RHEUMATIC HEART DISEASE• Rheumatic heart disease is a condition in which

the heart valves are damaged by rheumatic fever.• Rheumatic fever occurs equally in both sexes and

at all ages, but it is more common in children with the peak incidence occuring between ages 5 and 15 years.

Causesfever only develops in children and adolescents

following group A beta-hemolytic streptococcal pharyngitis.

• Genetic studies show strong correlation between progression to rheumatic heart disease and human leukocyte antigen (HLA)-DR class II alleles and the inflammatory protein-encoding genes MBL2 and TNFA.2 Furthermore, both clones of heart tissue–infiltrating T cells and antibodies have been found to be cross-reactive with beta-hemolytic streptococcus. Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10-(+) cells are consistently predominant in valvular tissue, whereas IL-4 regulatory cytokine expression is consistently low.

MORPHOLOGY• In acute RF focal inflammatory lesions are found in

various tissues.• Distinctive lesions occur in the heart called Aschoff

bodies which consist of foci of lymphocytes, ocassionally plasma cells and plump activated macrophages called Anitschkow cells.

• These macrophages hve abundant cytoplasm nd central round to ovoid nuclei, in whch chromatin is disposed in central,s lender wavy ribbon hence named “caterpillar cells” nd may bcum multninucleated.

• Aschof bodies may found in any of three layers of heart cause pancarditis

• Fibrinoid necrosis and and vagitation called verrucae found along the line of closure of valve.

• MacCallum plaque the Irregular thickening usually in left atrium is seen.

• In chroni RHD leaflet thickening,connisural fusion, shortning ,thickening and fusion of tendinous cord are cardinal changes .

• Fibrous bridging across valvular commisure and calcification creat fish mouth or button hole stenosis

Here is an Aschoff nodule at high magnification. The most characteristic component is the Aschoff giant cell. Several appear here as large cells with two or more nuclei that have prominent nucleoli. Scattered inflammatory cells accompany them and can be mononuclears or occasionally neutrophils.

Microscopically, acute rheumatic carditis is marked by a peculiar form of granulomatous inflammation with so-called "Aschoff nodules" seen best in myocardium. These are centered in interstitium around vessels as shown here. The myocarditis may be severe enough to cause congestive heart failure.

Stenotic mitral valve seen from left atrium. Both commissures are fused; the cusps are severely thickened. The left atrium is huge. The valve is both incompetent and stenotic

Opened stenotic mitral valve showing thickening distorted cusps, adherent commissures with calcification and thrombus deposition, and thickening, fusion and shortening of chordae tendinae

Aortic valve showing active valvulitis. The valve is slightly thickened and displays small vegetations – "verrucae"

Stenotic mitral valve seen from left atrium, showing fusion of commissures, thickening and calcification of the cusps

Another peculiar cell seen with acute rheumatic carditis is the Anitschkow myocyte. This is a long, thin cell with an elongated nucleus.

Guidelines for the diagnosis of initial attack of rheumatic fever (Jones Criteria)

Major manifestations• Carditis (murmur,

cardiomegaly, pericarditis, and congestive heart failure)

• Polyarthritis• Sydenham’s chorea• Subcutaneous nodules • reactants Erythema

marginatum

Minor manifestations• Fever• Arthralgia • Elevated sedimentation

rate, positive test for C-reactive protein, leukocytosis)

• Prolonged PR interval

Differential diagnosis of rheumatic fever• Juvenile rheumatoid

arthritis• SLE• Infective endocarditis• Reactive arthritis• Sickle cell disease• Drug reactions

• Other connective tissue diseases

• Septicaemia• Leukaemia• Gonoccocal arthritis• Tuberculosis• Lyme disease• Serum sickness

Subcutaneous nodule on the extensor surface of elbow of a patient with acute RF

Closer view of erythema marginatum

Erythema marginatum on the trunk, showing erythematous lesions with pale centers and rounded or serpiginous margins

Sydenham's Chorea

Fate of the patients with rheumatic fever:• Complete recovery after an acute attack of rheumatic fever is

possible.• - Adhesive pericarditis, which follows the fibrinous pericarditis

of the acute attack, almost never results in constrictive pericarditis.

• - Most significant late result of rheumatic fever is scarring of the heart valve.

• - There is increased susceptibility to the localization of infectious agents on the heart valves.

• The irregular scarred nature of the valves provides a suitable environment to bacteria that would originally pass by.

• The organism settle down to establish bacterial endocarditis.

• Because bacteremia frequenly follows a tooth extraction or urethral catheterization, a person who has prior diagnosis of rheumatic heart disease should be treated prophylactically with penicillin before performing these procedures.

• - Mural thrombi can form in the atrial or ventricular chambers and give rise to thromboembolic and infarction of various organs.

• Atrial thrombosis occurs in about 40% of patients with rheumatic valvular disease. Rarely a large thrombs in the left atrial appendage develops a stalk and acts as a ball valve that obstructs the mitral valve orifice.

• Causes of death in rheumatic fever and rheumatic heart disease:

• Cardiac failure ; Infective endocarditis ; Embolism ( involve brain followed by the kidneys, spleen and lungs) ; Sudden death occur as a result of obstruction of the mitral valve orifice by a ball thrombus in the left atrium or as a result of coronary ischemia associated with aortic stenosis ; Thrombophlebitis of leg veins and pulmonary embolism ; Death may occur from various other conditions such as pneumonia.

Extracardiac lesions: • Subcutaneous nodules : ( Painless nodules occur in

wrist, elbows, ankles and knees. Nodules occur in children and last for 4 to 6 days unlike rheumatoid nodules which may persist for months or years and may be painfull and tender .

• Microscopic features: Consist of a central core of fibrinoid necrosis surrounded by a zone of radially palisading histiocytes and fibroblasts ).

• - Arteritis : (coronary artery inflammation-rheumatic arteritis ) ;

• -Polyarthritis

• Lesions in lungs and pleura : (Pleuritis ; Pleural effusion ; Rheumatic pneumonia ; Lungs are usually congested , hemosiderin-laden heart failure cells are seen within alveoli, together with fibrosis of the alveolar septal walls . In addition, there is usually some pulmonary vascular change, principally muscular and intimal arteriolar thickening. Right ventricular hypertrophy -cor pulmonale may develop as a result of a reactive pulmonary hypertension)

• Lesions of the central nervous system : (Sydenham's chorea : disordered and involuntary movements of the trunk and extremities).

Chest radiograph of an 8 year old patient with acute carditis before treatment

same patient after 4 weeks

Laboratory studies

• Acute phase reactants are useful in helping to recognize acute RF and also to exclude other diseases. C-reactive protein and erythrocyte sedimentation rates are helpful in monitoring inflammatory activity.24

• Laboratory evidence of a preceding GAS infection should be sought, either by demonstration of GAS in the throat by culture or rapid streptoccocal antigen test, or using streptococcal antibody tests. Elevated or rising titers of antistreptolysin O (ASO) occur in more than 80% of patients with acute GAS pharyngitis.24 There is a remarkable response during the acute phase of RF. The test specificity has been shown to be 93% with ASO titers above 960 IU/ml.33

• Prolonged P-R interval relative to heart rate is a nonspecific finding, present in more than one third of the patients.

• Low-voltage QRS complexes and ST segment changes may be found in the presence of pericarditis and pericardial effusion.

• Inverted or flattened T waves indicate myocaditis• Endomyocardial biopsy is invasive and does not appear to

provide additional diagnostic information where there is a clinical consensus about the diagnosis of RF, with a diagnostic sensitivity in one relatively large study of 27%. It should be limited to clinical investigation.23,34

• Cardiac scanning scintigraphy has been shown to be a reliable method distinguishing acute from chronic, inactive RHD and also in the follow-up of active carditis