Download Rheumatic Fever and Heart Disease

Rheumatic Fever and Heart Disease
• Definition: rheumatic fever is an acute,
immunologically mediated, multi-system
inflammatory disease that follows, after a few
weeks, an episode of group A streptococcal
pharyngitis (3% of patients).
• The incidence and mortality of rheumatic fever
has declined over the past 30 years (due to
improved socioeconomic condition and rapid
diagnosis and treatment of strep. pharyngitis.
Rheumatic Fever: Heart
• Affect the heart during its acute phase 
acute rheumatic carditis.
• Cause chronic valvular deformities (many
years after the acute disease.
Pathogenesis and Key Morphologic Changes of Acute
Rheumatic Heart Disease
Hypersensitivity
reaction induced by
group A strept. (ab.
Against protein M
Cross-reaction /
Autoimmune response
Morphology: Acute Rheumatic Fever
• Inflammatory infiltrates occur in a wide
range of tissues: synovium, joints, skin,
heart.
• Focal fibrinoid necrosis  mixed
inflammatory reaction (diffuse or localized)
 Fibrosis (chronic rheumatic heart disease) .
Acute Rheumatic Carditis
• Pancarditis (endo- myo- pericarditis).
• Multiple foci of inflammation within the connective
tissue of the heart. (Aschoff bodies: central fibrinoid
necrosis, surrounded by chronic mononuclear
inflammatory infiltrate and occasional large
histiocytes).
• Diffuse interstitial inflammatory infiltrates (may lead
to generalized dilation of the cardiac chambers).
Acute Rheumatic Carditis
• Pericardial involvement: fibrinous pericarditis,
sometime associated with serous or
serosanguinous effusion.
• Endocardium:
– Mostly mitral and aortic valve.
– Valves are edematous and thickened with foci of
fibrinoid necrosis. (Aschoff nodules uncommon).
– Verrucous endocarditis (small vegetations along lines
of valve closure).
• Acute changes may resolve completely or progress
to scarring and chronic valvular deformities.
Rheumatic Fever: Involvement of
Other Organs
• Arthritis: large joints, self limited, no
chronic deformities.
• Lung: uncommon, chronic interstitial
inflammation and fibrinous pleuritis.
• Skin: skin nodules, erythema marginatum.
Chronic Rheumatic Heart Disease
• Irreversible deformity of one or more
cardiac valves (previous acute valvulitis).
• Left side of heart > right.
• Reduction of diameter (stenosis), or
improper closure (regurgitation), or both.
• May lead to cardiac failure (overload)
• May predispose to infective endocarditis.
Chronic Rheumatic mitral valvulitis
• Stenosis > regurgitation.
• Females > males.
• In stenosis:
–
–
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–
Leaflets are thick, rigid, and interadherent.
Dilatation and hypertrophy of left atrium.
Mural thrombi may be present systemic emboli.
Lungs are firm and heavy (chronic passive congestion).
Right heart may be affected later.
• In regurgitation:
– Retracted leaflets.
– Left ventricular hypertrophy and dilatation.
Chronic Aortic Valvulitis
• Males > females.
• Associated with mitral valvulitis.
• Aortic stenosis:
– Valve cusps are thickened, firm and
interadherent  rigid triangular channel.
– Left ventricular hypertrophy.
– Subsequent left ventricular failure and dilation.
• Aortic regurgitation: retraction of leaflets.
Acute Rheumatic Fever: Clinical
•
•
•
•
Occurs 10 days to 6 weeks after pharyngitis.
? Of genetic susceptibility.
Peak incidence: 5-15 years.
Pharyngeal culture may be negative, but anti
streptolysin O (ASO) titer will be high.
• Arthritis: large joints, migratory.
• Acute carditis: pericardial friction rubs, weak heart
sounds, tachycardia and arrhythmias.
myocarditis  cardiac dilation  functional mitral
valve insufficiency or even congestive heart failure.
Major criteria for diagnosis of
rheumatic fever
• Migratory polyarthritis: a temporary
migrating inflammation of the large joints,
usually starting in the legs and migrating
upwards.
• Carditis: inflammation of the heart muscle
which can manifest as congestive heart
failure with shortness of breath, pericarditis
with a rub, or a new heart murmur.
Major criteria for diagnosis of
rheumatic fever contd
• Subcutaneous nodules: painless, firm
collections of collagen fibers over bones or
tendons. They commonly appear on the
back of the wrist, the outside elbow, and the
front of the knees.
• Erythema marginatum: a long lasting rash
that begins on the trunk or arms. This rash
never starts on the face and it is made worse
with heat.
Major criteria for diagnosis of
rheumatic fever contd
• Sydenham's chorea (St. Vitus' dance): a
characteristic series of rapid movements
without purpose of the face and arms. This
can occur very late in the disease.
Minor criteria for diagnosis of
rheumatic fever
• Fever
• Arthralgia: Joint pain without swelling
• Raised Erythrocyte sedimentation rate or C
reactive protein
• Leukocytosis
Minor criteria for diagnosis of
rheumatic fever
• ECG showing features of heart block
• evidence of Streptococcal infection:
elevated or rising Antistreptolysin O titre or
DNAase.[1].
• Previous episode of rheumatic fever or
inactive heart disease
Chronic Rheumatic Carditis: Clinical
• Manifestation after years or decades after
the initial episode of rheumatic fever.
• Signs and symptoms depend on which
involved valve(s): cardiac murmurs,
hypertrophy, dilation, congestive heart
failure, arrhythmia, thromboembolic
complications and infective endocarditis.
A. Acute rheumatic mitral valvulitis superimposed on chronic rheumatic heart disease. Small vegetations (verrucae) are visible
along the line of closure of the mitral valve leaflet (arrowheads). Previous episodes of rheumatic valvulitis have caused fibrous
thickening and fusion of the tendinous cords.
Slide 13.34
B. Microscopic appearance of an Aschoff body in a patient with acute
rheumatic carditis. The myocardial interstitium has a circumscribed collection
of mononuclear inflammatory cells, including some large histiocytes with
prominent nucleoli, a prominent binuclear histiocyte, and central necrosis.
Slide 13.35
C. & D. Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrow in C),
and thickening and shortening of the tendinous cords. Marked dilation of the left atrium is noted in the left atrial view ( C).
Slide 13.36
D. Opened valve. Note the neovascularization of the anterior mitral leaflet (arrow).
Slide 13.37
E. Surgically removed specimen of rheumatic aortic stenosis demonstrating
thickening and distortion of the cusps with commissural fusion ( E from
Schoen FJ, St. John-Sutton M:
Contemporary issues in the pathology of valvular heart disease. Hum Pathol
18:568, 1967.)
Slide 13.38
Infective Endocarditis
• Definition: infection of the cardiac valves or
mural surface of the endocardium, resulting
in the formation of an adherent mass of
thrombotic debris and organisms.
• Divided into:
– Acute: high virulent organisms (staphylococcus
aureus), infect even normal valves, progress
rapidly, little local host reaction.
– Subacute: infection of previously abnormal
valves by organisms of low virulence (hemolytic streptococci), progress slowly,
induce local inflammatory reaction.
Infective Endocarditis: Etiology, Pathogenesis
• Bacteremia: i.v. drug abusers, elsewhere infection,
previous dental, surgical or interventional
procedure (catheterization).
• In some cases the source of bacteremia is occult.
• Infective endocarditis is a particularly difficult
infection to eradicate because of the avascular
nature of the heart valves.
Infective Endocarditis: Risk Factors
• Cardiac abnormalities: chronic valvular
diseases, high pressure shunts within the
heart (small ventricular septal defects).
• Prosthetic heart valves.
• Intravenous drug abusers.
Infective Endocarditis: Causative
Organisms
• Most common of non prosthetic valves (50-60%):
-Hemolytic (viridans) streptococci, which
attack previously damaged valves.
• Staphylococcus attack healthy or deformed
valves (10-20%).
• Prosthetic valve endocarditis is caused
commonly by coagulase-negative
staphylococci (e.g., S. epidermidis).
Infective Endocarditis: Morphology
• Valvular vegetations containing bacteria or
other organisms.
• Aortic and mitral valves are the most
common sites. (right side valves in i.v.users)
• Vegetations may be single or multiple,
involve one or more valve(s), differ in
appearance according to the causative agent.
Infective Acute Endocarditis:
Morphology
• Vegetations: may obstruct valve orifice, lead to
rupture of ( the leaflets, cordae tendineae, or
papillary muscles), abscess in perivalvular tissue
(ring abscess), friable vegetations may become
systemic emboli infarcts + abscesses.
• Micro: large number of organisms + fibrin and
blood cells. Neutrophilic inflammatory reaction
occurs the infection extends beyond the avascular
valves.
Infective Subacute Endocarditis:
Morphology
• Vegetations are firmer, less destructive, and
ring abscess are uncommon.
• Micro: Granulation tissue is seen at the base
of the vegetations, later: fibrosis,
calcifications and chronic inflammatory
infiltrates. Systemic emboli may develop
but they don’t undergo suppuration.
Infective Endocarditis: Clinical
• Onset: gradual or explosive (~organisms).
– Low-grade fever, malaise, weight loss.
– High fever, shaking chills.
• Cardiac murmurs.
• Enlargement of spleen, clubbing of digits (particularly in subacute cases).
• Systemic emboli (neurologic deficits, retinal abnormalities, necrosis of digits, and
infarcts of the myocardium.
• Pulmonary emboli in right-sided endocarditis.
• Mycotic aneurysms.
• Petechiae (due to micro emboli or deposition of immune complexes.
• Renal lesions: renal infarcts and glomerulonephritis.
• Valvular regurgitation and congestive heart failure due to progressive valvular
destruction.
• Blood culture for aerobic and anaerobic organisms is very important (only minority
of cases remain negative).
Endocarditis of the mitral valve (subacute, caused by Streptococcus viridens). The irregular, large friable vegetations are denoted by arrows.
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B. Acute endocarditis of a congenitally bicuspid aortic valve (caused by Staphylococcus aureus) with severe cuspal destruction and ring abscess (arrow).
Slide 13.41
C. Histologic appearance of vegetation of endocarditis with extensive acute inflammatory cells and fibrin. Bacterial organisms were
demonstrated by tissue Gram stain.
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D. Gross photograph illustrating healed endocarditis with perforations on bicuspid aortic valve
Slide 13.43
Nonbacterial Thrombotic Endocarditis
NBTE (marantic endocarditis)
• Characterized by the deposition of small
masses of fibrin, platelets, and other blood
components on the leaflets of the cardiac
valves (sterile).
• Pathogenesis/ association:
– Subtle endothelial abnormalities.
– Hypercoagulability.
– Association with malignancy (50%).
Nonbacterial Thrombotic Endocarditis
• Gross:groups of small nodules on the lines
of valve closure (similar to those of acute
rheumatic fever), valve leaflets are normal.
• Aortic valve most common site.
• Micro: fibrin and platelets aggregates, no
inflammation or fibrosis.
• Clinically asymptomatic, if large: may
embolize, may become infected.
(Libman-Sacks) endocarditis
• Less commonly, noninfective, verrucous
(Libman-Sacks) endocarditis attributable
to elevated levels of circulating immune
complexes may occur in patients with
systemic lupus erythematosus
Diagrammatic comparison of the lesions in the four major forms of vegetative
endocarditis. The rheumatic fever phase of RHD (rheumatic heart disease) is
marked by a row of warty, small vegetations along the lines of closure of the
valve leaflets. IE (infective endocarditis) is characterized by large, irregular
masses on the valve cusps that can extend onto the cords (see Fig. 13–18 A).
NBTE (nonbacterial thrombotic endocarditis) typically exhibits small, bland
vegetations, usually attached at the line of closure. One or many may be
present (see Fig. 13–20). LSE (Libman-Sacks endocarditis) has small or
medium-sized vegetations on either or both sides of the valve leaflets.
Slide 13.44
Nonbacterial thrombotic endocarditis (NBTE).
A. Nearly complete row of thrombotic vegetations along the line of closure of
the mitral valve leaflets.
B. Photomicrograph of NBTE showing bland thrombus, with virtually no
inflammation in the valve cusp (c) or the thrombotic deposit. The thrombus is
only loosely attached to the cusp (arrow).
Slide 13.45
Pericarditis
• Primary: mostly viral, sometimes by other
microorganisms (pyogenic bacteria, mycobacteria
and fungi.
• Secondary to: acute myocardial infarction, cardiac
surgery, or radiation to the mediastinum.
• Associated systemic disorders, mostly with
uremia.
• Less common 2ndry causes: rheumatic fever, SLE,
and metastatic malignancies (bloody effusions).
Pericarditis
• Cause immediate hemodynamic
complications, if significant effusion is
present.
• Resolve without significant sequelae.
• Progress to chronic fibrosing process.
Acute Pericarditis: Morphology
• In uremia, and acute rheumatic fever: the exudate is
fibrinous and impart a shaggy irregular pericardial surface
(bread and butter pericarditis).
• Viral pericarditis  fibrinous exudate.
• Acute bacterial pericarditis  fibrinopurulent pericarditis.
• Tuberculosis caseous materials.
• Pericardial metastases: irregular nodules.
• Exudate usually resolve unless there is excessive
suppuration or caseation, where healing leads to chronic
pericarditis.
Chronic Pericarditis: Morphology
• Ranges from delicates adhesions to dense
fibrotic scars that obliterate the pericardial
space.
• In extreme cases the heart can’t expand
during diastole : constrictive pericarditis.
Pericarditis: Clinical
• Atypical chest pain (worse on reclining).
• High pitch friction rub.
• Significant exudate cardiac tamponade 
faint distant heart sounds, distended neck
veins, declining cardiac output, and shock.
• Chronic constrictive pericarditis  venous
distension and low cardiac output.
Hemopericardium
• Accumulation of large amounts of blood in
the pericardial space is called as
hemopericardium.
• Hemopericardium can be seen in rupture of
the myocardium secondary to acute
myocardial infarction. It may also be seen
in pericarditis especially when it is
secondary to metastatic nodule in the
pericardial space.
Acute suppurative pericarditis
as an extension from
pneumonia. Extensive
purulent exudate is evident in
this in situ photograph.
Slide 13.56