Rheumatic Fever & Rheumatic Heart Disease

Rheumatic Fever Rheumatic fever (RF) is an acute, immunologically mediated, multisystem inflammatory disease that occurs a few weeks following an episode of group A streptococcal pharyngitis. Major involvement of systemic connective tissue, it often violate connective tissue of heart, joint, skin, and subcutaneous and vascular connective tissue. Key pathologic features is Rheumatic Granuloma. It occurs in children in age 5 to 15 years, 20% -adults The clinical course of rheumatic fever involves a childhood infection with complications in adulthood (cardiac defect).

Etiology and pathogenesis It is an immune response associated with streptococcal infection, but it is not caused by bacteria directly effects.

The evidence related with group A β-hemolytic streptococcus infection including: There is a streptococcus infection history before the onset of RF. A variety of antibodies of the streptococcus and its products can be detected in the onset phase. serous "O" antibody in 95% patients is high, > 500 units. Regional distribution consistent with area of streptococcal infection. Antibiotic prophylaxis treatment is effective.

The evidence which is not directly caused by streptococcus infection including: The disease is not appeared in infected at the time, but in 2-3 weeks later, it is in line with emergence period of the general immune response. No evidence of direct invasion of organ by streptococcus. Streptococcus has never been found in the RF patient's blood . Not purulent inflammation, but the fibrinoid necrosis.

Antigen and antibody cross-reactivity: The antigens of streptococcus may stimulate the immunological cross-reactivity in patients.

Pathogenesis M antibody+Vascular smooth muscle C antibody+Cardiovascular connective tissue Antigen antibody complex activation of coagulation system Local deposition alexin platelet Embolism, bleeding Neutrophil infiltration Release of lysosomal enzymes(Neutral, acid hydrolases, elastase, collagenase and so on Blood vessel, tissue injury

Basic pathological changes Exudative and degenerative phase The proliferative phase (Granulomatous period) Scar phase (healed phase\Fibrosis phase\Hardening phase)

Exudative and degenerative phase It is characterized by serofibrinous exudate, with deposits of immune precipitate on collagen fibers that lead to fibrinoid necrosis. About 1 months.

The proliferative phase (Granulomatous period) Aschoff Body: pathognomonic for RF Structure: center： fibrinoid necrosis around the center：Anitschkow cells , lymphocytes, occasional plasma cells Distribution: Myocardial interstitial, subendocardial and subcutaneous connective tissue. Epicardial, joints and blood vessels is rare.

Anitschkow cells: These distinctive cells have abundant cytoplasm and central round-to-ovoid nuclei in which the chromatin is disposed in a central, slender, wavy ribbon (hence the designation "caterpillar cells“-- cross section named Owl 's eye cells). Some of the larger macrophages become multinucleated to form Aschoff cells(inflammatory giant cells).

The myocardial interstitium has a circumscribed collection of mononuclear inflammatory cells, including some large histiocytes with prominent nucleoli and a prominent binuclear histiocyte, and central necrosis

Aschoff cells Owl 's eye cells

Scar phase Emergence of fibroblasts and collagen production, formation of small spindle scar, 2-3 months or so. The above three stages repeated attacks, the old and new lesions coexist. The whole course about 4-6 months.

RF involves various organs Rheumatic heart disease Rheumatic arthritis Rheumatic arteritis Rheumatic disease of skin Rheumatic disease of brain

Rheumatic heart disease Divided into rheumatic endocarditis, rheumatic myocarditis and rheumatic pericarditis, often for rheumatic pancarditis. 60% to 80% children associated with pancarditis。

Key morphologic features of acute rheumatic heart disease.

rheumatic endocarditis The most important lesions caused by rheumatism, valvular deformity and dysfunction Lesions were most often involved: mitral valve Secondly: both mitral and aortic valve

Pathological changes: early stage: serous endocarditis , valve swelling,translucent Microscopically: valve become loose due to serous exudate , accompanied by macrophages entering and fibrinoid necrosis of collagen fiber. Concomitant involvement of the endocardium and the left- sided valves by inflammatory foci typically results the small (diameter 1- to 2-mm) vegetations . Vegetations: White thrombus consist of platelet and cellulose.

Acute rheumatic endocarditis: small (diameter 1- to 2-mm) vegetations along the mitral valve margin, insufficient to cause valvular deformation.

Small vegetations (verruca) are visible along the line of closure of the mitral valve leaflet (arrows).

Advanced: vegetations organization, recurrent organization cause chronic heart valve disease ( valvular stenosis and / or valvular insufficiency )

Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets, commissural fusion (arrows), and thickening and shortening of the chordae tendineae.

rheumatic myocarditis location:Myocardial interstitial connective tissue pathological changes: Rheumatic Granuloma

Perivascular Rheumatic Granuloma formation Perivascular Rheumatic Granuloma formation. Children often occurred to diffuse myocardial interstitial edema, inflammatory cell infiltration, congestive heart failure. Late effects myocardial contractile force.

rheumatic pericarditis A serous or serous fibrinous inflammation. Can form a pericardial effusion, trichocardia and constrictive pericarditis.

Serous pericarditis Fibrinous pericarditis

Can lead to heart sound far, around the heart boundary expanding, serious cardiac X-ray showed a flask pericardial effusion

Adhesive pericardit is in cardiac surface of patients Adhesive pericardit is in cardiac surface of patients. From the epicardial surface to the pericardial sac visible fibrinous exudate, which is typical for a fibrinous pericarditis.

trichocardia Can lead to precordial pain, pericardial friction sound, serious cause constrictive pericarditis, influence on cardiac function.

lick the knee but bite the heart. Rheumatoid arthritis predilection age: Adults predilection site: involving the large joints, most commonly in the knee and ankle joint, followed by the shoulder, wrist, elbow and other joints Lesion characteristics: migratory polyarthritis. Local serous exudate, appear red, swelling, heat, pain and dysfunction. As the heals , serous exudate is absorbed, generally no sequela. Microscopic lesions mainly for serous inflammation. lick the knee but bite the heart.

rheumatic arteritis Involving the coronary arteries, renal artery, brain artery etc, small arteries see more. Vascular wall connective tissue myxoid degeneration and fibrinoid necrosis. There can see Rheumatic Granuloma, and later wall narrow even block, with thrombosis. Rheumatoid coronary artery inflammation.

Rheumatic disease of skin Mainly in acute period 1 subcutaneous nodules ( hyperplasia ): 2 The annular erythema (exudative lesions) : Appear on the extremities and the trunk skin. 1-2 days. Hyperemia, edema changes of the superficial layer of dermis. (pathognomonic )

annular erythema

Rheumatic disease of brain Mainly involving the cerebral cortex, basal ganglia, thalamus and cerebellum cortex. Lesions to rheumatic arteritis and subcortical encephalitis. In 5-12 years old children, girls see more.

Infective endocarditis (IE) Infective endocarditis, one of the most serious of all infections, is characterized by colonization or invasion of the heart valves or the mural endocardium by a microbe, leading to the formation of bulky, friable vegetations composed of thrombotic debris and organisms, often associated with destruction of the underlying cardiac tissues.

Traditionally, IE has been classified on clinical grounds into acute and subacute forms. Acute IE Subacute IE

1Acute IE :The strong pathogenic pyogenic bacteria（carbuncle, puerperal fever, osteomyelitis ）---resistance down---bacteria into the blood---sepsis---normal endocardium ---invasion of mitral valve, aortic valve---acute septic endocarditis---bacterial vegetations 2Subacute IE: Streptococcus viridans (localized infection focus in vivo or iatrogenic infection)---- bacteria into the blood---the mitral valve or/and aortic valve with original lesions （80%, congenital heart disease, RHD or valve repair)-- Subacute IE--bacterial vegetations

Pathological change In both the subacute and acute forms of the disease, friable, bulky, and potentially destructive vegetations containing fibrin, inflammatory cells, and bacteria or other organisms are present on the heart valves.

vegetations ( microscopic ): cellulose + platelet +inflammatory cell + bacteria group

In the aortic opening a larger, irregular red vegetations, this mostly by Staphylococcus aureus infection.

Acute IE :Caused the distant organ septic infarction and abscess Acute IE :Caused the distant organ septic infarction and abscess. Valve rupture, perforation, rupture of chordae tendineae, leading to chronic valvular heart disease. 50% died in days or weeks.

Subacute IE

End and complications： 1.Fever: it is the most consistent sign of IE. However, with subacute disease, particularly in the elderly, fever may be slight or absent, and the only manifestations are sometimes nonspecific fatigue, loss of weight, and a flulike syndrome. In contrast, acute endocarditis has a stormy onset with rapidly developing fever, chills, weakness, and lassitude. 2.Arterial embolization ( 20%-40% ): embolism of brain ,heart, kidney, spleen, mesenteric, limbs and pulmonary.

3.Chronic valvular disease 4.non-specific symptoms: Splenomegaly (15%-50% ) Anemia Clubbing finger / toe 5. Peripheral symptoms

Peripheral symptoms: Micro vasculitis or micro thrombus

splinter or subungual Hemorrhages:petechiae, red, linear, or flame-shaped streaks in the nail bed of the digits

Osler nodes : retinal hemorrhages

Janeway lesions: are small erythematous or hemorrhagic, macular, nontender lesions on the palms and soles and are the consequence of septic embolic events.

Osler nodes: are small, tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers and persist for hours to several days.

杵状指/趾

rheumatic endocarditis Subacute IE Etiology immunologically mediated bacterial infection grossly White, small, compact vegetations gray red, large, loose vegetations, fall off easily microscopically white thrombus White thrombus with necrosis, colony etc. clinical feature Valvular Disease Valvular heart disease, thromboembolism, infarction, Septicemia connection SIE often occurs on the basis of RE