology-india.net/HeartIndex.htm


16/64

Occur in 40-50% cases

Most serious manifestations

May lead to death in acute phase or at later stage

Common in the first 3 weeks

The single most important prognostic factor in RF;only valvulitis leads to permanent damage and its

presence determines the prophylactic strategy Valves affected: Mitral (60%), Aortic (10%); Mitral

and Aortic (30%), Tricuspid and pulmonary valverarely affected

Rheumatic Carditis


17/64

Rheumatic Carditis (cont)

Clinical features

Endokarditis/valvulitis: Presence of apical holosystolic

murmur of MR (with or without apical mid-diastolicmurmur, Carey Coombs), or basal early diastolic murmur.

Children with previous RHD, a definite change in the

character of any of these murmurs or the appearance of a

new significant murmur indicates the presence of carditis

Miokarditis: Unexplained CHF or cardiomegaly

Pericarditis: friction rub, chest pain, effusion, ECG changes

Congestive Heart Failure


18/64

CXR in a child with acute carditis

After 4 weeks of treatment

Rheumatic Carditis (cont)


19/64

Rheumatic Arthritis

The most frequent major manifestation

Occurring in up to 75% of patients in the first attack & early in the course of the

disease

The involvement of joints may present as arthralgia to disabling arthritis

Typically present as migratory polyarthritis

Most often in the larger joints (commonly in the knees and ankles); the wrists,

elbows, shoulders and hips are less frequently involved; and the small joints of the

hands, feet and neck are rarely affected

Inflamed joints are characteristically warm, red and swollen, and an aspirated

sample of synovial fluid may reveal a high average leukocyte count (29000mm-3,

range 200096 000mm-3)

Tenderness may be out of proportion to the objective findings and severe enough

to result in excruciating pain on touch


20/64

Subcutaneous rheumatic nodules

The incidence varies; reported in up to 20% of cases

Round, firm, freely movable, painless lesions, size 0.52.0 cm

Easily be missed if not carefully sought on physical exam

They occur in corps over bony prominences or extensor tendons Common locs: the elbows, wrists, knees, ankles & Achilles tendons

The number varies from one to a few dozen, but usually 3-4

Persist from days to 12 weeks to, rarely > a month

Similar lesions occur in SLE and rheumatoid arthritis.

Associated with the presence of carditis


21/64

Subcutaneous rheumatic nodules


22/64

Erythema marginatum

Present in 7-15% of patients

Usually occurs early in the course of a rheumatic attack & highly specific to RF

Associated with carditis & tend to occur together with subcutaneous nodules.

May be missed if not specifically sought, particularly in dark-skinned patients

Appear first as a bright pink macule or papule that spreads outward in a circular

or serpiginous pattern

The lesions are multiple, nonpruritic & nonpainful, blanch under pressure, and are

only rarely raised. Individual lesions may come and go in minutes to hours;

appearing like smoke rings beneath the skin Usually on the trunk or proximal extremities, rarely on the distal extremities, &

never on the face

May persist or recur for months or even years

Not influenced by anti-inflammatory therapy


23/64

Erythema marginatum


24/64

Sydenhams Chorea

Occurs primarily in children, females and rare after 20 years old The prevalence 536%

May occur alone, or in association with other manifestations

Usually benign and can last for 1 week - 2 years (median 15 weeks)

Has a longer latency period after GAS infection, as long as 17 months Characterized by emotional lability, uncoordinated movements & muscular

weakness

The onset may be difficult to determine. First sign: difficulty walking, talking,

writing, then the movements are abrupt and erratic (esp. on the hands, feet and

face are most evident)

tongue bag of worms, speech is jerky and staccato, spoon or dish

configuration , pronator sign, milkmaid grip

Disappear during sleep, decrease with rest & sedation, & can be suppressed by

volition for few movements


25/64


26/64

Other Clinical Features

Less frequent or less specific to ARF

Epistaxis

Abdominal pain (5%) due to peritonitis Hematuria (5%)/renal involvement

- When routine biopsy done, in up to 39%

Pneumonitis Mild pleuritis (5 - 10%)

Encephalitis (extremely rare)


27/64

Diagnosis


28/64

The Revised Jones Criteria 1992

2 mayor manifestations 1 mayor + 2 minor manifestations With proved evidence of GAS

infection (culture or ASTO)

Highly

probable

2 mayor manifestations

1 mayor + 2 minor manifestations Without proved evidence of GAS

infectionDoubtful


29/64

20022003 WHO Criteria for The Diagnosis of ARF &

RHD (Based on The Revised Jones Criteria)

DIAGNOSTIC CATEGORIES CRITERIA

Primary episode of RF 2 Mayor/1 Mayor+2 Minor

manifestations + evidence of a

preceding GAS infectionRecurrent attack of RF in a patient without

established RHD2 Mayor/1 Mayor+2 Minor

manifestations + evidence of a

preceding GAS infection

Recurrent attack of RF in a patient with

established RHD

2 Minor plus evidence of a

preceding GAS infectionRheumatic chorea

Insidious onset of rheumatic carditis

Other major manifestations or evidence of

GAS infection not required

Chronic valve lesions of RHD Do not require any other criteria to be

diagnosed as having RHD


30/64

Investigations in Suspected ARFRECOMMENDED FOR ALL CASES

White blood cell count

Erythrocyte sedimentation rate (repeat weekly once diagnosis confirmed)

C-reactive protein

Blood cultures if febrile

Electrocardiogram (repeat as necessary if conduction abnormality more than first degree)

Chest x-ray if clinical or echocardiographic evidence of carditis

Echocardiogram (repeat as necessary in 2-4 weeks if equivocal, or if serious carditis)

Throat swab (preferably before giving antibiotics) - culture for group A streptococcus

Anti-streptococcal serology: both anti-streptolysin O and anti-DNase B titres, (repeat 10-14 days later if

first test not confirmatory)

TESTS FOR ALTERNATIVE DIAGNOSES, DEPENDING ON CLINICAL FEATURES

Repeated blood cultures if possible endocarditis or septic arthritis Joint aspirate (microscopy and culture) for possible septic ar thritis

Joint X-ray

Copper, ceruloplasmin, anti-nuclear antibody, drug screen, and consider CT/MRI head for choreiform

movements

Serology and auto-immune markers for auto-immune or reactive arthritis (including ANA - Anti Nuclear

Antibody).


31/64

Diagnosis of Streptococcal Infection

The gold standard for detecting Streptococcus

pyogenes remains a throat swab cultured on blood

agar

If possible, throat swabs should be examined for allpatients with clinically suspected streptococcal

upper respiratory tract infection

Antibody to GAS (Anti-streptolysin O; Anti-Dnase)


32/64

Diagnosis of Streptococcal Infection (cont):Variation in normalantibody titers with age and/or geography


33/64

Role of Echocardiography

Provide early evidence of valvular involvement

Confirm suspected valvular regurgitation

Exclude non-rheumatic causes of valvular involvement

Support the diagnosis, but not a criteria for diagnosis


34/64

Role of Echocardiography

Prevalence of Rheumatic

Valvular Abnormalities

among Schoolchildren

N Engl J Med 2007;357:470-6.


35/64

Diagnosis: Differential Diagnosis of ARF

Juvenile rheumatoid arthritis

Systemic lupus erythematosus

Other connective tissue diseases, including vasculitidies

Bacterial endocarditis

Reactive arthritis

Seronegative spondyloarthropathies

Infections (Hansens Disease, Lyme, Yersinia)

Familial Mediterranean Fever

Antiphospholipid Syndrome

Leukemias

Sickle cell anemia and other hemoglobin disorders

Sarcoidosis


36/64

Management

General measures: Bed rest

Antimicrobial therapy: 1). Eradication of the

pharyngeal streptococcal infection, 2). Preventrecurrent streptococcal infection, RF, and RHD, & 3).

Provide prophylaxis against bacterial endocarditis

Suppression of the inflammatory process

Management of heart failure

Management of chorea


37/64

General Measures

Arthritis Mild Carditis Moderate

Carditis

Severe

Carditis

Bed rest

(Hospitalization)

1-2 weeks 2-3 weeks

(up to 4 weeks)

4-6 weeks 2-4 months

(CHF -)

Indoor

ambulation

1-2 weeks 2-3 weeks

(up to 4 weeks)

4-6 weeks 2-3 months

Outdoor activity 2 weeks 2-4 weeks 1-3 months 2- 3 months

Full activity After 6-10

weeks

After 3 (6-10)

weeks

After 3-6

months

Variable

These guidelines should be individualized by clinician(s) according to

patient and family circumstances.


38/64

Eradication of The Pharyngeal Streptococcal Infection

Benzathine benzylpenicillin

600.000 U IM: weight < 30 kg

1,2 juta U IM: weight > 30 kg

As a first dose of 2nd-prophylaxis

Allergy to Benzathine benzylpenicillin

Erythromisine 40-50 mg/Kg/day in 2-4 doses for 10 days


39/64

Suppression of The Inflammatory Process

Clinical Manifestation Therapy

ATHRALGIA ANALGESIC (PARACETAMOL)

ARTHRITIS SALICYLATES 90-100

mg/Kg/day for 2 weeks

25 mg/Kg/day for 4-6 weeksCARDITIS Prednisone 2 mg/Kg/day for

2 weekstapp off 2 weeks

salisilate 75 mg/Kg/day

for 2-6 weeks


40/64

Suppression of The Inflammatory Process

Arthritis Mild carditis Moderatecarditis

Severecarditis

Prednisone 0 0 2-4 weeks 2-6 weeks

Salicylates 1-2 weeks 2-4 weeks 6-8 weeks 2-4 months

Prednisone:12mg/kg-day, to a maximum of 80mg/day given in divided

doses). After 2

3 weeks of therapy the dosage may be decreased by 20

25% each week. While reducing the steroid dosage, a period of overlap

with aspirin is recommended to prevent rebound of disease activity

Salicylates: 90-100 mg/kg/day/divided into 4-5 doses for 2 weeks6070mg/kg-day for 36 weeks


41/64

Management of Chorea

Reducing activity & emotional disturbance

The signs and symptoms of chorea generally do not respond

well to anti-inflammatory agents

In severe case:

Neuroleptics, benzodiazepines and antiepileptics areindicated, in combination with supportive measures such as restin a quiet room

Carbamazepine 710 mg/kg/day po tid

Phenobarbital 35 mg/kg/day po bid

Haloperidol 0.010.03 mg/kg/day po bid

Valproic acid 1520 mg/kg/day po tid


42/64


43/64

Potential Preventive Measures for Rheumatic Fever and

Rheumatic Heart Disease

The most important way to prevent

rheumatic fever is by proper andprompt treatment of GAS pharyngitis


44/64

Primordial Prevention

Primordial prevention of the disease Immunization (?)

Socio economic

Nutrition

Public education (school going age, parents, teachers,all personnel 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


45/64


46/64

GAS PHARYNGITIS

ARF

RHD

PRIMARY

XXX

SECONDARY

XXX

Primary vs Secondary Prevention

The most important way to preventrheumatic fever is by proper and prompt

treatment of GAS pharyngitis


47/64

Rationale decision making

The WHO Acute Respiratory

Infection:

In the absence of laboratory

diagnosis for children under

15 years of age, Acute GASpharyngitis should be

suspected & presumptively

treated when pharyngeal

exudate plus enlarged &tender cervical lymph nodes

are found

The most important way to prevent

rheumatic fever is by proper and prompt

treatment of GAS pharyngitis


48/64

GAS pharyngitis th options

Reasons to treat GAS pharyngitis with AB:

To prevent RF

To prevent peritonsilar abcess

To reduce symptoms---there is a modest (-1 day)

reduction in symptoms with early treatment

To prevent transmission-this is important in pediatric

due to extensive exposure but not in adults


49/64

Modified CENTOR score (JAMA 2007)

Criteria Points

Temperature >38C 1

Absence of cough 1

Swollen & tender cervical node 1

Tonsillar swelling /exudate 1Ages: 3-14 years 1

15-44 years 0

>44 year -1

TOTAL

0-1 No further test or AB th/

2-3 Culture all

>4 Treat empirically

Si & S f GAS I f i


50/64

Sign & Symptom of GAS Infection

SIGNS/SYMPTOMS INFANT CHILDREN ADOLESCENT/ADULT

ANTERIOR CERVICAL

LYMPHADENITIS (PAIN)

++++ ++++ ++++

CONTACT ++++ ++++ ++++

SCARLATINIFORM RASHES + ++++ ++++

NOSE EXCORIATION ++++ ++++ ++++

TONSILEXUDATE/PHARYNX + ++++ ++++

THROAT CULTURE (+) ++++ ++++ ++++

FEVER ++ ++ ++

ACUTE ONSET + ++ ++

ABDOMINAL PAIN ++ ++ +

CORYZA ++ + +

PHARYNX

ERYTHEMATOUS

++ ++ ++

HOARSENESS + + +

COUGH + + +

P i S d P i


51/64

PRIMARY SECONDARY

BENZATHINE BENZYHL PENICILLIN G

600.000 U IM wt < 30 kg

1,2 juta U IM wt > 30 kg

BENZATHINE BENZYHL PENICILLIN G

(every 3-4 weeks)

600.000 U IM wt < 30 kg

1,2 juta U IM wt 30 kg

PHENOXYMETHYL PENICILLIN (PENICILIN V)

3-4x 250 mg for 10 days

PENICILLIN V 2 x 250 mg

ERYTRHOMYCIN

20-40 mg/kg/day /2-4 doses/10 days

ERITHROMYCIN 250 mg twice daily

Azithromycine :12.5 mg/kg/day once daily

500 mg on first day, 250 mg per day for the next 4 days

Clindamycin 20 mg/kg per day divided in 3 doses

(maximum 1.8 g/d) Oral 10 days

Clarithromycin 15 mg/kg per day divided BID (maximum

250 mg BID) Oral 10 days

SULFONAMID po

Wt


52/64

Suggested Duration of Secondary Prophylaxis

Category of patient Duration of prophylaxis

Patient without proven carditis For 5 years after the last attack,

or until 18-21 years of age

(whichever is longer)

Patient with carditis

(mild MR or healed carditis)

For 10 years after the last attack,

or until 21-25 years of age

(whichever is longer)

More severe valvular disease 10 years or until 40 years of age

(whichever is longer), sometimes

lifelong prophylaxis

After valve surgery Lifelong


53/64

Lancet 2005; 366: 15568

Pathogenesis pathway for ARF and RHD

CHRONIC LESIONSMITRAL REGURGITATION/STENOSIS

AORTIC REGURGITATION/STENOSIS


54/64

54

INDICATION FOR SURGERY

CHF >NYHA II

Progressive LV dilatation

Pulmonary Hypertension Atrial Fibrillation

Thromboembolism

Endocarditis

Diastolic dysfunction with LVEDD >45mm & EF


55/64

Katup Starr-Edward

A. Hancockporcine valve

B. Carpentier-Edwardpericardial valve


56/64

CLINICAL CHARACTERISTIC AND

OUTCOMES OF MITRAL VALVE

SURGERY IN CHILDREN WITH

RHEUMATIC HEART DISEASE

Kuswiyanto RB Et Al. Sari Pediatri 2009


57/64

Clinical characteristic

Median of age at surgery (year)

14 2.7

Female 14 (50%)

Preoperative NYHA class 3 / 4

22 (79%)

Rhythm

Sinus 27 (96%)

AF

1 (4%)

Endocarditis

4 (14%)


58/64

mitral aortic tricuspid pulmonary

stenotic/mixedsevere reg

moderate reg

mild regurgitation

Result; pre-op assessment

N=28


59/64

MV repaired MV replacement doublereplacement

tricuspidanuloplasty

29%

Result; type of surgery

57%

14%

21%

N=28


60/64

paravalvular leak Mild MR Moderate/severe MR mild stenosis mixed MRMS

4%

0%

21%

7%

Result; immediate post-op

14%

N=28


61/64

Result; echocardiography

Pre-op

1 weekPost-op

p

LVEF (%)

61.5 10.4

60.3 9.9

< 0.530

LVEDD (mm)

50.8 7.3

47.9 7.4

< 0.064

LVFS (%)

32.7 5.0

34.2 5.6

< 0.177


62/64

Long term management post-op

Restenosis detection or neo regurgitation

LV & valves function monitoring

Long life secondary prophylaxis

Long life anticoagulant


63/64

63

Long term outcome

Valves Thrombosis (0,01-0,5%/year)

Damage of the valve structures

Thromboembolic (2-5% / year) Endocarditis (0,2-1,2% /year )

Bleeding (1-4% /year)

Paravalvular leak (0,1-1,5% /year)


64/64

Date post:	16-Feb-2018
Category:	Documents
Upload:	galing-chandika-putra
View:	227 times
Download:	0 times

12. Acute Rheumatic Fever by Dr Budi (24 Oktober 2013)

Documents