Rheumatic diseases

1. Rheumatic diseases Assistant of professor Nechiporenko G.V.

2. COLLAGEN DISEASES • Rheumatic fever • Systemic lupus erythematosus • Rheumatoid arthritis • Systemic sclerosis • Polyarteritis nodosa • Siogren’s syndrome

3. Rheumatic fever (RF) • It is a systemic, post-streptococcal, non-suppurative inflammatory disease, principally affecting the heart, joints, central nervous system, skin and subcutaneous tissues.

4. Clinical-anatomical forms of RHEUMATIC FEVER 1.Cardiovascular form (endocarditis, myocarditis, pericarditis). Chronic stage of RF involves usually all layers of the heart (pancarditis) causing major consequence referred to as rheumatic heart disease (RHD). William Boyd many years ago gave the dictum “rheumatic licks the joint, but bites whole heart”. 2. Polyarthritic form (large joints). 3.Nodular form (nodules around vessels). 4.Cerebral form (chorea minor).

5. RHEUMATIC ENDOCARDITIS • Rheumatic valvulitis and mural endocarditis are chiefly responsible for the major cardiac manifestations in chronic rheumatic heart disease. • Acute stage of rheumatic valvulitis shows thickening and loss of translucency of the valve cusps with following development of verrucae (vegetations, warty) along the line of closure. Histological changes are disorganization of connective tissue with mucoid sweeling, fibrinoid degeneration, cellular reactions with formation of Aschoff bodies, thrombi.

6. The small verrucous vegetations are seen along the closure line of mitral valve with acute rheumatic fever. These warty vegetations average only a few millimeters

7. In time, chronic rheumatic valvulitis may develop by organization of the acute endocardial inflammation along with fibrosis, as shown here affecting the mitral valve. Note the shortened and thickened chordae tendineae.

8. RHEUMATIC MYOCARDITIS 1.Nonspecific exudative interstitial myocarditis. 2.Granulomatous myocarditis • The giagnostic perivascular nodules (Aschoff bodies) are most frequent in the interventricular septum, left ventricle and left atrium. • Evolution of fully-developed Aschoff bodies involves 3 stages: • Early (exudative or degenerative) stage- about 4th week of illness with progressive disorganization of connective tissue (hypersensitivity of immediate type with fibrinoid degeneration).

9. Intermediate (proliferative or granulomatous) stage-in 4th- to 13th week of ilness. Formation of lymphocytes, plasma cells, a few neutrophils and the characteristic cardiac histiocytes (Anitschkow cells) at the margin of lesion. Some of these modified cardiac histiocytes become multinucleate cells containing 1to 4 nuclei and are called Aschoff cells (hypersensitivity of delayed type with cellular infiltration).

10. Late (healing or fibrous) stage- about 12 to 16 weeks after the ilness.The Anitschkow cells in the nodule become spindle-shaped with diminished cytoplasm and the solid nuclear stain. These cells tend to be arranged in a palisaded manner. It is replaced by a small fibrocollagenous scar with little cellularity

11. Acute rheumatic myocarditis with "Aschoff nodules“. These are centered in interstitium around vessels. The myocarditis may cause congestive heart failure.

12. Fibrinous pericarditis. A window of adherent pericardium has been opened to reveal the surface of the heart. There are thin strands of fibrinous exudate that extend from the epicardial surface to the pericardial sac.

13. The pericardial surface shows strands of pink fibrin extending outward. Fibrin can be organized and cleared, though sometimes adhesions may remain.

14. Valvular diseases and deformities • Stenosis is the term used the failure of a valve to open completely during diastole resulting in obstruction to the forward flow of the blood. • Mitral stenosis occurs in about 40% of all patients with RHD. About 70% of the patients are women. • The valve cusps are diffusely thickened by fibrous tissue and/or calcific deposits. ”Purse-string puckering”, ”button-hole“ or “fish-mouth” mitral orifice. • Effects: dilatation and hypertrophy of the left atrium; pulmonary hypertension with following chronic venous congestion of the lungs, hypertrophy and dilatation of the right ventricle; right heart failure in time.

15. The mitral valve demonstrates the typical "fish mouth" shape with chronic rheumatic scarring.

16. Heart, rheumatic mitral stenosis, atrial changes - Gross, atrial endocardial surface  The mitral valve has been reduced to a narrow orifice. The left atrium is markedly dilated. Thrombi have formed on the atrial wall.  

17. Aortic stenosis comprises about 25% of all patients with chronic valvular heart disease. About 80% patients are males. There are non-calcific and calcific type, the latter being more common. The aortic cusps show characteristic fibrous thickening and calcific nodularity of the closing edges. • Effects: obstruction to the outflow resulting in concentric hypertrophy of the left ventricle, there is dilatation as well as hypertrophy of the left ventricle (eccentric hypertrophy). • Three cardinal symptoms of aortic stenosis are: exertional dyspnea, angina pectoris, syncope.

18. Rheumatic aortic stenosis

19. Insufficiency or incompetence or regurgitation is the failure of valve to close completely during systole resulting in back flow or regurgitation of blood. • Mitral insufficiency occurs in about 50% patients with RHD more often in men (75%). • Effects: dilatation and hypertrophy of the left ventricle; dilatation of the left atrium; pulmonary hypertension with following chronic venous congestion of the lungs, hypertrophy and dilatation of the right ventricle; right heart failure in time.

20. Aortic insufficiency occurs predominantly in males (75%) with RHD. • The aortic valve cusps are thickened, deformed and shortened and fail to close. There is generally distension and distortion of the ring. • Effects: hypertrophy and dilatation of the left ventricle producing massive cardiac enlargement so that the heart may weigh as much as 1000 gm. • The characteristic physical findings of aortic insufficiency are awareness of the beatings of the heart, poundings in the head with each heart beat, low diastolic and high pulse pressure, rapidly rising and collapsing water hammer pulse, booming ”pistol shot” sound over the femoral artery.

21. This is an excised porcine bioprosthesis; the undersurface is at the left and the outflow side is at the right. Note there are three cusps sewn into a synthetic ring.

22. Systemic lupus erythematosus • Systemic lupus erythematosus (SLE) is a chronic disease with many manifestations. SLE is an autoimmune disease in which the body's own immune system is directed against the body's own tissues. The etiology of SLE is not known. It can occur at all ages, but is more common in young women. • The production of autoantibodies leads to immune complex formation. The immune complex deposition in many tissues leads to the manifestations of the disease. • Immune complexes can be deposited in glomeruli, skin, lungs, synovium, mesothelium, and other places. Many SLE patients develop renal complications.

23. The young woman has a malar rash in DLE ("butterfly" rash because of the shape across the cheeks).

24. Face, malar (butterfly) rash of systemic lupus erythematosus -SLE

25. The skin in SLE may demonstrate a vasculitis and dermal chronic inflammatory infiltrates

26. Kidney, chronic lupus nephritis  Note the diffuse granularity of the cortex

27. Here is a glomerulus with thickened pink capillary loops, the so-called "wire loops“.

28. Crescentic lupus nephritisSeen here within the glomeruli are crescents composed of proliferating epithelial cells.

29. Immunofluorescence with antibody to IgG.A granular pattern of immunofluorescence is seen, indicative of deposition of immune complexes in the basement membranes of the glomerular capillary loops.

30. The thickened basement membrane (arrow) that results from immune complex deposition in the glomerular capillary loop is prominent in this electron micrograph. The dark immune deposits are located mainly in a subendothelial position.

31. The periarteriolar fibrosis ("onion skinning") is seen in the spleen.

32. RHEUMATOID ARTHRITIS • Rheumatoid arthritis (RA) is a chronic multisystemic inflammatory disease of unknown origin involving peripheral joints with symmetrical distribution. Its systemic manifestations include hematologic, pulmonary, neurological and cardio-vascular abnormalities. • RA is an autoimmune disease.

33. The characteristic feature is diffuse proliferative synovitis with formation of pannus. • Lesions affect small joints of hands and feet mainly. • The synovial membrane becomes thick, edematous, hyperplastic and covered by villous projections. • Chronic inflammatory cellular infiltrate in the synovium with predominance of lymphocytes, plasma cells and some macrophages, at places forming lymphoid follicles. • Organized fibrin deposit over the synovial surface. • Pannus creeps over the articular cartilage. • Erosion of the articular cartilage and subchondral bone. • Fibrous and osseous ankylosis.

34. Hand, acute rheumatoid arthritis

35. Synovium, rheumatoid arthritisPrimary lesion of rheumatoid arthritis is synovitis.  

36. You can see here in the synovium collections of dark blue lymphocytes.

37. Synovium, rheumatoid arthritis, pannusThe pannus isolates the articular cartilage from the synovial fluid, resulting in degeneration of articular cartilage

38. Rheumatoid nodules consist of a central zone of fibrinoid necrosis surrounded by a prominent rim of epithelioid histiocytes and numerous mononuclear cells

39. Polyarteritis nodosa (PAN) • It is necrotising-granulomatous vasculitis involving small and medium-sized muscular arteries of multiple organs and tissues (kidneys, heart, liver, GIT, muscles, pancreas, testes, nervous system, skin). • The condition is believed to result from deposition of immune complexes and tumor-related antigens. The disease occurs more commonly in adult males.

40. Acute stage. There is fibrinoid necrosis in the centre of nodules located in the media of vessels. An acute inflammatory response develops around it. The inflammatory infiltrate is present in the entire circumference of the affected vessel (periarteritis) and consists chiefly of eosinophils, mononuclear neutrophils. • Healing stage. This is characterised by marked fibroblastic proliferation producing firm nodularity. • Heales stage. The affected arterial wall is markedly thickened due to dense fibrosis.

41. Kidney, polyarteritis nodosa Two small renal infarcts of tissue supplied by small to medium-sized arteries are evidenced by pale necrotic areas at the top of this specimen. This is an immune-complex disease frequently associated with hepatitis B virus (HBV) and cytomegalovirus (CMV) antigens.    

42. Here is a vasculitis of a renal arterial branch. Lymphocytes are scattered in and around the vessel.

43. Systemic sclerosis or Scleroderma 1.Localized form - morphea It consists of lesions limited to the skin and subcutaneous tissue 2.Generalized form- progressive systemic sclerosis It consists of extensive involvement of the skin, subcutaneous tissue and has visceral lesions a) CREST-syndrome C= calcinosis R= Raunad’s phenomenon (functional vaso-spastic disorder affecting small vessels of fingers and hands) E= esophageal dismotility S=sclerodactylia T=telangiectasia

44. Hand, scleroderma, sclerodactyly Dense cutaneous fibrosis (note smooth shiny skin) hascausedimmobility of the fingers, causing the claw-like appearance seen here. In advanced cases, impairment of blood supply may lead toulcerationor autoamputation.  

45. Skin, scleroderma The dermis is thickened due to growth of connective tissue

46. Lung, lower lobe, systemic sclerosis

47. Cardiomyopathies

48. The heart in the middle is relatively normal. The one on the left shows concentric hypertrophy. The one on the right shows ventricular dilation in dilated cardiomyopathy

49. This very large heart has a globoid shape because all of the chambers are dilated. It felt very flabby, and the myocardium was poorly contractile.

50. Here is a large, dilated left ventricle typical of a dilated or congestive cardiomyopathy.