Acute Rheumatic fever Flashcards
ARF
Autoimmune inflammatory nonsupurative process that develops as a sequela of a streptococcal throat infection ( group A betahemolytic Strep) after 2-6 weeks , affecting different structures of conjuctive tissue :
- HEART
- SUBCUTANEOUS TISSUE
- JOINTS
- CNS
- SKIN
Rheumatic heart disease
Chronic damage of cardiac valves ( typically MITRAL STENOSIS)
- can be prevented and controlled
ARF - age
5-15 years –> Children
Incidence has steadily in the last 50 years
developed countries - 1/100000
developing countries 200/100000
Reccurence rate is high in 1st year after diagnosis 50%
AFR = Most frequent cause of
Acquired cardiac failure in children
Risk factors
- Age
- Untreated Strep throat
- Familial predisposition
- Crowding
- Poverty
- Lack of medical care
Etiology
Group A beta hemolytic streptococci :
- 80 strains
Gram positive bacteria / encapsulated / resistance to phagocytosis
Classical rheumatogenic strains emm types : 1,3,5,6,18 -> expression of its surface antigen - M protein
New data : Any strain can lead to streptococcal pharyngitis + ARF -new reinfections with different serotypes
Direct and toxic infectious hypothesis - EXCLUDED
Pathogenesis
- Abnormal ANTIGEN - ANTIBODY immune reaction
- Cross reaction b/w Streptococcal antigens and human tissular proteins - molecular mimicry
Immune Mechanism in ARF
- Increased specific HUMORAL immune response: There is no streptococcal genetic material in rheumatic heart lesion
The rheumatogenic serotypes : M protein antigen and Nacetilglucosamine will lead to an increased humoral response - specific autoantibodies to these tissues
- Myocardium ( against myosin + tropomyosin )
- Endothelium and valvular endocardium ( antilaminine)
Immune Mechanism in ARF
Extracellular antigens of rheumatic streptococci
- O and S hemolysins - streptolysins
- Treptokinase enzymes
- Hyaluronidase enzymes
- DNA - ases (deoxyribonucleases)
They are not pathogenic , are used only in diagnostic purposes
It is used frequently:
ASLO = Titration test of anti-streptolysin O antibodies
Cellular Immune response:
- Role in persistence of granulomatous lesions and aggravation of valvular lesions
Histological elements
- Exsudative phase
- conjuctive tissue edema
- collagen fibers edema
- inflammatory infiltrate
- fibrinoid necrosis
2.Granulomatous - proliferative phase (1-6 mnths)
ASCHOFF NODULES = pathognomonical
= Central necrosis + Multicellular surrounding with plurinuclear cells
Anitskchow cells
Multinucleated giant cells = macrophages from Aschoff nodules with the appearance of ‘‘owl’s eyes’’ or like a ‘‘catterpillar’’ ( chromatine)
SOS SOS SOS
Clinical presentation RF
MAJOR MANIFESTATIONS:
- Sydenham Chorea
- Polyarthritis
- Erythrema marginatum
- Subcutaneous nodules
- Carditis
Arthritis
75 - 80 %
typically polyarticular , but monoarthritis may occur with ARF in select high-risk populations
- 6-16 joints
- large joints - knees ,ankles,elbows,wrists
- very painful
- usually symmetrical
Arthritis
Migratory pattern
- 3-7 days until resolution and then appears the inflammation of another joint
Arthritis
TREATMENT
HIGH DOSE OF SALICYLATES
- Diagnostic test : clear improving or resolution of inflammation at 24hrs after aspirin initiation
The entire bout of arthritis subsides within 4-6 weeks without any permanent damage. If not , a different diagnosis should be considered
ARTHRALGIA -
MINOR CRITERIA
Arthritis associations
FREQUENTLY ASSOCIATES WITH CARDITIS !!!
Rheumatic fever licks at the joints , but bites at the heart
Subcutaneous nodules
20%
Late manifestation- after 6 wks of RF evolution Painless subcutaneous nodules : - 0.5 -2 cm - firm -symmetric On the extension areas and on the bony protruberences Complete resolution
Erythema marginatum
5%
- Early sign
- nonpruritic , painless, serpiginous, erythrematous eruption on the trunk ( macular , with pale central area )
- centrifugal extension
- trunk and proximal limbs
- they get worse with heat application
SYDENHAM CHOREA
20%
- Late neurological manifestation - over 3 months
- Autoantibodies reacting with brain ganglioside
- caudate nuclei
- thalamus - Involuntary limb movements , incoordination, speech disorders , facial grimaces
- More common in girls
- Self limited ,2-6 wks, complete resolution
- INCREASED RISK OF RF RECURRENCE - PHROPHYLAXIS MANDATORY
CARDITIS
50%
PANCARDITIS
Early onset aafter arthritis
Clinical signs :
- High pulse rate
Murmur - mitral /aortic regurgitation - endocardium involved
- Cardiomegaly - myocardium involvement
-Pericardial friction rub - Pericarditis
-Prolonged PR interval - myocardial inflammation affecting electrical conduction
- Cardiac failure
Endocarditis
Active inflammation of the heart tissues : valvular lesions
- exudative - proliferative , fibrinoid necrosis , +- vegetations
Acute onset -> Valve regurgitation
New murmurs / modifications of pre-existing ones
1.MITRAL SYSTOLIC MURMURS - 70 -80% of patients
- functional + organic
( edema,vegetations,papillary muscles ,hypotonia)
- CAREY-COOMBS MURMUR - Apical dyastolic murmur ( rapid filling of LV - increased blood flow across a thickened mitral valve )
- AORTIC DIASTOLIC MURMUR -10%
They disappear in evolution - STENOSES APPEAR LATE
Endocarditis
Chronic stages
- scars +-calcific lesions
Progressive destruction of the valvular apparatus
STENOSIS:
- Annulus tightening
- Commisurral fusions
- Chordal shortening/thickening
- Leaflet thickening - restricted motion
VALVE INVOLVEMENT IN RHD
STENOSIS :
Valve doesnt openall the way , not enough blood passes through
REGURGITATION:
Valve doesnt close all the way so blood leaks backwards
MYOCARDITIS
Myocardial lesions:
- Focal myocarditis with rheumatic nodules : oligosymptomatic
- Interstitial diffuse myocarditis : Acute HF
- Infiltration of conduction tissue : AV conduction disorders
MYOCARDITIS
CLINICAL
- Symptoms of acute left ventricular failure dyspnea
- > Acute pulm edema
- Tachycardia
- Rhythm disorders ( PB->sustained VT)
- Gallop S3 ( severe myocardial damage)
- functional murmurs - annular dilatation
- Cardiomegaly ( clinical /radiological )
PERCARDITIS
10%
NOT CONSTRICTIVE
Fibrinous pericarditis
Bread and butter pericarditis
PERICARDITIS
1.FIBRINOUS PERICARDITIS Significant anterior chest pain , accentuated by inspiration , changes position - Pericardial rub 2.EXUDATIVE PERICARDITIS Less severe pain / chest pressure -Anxiety - Mohammedan prayer sign Cardiac tamponate (rare)
Positive DIAGNOSIS OF RHEUMATISMAL CARDITIS
- New cardiac murmur ( Echo)
- Cardiac dilation
- Congestive cardiac failure
- Pericardial rub
MINOR CLINICAL CRITERIA
FEVER
acute phase
very responsive to NSAIDs
ARTHRALGIA
PARACLINICAL
LABORATORY
- Acute inflammatory syndrome + direct and indirect evidence of
- recent streptococcal infection
BLOOD ANALYSES
ESR and CRP
- minor criteria
- nonspecific
low in those with isolated chorea /NSAIDs
Inactive disease when ESR and PCR return to normal ( and remains N over 2 weeks)
These analyses usually remains increased even after complete clinical resolution
CRP is more specific ; it remains approximately 3 months , increased or even more in those with valvular damage ( 5% over 6 months )
EVIDENCE OF STREPTOCOCCAL INFECTION
1.Positive pharyngeal throat culture during streptococcal angina Pbs : carries ( absent ... 2.Elevated or ... ASLO > 500 - 600 U Maximum values Anti-DNA B ( 20% ...)
They remain raised for a long time ( chorea ) ; used when ASLO inconclusive
3.Rapid streptococcal sarbohydrate antigen test
90-100% specificity , less sensitivity ( 70%)
Use for prevention of ARF
MAJOR JONES CRITERIA
J Joints ( polyarthritis) O Carditis (pancarditis) N nodules E erythema marginatum S Sydenham's chorea
MINOR JONES CRITERIA
Clinical
Acute phase reactants ( ESR,CRP)
PR interval prolonging ( ECG)
DIAGNOSIS
2 MAJOR CRITERIA 1 MAJOR + 2 MINORS !!! AND EVIDENCE OF STREPTOCOCCAL INFECTION specificity - 97% sensitivity - 77%
2003 WHO CRITERIA ( based on JONES criteria )
- A primary episode of RF
- Recurrent attacks of RF in patients without RHD
- Recurrent attacks of RF in patients with RHD
- Rheumatic chorea
- Insidious onset rheumatic carditis
- Chronic RHD
Differential diagnosis
- Infectious ( bacterial ) endocarditis
- Septic polyarthritis
- Gonococcal arthritis
- SLE
- Rheumatoid arthritis
- Tuberculous arthritis
- Arthrus’s reaction to Penicillin
Evolution and Prognosis
RELAPSE
recurrence of clinical / paraclinical signs of the disease upon discontinuation of treatment ( rebound)
RECURRENCE
new episode of ARF after a new streptococcal infection (with another serotype)
more than 2 months after stopping treatment
Maximum frequency in the first year , increased incidence in the first 5 years
RECURRENCE
- Younger age at onset of ARF - increased risk of recurrence
- It decreases over time
- Recurrence repeats the clinical pattern of the first ARF attack
- More common in those with valvular lesions -> Mitral stenosis as first diagnosis of RHD suggests evolution with recurrences
- Highly increased antibody titer = high chances of recurrence
PROGNOSIS
- Vey good for those with extracardiac disorders
- Relatively good for those without valvular sequelae
- Reserved for those with valvular sequelae
50% of those with carditis without prophylaxis
10-20% years after the first ARF attack
Chronic rheumatic disease
- the result of repeated valvulitis after repeated episodes of ARF
- Multivalvular , left heart generally affected
- Mitral - aortic - tricuspid - pulmonar
65-70% - 20-25% -10% - rarely
Valvular chronic rheumatic disease
- Valve thickening
- Commissural fusion
- Shortening restricting , thickening of chordae
!!! Mitral stenosis as a chronic condition in adults ( regurgitation in children)
Mitral stenosis
the differences
The normal valve :
- Transparent
- Avascular
- Thin
- Flexible membrane
RHD:
- Thick
- Fibrous scarred stenotic & fixed (MS/MR) with blood vessels
TREATMENT
ARF treatment - symptomatic of acute manifestations -eradication of streptococcal infection Recurrence prevention - primary prophylaxis - secondary prophylaxis
CURATIVE TREATMENT
A.Eradication of streptococcal infection :
- Penicillin V250 mg ( children ) or 500 mg (adults), splitted in 2-3 doses/day,po,10 days
- Benzatin penicilin (Moldamin ) 600000 unit. im for children and 1.2 mil unit. for adults single injection-compliance
- For patients allergic to penicillines : Erythromycin oral 1.6-2 g/24hrs , 10 days
- Or oral Cephalosporins
CURATIVE TREATMENT
A.Eradication of streptococcal infection :
- Penicillin V250 mg ( children ) or 500 mg (adults), splitted in 2-3 doses/day,po,10 days
- Benzatin penicilin (Moldamin ) 600000 unit. im for children and 1.2 mil unit. for adults single injection-compliance
- For patients allergic to penicillines : Erythromycin oral 1.6-2 g/24hrs , 10 days
- Or oral Cephalosporins
CURATIVE TREATMENT
B.Anti- inflammatory treatment
ARF without carditis :
- Salicylates - Aspirin :6-8 g /24hrs ( 100-125 mg/kg/day for children over 12 yo) , gradually decreased in 6-8 wks
- Steroids are also effective but should probably be reserved for patients in whom salicylates fail
ARF with carditis :
From the beginning Prednisone 1-2 mg/kg/day 2-4 wks,overlap with Aspirin low doses in the last 2 wks ;
Prednisone has to be dcreased by 5mg every 4-5 days and continued only Aspirin to prevent relapse
ARF with chorea : sedatives , haloperidol , isolation
PROPHYLACTIC TREATMENT
Primary prevention
- Prompt recognition of pharyngotonsillitis plus treatment ( in the fist 10 days)
Benzathin benzylpenicillin (Moldamin) 1.2 mil u im single dose or
Penicilline V oral , 10 days
For penicilline allergic pts:
- Erythromycin 40 mg/kg/day x 2-4 hrs per day,oral ,10 days
- Cephalosporins I and II ( Cefuroxime) , 10 days
PROPHYLACTIC TREATMENT
SECONDARY PREVENTION
!!! As early as possible after ARF
- Benzhatin penicilline ( Moldamin) 1.2 mil u /lmonth , im
- ARF with a history of carditis + rheumatic valvulopathy
- minimum 10 years , until 40 yo or indefinite/for life
- ARF with carditis without valvulopathy
- minimum 10 years or until 21 yo
- RAA without carditis : minimum 5 years or until 21 yo
NOT TO GIVE TETRACYCLINE : RESISTANCE OVER 50%
Research for a Vaccine against Str.group A
