Rheumatic Fever and Rheumatic Heart Disease

Slide 1 · Rheumatic Fever and

Rheumatic Heart Disease

Acute post-streptococcal inflammation → chronic valvular fibrosis

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain how immune cross-reactivity follows group A streptococcal infection.

Recognize Aschoff bodies, rheumatic verrucae and chronic mitral distortion.

Connect valve scarring to hemodynamic and thromboembolic sequelae.

Apply the textbook description of clinical manifestations and Jones logic.

Slide 3 · One disease process, two clinical time scales

Streptococcal infection

Trigger

Acute rheumatic fever

Weeks later

Inflammation heals

Scar forms

Chronic RHD

Years / decades

An acute autoimmune illness can leave a delayed structural valve disease.

Schematic sequence; Intervals are not scaled

Slide 4 · Rheumatic fever: Definition and trigger

Acute, immunologically mediated multisystem inflammatory disease.

Classically follows group A streptococcal pharyngitis.

Occasionally follows streptococcal infection at other sites, including skin.

Carditis is a major active manifestation and may progress to chronic RHD.

Slide 5 · Chronic RHD: The structural endpoint

Deforming fibrotic disease of cardiac valves is the defining lesion.

Mitral valve is the dominant site of chronic involvement.

Healed injury restricts opening, distorts closure or both.

Clinical manifestations may not emerge until years after rheumatic fever.

Slide 6 · Public health distribution

RF and RHD have declined substantially in many regions.

Improved sanitation and timely treatment of streptococcal pharyngitis contributed.

RHD remains consequential in low-resource communities.

Crowding and socioeconomic deprivation sustain ongoing disease burden.

Slide 7 · Who develops acute RF?

First attacks occur most often at 5–15 years of age.

Adult first presentations are possible.

Only a minority develop RF after streptococcal infection.

Approximately 0.3%–3% after infection.

Slide 8 · Latency is a clue to pathogenesis

RF typically appears around 10 days to 6 weeks after infection.

The classic immunologic lag is about 2–3 weeks.

By presentation, throat cultures may already be negative.

The timing supports a delayed host immune response rather than direct invasion.

Slide 9 · Immune cross-reactivity initiates tissue injury

Streptococcal antigens share targets with host tissue.

The surface M protein is a key antigen.

Cardiac antigens may be recognized by the same response.

Both humoral and cellular responses participate.

Group A streptococcal M protein

Cross-reactive immune response

Cardiac antigen recognition

Inflammatory injury

Cross-reaction, not myocardial colonization

Schematic

Slide 10 · M protein provides the initiating antigen

M protein is expressed on the bacterial surface.

Antibodies and CD4⁺ T cells target its epitopes.

Subsets of these responses recognize cardiac proteins.

Predisposition influences which hosts mount damaging responses.

Streptococcal surface antigen

M protein-directed response

Cross-reactive cardiac recognition

Schematic

Slide 11 · Cardiac targets of the immune response

Pericardium

Immune injury can produce pericardial inflammation.

Myocardium

Cellular inflammation and Aschoff bodies may develop.

Valves

Endocardial and valvular injury can heal with scarring.

These compartments explain the pancarditis phenotype.

Slide 12 · Antibody-mediated injury in RF

Cross-reactive antibodies bind cardiac antigens.

Complement activation amplifies local inflammation.

Fc-receptor–bearing neutrophils and macrophages are recruited.

Injury reflects host effector mechanisms.

Antibody binds cardiac antigen

Complement and Fc-receptor activity

Recruitment of inflammatory cells

Tissue damage

Schematic

Slide 13 · T-cell–mediated injury in RF

Cross-reactive CD4⁺ T lymphocytes recognize cardiac antigens.

T-cell cytokines stimulate macrophage activation.

Activated macrophages populate characteristic Aschoff lesions.

Cell-mediated reactions coexist with antibody injury.

Activated CD4⁺ T cells

Inflammatory cytokines

Macrophage activation

Aschoff-body inflammation

Schematic

Slide 14 · A combined immunologic lesion

Antibodies

Complement activation and Fc-receptor effector cells.

CD4⁺ T cells

Cytokines and activation of tissue macrophages.

Outcome

Inflammatory injury in cardiac layers; Subsequent healing.

Neither mechanism requires living streptococci in cardiac tissue.

Slide 15 · Why direct infection is not the mechanism

Streptococci are absent from rheumatic cardiac lesions.

RF appears after a latent period rather than contemporaneously with pharyngitis.

Host-directed inflammation persists after the triggering infection resolves.

Distinguish RF from infective endocarditis containing microorganisms.

Slide 16 · Susceptibility is unequal across patients

Most individuals with group A streptococcal infections do not develop RF.

Intrinsic genetic susceptibility to cross-reactive responses.

Genetic predisposition is an explanatory inference, not a single-gene diagnostic test.

Exposure alone therefore cannot predict subsequent RF.

Slide 17 · How an acute lesion becomes chronic RHD

Acute injury leads to inflammation and tissue damage.

Organization and healing deposit fibrous tissue.

Repeated attacks may produce cumulative deformity.

The final clinical phenotype is dominated by valve fibrosis.

Acute immune injury

Organization of inflammation

Fibrosis and neovascularization

Deformed valve anatomy

Schematic

Slide 18 · Repeat attacks compound valve injury

After the initial episode, later streptococcal infections may reactivate RF.

The same clinical manifestations may recur.

Inflammatory episodes produce additive valve damage.

Secondary prevention is conceptually important because injury is cumulative.

Slide 19 · Valvular disease can amplify itself

Valvular scarring

Distorted flow / turbulence

Further fibrosis

Progressive deformity

Positive feedback

Schematic feedback loop

Slide 20 · Acute RF is multisystem disease

Migratory polyarthritis of large joints.

Carditis involving one or more cardiac layers.

Subcutaneous nodules over extensor surfaces.

Erythema marginatum: Circinate, irregular rash.

Sydenham chorea: Rapid involuntary movements.

Slide 21 · Acute carditis may affect all three layers

A tri-layer inflammatory process

Pericardium

Pericarditis → friction rub

Myocardium

Myocarditis → dilation / arrhythmia

Endocardium / valves

Valvulitis → verrucae and leaflet injury

Schematic: Three cardiac layers

Slide 22 · Pericardial rheumatic inflammation

Pericarditis is a manifestation of acute rheumatic carditis.

Pericardial inflammation can produce a friction rub.

It belongs to the acute inflammatory phase, not the defining chronic valve scar.

Rheumatic carditis may involve other layers at the same time.

Slide 23 · Myocardial rheumatic inflammation

Aschoff bodies can develop within the myocardium.

Myocarditis may cause cardiac dilation.

Dilation may lead to functional mitral insufficiency.

Severe myocardial involvement can produce heart failure.

Slide 24 · Acute endocardial and valve injury

Left-sided valves are commonly involved.

Inflammation is associated with fibrinoid necrosis in cusps and chordae.

Small, noninfective vegetations form at the closure lines.

Healing contributes to fibrous valve distortion.

Slide 25 · Aschoff bodies: Defining focal lesion

Interstitial inflammatory focus between myocardial fibers

Aschoff body

Inflammatory cells

Schematic only — not a histologic specimen

Slide 26 · Aschoff-body cellular composition

Focal cardiac inflammatory nodules in acute RF.

Contain T lymphocytes and occasional plasma cells.

Include large activated macrophages called Anitschkow cells.

Characteristic cytologic appearance helps identify the lesion.

Slide 27 · Anitschkow cells: Nuclear morphology

Plump activated macrophages with abundant cytoplasm.

Round-to-ovoid nuclei; Occasional binucleation.

Condensed nuclear chromatin arranged in a slender, wavy central ribbon.

The characteristic appearance is termed a “caterpillar cell.”

Slide 28 · Read an Aschoff body systematically

Setting

Myocardium or other cardiac layers during active RF.

Cellular milieu

Lymphocytes, occasional plasma cells, activated macrophages.

Specific clue

Anitschkow macrophages with ribbonlike nuclear chromatin.

Lesion recognition requires tissue context, not a standalone cell.

Slide 29 · Aschoff bodies are not a chronic requirement

Aschoff bodies characterize active inflammatory rheumatic injury.

They are rarely identified in late surgical or autopsy specimens.

Decades may separate acute inflammation from chronic valve dysfunction.

Absence of Aschoff bodies does not exclude chronic RHD.

Slide 30 · Rheumatic verrucae: Morphology and site

Small vegetations measure approximately 1–2 mm.

Located along the line of valve closure.

Overlie foci of fibrinoid necrosis.

Characteristically belong to acute rheumatic valvulitis.

Valvular immune injury

Fibrinoid necrosis

Small closure-line verrucae

Schematic

Slide 31 · Location helps interpret vegetations

RF: Small, warty vegetations along closure lines.

Infective endocarditis: Often larger irregular destructive masses.

RHD lesions are sterile despite being vegetative.

Morphology must be interpreted together with the clinical setting.

Slide 32 · MacCallum plaques: Endocardial response

Irregular subendocardial thickening, usually in the left atrium.

Occurs in the setting of rheumatic cardiac injury.

Regurgitant jets may contribute to repeated endocardial trauma.

Distinct from tiny verrucae directly on valve closure lines.

Slide 33 · Acute valvular morphology: Three clues

Tissue injury

Fibrinoid necrosis of affected cusps and chords.

Surface lesion

Tiny verrucae located along valve closure lines.

Healing response

Organization of inflammation sets the stage for fibrosis.

Slide 34 · Which valves are affected in chronic RHD?

Valve

Relative involvement

Interpretation

Mitral

Virtually always involved

Isolated in roughly two-thirds of cases

Aortic

May accompany mitral

Mitral + aortic in another ~25%

Tricuspid

Infrequent

Much less typical than left-sided valves

Pulmonary

Rare

Usually not the dominant valve lesion

The mitral valve is the signature chronic target.

Slide 35 · Chronic rheumatic mitral valve: Triad

Diffuse leaflet thickening with distortion.

Fusion and shortening of the commissures.

Thickened, shortened and fused chordae tendineae.

These are consequences of recurrent or healed inflammation.

Slide 36 · Commissural fusion narrows the mitral orifice

Schematic: Progressively restricted valve opening.

Unscarred valve

Rheumatic stenosis

Simplified en-face valve schematic — not a specimen

Slide 37 · Commissural fusion has a mechanical consequence

Bridging fibrosis fixes opposing leaflet margins together.

The valve cannot open fully during diastole.

Progressive restriction produces a stenotic mitral orifice.

Calcification may supervene on chronically scarred commissures.

Slide 38 · Chordal thickening adds valve distortion

Rheumatic inflammation involves tendinous cords as well as cusps.

Healing causes chordal thickening, shortening and fusion.

The mobile support apparatus becomes tethered and rigid.

Combined chordal and leaflet lesions impair normal valve mechanics.

Slide 39 · “Fish-mouth” mitral stenosis

Commissural fibrosis and calcification leave an elongated restricted aperture.

The narrowed opening is conventionally called fish-mouth or buttonhole stenosis.

It reflects fixed mechanical narrowing, not an acute transient spasm.

Gross inspection should evaluate leaflets, commissures and chordae.

Slide 40 · Microscopic chronic valve remodeling

Organization of earlier inflammation results in scarring.

Transmural fibrosis obliterates normal leaflet architecture.

Post-inflammatory neovascularization may be conspicuous.

These changes help distinguish longstanding remodeling from acute valvulitis.

Slide 41 · From acute to chronic: Lesion correspondence

Acute

Aschoff bodies, fibrinoid injury and verrucae.

Repair

Organization of inflammatory injury and fibrous healing.

Chronic

Commissural fusion, rigid leaflets and thickened chordae.

The lesion changes in character as the inflammatory episode heals.

Slide 42 · Mitral stenosis: Atrial-to-pulmonary consequences

Consequence of mitral outflow obstruction

Mitral orifice narrows

Left atrial pressure / dilation

Pulmonary congestion

Right-sided strain

Schematic causal pathway

Isolated pure mitral stenosis generally leaves the left ventricle largely unaffected.

Slide 43 · Left atrial remodeling in mitral stenosis

Fixed obstruction chronically elevates the pressure burden upstream.

The left atrium progressively dilates with tight mitral stenosis.

A dilated atrium is susceptible to rhythm disturbance.

Its cavity may contain mural thrombi.

Slide 44 · Why atrial thrombi matter

Left atrial dilation favors intracavitary stasis.

Mural thrombi may form in advanced rheumatic mitral stenosis.

Embolic fragments can enter the systemic circulation.

Thromboembolism is an important chronic RHD complication.

Chronic mitral narrowing

Left atrial dilation

Mural thrombosis

Potential embolization

Schematic

Slide 45 · Pulmonary consequences of mitral stenosis

Persistent left atrial outflow obstruction causes pulmonary congestion.

Long-standing congestive changes affect vessels and lung parenchyma.

Sustained pulmonary vascular loading may follow.

These changes contribute to right ventricular hypertrophy.

Slide 46 · Right ventricular adaptation

Pulmonary vascular consequences transmit pressure load to the right heart.

Right ventricular hypertrophy may develop over time.

The change is secondary to left-sided valvular disease.

Thus a mitral lesion can ultimately produce right-heart pathology.

Slide 47 · Why the left ventricle may be preserved

Pure isolated mitral stenosis obstructs flow before blood reaches the left ventricle.

The main pressure burden lies upstream in the left atrium and lungs.

The LV is largely unaffected in isolated pure stenosis.

Associated regurgitation or other lesions alter this expectation.

Slide 48 · Migratory polyarthritis is a clinical pattern

Typically affects large joints sequentially.

One joint becomes painful and swollen, then another is involved.

Each episode may last days before spontaneous resolution.

It ordinarily leaves no residual joint disability.

Slide 49 · Other major RF manifestations

Skin

Erythema marginatum: Irregular circinate rash.

Subcutaneous tissue

Nodules over extensor surfaces of the extremities.

Nervous system

Sydenham chorea: Involuntary rapid movements.

Slide 50 · How acute carditis presents

Pericardial friction rub suggests pericardial inflammation.

Tachycardia and arrhythmias reflect cardiac involvement.

Myocardial dilation can cause functional mitral insufficiency.

Fulminant cardiac inflammation may culminate in heart failure.

Slide 51 · Carditis and arthritis dominate presentations

Carditis and arthritis as predominant manifestations.

Joint involvement is reported more commonly in adults than children.

Joint disease is usually transient; Valvular injury can be permanent.

This divergence explains the long-term importance of cardiac disease.

Slide 52 · Streptococcal evidence may be serologic

The preceding pharyngeal infection may have resolved before clinical RF.

Throat culture can therefore be negative when RF develops.

Antibodies to streptococcal products may remain measurable.

Antistreptolysin O and anti-DNase B responses.

Slide 53 · Jones criteria: Textbook diagnostic logic

Begin with evidence of antecedent group A streptococcal infection.

Classical rule: Two major manifestations, or one major plus two minor.

Minor findings are nonspecific and include fever, arthralgia and acute-phase reactants.

The criteria are evolving and are applied differently across risk settings.

Slide 54 · Major and minor manifestations in the source

Major manifestations

Minor examples

Carditis

Fever

Migratory polyarthritis

Arthralgia

Subcutaneous nodules

Elevated acute-phase reactants

Erythema marginatum

Other Jones elements not reproduced here

Sydenham chorea

Risk-adjusted rules require current guideline reference

This is a textbook teaching summary, not a current diagnostic checklist.

Slide 55 · Diagnostic caution: Risk matters

Jones criteria evolve over time.

Low-risk and high-risk settings do not use identical applications.

Do not apply a simplified classroom list as an exhaustive clinical algorithm.

In actual practice, consult the current locally adopted diagnostic criteria.

Slide 56 · Acute rheumatic versus infective endocarditis

Feature

Rheumatic valvulitis

Infective endocarditis

Mechanism

Cross-reactive host immunity

Microbial infection of endocardium

Vegetations

Small; Line of closure

Typically bulky and irregular

Organisms in lesion

Absent

May be present in vegetation

Tissue effects

Fibrinoid injury; Later fibrosis

Potentially destructive infection

Vegetation size and distribution support, but do not replace, clinicopathologic diagnosis.

Slide 57 · Late presentation: Years after RF

Chronic valvular symptoms can appear years or decades after acute RF.

The manifestations depend on the valves involved.

Valve lesions may lead to murmurs, dilation, hypertrophy and heart failure.

Historical RF may no longer be clinically apparent at presentation.

Slide 58 · Atrial fibrillation links valve and embolic disease

Atrial fibrillation is particularly important in rheumatic mitral stenosis.

Chronically enlarged atria are vulnerable to rhythm disturbance.

Atrial arrhythmia and mural thrombosis can coexist.

Clinical morbidity can therefore extend beyond the valve opening itself.

Slide 59 · RHD predisposes to later infective endocarditis

Chronically scarred valves are abnormal endocardial substrates.

Infective endocarditis as a chronic RHD complication.

Superimposed infection is distinct from the initial sterile RF mechanism.

New infective lesions should not be interpreted simply as RF recurrence.

Slide 60 · Long-term outcome is heterogeneous

Severity differs with affected valves and degree of deformity.

Arrhythmias, embolic events and heart failure alter the course.

Repeated inflammation can drive cumulative valve damage.

Valve repair or replacement has improved prognosis in suitable patients.

Slide 61 · Case 1 — delayed systemic illness

A school-age child develops fever and sequential swelling of large joints several weeks after sore throat.

Which immune sequence connects the two illnesses?

Which cardiac finding would be important to look for?

Why might the throat culture already be negative?

Answer: Cross-reactive post-streptococcal immunity; Assess for carditis.

Slide 62 · Case 2 — ventricular inflammation

A patient with active RF develops tachycardia, an enlarged heart and functional mitral insufficiency.

Which heart layer is producing the major dysfunction?

What focal inflammatory lesion may be present?

What macrophage nuclear pattern characterizes that lesion?

Answer: Myocarditis; Aschoff bodies containing Anitschkow cells.

Slide 63 · Case 3 — chronic valvular sequelae

An adult with a remote history of RF develops mitral stenosis, left atrial dilation and an atrial arrhythmia.

Which structural valve lesions are expected?

Why may left atrial thrombus develop?

What right-sided cardiac consequence may follow?

Answer: Fused commissures/chordae; Stasis and embolism; Eventual RV hypertrophy.

Slide 64 · Acute RF versus chronic RHD

Feature

Acute RF

Chronic RHD

Primary biology

Cross-reactive inflammation

Fibrotic repair and distortion

Characteristic heart lesion

Aschoff bodies; Verrucae

Commissural / chordal fusion

Typical time relation

Weeks after infection

Often years to decades later

Predominant hazard

Active carditis

Stenosis, AF, embolism, failure

Both phases are manifestations of the same post-streptococcal disease process.

Slide 65 · Mechanism-to-morphology synthesis

Initiating pathogen is group A streptococcus.

Cross-reactive host immunity creates acute injury.

Aschoff bodies and tiny closure-line verrucae signify active disease.

Healing and recurrent inflammation produce distorted, stenotic valves.

Streptococcal infection

Autoimmune inflammatory lesion

Valve repair and scar

Chronic valvular dysfunction

Schematic

Slide 66 · Five morphological points to retain

Aschoff bodies are focal inflammatory cardiac lesions of active RF.

Anitschkow macrophages show wavy “caterpillar” nuclear chromatin.

Verrucae are tiny closure-line vegetations in rheumatic valvulitis.

Chronic mitral disease fuses commissures and chordae and thickens leaflets.

Fibrosis and neovascularization obliterate normal valve architecture.

Slide 67 · Five clinical links to retain

Antecedent streptococcal infection precedes an immune-mediated syndrome.

Migratory large-joint arthritis may resolve without deformity.

Carditis can generate lasting valvular lesions.

Mitral obstruction promotes atrial dilation, thrombosis and lung congestion.

Chronic RHD may present decades after the initial febrile episode.

Slide 68 · Reference and source boundaries

Primary textbook

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition (2026). Chapter 12, “The Heart.”

Visual provenance

Mechanism, valve and histology diagrams are original editable schematics, not diagnostic photographs or reproduced textbook figures.

The brief Jones summary follows the textbook wording; verify current risk-stratified criteria before clinical use.