Rheumatic diseases: general characteristics
Rheumatic diseases are a group of systemic connective tissue diseases (formerly referred to by the obsolete term «collagenoses») in which the body's entire connective tissue, including blood vessels, is affected due to impaired immune homeostasis. This group includes: rheumatic fever, rheumatoid arthritis, ankylosing spondylitis (Bechterew's disease), systemic lupus erythematosus, systemic sclerosis, polyarteritis nodosa, dermatomyositis, and Sjögren's syndrome.
Etiological factors include infections, genetic predisposition, physical factors (cooling, sun exposure), and drug intolerance. The pathogenesis is based on immediate and delayed type hypersensitivity immunopathological reactions (Types I–IV according to Gell and Coombs).
Morphogenesis includes four sequential stages: mucoid swelling, fibrinoid changes, cellular inflammatory reactions, and sclerosis.
Rheumatic fever: etiology and pathogenesis
Rheumatic fever (Sokolovsky-Bouillaud disease) is an infectious-allergic disease with predominant involvement of the heart and blood vessels and a relapsing course characterized by alternating periods of exacerbation and remission.
The leading etiological factor is group A β-hemolytic Streptococcus and sensitization of the body by recurrent sore throats. Age and genetic factors are important; rheumatic fever is classified as a polygenic disease.
Key links of pathogenesis:
- complex immune response to streptococcal antigens with immediate and delayed type hypersensitivity reactions;
- production of antibodies cross-reacting with streptococcal antigens and heart tissues (antigenic mimicry);
- proteolytic action of streptococcal enzymes destroying glycosaminoglycan-protein complexes of connective tissue;
- formation of immune complexes in response to streptococcal components and breakdown products of own tissues with the development of an autoimmune process.
Morphogenesis: phases of connective tissue disorganization
Rheumatic fever is based on systemic progressive disorganization of connective tissue with involvement of microvascular bed vessels. Changes are most pronounced in the connective tissue of the heart.
- Mucoid swelling is a reversible superficial change with hydration of the ground substance and increased metachromasia (upon staining with toluidine blue, unchanged tissue is blue, foci of swelling are purple).
- Fibrinoid changes represent irreversible deep disorganization, homogenization, and destruction of collagen fibers, impregnation with plasma proteins, including fibrin.
- Cellular reactions involve the formation of a specific rheumatic granuloma (Aschoff-Talalaev nodule): macrophages transform into large cells with hyperchromatic nuclei, arranged in a palisade-like or fan-like manner around the fibrinoid focus. Flowering (mature) granulomas with high phagocytic activity are distinguished from waning ones, which show the appearance of fibroblasts, resorption of fibrinoid, and scarring. The full cycle takes 3–4 months. Granulomas are surrounded by lymphocytes and plasma cells.
- Sclerosis is systemic, most pronounced in the heart membranes, blood vessels, and serous membranes; it can be primary or secondary.
Rheumatic endocarditis
Depending on localization, valvular, chordal, and mural endocarditis are distinguished. The mitral and aortic valves are most frequently affected; valves of the right side of the heart are rarely affected and usually in combination with left-sided involvement. Morphologically, dystrophy and necrobiosis of the endothelium, mucoid and fibrinoid swelling, granulomatosis, and thrombus formation are observed.
- Diffuse endocarditis is a diffuse involvement of the cusps without endothelial changes and thrombi.
- Acute warty endocarditis is damage to the endothelium with thrombotic deposits («warts») along the free edge of the cusps.
- Fibroplastic endocarditis is fibrosis and scarring following previous forms.
- Recurrent warty endocarditis is repeated disorganization during new attacks with thrombus formation against the background of sclerosis and cusp thickening.
The outcome is sclerosis, hyalinosis, thickening, and deformation of the valves with the formation of a valvular heart defect and left ventricular myocardial hypertrophy.
Rheumatic myocarditis and pericarditis
Three forms of myocarditis are distinguished:
- Nodular productive (granulomatous) myocarditis is the formation of rheumatic granulomas in the perivascular tissue of the myocardium, predominantly in the left atrial appendage, interventricular septum, and posterior wall of the left ventricle; the outcome is perivascular cardiosclerosis.
- Diffuse interstitial exudative myocarditis (according to Skvortsov) is edema, plethora, infiltration by lymphocytes, histiocytes, neutrophils, and eosinophils, rare granulomas; the heart is flabby with dilated chambers; characteristic of children and can lead to decompensation.
- Focal interstitial exudative myocarditis is insignificant infiltration, rare granulomas, often with a latent course.
Pericarditis can be serous, serous-fibrinous, or fibrinous, resulting in adhesions. A classic example is fibrinoid pericarditis («hairy heart») with easily detachable fibrin deposits in the form of threads and films. Involvement of the endocarditis and myocardium is designated as rheumatic carditis, and all three membranes as rheumatic pancarditis.
Vascular involvement, complications, and outcomes
Rheumatic vasculitis develops in blood vessels, predominantly in the microvascular bed: fibrinoid changes, thrombosis, endothelial and adventitial proliferation, and increased capillary permeability. The outcome is various forms of sclerosis. In rheumatic fever, joints, the nervous system, kidneys, and lungs are also affected.
Main complications:
- formation of heart defects due to endocarditis;
- thromboembolism from warty deposits leading to internal organ infarctions, foci of softening in the brain, and gangrene of the extremities;
- systemic sclerosis, especially cardiosclerosis;
- adhesions and obliteration of serous cavities (pleuritis, pericarditis).
The outcome of the disease can be death during an acute attack from thromboembolism or the development of a decompensated heart defect with chronic heart failure.
Key points
- Rheumatic fever is a systemic infectious-allergic connective tissue disease with a relapsing course and predominant cardiac involvement.
- The main etiological factor is group A β-hemolytic Streptococcus; pathogenesis includes antigenic mimicry and autoimmune reactions.
- Morphogenesis undergoes four stages: mucoid swelling, fibrinoid changes, cellular reactions, sclerosis.
- The specific morphological marker is the Aschoff-Talalaev granuloma; its development cycle is 3–4 months.
- Endocarditis most frequently affects the mitral and aortic valves; diffuse, acute warty, fibroplastic, and recurrent warty variants are distinguished.
- Myocarditis can be nodular productive, diffuse, and focal interstitial exudative; pericarditis is often fibrinous («hairy heart»).
- Involvement of all heart membranes is designated as rheumatic pancarditis.
- The main outcomes are heart defects, thromboembolism, and cardiosclerosis with the development of circulatory decompensation.