Etiology and Pathogenic Factors
Modern terminology divides the disease into acute rheumatic fever (active phase) and chronic rheumatic heart disease (inactive phase). 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, and 24).
The bacterium secretes several aggressive enzymes and substances that damage host tissues:
- Streptolysins O and S — trigger the conversion of plasminogen to streptokinase and subsequently to plasmin, dissolving fibrin.
- Hyaluronidase — facilitates bacterial spread through connective tissue.
- Pneumolysin — damages target cell membranes.
- C5a peptidase — degrades the chemotactic factor.
- DNase.
Long-term persistence of the infection is maintained by the transition of bacteria into L-forms and mutations in emm genes, which encode the protective cell-wall M-protein. Reversion of L-forms to their original state triggers relapses and flare-ups of the disease.
Pathogenesis and Autoimmunization
The core mechanism relies on molecular mimicry (antigenic similarity). Streptococcal antigens structurally resemble host tissues: the M-protein mimics cardiac myosin and sarcolemma membranes, while hyaluronic acid resembles connective tissue proteoglycans.
Consequently, cross-reacting antibodies produced against the infection begin attacking the body's own cells. T-cell tolerance to host connective tissue (primarily in the heart) is breached. Immune complexes form and deposit on the basement membranes of microvessels. Both immediate-type hypersensitivity (Type I/III reactions) and delayed-type hypersensitivity (Type IV reactions) are involved.
Morphogenesis
Tissue changes in rheumatic fever progress through four sequential stages reflecting systemic connective tissue and microvascular disorganization:
- Mucoid swelling — the 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-Talaลาev (Aschoff) granulomas in the perivascular stroma. They consist of macrophages and activated cells producing cytokines and growth factors.
- Sclerosis — transition 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.
Diagnostic Criteria
Diagnosis relies on the modified Jones criteria (supported by WHO guidelines). It requires evidence of a preceding streptococcal infection combined with either two major criteria, or one major and two minor criteria.
Major criteria:
- Carditis — the leading sign, present in 70–85% of children during their first attack.
- Migratory polyarthritis — symmetrical, shifting involvement of large joints. It has a benign course: function fully recovers, and radiographic changes are absent.
- Sydenham chorea (St. Vitus' dance) — characterized by a triad of hyperkinesia, incoordination, and muscle hypotonia. It develops in 10–15% of patients (predominantly girls aged 6–15).
- Erythema marginatum — transient pink or red rings with pale centers and irregular borders on the trunk and limbs.
- Subcutaneous nodules — firm, painless lumps located over bony prominences and tendon sheaths.
Minor criteria include clinical findings (fever, arthralgia), laboratory markers (elevated ESR, CRP, leukocytosis), and instrumental signs (prolonged P–R interval on ECG).