Scleroderma

Scleroderma is a systemic connective tissue disease of unknown etiology, which is based on progressive collagen disorganization. The process consists of several links: mucoid swelling, fibrinoid changes, cellular reactions and sclerosis.

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Epidemiology

Cases of scleroderma are registered in all regions of the world, however, the prevalence of the disease in different geographical zones and ethnic groups is not the same. Primary incidence is from 3.7 to 20.0 cases per 1 million population. Prevalence is on average 240-290 per 1 million population. In the Russian Federation, primary incidence is 0.39 per 1000 population, in Moscow - 0.02 cases per 1000 population.

Based on clinical signs, course and prognosis, a distinction is made between limited and systemic forms.

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Limited scleroderma

Limited scleroderma manifests itself in the form of plaque, linear, deep nodular and small-spotted (droplet) superficial lesions (white spot disease, white lichen of Zumbusch, etc.).

Plaque scleroderma

The most common form of scleroderma is plaque, clinically characterized by the presence of spots of various sizes, oval, round or irregular outlines, located mainly on the trunk and limbs, sometimes unilaterally. In their area there are superficial compactions, only in rare cases the process captures deep-lying tissues (deep form). The color of the elements is initially pink, then changes to waxy white in the center of the lesion. Along its periphery, a narrow lilac ring remains, the presence of which indicates the activity of the process. Sometimes there may be blisters on the surface of individual plaques. With regression of the process, atrophy, pigmentation and telangiectasias remain.

At the same time, there may be small lesions of the lichen aibus Zumbusch or lichen sclerosus et atrohicus type, which has given a number of authors reason to consider the latter as a superficial variant of scleroderma.

Linear scleroderma

Linear scleroderma most often occurs in childhood, but can also develop in the elderly. The lesions are located mainly on the scalp with a transition to the skin of the forehead, nose, accompanied by pronounced atrophy of not only the skin, but also the underlying tissues, which makes them similar to a scar after a sabre blow, sometimes combined with Romberg's hemiatrophy of the face. The lesions can also be localized on the limbs, causing atrophy of deep tissues, and also in the form of a ring on the penis.

Pathomorphology of limited scleroderma

In the early stage of the process (erythema stage), a pronounced inflammatory reaction of varying intensity is observed in the dermis. It can be perivascular or diffuse, involving the entire thickness of the dermis and subcutaneous tissue. Infiltrates can be localized around hair follicles, eccrine glands, nerves and consist mainly of lymphocytes, histiocytes, sometimes with an admixture of a small amount of eosinophils. Structures resembling lymphatic follicles are encountered. Electron microscopy of inflammatory infiltrates revealed that they consist mainly of immature plasma cells containing in their cytoplasm dilated cisterns of the granular endoplasmic reticulum and nuclei with dispersed chromatin. Among them, in addition, there is a large number of macrophages with large globules and myelin figures. Lymphocytes resemble blast cells with massive cytoplasm and a large number of free ribosomes in their structure. Among the described cellular elements, cellular detritus is sometimes detected. Immunological methods have shown that T-lymphocytes predominate in the infiltrate. Among the cells of the inflammatory infiltrate, thin newly formed collagen fibers can be seen, representing type III collagen. As the process progresses, the connective tissue becomes denser, homogenization areas appear, but among them there are many fibroblasts, glycosaminoglycans and glycoproteins. Over time, collagen fibers become more mature, their thickness reaches 80-100 nm, the method of indirect immunofluorescence using antibodies against various types of collagen revealed that collagen types I and III are detected during this period. Histochemically, the presence of collagen and glycosaminoglycans of the dermatan sulfate type is shown, although there are chondroitin sulfates - 4 or 6. The content of hyaluronic acid is reduced, despite the large number of fibroblasts. This is explained by the fact that there are different types of fibroblasts capable of producing normal collagen.

In the late (sclerotic) stage, inflammatory phenomena disappear, and collagen fiber bundles become homogenized and hyalinized. At the beginning of the process, they are stained with eosin intensely, and then - pale. There are very few cellular elements and vessels, the walls of the latter are thickened, the lumens are narrowed. The epidermis is usually slightly changed, in the inflammatory stage it is somewhat thickened, in the sclerotic stage - atrophic.

Histogenesis

Antinuclear antibodies are detected in 70% of patients with limited scleroderma; rheumatoid factor, antibodies to native DNA (nDNA) and anticentromere antibodies are also often detected. TJ Woo and JE Rasmussen (1985) detected antinuclear antibodies in 13 of 24 patients with limited scleroderma, rheumatoid factor in 7 of 17, and antinuclear antibodies were also detected in 5 of them. Systemic manifestations (nephritis, Raynaud's phenomenon) were detected in 2 patients of this group, which indicates the potentially systemic nature of this form of scleroderma. In the linear form, the nervous system is more often involved in the process than in others.

Systemic scleroderma

Systemic scleroderma is an autoimmune disease of connective tissue, the main clinical manifestations of which are associated with widespread ischemic disorders caused by obliterating microangiopathy, fibrosis of the skin and internal organs (lungs, heart, digestive tract, kidneys), and damage to the musculoskeletal system.

Systemic scleroderma is a generalized lesion of connective tissue and blood vessels involving the skin and internal organs. Clinically, it can manifest itself as a diffuse lesion of the entire skin with the most significant changes in the skin of the face and distal parts of the extremities. The edema stage is replaced by atrophy of the skin and muscles, the face becomes amimic, hyper- and depigmentation, telangiectasias, trophic disorders are observed, especially on the fingertips, acroosteolysis, ulceration, calcinosis (Thiberge-Weissenbach syndrome), contractures. The combination of calcinosis, Raynaud's phenomenon, sclerodactyly and telangiectasia is called CRST syndrome, and in the presence of esophageal damage - CREST syndrome. Keloid-like lesions may be observed, the occurrence of which is considered a peculiar reaction to the inflammatory component in individuals predisposed to keloids.

Pathomorphology of systemic scleroderma

The changes are similar to those in the limited form, as a result of which they are sometimes impossible to differentiate. However, in the early stage, the inflammatory reaction in systemic scleroderma is weak, in later stages, pronounced changes in the vessels are noted, and fibroblasts are found in greater quantities among the hyalinized collagen fibers. Vascular changes in systemic scleroderma are expressed significantly, which determines the appearance of the Raynaud phenomenon. Small arteries and capillaries of the skin and internal organs are affected. Their walls are thickened, the lumens are narrowed, sometimes obliterated, the number of capillaries is reduced. Electron microscopy reveals alteration, vacuolization and destruction of endotheliocytes, reduplication of the basement membrane, elongation of pericytes and the presence of mononuclear cells of the perivascular infiltrate. Active fibroblasts with a pronounced endoplasmic reticulum in the cytoplasm are located around them. The capillaries of the subepidermal dermis, on the contrary, are sharply dilated with phenomena of endothelial cell proliferation and their increased activity, which probably represents a compensatory act. The method of indirect immunofluorescence in the walls of the affected capillaries and small arteries revealed subintimal deposits of type III collagen and fibronectin, but type I collagen is absent. In later stages of systemic scleroderma, atrophy of the epidermis, thickening and fusion of collagen fiber bundles with the formation of extensive areas of hyalinosis, sometimes with the deposition of calcium salts, are noted.

Histogenesis

In the development of the disease, great importance is attached to the disorders of collagen synthesis, as evidenced by the increased activity of fibroblasts in culture and collagen production in the acute phase of the disease; increased excretion of oxyproline; microcirculation disorders due to generalized damage to the capillary network and small arteries; a defect of the immune system, characterized by the presence of autoantibodies - antinuclear, anticentromere, against RNA (Sm, Ro (SS-A), PM-Scl-70), collagen, etc., immune complexes. Antibodies against DNA, unlike systemic lupus erythematosus, are not determined. A high frequency of positive serological reactions in systemic scleroderma, unequal association of various indicators with different forms of the disease have been established. Thus, CREST syndrome is associated with anticentromere antibodies, antibodies to Scl-70 are considered as a marker of diffuse scleroderma. The state of immunodeficiency is noted. The involvement of histamine and serotonin in the pathogenesis of the disease has been shown.

Although there are observations of familial cases of the disease, an association with some tissue compatibility antigens such as B37, BW40, DR1 and DR5 has been found, but the role of hereditary predisposition seems to be small. The role of viral infection has not been proven either. An opinion has been expressed about the connection of scleroderma with borreliosis caused by the spirochete Borrelia burgdorferi, which has also not yet been proven.

Scleroderma-like changes are observed in eosinophilia-myalgia syndrome caused by the intake of products containing L-tryptophan; in the late stage of graft-versus-host disease; with prolonged contact with silicone, organic solvents, epoxy resins, vinyl chloride; during treatment with bleomycin or L-5-hydroxytryptophan.

History of the issue

The term "scleroderma" ("hard-skinned") was introduced by Gintrac in 1847, but the first detailed description of the disease belongs to Zacutus Lusitanus (1643). Only in the 40s of the XX century began an intensive study of visceral pathology in scleroderma, its systemic nature and scleroderma group of diseases were described. In 1985, the famous English rheumatologist E. Bywaters wrote: " Systemic scleroderma is a mystery of our generation, dramatic and unexpected in its manifestation, unique and mystical in its clinical manifestations, progressive and stubbornly resistant to treatment, driving both patients and doctors to despair..." [Bywaters E. "Foreword History of scleroderma" in "Systemic Sclerosis (Scleroderma)". Black Ed, C., Myers A., 1985]. Over the past decades, there has been significant progress in the study of SSD as a multiorgan disease.

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