Rheumatic Rheumatic diseasesdiseases

Assistant of professor Assistant of professor

Nechiporenko G.V.Nechiporenko G.V.

COLLAGEN DISEASESCOLLAGEN DISEASES

Rheumatic feverRheumatic fever Systemic lupus erythematosusSystemic lupus erythematosus Rheumatoid arthritisRheumatoid arthritis Systemic sclerosisSystemic sclerosis Polyarteritis nodosaPolyarteritis nodosa Siogren’s syndromeSiogren’s syndrome

Rheumatic fever (RF)Rheumatic fever (RF)

It is a systemic, post-It is a systemic, post-streptococcal, non-streptococcal, non-suppurative inflammatory suppurative inflammatory disease, principally disease, principally affecting the heart, joints, affecting the heart, joints, central nervous system, central nervous system, skin and subcutaneous skin and subcutaneous tissues.tissues.

Clinical-anatomical forms of Clinical-anatomical forms of RHEUMATIC FEVERRHEUMATIC FEVER

1.Cardiovascular form (endocarditis, 1.Cardiovascular form (endocarditis, myocarditis, pericarditis). Chronic myocarditis, pericarditis). Chronic stage of RF involves usually all layers stage of RF involves usually all layers of the heart (pancarditis) causing major of the heart (pancarditis) causing major consequence referred to as rheumatic consequence referred to as rheumatic heart disease (RHD). William Boyd heart disease (RHD). William Boyd many years ago gave the dictum many years ago gave the dictum “rheumatic licks the joint, but bites “rheumatic licks the joint, but bites whole heart”.whole heart”.

2. Polyarthritic form (large joints).2. Polyarthritic form (large joints).3.Nodular form (nodules around vessels).3.Nodular form (nodules around vessels).4.Cerebral form (chorea minor). 4.Cerebral form (chorea minor).

RHEUMATIC RHEUMATIC ENDOCARDITISENDOCARDITIS

Rheumatic valvulitisRheumatic valvulitis and and mural mural endocarditisendocarditis are chiefly responsible for are chiefly responsible for the major cardiac manifestations in the major cardiac manifestations in chronic rheumatic heart disease. chronic rheumatic heart disease.

Acute stage of Acute stage of rheumatic valvulitisrheumatic valvulitis shows shows thickening and loss of translucency of the thickening and loss of translucency of the valve cusps with following development of valve cusps with following development of verrucae (vegetations, warty) along the verrucae (vegetations, warty) along the line of closure. Histological changes are line of closure. Histological changes are disorganization of connective tissue with disorganization of connective tissue with mucoid sweeling, fibrinoid degeneration, mucoid sweeling, fibrinoid degeneration, cellular reactions with formation of Aschoff cellular reactions with formation of Aschoff bodies, thrombi.bodies, thrombi.

The small verrucous vegetations The small verrucous vegetations are are seen along the seen along the closure line of mitral valve with acute rheumatic closure line of mitral valve with acute rheumatic

fever. These warty vegetations average only a few fever. These warty vegetations average only a few millimeters millimeters

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

RHEUMATIC RHEUMATIC MYOCARDITISMYOCARDITIS 11.Nonspecific exudative interstitial .Nonspecific exudative interstitial

myocarditis.myocarditis.22.Granulomatous myocarditis.Granulomatous myocarditis The giagnostic perivascular nodules The giagnostic perivascular nodules

(Aschoff bodies) are most frequent in the (Aschoff bodies) are most frequent in the interventricular septum, left ventricle and interventricular septum, left ventricle and left atrium.left atrium.

Evolution of fully-developed Aschoff bodies Evolution of fully-developed Aschoff bodies involves 3 stages:involves 3 stages:

Early (exudative or degenerative) stage- Early (exudative or degenerative) stage- about 4th week of illness with progressive about 4th week of illness with progressive disorganization of connective tissue disorganization of connective tissue (hypersensitivity of immediate type with (hypersensitivity of immediate type with fibrinoid degeneration).fibrinoid degeneration).

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

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

AAcute rheumatic cute rheumatic myomyocarditis carditis withwith "Aschoff nodules“ "Aschoff nodules“.. These are centered in interstitium around vessels These are centered in interstitium around vessels..

The myocarditis may cause congestive heart The myocarditis may cause congestive heart failure.failure.

FFibrinous ibrinous pericarditis.pericarditis.

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

TThe pericardial surface shows strands of he pericardial surface shows strands of pink fibrin extending outward. pink fibrin extending outward. FFibrin can be ibrin can be organized and cleared, though sometimes organized and cleared, though sometimes

adhesions may remain.adhesions may remain.

Valvular diseases and Valvular diseases and deformitiesdeformities

StenosisStenosis is the term used the failure of a valve to is the term used the failure of a valve to open completely during diastole resulting in open completely during diastole resulting in obstruction to the forward flow of the blood.obstruction to the forward flow of the blood.

Mitral stenosis occurs in about 40% of all patients Mitral stenosis occurs in about 40% of all patients with RHD. About 70% of the patients are women. with RHD. About 70% of the patients are women.

The valve cusps are diffusely thickened by fibrous The valve cusps are diffusely thickened by fibrous tissue and/or calcific deposits. ”Purse-string tissue and/or calcific deposits. ”Purse-string puckering”, ”button-hole“ or “fish-mouth” mitral puckering”, ”button-hole“ or “fish-mouth” mitral orifice.orifice.

Effects: dilatation and hypertrophy of the left atrium; Effects: dilatation and hypertrophy of the left atrium; pulmonary hypertension with following chronic pulmonary hypertension with following chronic venous congestion of the lungs, hypertrophy and venous congestion of the lungs, hypertrophy and dilatation of the right ventricle; right heart failure in dilatation of the right ventricle; right heart failure in time.time.

The mitral valve demonstrates the The mitral valve demonstrates the typical "fish mouth" shape with chronic typical "fish mouth" shape with chronic

rheumatic scarring.rheumatic scarring.

Heart, rheumatic mitral Heart, rheumatic mitral stenosisstenosis, atrial changes - , atrial changes - Gross, atrial endocardial surface Gross, atrial endocardial surface

 The mitral valve has been reduced to a narrow orifice. The  The mitral valve has been reduced to a narrow orifice. The left atrium is markedly dilated. Thrombi have formed on the left atrium is markedly dilated. Thrombi have formed on the

atrial wall.  atrial wall.  

Aortic stenosis Aortic stenosis comprises about 25% of all comprises about 25% of all patients with chronic valvular heart disease. patients with chronic valvular heart disease. About 80% patients are males. There are About 80% patients are males. There are non-calcific and calcific type, the latter being non-calcific and calcific type, the latter being more common. The aortic cusps show more common. The aortic cusps show characteristic fibrous thickening and calcific characteristic fibrous thickening and calcific nodularity of the closing edges. nodularity of the closing edges.

Effects: obstruction to the outflow resulting Effects: obstruction to the outflow resulting in concentric hypertrophy of the left in concentric hypertrophy of the left ventricle, there is dilatation as well as ventricle, there is dilatation as well as hypertrophy of the left ventricle (eccentric hypertrophy of the left ventricle (eccentric hypertrophy). hypertrophy).

Three cardinal symptoms of aortic stenosis Three cardinal symptoms of aortic stenosis are: exertional dyspnea, angina pectoris, are: exertional dyspnea, angina pectoris, syncope.syncope.

RRheumatic aortic stenosis heumatic aortic stenosis

InsufficiencyInsufficiency or incompetence or or incompetence or regurgitation is the failure of valve to close regurgitation is the failure of valve to close completely during systole resulting in back completely during systole resulting in back flow or regurgitation of blood.flow or regurgitation of blood.

Mitral insufficiency occurs in about 50% Mitral insufficiency occurs in about 50% patients with RHD more often in men patients with RHD more often in men (75%).(75%).

Effects: dilatation and hypertrophy of the Effects: dilatation and hypertrophy of the left ventricle; dilatation of the left atrium; left ventricle; dilatation of the left atrium; pulmonary hypertension with following pulmonary hypertension with following chronic venous congestion of the lungs, chronic venous congestion of the lungs, hypertrophy and dilatation of the right hypertrophy and dilatation of the right ventricle; right heart failure in time.ventricle; right heart failure in time.

Aortic insufficiency occurs predominantly in Aortic insufficiency occurs predominantly in males (75%) with RHD.males (75%) with RHD.

The aortic valve cusps are thickened, The aortic valve cusps are thickened, deformed and shortened and fail to close. deformed and shortened and fail to close. There is generally distension and distortion There is generally distension and distortion of the ring.of the ring.

Effects: hypertrophy and dilatation of the left Effects: hypertrophy and dilatation of the left ventricle producing massive cardiac ventricle producing massive cardiac enlargement so that the heart may weigh as enlargement so that the heart may weigh as much as 1000 gm.much as 1000 gm.

The characteristic physical findings of aortic The characteristic physical findings of aortic insufficiency are awareness of the beatings insufficiency are awareness of the beatings of the heart, poundings in the head with of the heart, poundings in the head with each heart beat, low diastolic and high pulse each heart beat, low diastolic and high pulse pressure, rapidly rising and collapsing water pressure, rapidly rising and collapsing water hammer pulse, booming ”pistol shot” sound hammer pulse, booming ”pistol shot” sound over the femoral artery.over the femoral artery.

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

into a synthetic ring. into a synthetic ring.

Systemic lupus Systemic lupus erythematosuserythematosus Systemic lupus erythematosus (SLE) is a Systemic lupus erythematosus (SLE) is a

chronic disease with many manifestations. chronic disease with many manifestations. SLE is an autoimmune disease in which SLE is an autoimmune disease in which the body's own immune system is directed the body's own immune system is directed against the body's own tissues. The against the body's own tissues. The etiology of SLE is not known. It can occur etiology of SLE is not known. It can occur at all ages, but is more common in young at all ages, but is more common in young women. women.

The production of autoantibodies leads to The production of autoantibodies leads to immune complex formation. The immune immune complex formation. The immune complex deposition in many tissues leads complex deposition in many tissues leads to the manifestations of the disease. to the manifestations of the disease.

Immune complexes can be deposited in Immune complexes can be deposited in glomeruli, skin, lungs, synovium, glomeruli, skin, lungs, synovium, mesothelium, and other places. Many SLE mesothelium, and other places. Many SLE patients develop renal complications.patients develop renal complications.

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

Face, malar (butterfly) rash of Face, malar (butterfly) rash of systemic lupus erythematosus systemic lupus erythematosus

-SLE-SLE

TThe skin in SLE may demonstrate he skin in SLE may demonstrate a vasculitis and dermal chronic a vasculitis and dermal chronic

inflammatory infiltratesinflammatory infiltrates

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

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

loops“loops“..

Crescentic lupus nephritisCrescentic lupus nephritisSeen here within the glomeruli are Seen here within the glomeruli are

crescents composed of proliferating crescents composed of proliferating epithelial cells. epithelial cells.

IImmunofluorescence with antibody to IgGmmunofluorescence with antibody to IgG..AA granular pattern of immunofluorescence is seen, granular pattern of immunofluorescence is seen, indicative of deposition of immune complexes in indicative of deposition of immune complexes in

the basement membranes of the glomerular the basement membranes of the glomerular capillary loops.capillary loops.

The thickened basement membrane (arrow) that The thickened basement membrane (arrow) that results from immune complex deposition in the results from immune complex deposition in the

glomerular capillary loop is prominent in this glomerular capillary loop is prominent in this electron micrograph. The dark immune deposits are electron micrograph. The dark immune deposits are

located mainly in a subendothelial position. located mainly in a subendothelial position.

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

RHEUMATOID ARTHRITIS RHEUMATOID ARTHRITIS

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

RA is an autoimmune disease.RA is an autoimmune disease.

The characteristic feature is diffuse proliferative The characteristic feature is diffuse proliferative synovitis with formation of pannus.synovitis with formation of pannus.

Lesions affect small joints of hands and feet Lesions affect small joints of hands and feet mainly.mainly.

The synovial membrane becomes thick, The synovial membrane becomes thick, edematous, hyperplastic and covered by villous edematous, hyperplastic and covered by villous projections.projections.

Chronic inflammatory cellular infiltrate in the Chronic inflammatory cellular infiltrate in the synovium with predominance of lymphocytes, synovium with predominance of lymphocytes, plasma cells and some macrophages, at places plasma cells and some macrophages, at places forming lymphoid follicles.forming lymphoid follicles.

Organized fibrin deposit over the synovial Organized fibrin deposit over the synovial surface.surface.

Pannus creeps over the articular cartilage.Pannus creeps over the articular cartilage. Erosion of the articular cartilage and Erosion of the articular cartilage and

subchondral bone.subchondral bone. Fibrous and osseous ankylosis.Fibrous and osseous ankylosis.

Hand, Hand, acute acute rheumatoid rheumatoid arthritis arthritis

Synovium, rheumatoid arthritisSynovium, rheumatoid arthritis

PPrimary lesion of rheumatoid arthritis is synovitis.  rimary lesion of rheumatoid arthritis is synovitis.  

You can sYou can see here in the synovium collections ee here in the synovium collections of dark blue of dark blue lymphocyteslymphocytes..

Synovium, rheumatoid arthritis, pannusSynovium, rheumatoid arthritis, pannus TThe pannus isolates the articular cartilage from the he pannus isolates the articular cartilage from the synovial fluid, resulting in degeneration of articular synovial fluid, resulting in degeneration of articular

cartilagecartilage

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

cellscells

Polyarteritis nodosa Polyarteritis nodosa (PAN)(PAN)

It is necrotising-granulomatous vasculitis It is necrotising-granulomatous vasculitis involving small and medium-sized involving small and medium-sized muscular arteries of multiple organs and muscular arteries of multiple organs and tissues (kidneys, heart, liver, GIT, muscles, tissues (kidneys, heart, liver, GIT, muscles, pancreas, testes, nervous system, skin).pancreas, testes, nervous system, skin).

The condition is believed to result from The condition is believed to result from deposition of immune complexes and deposition of immune complexes and tumor-related antigens. The disease tumor-related antigens. The disease occurs more commonly in adult males.occurs more commonly in adult males.

Acute stage. There is fibrinoid necrosis Acute stage. There is fibrinoid necrosis in the centre of nodules located in the in the centre of nodules located in the media of vessels. An acute media of vessels. An acute inflammatory response develops around inflammatory response develops around it. The inflammatory infiltrate is present it. The inflammatory infiltrate is present in the entire circumference of the in the entire circumference of the affected vessel (periarteritis) and affected vessel (periarteritis) and consists chiefly of eosinophils, consists chiefly of eosinophils, mononuclear neutrophils.mononuclear neutrophils.

Healing stage. This is characterised by Healing stage. This is characterised by marked fibroblastic proliferation marked fibroblastic proliferation producing firm nodularity.producing firm nodularity.

Heales stage. The affected arterial wall Heales stage. The affected arterial wall is markedly thickened due to dense is markedly thickened due to dense fibrosis.fibrosis.

Kidney, polyarteritis nodosaKidney, polyarteritis nodosa  Two small renal infarcts of tissue supplied by small to  Two small renal infarcts of tissue supplied by small to

medium-sized arteries are evidenced by pale necrotic areas at medium-sized arteries are evidenced by pale necrotic areas at the top of this specimen. This is an immune-complex disease the top of this specimen. This is an immune-complex disease

frequently associated with hepatitis B virus (HBV) and frequently associated with hepatitis B virus (HBV) and cytomegalovirus (CMV) antigens.    cytomegalovirus (CMV) antigens.    

Here is a vasculitis of a renal arterial Here is a vasculitis of a renal arterial branch. Lymphocytes are scattered in branch. Lymphocytes are scattered in

and around the vessel.and around the vessel.

Systemic sclerosis or Systemic sclerosis or SclerodermaScleroderma

1.Localized form - morphea 1.Localized form - morphea It consists of lesions limited to the skin and It consists of lesions limited to the skin and

subcutaneous tissuesubcutaneous tissue

2.Generalized form- progressive systemic sclerosis2.Generalized form- progressive systemic sclerosisIt consists of extensive involvement of the skin, It consists of extensive involvement of the skin,

subcutaneous tissue and has visceral lesionssubcutaneous tissue and has visceral lesionsa) CREST-syndrome a) CREST-syndrome C= calcinosisC= calcinosisR= Raunad’s phenomenon (functional vaso-spastic R= Raunad’s phenomenon (functional vaso-spastic

disorder affecting small vessels of fingers and disorder affecting small vessels of fingers and hands)hands)

E= esophageal dismotilityE= esophageal dismotilityS=sclerodactyliaS=sclerodactyliaT=telangiectasiaT=telangiectasia

Hand, sclerodermaHand, scleroderma, , sclerodactyly sclerodactyly DDense cutaneous fibrosis (note smooth shiny skin) hasense cutaneous fibrosis (note smooth shiny skin) has causedcaused

immobility of the fingers, causing the claw-like appearance immobility of the fingers, causing the claw-like appearance seen here. In advanced cases, impairment of blood supply seen here. In advanced cases, impairment of blood supply

may lead tomay lead to ulcerationulceration or autoamputation.  or autoamputation.  

Skin, scleroderma Skin, scleroderma TThe dermis is thickened he dermis is thickened due to growth of due to growth of

connective tissueconnective tissue

Lung, lower lobe, systemic Lung, lower lobe, systemic sclerosis sclerosis

Cardiomyopathies Cardiomyopathies Type of CMP Type of CMP Findings Findings

Dilated Dilated (Congestive)(Congestive)

All four chambers are dilated, and there is All four chambers are dilated, and there is also hypertrophy. The most common cause also hypertrophy. The most common cause is chronic alcoholism, though some may be is chronic alcoholism, though some may be the end-stage of remote viral myocarditis.the end-stage of remote viral myocarditis.

HypertrophicHypertrophic The most common form, idiopathic The most common form, idiopathic hypertrophic subaortic stenosis (IHSS) hypertrophic subaortic stenosis (IHSS)

results from asymmetric interventricular results from asymmetric interventricular septal hypertrophy, resulting in left septal hypertrophy, resulting in left

ventricular outflow obstruction. ventricular outflow obstruction.

RestrictiveRestrictive The myocardium is infiltrated with a material The myocardium is infiltrated with a material that results in impaired ventricular filling. that results in impaired ventricular filling. The most common causes are amyloidosis The most common causes are amyloidosis

and hemochromatosis. and hemochromatosis.

The heart in the middle is relatively normal. The one The heart in the middle is relatively normal. The one on the on the leftleft shows concentric hypertrophy. The one shows concentric hypertrophy. The one on the on the rightright shows ventricular dilatio shows ventricular dilationn in dilated in dilated

cardiomyopathycardiomyopathy

This very large heart has a globoid shape because This very large heart has a globoid shape because all of the chambers are dilated. It felt very flabby, all of the chambers are dilated. It felt very flabby,

and the myocardium was poorly contractile.and the myocardium was poorly contractile.

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

cardiomyopathy.cardiomyopathy.

HHypertrophic ypertrophic cardiomyopathycardiomyopathy..

There is marked There is marked left ventricular left ventricular hypertrophy, hypertrophy, with asymmetric with asymmetric bulging of a very bulging of a very large large interventricular interventricular septum into the septum into the left ventricular left ventricular chamber. chamber.

Heart, hypertrophic Heart, hypertrophic cardiomyopathy cardiomyopathy

TThe heart in cardiomyopathy demonstrates he heart in cardiomyopathy demonstrates hypertrophy of myocardial fibers (which also hypertrophy of myocardial fibers (which also

have prominent dark nuclei) along with have prominent dark nuclei) along with interstitial fibrosis.interstitial fibrosis.

AAmorphous deposits of pale pink material morphous deposits of pale pink material (amyloid) are (amyloid) are between myocardial fibers. between myocardial fibers. Amyloidosis is a cause oAmyloidosis is a cause off "infiltrative" or "infiltrative" or

"restrictive" cardiomyopathy."restrictive" cardiomyopathy.