Scleroderma

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

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Epidemiology

Cases of scleroderma are recorded in all regions of the world, but the prevalence of the disease in different geographical areas and ethnic groups is not the same. The primary incidence ranges from 3.7 to 20.0 cases per million people. The prevalence of an average of 240-290 per 1 million population In the Russian Federation, the primary incidence is 0.39 per 1000 population, in Moscow - 0.02 cases per 1000 population.

According to clinical signs, the current and the prognosis are distinguished by a limited and systemic form.

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Limited scleroderma

Limited scleroderma manifests itself in the form of plaque, linear, deep nodular and small-spotted (drip) surface foci (white spot disease, white lichen Zumbusha, etc.).

Plaque Scleroderma

The most common plaque form of scleroderma, clinically characterized by the presence of spots of various sizes, oval, round or irregular contours, located mainly on the trunk and extremities, sometimes unilateral. In their zone there are surface densities, but in rare cases the process captures deep tissue (deep form). The color of the elements is pink at first, then changes to waxy-white in the center of the hearth. On the periphery of it a narrow lilac ring is preserved, the presence of which indicates the activity of the process. Sometimes on the surface of individual plaques there may be blisters. When the process regresses, atrophy, pigmentation and telangiectasia remain.

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

Linear scleroderma

Linear scleroderma often occurs in childhood, but can develop in the elderly. The foci are located mainly on the scalp with a transition to the skin of the forehead and nose, accompanied by a pronounced atrophy not only of the skin but also of the underlying tissues, which gives them a resemblance to the scar after a saber attack, sometimes combined with the hemiatrophy of Romberg's face. The foci can also be localized on the extremities, causing atrophy of deep tissues, as well as in the form of a ring on the penis.

Pathomorphology of limited scleroderma

In the early stage of the process (stage of erythema), a marked inflammatory reaction of various intensity is observed in the dermis. It can be perivascular or diffuse, involves the entire thickness of the dermis and subcutaneous tissue. Infiltrates can be localized around the hair follicles, eccrine glands, nerves and consist mainly of lymphocytes, histiocytes, sometimes with a small admixture of eosinophils. There are structures resembling lymphatic follicles. 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 patterns. Lymphocytes in structure resemble blast cells with massive cytoplasm and a large number of free ribosomes. Among the cellular elements described, cellular detritus is sometimes found. With the help of immunological methods it is shown that T-lymphocytes predominate in the infiltrate. Among the cells of the inflammatory infiltrate, one can see thin newly formed collagen fibers, which are type III collagen. With the progression of the process, 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, indirect immunofluorescence method using antibodies against different types of collagen revealed that during this period collagen I and III types are found. The presence of collagen and glycosaminoglycans such as dermatan sulfate is histochemically shown, although there are chondroitin sulfates - 4 or 6. The content of hyaluronic acid is reduced, despite the large number of fibroblasts. This is because there are different types of fibroblasts that can produce normal collagen.

In the late (sclerotic) stage, the inflammatory phenomena disappear, and the bundles of collagen fibers become homogenized and hyalineized. At the beginning of the process, they are stained with eosin intensively, and then - pale. Cellular elements and vessels are very small, the walls of the latter are thickened, the lumens narrowed. The epidermis is usually changed little, in the inflammatory stage it is somewhat thickened, in the sclerotic phase it is atrophic.

Histogenesis

In 70% of patients with limited scleroderma, antinuclear antibodies are detected, and rheumatoid factor, antibodies to native DNA (nDNA) and anti-centromeric antibodies are also often found. TJ. Woo and JE Rasmussen (1985) found antinuclear antibodies in 12 of 24 patients with scleroderma limited, 7 of 17 had a rheumatoid factor, and 5 of them had antinuclear antibodies. In 2 patients of this group, systemic manifestations (nephritis, Raynaud's phenomenon) were found, which indicates the potentially systemic nature of this form of scleroderma. With linear form more often than in others, the nervous system is involved in the process.

Systemic scleroderma

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

Systemic scleroderma is a generalized lesion of connective tissue and vessels with the involvement of the skin and internal organs. Clinically, it can manifest as a diffuse lesion of the entire skin with the most significant changes in the facial skin and distal limbs. The edema stage is replaced by atrophy of the skin, muscles, the face becomes amytic, hyper- and depigmentation, telangiectasia, trophic disorders, especially at the fingertips, acroosteolysis, ulceration, calcification (Tibierja-Weissenbach syndrome), contractures. The combination of calcification, the phenomenon of Raynaud, sclerodactylia and telangiectasia is called CRST-syndrome, and in the presence of lesion of the esophagus - CREST-syndrome. Keloid-like foci can be observed, the occurrence of which is considered as a kind of reaction to the inflammatory component in persons predisposed to keloids.

Pathomorphology of systemic scleroderma

Changes are similar to those in a limited form, as a result of which they can sometimes not be differentiated. However, in the early stage, the inflammatory reaction in systemic scleroderma is weak, in the later stages marked changes in the vessels are noted, and fibroblasts are found among more hyalineized collagen fibers. Vascular changes with systemic scleroderma are expressed significantly, which determines the appearance of the Raynaud phenomenon. Small arteries and capillaries of skin and internal organs are affected. The walls are thickened, lumens narrowed, sometimes obliterated, the number of capillaries reduced. Electron microscopy reveals alteration, vacuolization and destruction of endotheliocytes, reduplication of the basal membrane, lengthening of pericytes, and the presence of mononuclear cells of the infiltrate perivascularly. Around them are active fibroblasts with a pronounced endoplasmic reticulum in the cytoplasm. The capillaries of the subepidermal section of the dermis, on the contrary, are sharply expanded with the phenomena of proliferation of endotheliocytes and their increased activity, which is probably the compensatory act. Indirect immunofluorescence in the walls of the affected capillaries and small arteries revealed sub-type deposits of type III collagen and fibronectin, however, type I collagen is absent. In later stages of systemic scleroderma, atrophy of the epidermis, thickening and fusion of collagen fiber bundles are noted with the formation of extensive areas of hyalinosis, sometimes with the deposition of calcium salts.

Histogenesis

In the development of the disease, great importance is attached to violations of collagen synthesis, as evidenced by the increased activity of fibroblasts in culture and the production of collagen in the phase of exacerbation of the disease; enhanced excretion of hydroxyproline; disorders of microcirculation in connection with generalized lesions of the capillary network and small arteries; defect of the immune system, characterized by the presence of autoantibodies - antinuclear, anti-centromeric, against RNA (Sm, Ro (SS-A), PM-Scl-70), collagen, etc., immune complexes. Antibodies against DNA, in contrast to systemic lupus erythematosus, are not determined. A large frequency of positive serological reactions was revealed in systemic scleroderma, a different association of different indicators with different forms of the disease. So, the CREST-syndrome is associated with anti-centromeric antibodies, antibodies to Scl-70 are considered as a marker of diffuse scleroderma. The state of immunodeficiency was noted. The participation of histamine and serotonin in the pathogenesis of the disease is shown.

Although there are observations of family cases, an association with some tissue compatibility antigens, such as B37, BW40, DR1 and DR5, has been identified, but the role of hereditary predisposition appears to be small. The role of a viral infection has not been proven. There was an opinion on the relationship between scleroderma and Borrelia borreliosis caused by spirochaetes of Borrelia burgdorferi, which has not been proven yet.

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

Background

The term "scleroderma" ("hard skin") was introduced by Gintrac in 1847, but the first detailed description of the disease belongs to Zacutus Lusitanus (1643). Only in the 40's. XX century. Intensive study of visceral pathology with scleroderma began, its systemic character and scleroderma group of diseases were described. In 1985, the famous English rheumatologist E. Bayoters wrote: " Systemic scleroderma is a mystery of our generation, dramatic and unexpected when manifested, unique and mystical in its clinical manifestations, progressing and stubbornly resisting treatment, resulting in despair of both patients and doctors .. . "[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 STD as a multi-organ disease.

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