Rheumatic diseases represent a heterogenous group of diseases with autoimmune disorders characterized by systemic disorganization of connective tissue. Rheumatic diseases include over 120 entities and syndromes characterized by predominant lesions of the connective tissue (including stroma) of both internal organs and the locomotor system, which are also associated with autoimmune disorders.
Common signs for the whole group of rheumatic diseases include systemic connective tissue lesions, impaired immune homeostasis (ITH and DTH reactions), generalized vasculitis, and chronic recurrent course of disease. Chronic infectious focus may also be present in specific cases.
The most common rheumatic diseases include:
- rheumatic fever and chronic rheumatic diseases;
- rheumatoid arthritis;
- ankylosing spondylitis;
- systemic lupus erythematosus (SLE);
- systemic sclerosis;
- dermatomyositis;
- polymyositis;
- Sjogren disease/syndrome;
- polyarteritis nodosa.
Connective tissue lesions in these diseases presume the systemic progressive degeneration of the tissue. There are 4 consequent disorganization phases:
- mucoid degeneration;
- fibrinoid degeneration;
- inflammatory cellular reactions;
- sclerosis and hyalinosis.
The mucoid degeneration phase is characterized by reversible and superficial connective tissue damage characterized by focal accumulation and/or redistribution of acidic glycosaminoglycans, a component of the ground substance in the extracellular matrix of connective tissue. Glycosaminoglycan molecules are hydrophilic, binding a large amount of water molecules and ions (Na+ in particular) from the extracellular fluid. As vascular permeability increases, the ground substance becomes swollen, and glycosaminoglycans accumulate there. When stained with toluidine blue, mucoid degeneration foci become purple or crimson. Such color change is called metachromasia. Collagen fibers usually swell as well, while their resistance to collagenase decreases. Apart from disorders of the ground substance and collagen fiber, affected areas demonstrate lymphoplasmocytic infiltration by macrophages. Mucoid degeneration becomes most prominent in blood vessel walls, cardiac valves, endocardium (fig. 15.1), which are the most common targets for immune-mediated lesions. During the mucoid degeneration phase, the appearance of organs does not change much, but their function is impaired. In this phase, the process of connective tissue damage may be reversible; however, it usually progresses to fibrinoid changes.
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Fig. 15.1. Mucoid degeneration of the endocardium in rheumatic fever. Toluidine blue staining
Fibrinoid degeneration is the next phase of connective tissue disorganization, which is characterized by deep and irreversible damage of its extracellular matrix. This stage is characterized by destruction of the basal substance and fibers, while also associated with a significant increase in vascular permeability and fibrinoid formation. Lesions develop both in the stroma of organs and the vessel wall. Fibrinoid is a complex substance consisting of proteins and polysaccharides, degrading collagen fibers, the ground substance, blood plasma, and cellular nucleoproteins. The composition of fibrinoid is variable, but fibrin is its mandatory component. It is formed from fibrinogen under the action of tissue thromboplastin. Fibrinoid also includes immune complexes and immunoglobulins. Electron microscopy of the fibrinoid shows collagen fiber destruction, loss of their typical cross-striation, and fibrin accumulations. Significant and diffuse fibrinoid changes lead to fibrinoid necrosis associated with the decreased organ function or its complete loss (e.g., acute renal failure in lupus nephritis). The inflammatory reaction develops in response to the damage. Its features depend on the pathogenesis of rheumatic diseases, damage location, and stage of the disease.
Sclerosis is the final connective tissue disorganization phase. As the course of rheumatic diseases is chronic and recurrent, affected organs may demonstrate almost all connective tissue disorganization phases with inflammatory exudative and proliferative reactions, sclerosis and hyalinosis areas.
Blood vessel lesions play an extremely important role in the pathogenesis of rheumatic diseases. Immune disorders primarily affect arterioles, capillaries, and venules. Vascular lesions in these diseases are characterized by variable pathological reactions even in a single disease. When ITH reactions predominate, we note plasmorrhagia, mucoid and fibrinoid degeneration, fibrinoid necrosis, infiltration with polymorphonuclear leukocytes and macrophages; thromboses and hemorrhages are also possible. When DTH reactions predominate, cellular reactions occur (lymphohistiocytic infiltrate, granuloma, productive vasculitis) with proliferation of intimal and adventitial cells, which erases vascular wall borders. It is important that in the majority of rheumatic diseases, hypersensitivity reaction types change according to stages of the disease. ITH reactions are typical of the disease onset and exacerbations, which alternate with DTH reactions.