Etiology and pathogenicity factors
Modern terminology divides the disease into acute rheumatic fever (active phase) and chronic rheumatic heart disease (inactive phase). The development of the pathology is directly linked to a prior pharyngeal infection caused by Streptococcus pyogenes (predominantly rheumatogenic M-serotypes: 1, 3, 5, 6, 14, 18, 19, 24).
The bacterium secretes a number of aggressive enzymes and substances that damage host tissues:
- Streptolysins O and S — trigger the transformation of plasminogen into streptokinase and subsequently into plasmin, dissolving fibrin.
- Hyaluronidase — facilitates bacterial movement through connective tissue.
- Pneumolysin — damages target cell membranes.
- C5a peptidase — destroys the chemotactic factor.
- DNase.
Long-term persistence of the infection is ensured by the transition of bacteria into L-forms and mutations in the emm genes encoding the protective cell wall M-protein. The reversion of L-forms to their original state triggers relapses and flare-ups of rheumatism.
Pathogenesis and autoimmunity
The disease is based on the phenomenon of molecular mimicry (antigenic similarity). Streptococcal antigens are structurally similar to the body's own tissues: M-protein resembles cardiac myosin and sarcolemmal membranes, while hyaluronate resembles connective tissue proteoglycans.
Because of this, cross-reacting antibodies produced against the infection begin to attack the body's own cells. T-cell tolerance to the body's own connective tissue (primarily of the heart) is broken. Immune complexes are formed and deposit on the basement membrane of microvessels. Both immediate-type (type I hypersensitivity) and delayed-type (type IV hypersensitivity) hypersensitivity reactions participate in the process.
Morphogenesis of rheumatism
Tissue changes in rheumatism go through four consecutive stages reflecting progressive systemic disorganization of connective tissue and microvessels:
- Mucoid swelling — early phase of acute immune inflammation (immediate hypersensitivity reaction).
- Fibrinoid changes — progression of the process leading up to necrosis of the vessel wall and perivascular tissue (vasculitis).
- Granulomatosis — formation of specific "mature" Aschoff–Talalaev granulomas in the perivascular stroma. They consist of macrophages and activated cells producing cytokines and growth factors.
- Sclerosis — transition from immediate-type to delayed-type hypersensitivity, "fading" of granulomas, and replacement of damaged areas with scar tissue (in the heart and joints).
General pathological changes also include plasmacytic transformation, lymphoid tissue hyperplasia, and polyserositis.
Clinical diagnostic criteria
WHO criteria (1989) are used to confirm the diagnosis. It is necessary to prove the presence of a streptococcal infection combined with either two major criteria or one major and two minor criteria.
Major criteria:
- Rheumatic carditis — the leading sign, occurring in 70–85% of children during their first attack.
- Migratory polyarthritis — symmetrical involvement of large joints of a migratory nature. Characterized by a benign course: function is fully restored, and radiographic changes are absent.
- Sydenham's chorea (St. Vitus' dance) — manifests as a triad: hyperkinesia, discoordination, and muscle hypotonia. Develops in 10–15% of patients (predominantly girls aged 6–15 years).
- Erythema marginatum (annular rash) — transitory pink or red macules with a pale center and irregular borders on the trunk and limbs.
- Subcutaneous nodules — firm, painless formations in the periarticular tissue.
Minor criteria include clinical (fever, arthralgia), laboratory (elevated ESR, CRP, leukocytosis), and instrumental signs (prolonged P–R interval on ECG).
Briefly: answers to topical questions
What specific cells make up Aschoff–Talalaev granulomas?
Aschoff–Talalaev granulomas consist of macrophage-histiocytes and two types of specific cells.
- Anichkov cells — large epithelioid cells with basophilic cytoplasm. Their round or oval nuclei have centrally located chromatin, making the nucleus look like an "owl's eye" in cross-section and a "caterpillar" in longitudinal section. These cells are pathognomonic for rheumatic carditis.
- Aschoff cells — multinucleated giant histiocytes.
Also, in the initial stage, macrophages accumulate around the focus of fibrinoid necrosis and subsequently transform into epithelioid cells.
What macroscopic forms of rheumatic endocarditis are distinguished in pathological anatomy?
Pathological anatomy distinguishes four forms of valvular rheumatic endocarditis:
- Diffuse endocarditis (valvulitis).
- Acute verrucous endocarditis — characterized by the formation of small (1–2 mm) easily detachable thrombi ("vegetations") along the closure line of the cusps.
- Fibroplastic endocarditis — distinguished by enhanced sclerosis processes; the valve tissue is thickened and has a grey, translucent appearance.
- Recurrent verrucous endocarditis — develops during repeated attacks on already sclerosed and deformed valves; new masses of fibrin are deposited on top of old thrombotic masses.
What morphological types of rheumatic myocarditis are distinguished?
Three main morphological forms of rheumatic myocarditis are distinguished.
- Nodular myocarditis (granulomatous) — characterized by the formation of typical Aschoff–Talalaev granulomas in the perivascular connective tissue of the stroma.
- Diffuse interstitial exudative myocarditis — manifests as vascular congestion, impregnation of the interstitium with serous exudate, cellular infiltration, as well as pronounced dystrophic changes and foci of muscle cell necrosis.
- Focal interstitial exudative myocarditis — is characterized by the presence of foci of minor lymphohistiocytic infiltration mixed with band neutrophils in the interstitium, as well as focal dystrophy and cardiomyocyte necrosis.
What morphological changes occur in the joint cavity and tissues during rheumatic polyarthritis?
In rheumatic polyarthritis, morphological changes predominantly affect large joints and their tissues.
- Synovitis — the appearance of foci of disorganization in the synovial membrane.
- Vascular reactions — the development of vasculitis with hyperemia and the formation of perivascular lymphoid infiltrates (sheaths).
- Exudation — accumulation of serous or serofibrinous effusion in the joint cavity.
An important morphological feature is that the articular cartilage is not involved in the inflammatory process, therefore anatomical joint deformation does not occur.
To easily remember the five major criteria, group them by target organs: Heart (rheumatic carditis), Joints (polyarthritis), Nervous system (Sydenham's chorea), Skin (erythema marginatum and subcutaneous nodules).
Class and exam questions
Which tests confirm streptococcal etiology?
Isolation of group A Streptococcus from the pharynx and evaluation of antibody titers are used. The combination of antistreptolysin O (ASO) tests together with anti-DNase B or antihyaluronidase has the highest sensitivity.
What is Jaccoud's syndrome?
This is a painless hand deformation with characteristic ulnar deviation that is sometimes seen in rheumatic fever. At the same time, inflammation is absent, and joint function is fully preserved.
Who is more prone to rheumatic fever — men or women?
The overall incidence is similar, but chorea and mitral stenosis are more common in women, while aortic stenosis is more common in men.
How long does the active phase of the disease last?
On average, the duration of a single rheumatic attack is about 12 weeks. The clinical course can be acute, subacute, protracted, or latent.
What else to study on this topic
- Mechanisms of streptococcal persistence: the role of L-forms and emm gene mutations
- Detailed morphology and cellular composition of Aschoff-Talalaev bodies
- Features of articular syndrome and differential diagnosis of arthritis
- Clinical variants of the course of a rheumatic attack
- Pathogenesis of heart valve defects (mitral and aortic stenosis)
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