Rheumatic Heart Disease By Dr Bashir Ahmed Dar Associate Professor Medicine Sopore Kashmir

RHEUMATIC FEVER By Dr Bashir Ahmed Dar Chinkipora Sopore Kashmir Associate Professor Medicine Email [email protected]

RHEUMATIC FEVER  Is

a post streptococcal infection caused by group A beta hemolytic streptococci.Occurs usually after an attack of phyrangitis  Between age group of 5-15years.  Male and female equally affected  Can also occur at any age

What are these Streptococci A ‘coccus’ is a spherical bacteria Staphylococcus tend to cluster in groups While Streptococcus tend to line up in strings Some are pyogenic while others are non pyogenic.

Classification of Streptococci  Streptococci

are classified according to their hemolytic ability after incubation overnight on blood agar medium.

 Beta-hemolytic

streptococci produce an enzyme that completely lyses the red blood cells in the medium, leaving a clear zone of hemolysis around the colony. This pattern is best characterized by Streptococcus pyogenes.

Classification of Streptococci  Alpha-hemolytic

streptococci produce an enzyme that partially lyses the RBCs and converts red hemoglobin to green methemoglobin leaving a greenish discoloration of the culture medium surrounding the colony. This discolored area contains unlysed red blood cells and a greencolored metabolite of hemoglobin. This pattern is seen with the some Viridans streptococci and Streptococcus pneumoniae.

Classification of Streptococci  Gamma-hemolytic

streptococci are unable to hemolyze the RBCs, and therefore we should really not use the word "hemolytic" in this situation. This pattern is seen with most Lancefield group D streptococci.

Common streptococci  The

most common Streptococcus species isolated from humans are as follows  Streptococcus Pyogenes  Streptococcus Agalactiae  Streptococcus bovis  Streptococcus pneumoniae  and the Streptococcus Viridans group.

Common streptococci  1.Streptococcus

Pyogenes is a beta hemolytic streptococci and cause bacterial phyrangitis  It also causes Scarlet fever due to the erythrogenic toxin . They are also known as "flesh eating" bacteria and can cause life-threatening disease, necrotising facitis.it also causes Skin infections and Streptococcal toxic shock syndrome.

Pharyngitis

Scarlet fever

Necrotising fascitis

Skin infections

Common streptococci  2.Streptococcus

agalacticae is also B beta streptococci. associated with neonates. They are normal flora of the GI tract and vaginal secretions. This bacteria can cause s  neonatal sepsis during birth, neonatal meningitis, postpartum fever, and wound infections, endocarditis, pneumonia, pyelonephritis in the immunosuppressed individuals.

Common streptococci  Post

Streptococcus pyogenes infection also cause non suppurative infection like Rheumatic Fever and Post streptococcal glomerulonephritis

Common streptococci  3.Streptococcus

bovis is a group D Streptococcus, non-Enterococcus. It is usually gamma-hemolytic but may be alpha-hemolytic. They may cause wound infection, urinary tract infection, and abdominal abscesses.

Common streptococci  4.Streptococcus

pneumoniae are grampositive, lancet shaped diplococci. They are alpha-hemolytic. They are typically normal respiratory flora but may cause lobar pneumonia in the elderly and alcoholics, otitis media in infants and children, meningitis, and community-acquired bacterial pneumonia.

Common streptococci  5.Streptococcus

viridans form large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), or non-hemolytic. They possess no Lancefield antigens.

Common streptococci  These

organisms are most abundant in the mouth and one member of the group, S. mutans, is the etiologic agent of dental caries. Others may be involved in other mouth or gingival infections.  Viridans group are difficult to classify due to changing nomenclature and significant problems of identification by phenotypic analysis.

Lancefield classification Based on antigens on streptococcal cell wall antigens Ag-17 groups (A, B, C….).those that are not possessing antigens are non groupable e.g. Viridans streptococci.

Common streptococci  Streptococcal

viridans if introduced into the bloodstream they have the potential of causing endocarditis, particularly in individuals with damaged heart valves. They are the most common causes of subacute bacterial endocarditis especially after dental procedures.

Antigenic Structure Capsule: . The capsule of group A streptococci is composed of hyaluronic acid (hyloronidase) that breaks down connective tissue and is antiphagocytosis The group B streptococci contain M protein binds IgM, IgG and α2-macroglobulin; interfere with phagocytosis. Lipoteichoic acid: binds to epithelial cells. F protein: a major adhesin of S. pyogenes, binding with fibronectin.

Pathogenesis So streptococci is able to cause Adherence to the epithelial cells; invasion into the epithelial cells; Which in turn is mediated by M protein and F protein and is important for persistent infections and invasion into deep tissues

Enzymes and toxins secreted or produced by S.cocci Streptokinase (fibrinolysin) Can lyse blood clots and may be responsible for the rapid spread of the organism. Used (IV injection) for treatment of pulmonary emboli, coronary artery thrombosis and venous thrombosis. Streptodornase (DNases A to D) Decreases viscosity of DNA suspension. A mixture of this and streptokinase is used in enzymatic debridement-liquifies exudates and facilitates removal of pus and necrotic tissue. C5a peptidase Prevents streptococci from C5a-mediated recruitment and activation of phagocytes, and is important for survival of S. pyogenes in tissue and blood.

Also produces Hemolysins like Streptolysin O: O2-labile; causes hemolysis deep in blood agar plates. ASO (antistreptolysin O) titer >160-200 units suggests recent infection or exaggerated immune response to an earlier respiratory infection. However, skin infection does not induce ASO.

Streptolysin S: O2-stable. Causes β-hemolysis on the surface of blood agar plates. Cell-bound, not antigenic. Produced in the presence of serum. Kills phagocytes by releasing the lysosomal contents after engulfment.

pyogenic toxin (erythrogenic) – induces fever and typical red rash superantigens – strong monocyte and lymphocyte stimulants that cause the release of tissue necrotic factor

Epidemiology . Crowding increases the opportunity for the pathogen to spread, particularly during the winter months. the organisms are introduced into the superficial or deep tissue through a break in the skin. Low social economic conditions are at risk. Portal of entry through droplets,contact,food,fomites.

How does streptococci cause Rheumatic fever  The

streptococci contain antigens as already said , to these antigens antibodies are formed in the body.  But before these antibodies are formed the streptococcal infection is over

How does streptococci cause Rheumatic fever  So

these antibodies are searching streptococci but find none there  Instead these antibodies now react to various tissues in the body.  Since most cells of body have same constituents as that of streptococcal cells therefore react with cells of body causing antigen antibody reaction.thus rheumatic fever is immune mediated.

How does streptococci cause Rheumatic fever  These

auto immune antibodies produce inflammatory lesions primarily involving the heart, joints, and subcutaneous tissue producing e.g cardiac leisions etc.

Cardiac Lesions  Involvement

of the interstitial tissue of all the three layers of the heart, the so-called pancarditis takes place in RF.  The characteristic feature of pancarditis in RF is the presence of Aschoff nodules or Aschoff bodies.

The Aschoff nodules or bodies  Are

spheroidal or fusiform distinct tiny structures or granulomas, 1-2 mm in size, occurring in the interstitium of the heart in RF and may be visible to naked eye.especially found in the vicinity of small blood vessels in the myocardium and endocardium and occasionally in the pericardium.Lesions similar to the Aschoff nodules may be found in the extracardiac tissues.

Vegetation

Stick in Perforation

Mitral Valve

Acute Rheumatic vegetations: Mitral v. Va lve

Vegetations

Papillary muscle

How are Aschoff bodies formed  Formed

in 3 stages.  1. Early (Exudative or degenerative) stage.  Initially, there is oedema of the connective tissue and increase in acid mucopolysaccharide in the ground substance.This results in separation of the collagen fibres by accumulating ground substance.Eventually, the collagen fibres are fragmented and disintegrated,that takes the stain of a fibrin.hence called fibrinoid degeneration.

How are Aschoff bodies formed  2.

2nd stage (Proliferative or granulomatous)  This includes infiltration by lymphocytes (mostly T cells),plasma cells, a few neutrophils and the characteristic cardiac  histiocytes (Anitschkow cells) at the margin of the lesion.

Acute RF: Aschoff body 

Aschoff body: – Fibrinoid degeneration – T lymphocytes – Plasma cells – Macrophages  

Anitschkow cells Aschoff giant cells

– Around blood vessel.

Aschoff body in Acute RF    

Anitschkow cells Capillary T lymphocyte Myocyte

Aschoff body in Acute RF   

Fibrinoid necrosis Aschoff giant cells. Cardiac Muscle fibres.

Cardiac histiocytes or Anitschkow cells  Are

present in small numbers in normal heart but their number is increased in the Aschoff bodies; therefore they are not characteristic of RHD.

Cardiac histiocytes or Anitschkow cells  These

are large mononuclear cells having central round nuclei and contain moderate amount of amphophilic cytoplasm. The nuclei are vesicular and contain prominent central chromatin mass which is longitudinal section appears serrated or caterpillar-like, while in cross-section the chromatin mass appears as a small rounded body in the centre of the vesicular nucleus, just like an owl's eye.

Cardiac histiocytes or Anitschkow cells  Some

of these modified cardiac histiocytes become multinucleate cells containing 1 to 4 nuclei and are called Aschoff cells and are characteristic of RHD.

Aschoff Body & Anitskow cell y d o B f f o h c As

Aschoff Giant Cells:

Acute Rheumatic Fever-Rh nodule

How are Aschoff bodies formed  3.

3rd stage Late (healing or fibrous) stage.  This stage is healing by fibrosis of the Aschoff nodule and occurs in about 12 to 16 weeks after the illness resulting in fibrous scar.

Rheumatic Valvulitis  The

valves in acute RF show thickening and loss of translucency of the valve leaflets or cusps. This is followed by the formation of characteristic, small (1 to 3 mm in diameter), multiple,warty vegetations or verrucae, chiefly along the line of closure of the leaflets and cusps. These tiny vegetations are almost continuous so that the free margin of the cusps or leaflets appear as a rough and irregular ridge.

Acute Rheumatic vegetations: Mitral v. Va lve

Vegetations

Papillary muscle

Fish mouth stenosis:

Rheumatic Valvulitis  The

vegetations in RF appear grey-brown, transuuent and are firmly attached so that they are not likely to get detached to form emboli, unlike the friable vegetations of infective endocarditis.

Chronic RHD:  Valve

leaflet thickening.  Shortening, thickening and fusion of chordae tendineae.

Acute on Chronic RHD

Note: Thickening of valve, opaque, inflammed, irregular border, shortening of chordae tendinae also seen.

Chronic RHD

Note: Thickening of valve, opaque, vascularized irregular border, shortening of chordae tendinae. (no significant inflammation)

Rheumatic Valvulitis  Through

all the four heart valves are affected, their frequency and severity of involvement varies: mitral valve alone being most common site, followed in decreasing order of frequency, by combined mitral and aortic valve. The tricuspid and pulmonary valves usually show infrequent and slight involvement.

Rheumatic Valvulitis  The

higher incidence of vegetations on  left side of heart is possibly because of the greater mechanical stresses on the valves of the left heart, especially along the line of closure of the valve cusps.

Rheumatic Valvulitis  Due

to vegetations and thickening the mitral valve may look like 'fish mouth' or 'button hole'. Mitral stenosis and insufficiency are commonly combined in chronic RHD. Calcific aortic stenosis may also be found.

Fish mouth Mitral stenosis

Scar nodule

Mitral Valve

Left Atrium

Chronic RHD - Aortic Valve Sten otic , Fu sed valv e

Cor ona ry A rter y (n orm al)

Fish mouth Mitral stenosis:

Rheumatic Valvulitis Thickening, shortening and fusion of the chordae tendineae further contribute to the chronic valvular lesions.

Rheumatic Valvulitis  Vegetations

present at the free margins of cusps appear as tiny structures mainly consisting of fibrin with superimposed platelet thrombi and do not contain bacteria.

Rheumatic Valvulitis  In

the healed (chronic) stage, the vegetations have undergone organization and fibrous formation., and often calcification. Vascularisation of the valve cusps may still be evident in the form of thick-walled blood vessels.Aschoff bodies are rarely seen in the valves at this stage.

Vegetation

Stick in Perforation

Mitral Valve

Infective endocarditis with perforation of mitral valve leaflet

Rheumatic Mural Endocarditis  Mural

endocardium may also show features of rheumatic carditis though the changes are  less conspicuous as compared to valvular changes.

Rheumatic Mural Endocarditis  Grossly,

the lesions most commonly seen is MacCallum's patch which is region of endocardial surface in the posterior wall of the left atrium just above the posterior leaflet of the mitral valve. MacCallum's patch appears as a map-like area  of thickened, roughened and wrinkled part of the  endocardium.

Rheumatic Mural Endocarditis  Microscopically,

the appearance of MacCallum's patch is similar to that seen in rheumatic valvulitis. The affected area shows oedema, fibrinoid change in the collagen, and cellular infiltrate of lymphocytes, plasma cells and macrophages with many Anitschkow cells.

Rheumatic Myocarditis  Grossly

in early (acute) stage, the myocardium, especially of the left ventricle, is soft and flabby.In the intermediate stage, the interstitial tissue of the myocardium shows small foci of necrosis. Later, tiny pale foci of the Aschoff bodies may be visible throughout the myocardium.  Microscopically, the most characteristic feature of rheumatic myocarditis is the presence of distinctive Aschoff bodies..

Rheumatic Myocarditis  These

nodules are scattered throughout the interstitial tissue of the myocardium and are most frequent in the interventricular septum, left ventricle and left atrium.

Rheumatic pericarditis.  Grossly,

the usual findings is fibrinous pericarditis in which there is loss of normal shiny pericardial surface due to deposition of fibrin on its surface and accumulation of exudate in the pericardial sac. If the parietal pericardium is pulled off from the visceral pericardium, the two separated surfaces are shaggy due to thick fibrin covering them.

Rheumatic pericarditis  This

appearance is often likened to 'bread and butter appearance' i.e. resembling the buttered surfaces of two slices in a sandwich when they are gently pulled apart.If fibrinous pericarditis fails to resolve and, instead,undergoes organization, the two layers of the pericardium form fibrous adhesions resulting in chronic adhesive pericarditis.

Granular Visceral Pericardial Surface of Fibrinous Pericarditis

Fibrinous Pericarditis:

Extracardiac Lesion  Develop

in joint, subcutaneous tissue, arteries, brain and lungs.  Polyarthritis acute and painful inflammation of the  synovial membranes of some of the joints, especially the larger joints of the limbs, is seen in about 90% cases of RF in adults and less often in children. As pain and swelling subside in one joint, others tend to get involved, producing  the characteristic 'migratory polyarthritis' involving two or more joints at a time.

Migratory arthritis

Subcutaneous nodules  The

subcutaneous nodules of RF occur more often in children than in adult. These nodules are  small (0.5 to 2 cm in diameter), spherical or ovoid and painless. They are attached to deeper structures like tendons,ligaments, fascia or periosteum and therefore often remain  unnoticed by the patient. Characteristic locations are extensor surface of the wrists, elbows, ankles and knees.

Subcutaneous nodules

Subcutaneous nodules  Subcutaneous

nodules of RF are larger, painful and tender and persist for months to years than that of rheumatoid arthritis that are painless and non-tender.

Erythema marginatum  This

non-pruritic erythematous rash is characteristic of RF. The lesions occur mainly on the trunk and proximal parts  of the extremities. The erythematous area develops central clearing and has slightly elevated red margins.The erythema is transient and migratory.

Acute Rh Fever: Erythema Marginatum

Rheumatic Arteritis  Arteritis

in RF involves not only the coronary arteries and aorta but also occurs in arteries of various other organs such as renal,mesenteric and cerebral arteries. The lesions in the coronaries are seen mainly in the small intramyocardial branches.

Chorea Minor  Chorea

minor or Sydenham's chorea or Saint Vitus' dance is a delayed manifestation of RF as a result of involvement of the central nervous system. The condition is characterized by disordered and involuntary jerky movements of  the trunk and extremities accompanied by some degree of emotional instability. The condition occurs more often in younger age, particularly in girls.

Chorea Minor  Histologically,

the lesions are located in the cerebral hemispheres,brainstem and the basal ganglia. They consist of small haemorrhages, oedema and perivascular infiltration of lymphocytes. There may be endarteritis obliterans and thrombosis of cortical and meningeal vessels.

Rheumatic pneumonitis and pleuritis  Involvement

of the lungs and pleura occurs rarely in RF. Pleuritis is often accompanied  with serofibrinous pleural effusion but definite Aschoff bodies are not present. In rheumatic pneumonitis, the lungs are large, firm and rubbery.

Diagnosis of RF  The

following set of guidelines called revised Jones' criteria are followed for diagnosis of RF.

Major criteria  1.

Carditis  2. Polyarthritis.  3. Chorea (Sydenham's chorea)  4. Erythema marginatum  5. Subcutaneous nodules

Minor criteria  1.

Fever  2. Arthralgia  3. Previous history of RF  4. Laboratory findings of elevated ESR, raised C reactive protein, and leucocytosis.  5.ECG finding of prolonged PR interval

You should have  Two

major or one major and two minor of the criteria.

Supportive evidence  Positive

throat culture .  Raised titers of (antispreptolysin O and S, antistreptokinase, anti-streptohyaluronidase and anti DNAase)

Outcome and complications  Myocarditis,

in particular, is the most lifethreatening due to involvement of the conduction system of the heart and results in serious arrhythmias. The long term sequelae or stigmata are the chronic valvular deformities,especially the mitral stenosis, AS, AI,etc as already explained.

Normal & Rheumatic Mitral valve:  Recurrent Inflammation Scarring 

Normal valve is Transparent, avascular, thin flexible membrane.

RHD: Thick, fibrous scarred stenotic & fixed (MS/MR) with Blood Vessels.

Outcome and complications a

stage of compensation occurs, while later decompensation of the heard leads to fullblown cardiac failure. Currently, surgical replacement of the damaged valves can alter the clinical course of the disease.

Outcome and complications  The

major causes of death in RHD are cardiac failure, bacterial endocarditis and embolism:

Secondary effects Marked left atrial dilatation may result from severe mitral stenosis or insufficiency.  formation of mural thrombi.  Cor pulmonale may develop as a consequence of secondary pulmonary hypertension induced by severe mitral valve disease 

Course and diagnosis  Valve

replacement may become necessary. those who suffer recurrent attacks and complications.

Treatment of Rheumatic Fever  Bed

rest  Patients who have not had carditis should be advised bed rest until temperature and ESR become normal.  Patients who have had carditis should continue bed rest for 2-6 weeks after ESR and temperature became normal.

Anti-streptococcal theraphy A

course of antibiotic should be given to eradicate the streptococci.  Even if throat culture is negative.  One of the following may be used  1.single injection of benzathine penicillin 1.2 million units intramascularly.  2.daily injection of procaine penicillin 600000 units I/M x10days.

Anti-streptococcal theraphy  Oral

erythromycin 250-500mg 6-8 hrly if patient is sensitive to pencillin.

Salicylates  Aspirin

is effective in providing symptomatic

relief.  5-8 grams given daily in divided doses upto six times a day.until clinical improvement or systemic toxicity develops like tinnitus ,headache,hyperpnoea.  Aspirin at this dose continued until ESR is normal and then gradually tapered over 4-6 weeks.

Corticosteroids  Indications

are  Severe carditis  CCF  Not responding to aspirin  Prednisolone 60-120 mg/day QID until ESR normal, then tapered over 2 weeks.  Monitoring of corticosteroids also based on ESR, CRP.

Supportive theraphy  Includes

treatment of CCF, valvular leisions, heart blocks and chorea.

Prevention of Rheumatic Fever  Primary

prevention  Treat group A streptococcal pharyngitis when ever it occurs  Mass pencillin treatment of population if outbreak of rheumatic fever occurs.  Treat streptococcal pharyngitis by pencillin or erythromycin.

Secondary prevention(prophylaxis of RF)  Should

be given to all patients who have experienced attack of rheumatic fever.  Broad outlines are  Those under age of 18 should receive continuous prophylaxis.  Those who are over 18yrs who develop RF without carditis should receive prophylaxis for a minimum period of 5 yrs..

Secondary prevention(prophylaxis of RF)  Decision

to continue prophylaxis beyond 5 yrs in second group depend on many factors like age of patient, relative risks like acquiring infection, socioecnomic state, presence of rheumatic heart disease etc.

Secondary prevention(prophylaxis of RF)  One

of the following regimens may be used.  I/M injection of 1.2 million units of benzathine pencillin G every 3 weeks.  Oral pencillin V 250 mg twice a day.  Erythromycin 250 mg BD orally in case allergic to pencillin.

Chorea  Intermittent

or continuous fast jerky involuntary movements of parts of body.  Movements may be more on one side called hemichorea.  Facial chorea results from infrequent grimacing,blinking and slurring of speech.  The movements subside in sleep.  Hypotonia may be present.

Treatment of Sydenham's chorea/saint vitus dance  Padded

side boards for bed to prevent

injury.  Haloperidol/sodium valproate with diazepam.  Rheumatic fever prophylaxis.  Carbamazepine.

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