Rhuematic Fever and Infective Endocarditis Flashcards
Acute Rheumatic Fever:
Definition:
Acute Rheumatic Fever(ARF) is an autoimmune non-suppurative inflammatory disease caused by Streptococcus pyogenes
A complication of Strep pyogenes pharyngitis
Tissues commonly affected include: Connective tissues of heart, joints, brain, and skin
Endocardial, myocardial, epicardial damage = cardiac
enlargement, valvar murmurs, effusions
Joints = arthralgia to arthritis (migratory or flitting)
Acute Rheumatic Fever:
Pathogenesis
The disease process starts when the S. pyogenes bacterium affects an individual which causes an acute episode of pharyngitis
Following the infection, there is an activation of the innate immune system
S. pyogenes antigens are introduced to T and B cells
This leads to activation of CD4+ T cells which further
activates B cells to produce IgG and IgM antibody
The CD4+T cells identify Streptococcal M5 protein peptides and generate various inflammatory cytokines which can further cause fibrotic valvular lesions
There is cross-activation of antibodies and at the same time the human proteins are attacked by the Tcells
The infected person’s peripheral blood lymphocyte gives rise to monoclonal antibodies which cross-reacts with myosin resulting in valvular heart disease
Acute Rheumatic Fever:
Clinical Presentation
Acute fever, tiredness and breathlessness from cardiac
failure, with or without other manifestations (most
commonly joint pain and/or swelling) and pansystolic
murmur of mitral regurgitation
Large joint arthritis and/or arthralgia, usually with fever, and sometimes with pansystolic murmur of mitral regurgitation
Choreiform movements, commonly with behavioural
disturbance but often without other manifestations
Gradual onset of tiredness and breathlessness, which is indicative of cardiac failure, without fever or other
manifestations, and pansystolic murmur of mitral
regurgitation, which indicates the insidious onset of carditis
N/B: Skin manifestations (erythema marginatum and
subcutaneous nodules) are less commonly observed in acute
rheumatic fever (ARF)
Rheumatic Heart Disease:
Definition
A chronic disease caused by accumulated heart valve
damage from a single severe or, more commonly, multiple recurrent ARF episodes
Rheumatic Heart Disease:
Pathogenesis
Repeated upper respiratory attacks by Streptococcus
pyogenes/Group A streptococcus (triggered by the new M
types)
Antibodies formed against Streptococcal M proteins cross react with sarcolemma of the heart
Inflammation of the endocardium and heart valves
Rheumatic Heart Disease:
Diagnosis
1.Based on clinical findings (Jones’s criteria)
- Recent evidence of Streptococcus pyogenes infection
- laboratory
Recent evidence of Streptococcus pyogenes infection:
Culture Based Tests
Non Culture Based Tests
• Cult Non culture based tests
•
• Increase in anti-ASO or anti-DNAse B – Antibody test • Anti-streptolysin O titers get raised within 1 week
• Antideoxyribonucleas (Anti DNAse) B titers get raised within 1-2 week
• PCR based diagnosis
• For identifying the Streptococcus pyrogenic exotoxin B gene
•
Rheumatic Heart Disease:
Culture Based Tests
Positive throat culture for Streptococcus pyogenes
Rheumatic Heart Disease:
Non-Culture Based Tests
Positive Streptococcus pyogenes antigen test on throat swab
Increase in anti-ASO or anti-DNAse B – Antibody test:
- Anti-streptolysin O titers get raised within 1 week
- Antideoxyribonucleas (Anti DNAse) B titers get raised within 1-2 week
PCR based diagnosis:
-For identifying the Streptococcus pyrogenic exotoxin B gene
Rheumatic Heart Disease:
Prevention
Involves prophylactic strategies to avoid GAS infection
ARF is triggered by GAS pharyngitis and the GAS transmission is facilitated by close contact between people
Thus, living conditions, knowledge regarding the importance of a sore throat caused by GAS and an understanding of the mechanisms of transmission are important
*GAS-Group A Streptococcus
Rheumatic Heart Disease:
Prophylactic Treatment
- Primary Prophylaxis
2. Secondary Prophylaxis
Primary Prophylaxis
Treatment of throat infections
- Benzathine Penicillin G 1,2 MU IMI
- Penicillin VK 500 mg po 4 times a day for 10 days
Individuals allergic to penicillin: Erythromycin for 10 days
Secondary Prophylaxis
Prevention of recurrence
Continuous prophylaxis for:
- Documented rheumatic fever
- Definite rheumatic heart disease
Duration of therapy is dependent on whether the patient has developed carditis or chronic valvular heart disease.
- Rheumatic fever with carditis and persistent valvular disease-10 years or until age 40 years (whichever is longer); lifetime prophylaxis may be needed
- Rheumatic fever with carditis but no residual heart disease-10 years or until age 21 years (whichever is longer)
- Rheumatic fever without carditis- 5 years or until age 21 years (whichever is longer)
Rheumatic Fever/Heart Disease:
Treatment
Benzathine Pen G 1.2 MU IMI every 3 to 4 weeks
OR
Penicillin V 250mg twice daily orally
OR
Erythromycin 250mg twice daily po
Infective Endocarditis:
Definition
Infective Endocarditis (IE) • Refers to infection of the endocardial surface of the heart and the physical presence of microorganisms in the lesion
Typically involves cardiac valves (native / prosthetic) or an indwelling cardiac device
Disease may also occur within septal defects or mural
endocardium
Infective Endocarditis:
Heart valves involved
Mitral valve alone 28 – 45%
Aortic valve alone 5 – 36%
Aortic and mitral valves combined 0 - 35%
Tricuspid valve rarely involved 0 – 6%
Both right and left-sided disease present in 0 – 4% of cases
NB:
Rheumatic heart disease underlying lesion in 37 – 76% of infections
Important causes of cardiac valve damage:
•
Infective Endocarditis:
Predisposing Factors
Rheumatic fever
Congenital cyanotic heart abnormalities
Atherosclerotic aortic valve
Prosthetic valve replacements
Intravenous drug abuse
Infective Endocarditis:
Causative Organisms
As patient risk factors change, the microbiology of IE also shifts
Streptococci and staphylococci have collectively accounted for approximately 80% of IE cases-the proportion of these two organisms varies by region and has
changed over time
The emergence of health care-associated IE has been
accompanied by an increase in the prevalence of
Staphylococcus aureus and coagulase-negative staphylococci
The proportion of IE due to viridans group streptococci (VGS) has declined
Enterococci are the third leading cause of IE and are increasingly linked to health care contact
Infections that involve Gram-negative and fungal pathogens in IE are rare and are primarily health care-associated when they do occur
In approximately 10% of cases of IE, blood cultures are negative, most commonly due to patient receipt of antibiotics before the diagnostic
work-up
‘True’ culture-negative IE is caused by fastidious microorganisms that are difficult to isolate with conventional microbiological techniques
Infective Endocarditis:
Organisms responsible
Staphylococcus aureus
Coagulase negative Staphylococci
Viridans group Streptococci
Other Streptococci
Enterococci
Pseudomonas aeruginosa
Enteric Gram negative bacilli
Fungi
Infective Endocarditis:
HACEK Group
Haemophilus aphrophilus
Actinobacillus actinomycetemcomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae
Commensals of the human oropharynx
Previously, HACEK organisms were implicated as a cause of culture negative in endocarditis
This was attributed to slow growth in old formulations of blood culture bottles
However, modern blood culture
instruments reliably detect
HACEK organisms
Infective Endocarditis-Causative Organisms:
Uncommon
Bartonella species
Coxiella burnettii
Chlamydophila psittaci
Brucella species
Rickettsiae
Usually diagnosis made with serology not culture =
“culture negative IE”
Infective Endocarditis:
The culture is negative due to several factors
Fastidious organisms
Prior administration of antibiotics
Fungal endocarditis
Endocarditis caused by intracellular organisms
Mural endocarditis e.g. ventricular septal defects (VSD)
Infective Endocarditis:
Classification
This classification is based on the progression of the untreated disease-It ignores the nonbacterial forms of IE and the frequent overlap in
manifestations of infection by specific organisms
- Acute bacterial endocarditis
- Sub-acute bacterial endocarditis
- Chronic bacterial endocarditis
The acute form:
More likely to affect the normal valves
Follows a fulminant course, usually with high fever, systemic toxicity, and leukocytosis
Death occurs in several days to less than 6 weeks
The most common bacterial cause is Staphylococcus aureus
Other organisms involved are: Streptococcus pyogenes, Streptococcus pneumoniae, or Neisseria gonorrhoeae
The subacute form and the chronic form usually are considered together:
They commonly occur in the setting of prior valvular disease
Are characterized by a slow, indolent course with low-grade fever,
night sweats, weight loss, and vague systemic complaints
These two forms of IE classically are caused by the viridans
streptococci
Subacute - death occurring in 6 weeks to 3 months
Chronic - death occurring later than 3 months
Prosthetic valvular Endocarditis:
Develop in some patients a year following the artificial
(prosthetic) valve replacement or tissue valve replacement
The number of cases are high with artificial aortic valve
replacement
Most common cause is the Coagulase negative Staphylococci
E.g.Staphylococcus epidermidis
The most common bacteria causing Infective endocarditis among patients who are injection drug users (IDUs) is Staphylococcus aureus
A classification based on the etiologic agent responsible is preferable because it has implications for:
The course usually followed
The likelihood of preexisting heart disease
The appropriate antimicrobial agents to employ
Infective Endocarditis:
Pathogenesis
The valve surface first must be altered to produce a suitable site for bacterial attachment and colonization
The endothelium may be damaged by high blood velocity or mechanical damage and or foreign bodies in the circulation
These alterations result in the deposition of platelets, fibronectin, fibrin, and other matrix ligands to form the “sterile vegetation”—the lesions of nonbacterial thrombotic endocarditis (NBTE)
This facilitates bacterial adherence during transient bacteraemia
Platelets and fibrin deposits at the injury site provide an adherent surface for further multiplication and vegetation growth
Transient bacteremia occurs when mucosal surfaces heavily colonized with bacteria are traumatized:
- Dental extractions and other dental procedures
- Gastrointestinal procedures
- Urologic procedures
- Gynecological procedures
Infective Endocarditis:
Clinical Features
There has to be a high index of suspicion
Fever in a patient with a valve lesion is most likely Endocarditis
• Fever • Chills • Weakness • Dyspnea • Sweats
• Anorexia • Weight loss • Malaise • Cough • Skin lesions • Nausea • Headache • Myalgia • Chest pain
• Janeway lesions • Petechiae • Splinter hemorrhages
• Splenomegaly • Clubbing • Signs of renal
failure
• Heart murmur
-Changing murmur
-New murmur
• Embolic phenomena • Osler nodes
Modified Duke Criteria
Major Criteria
Minor Criteria
Modified Duke Criteria:
Major Criteria
Positive Blood cultures
-Typical microorganisms for IE from 2 separate blood cultures
-Persistently positive blood cultures:
•From blood cultures drawn more than 12 hours apart
•All of 3 separate blood cultures positive, with first and last drawn 1 hour apart
-Single positive blood culture for Coxciella burnetti or antiphase 1 IgG
antibody titer of >1:8000 (serology)
Evidence of endocardial involvement: positive echocardiogram findings
New vulvular regurgitation
Modified Duke Criteria:
Minor Criteria
Predisposing heart condition
or IV drug abuse
Fever: T0 >38°C
Vascular phenomena:
- arterial embolism,
- pulmonary infarcts,
- mycotic aneurism,
- intracranial haemorrhage,
- Janeway lesions
Immunological phenomena:
- glomerulonephritis,
- Osler nodes,
- Roth spots
- Rheumatoid factor • Echocardiogram, not meeting major criteria
Positive blood culture not meeting major criteria
Infective Endocarditis:
Diagnosis Types
Definite Infective Endocarditis
Possible Infective Endocarditis
Rejected Infective Endocarditis
Blood Culture
Other Cultures
Serological Test
Histology
Non-specific findiings
Urinalysis
Echocardiography
IE Diagnosis
Definitive Infective Endocarditis
Pathologic criteria
• Microorganisms: demonstrated by culture
• Pathologic lesions: vegetations or intra-cardiac abscess present (sonar)
Clinical criteria
• Two Major criteria
• One Major + Three Minor criteria
• Five Minor criteria
IE Diagnosis
Possible Infective Endocarditis
Findings consistent with IE that fall short of definite IE but not rejected
IE Diagnosis
Rejected Infective Endocarditis
Firm alternate diagnosis
No pathologic evidence of IE after antibiotic therapy of 4 days or less
Does not meet criteria for possible IE as above
IE Diagnosis:
Blood Culture
Most important laboratory test
At least 3 blood cultures, with first and last drawn 1
hour apart
More if patient received antibiotics in preceding 2 weeks
IE Diagnosis:
Other Cultures
Infective emboli dissected from the skin for culture and microscopy
Cardiac valves removed during
surgery - sent to the microbiology lab for culture
IE Diagnosis:
Serological Test
Chlamydophila psittaci and Coxiella
burnetii diagnosed by serological tests
IE Diagnosis:
Non-specific findings
Elevated:
White cell count
Erythrocyte sedimentation rate (ESR)
C-reactive protein (CRP)
IE Diagnosis:
Urinalysis
Proteinuria
Microscopic haematuria
Pyuria
IE Diagnosis;
Echocardiography
Trans-aortic or transesophageal
To visualize vegetations on the
cardiac valve
Infective Endocarditis:
Complications
Cardiac
Neurological
Kidneys
Emboli
IE Complications:
Cardiac
Valve destruction with acute heart failure
Myocarditis
Pericarditis
Abscess of the valve ring
Dysrhythmias
IE Complications:
Neurological
Toxic delirium
Meningitis/meningeal
Reactions
Cerebritis
Brain abscess
Infarctions
Mycotic aneurysm
IE Complications:
Kidney
Renal abscess or Renal infarctions with hematuria
Glomerulonephritis due to circulating immune complexes
Infective Endocarditis
Prevention
Maintenance of optimal oral health and hygiene
Prophylactic antibiotic therapy must be administered to high-risk patients
Recommended prophylactic antibiotic - Amoxicillin and in penicillin allergic patients erythromycin/ azythromycin/ clindamycin
Who needs prophylaxis?
- All prosthetic valves
- Previous IE
- A heart transplant with abnormal heart valve function
- Congenital cyanotic heart defects
- Rheumatic fever valve lesions
Which procedures?
-Dental procedures that involve manipulation of
gingival tissue or the periapical region of teeth,
or perforation of the oral mucosa
-Tonsillectomy,
Adenoidectomy
Antibiotics not recommended solely to prevent endocarditis for patients who are undergoing procedures involving the reproductive, urinary or
gastrointestinal tracts
Infective Endocarditis:
Treatment
Penicillin-susceptible streptococci;
-Penicillin
Streptococci and enterococci showing reduced susceptibility to penicillin:
-Penicillin/ampicillin plus gentamicin
Cloxacillin- (methicillin-) susceptible staphylococci (MSSA):
-Cloxacillin ± gentamicin
Cloxacillin-resistant staphylococci
(MRSA):
-Vancomycin + gentamicin
Fungi;
-Amphotericin B
Chlamydia psittaci/,Coxiella burnetii:
-Tetracycline
HACEK organisms:
-3rd generation cephalosporin
Pseudomonas species:
-Piperacillin/tazobactam+Tobramycin
