Pathology of rheumatic fever IE Valvular diseases DR

Pathology of rheumatic fever, IE & Valvular diseases DR. AMMAR AL-RIKABI / Dr Shaesta Naseem

RHEUMATIC FEVER (RF)

Rheumatic fever (RF) • Acute, immunologically mediated, multisystem inflammatory disease. • Involves heart, blood vessels, joints, subcutaneous tissue and CNS. • Occurs in 3% of patients, a few weeks after an episode of group A streptococcal pharyngitis. • Most often in children between ages 5 and 15. • Deforming fibrotic valvular abnormalities (esp MS) are important cardiac complications.

Pathologic sequence and key morphologic features of acute RHD

Diagnosis of acute RHD Ø Serologic evidence of a previous streptococcal infection + two or more of the following major Jones criteria: (1) carditis, (2) migratory polyarthritis of the large joints, (3) subcutaneous nodules, (4) erythema marginatum of the skin, and (5) Sydenham chorea, a neurologic disorder with involuntary purposeless, rapid movements. OR Jones minor criteria: nonspecific signs and symptoms : include fever, arthralgia, or elevated blood levels of acute-phase reactants One of the Jones major criteria manifestations and two minor manifestations also leads to diagnosis of acute RHD

PATHOLOGY of RF • Pathological hallmark : Aschoff bodies. • Aschoff bodies consist of foci of fibrinoid degeneration surrounded by lymphocytes (primarily T cells), occasional plasma cells, and plump activated macrophages called Anitschkow cells. • Anitschkow cells : have abundant cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, slender, wavy ribbon ("caterpillar cells") • It may become multinucleated.

Aschoff nodule and Anitschkow cell • During acute RF, diffuse inflammation and Aschoff bodies may be found in any of the three layers of the heart, causing pericarditis, myocarditis, or endocarditis (pancarditis)

. Rheumatic Heart Disease

Rheumatic endocarditis • Inflammation results in fibrinoid necrosis within the cusps or along the tendinous cords. • Overlying these necrotic foci are small (1 - to 2 -mm) vegetations, called verrucae, along the lines of closure. • Subendocardial lesions, aggravated by regurgitant jets, may induce irregular thickenings called Mac. Callum plaques, usually in the left atrium.

Chronic rheumatic heart disease • More likely to occur when the first attack: – In early childhood – Severe – Recurrence • The long-term prognosis is highly variable • Surgical repair or replacement of diseased valves has greatly improved the outlook for patients with RHD

Chronic RHD • Organization of the acute inflammation and subsequent scarring • Aschoff bodies are replaced by fibrous scar, so diagnostic forms of these lesions are rarely seen in chronic RHD • The major functional consequence of RHD is: Valvular stenosis and regurgitation

• In chronic disease the mitral valve is virtually always involved. • Mitral valve in chronic RHD : Ø leaflet thickening Ø commissural fusion Ø shortening, thickening and fusion of the tendinous cords

Chronic RHD-Signs /Symptoms The signs and symptoms of valvular disease depend on which valve(s) are involved • Mitral stenosis is the most common manifestation • Cardiac murmurs • Cardiac hypertrophy and dilation • CHF • Arrhythmias (atrial fibrillation in the setting of mitral stenosis) • Thromboembolic complications • Increased risk of subsequent infective endocarditis.

Small vegetations (verrucae) are visible along the line of closure of the mitral valve leaflet Aschoff body in myocardium Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets and commissural fusion (arrows, C), and thickening of the chordae tendineae Rheumatic aortic stenosis

. Schematic representation of the anatomic regions of involvement and location of vegetation in rheumatic endocarditis.

. Rheumatic Heart Disease

INFECTIVE ENDOCARDITIS (IE)

Infective endocarditis (IE) • It is a serious infection characterized by colonization or invasion of the heart valves or the mural endocardium by a microbe. • This leads to the formation of vegetations • Most cases are caused by bacterial infections (bacterial endocarditis). • Congenital heart disease is the most frequent factor that may predispose young children to IE.

IE - Pathogenesis • Bacteremia is a pre-requisite, the source could be: • • ü In damaged valves: Alpha hemolytic streptococci IV drug abuse: Usually Staph aureus, (right heart side valve affected; Dental or surgical procedure Trivial injury, skin, gut, urinary bladder Contributory conditions are immunosuppression and neutropenia • Diagnosis is largely made on the basis of: – positive blood cultures – evidence of endocardial involvement – echocardiographic findings – other clinical and laboratory findings

Clinical presentation and complications • Acute: – Fever, rigor, malaise – Large vegetation => emboli: • Infarction • Metastatic infection • Kidney: Ag-Ab complex => GN=> nephrotic syndrome or Renal failure – Congestive heart failure due to valve disease – Can lead to ring abscess and perforation of the aorta and myocardium – Death up to 60% • Subacute: – Insidious – Splenomegaly • Non specific fever, weight loss • Smaller vegetations, so less embolic

• The hallmark of IE is the presence of friable, bulky, potentially destructive vegetations. • The aortic and mitral valves are the most common sites of infection. • Vegetations containing fibrin, inflammatory cells, and bacteria on the heart valves • Vegetation sometimes erode into the underlying myocardium and produce an abscess (ring abscess).

. Infective endocarditis

Infective (bacterial) endocarditis. Endocarditis of mitral valve Acute endocarditis of congenitally bicuspid aortic valve Extensive acute inflammatory cells and fibrin. Healed endocarditis

NONINFECTED VEGETATIONS(sterile) • Nonbacterial thrombotic endocarditis NBTE and the endocarditis of SLE called Libman-Sacks endocarditis. • NBTE is often encountered in debilitated patients, such as those with cancer or sepsis. • It frequently occurs concomitantly with deep venous thromboses, pulmonary emboli.

NBTE • NBTE is characterized by the deposition of small sterile thrombi on the leaflets of the cardiac valves. • The lesions are 1 mm to 5 mm in size, and occur singly or multiply along the line of closure of the leaflets or cusps. • Histologically they are composed of bland thrombi that are loosely attached to the underlying valve. • The vegetation are not invasive and do not elicit any inflammatory reaction.

Nonbacterial thrombotic endocarditis (NBTE). A, Nearly complete row of thrombotic vegetations along the line of closure of the mitral valve leaflets (arrows). B, Photomicrograph of NBTE, showing bland thrombus, with virtually no inflammation in the valve cusp (c) or the thrombotic deposit (t). The thrombus is only loosely attached to the cusp (arrow

Comparison of the four major forms of vegetative endocarditis. The rheumatic fever phase of rheumatic heart disease (RHD) is marked by small, warty vegetations along the lines of closure of the valve leaflets. Infective endocarditis (IE) is characterized by large, irregular masses on the valve cusps that can extend onto the chordae Nonbacterial thrombotic endocarditis (NBTE) typically exhibits small, bland vegetations, usually attached at the line of closure. One or many may be present. Libman-Sacks endocarditis (LSE) has small or medium-sized vegetations on either or both sides of the valve leaflets.

. Cardiac squeal of infective endocarditis Extra-cardiac Complications

VALVULAR HEART DISEASE

Valvular Heart Disease • Can come to clinical attention due to stenosis, insufficiency (regurgitation or incompetence), or both. • Stenosis is the failure of a valve to open completely, which impedes forward flow. • Insufficiency, in contrast, results from failure of a valve to close completely, thereby allowing reversed flow.

The most frequent causes of the major functional valvular lesions are: • • Aortic stenosis: stenosis calcification of anatomically normal and congenitally bicuspid aortic valves • • Aortic insufficiency: dilation of the ascending aorta, usually related to hypertension and aging • • Mitral stenosis: rheumatic heart disease • • Mitral insufficiency: myxomatous degeneration (mitral valve prolapse)

Calcific Aortic Stenosis • The most common of all valvular abnormalities • The consequence of age-associated "wear and tear. • heaped-up calcified masses within the aortic cusps. • It ultimately protrude preventing the opening of the cusps. • Microscopically, the layered architecture of the valve is largely preserved.

Calcific valvular degeneration.

Aortic Stenosis • Valve becomes stiff and fibrotic, impeding blood flow with LV contraction • Results in LV hypertrophy, increased O 2 demands, and pulmonary congestion. • Causes – rheumatic fever, congenital, arthrosclerosis Atherosclerosis and calcification is primary cause in the elderly Symptoms • • • Angina Syncope Congestive Heart Failure (CHF) • Complications – right sided heart failure, pulmonary edema, and A-fib

Aortic Regurgitation Etiologies • Abnormalities of the Leaflets • Rheumatic, Bicuspid, Degenerative • Endocarditis • Dilation of the Aortic Annulus • Aortic Aneurysm / Dissection • Inflammatory • Inheritable (Marfans syndrome)

Mitral Stenosis Etiologies • Rheumatic – almost all cases in adults • Congenital – rare

Mitral Regurgitation Etiology: Abnormalities of leaflets and commissures eg Post inflammatory scarring, IE Symptoms: • Fatigue and weakness • Dyspnea and orthopnea • Right sided Heart failure