SCLERODERMA

From Big Medical Encyclopedia

SCLERODERMA (sclerodermia; Greek skleros firm, dense + derma skin; synonym sclerodermitis). The term «scleroderma» is for the first time offered by E. Gintrac in 1847. Distinguish system and narrow S. Sistemnaya S. it is characterized by the generalized progressing scleroderma and internals, limited — preferential focal damage of skin without signs of systemacity.

System scleroderma

System scleroderma (sclerodermia systemica; synonym: the progressing, universal, generalized, diffusion scleroderma, the progressing system sclerosis) treats group of rheumatic diseases, in particular diffusion diseases of connecting fabric (see. Collagenic diseases ). It represents the polysyndromic disease which is shown the progressing fibrosis of skin, internals (hearts, lungs, went. - kish. a path, kidneys), a peculiar vascular pathology like the regional iterating endarteriolit with widespread vasospastic disturbances.

Incidence, according to various researchers, fluctuates from 0,27 — 1,2 on 100 thousand population. Mortality, according to Ointment (A. T. of Masi) et al., makes 0,14 — 0,53 on 100 thousand. Women are ill preferential. According to various statistical data, the relation between incidence of women and men makes 3:1 — 7:1. Average age of sick 20 — 50 years. On domestic classification of N. G. Guseva (1975), distinguish the acute (quickly progressing), subacute and chronic system S. (the last two options of a current meet more often); typical S. with characteristic generalized damage of skin and its atypical forms with focal damage of skin; Page with preferential damage of internals; Page, combined with other rheumatic diseases. G. P. Rodnan, etc. allocate the following forms of system S.: a classical form with diffusion damage of skin; CREST syndrome — a combination calcification (see), Reynaud's syndrome (see below), damages of a gullet, a sclerodactylia and teleangiectasias (see); the name of a syndrome is formed of the first letters of names of the symptoms making it; Page, combined with other rheumatic diseases.

The first descriptions of damage of separate internals at S. and attempts to present it as generalized process belong to J. L. Steven, U. Osle-r (1898), A. To E. Yanishevsky and G. I. Markelov (1907). Klemperer's (P. Klemperer) doctrine about collagenic diseases was a powerful incitement to studying of system displays of this disease. In 1945 Getz (R. The N of Goetz) was offered the term «progressing system sclerosis». The subsequent studying a wedge, displays of a disease promoted improvement of diagnosis, including atypical and early options C., formed a basis for further pathogenetic and therapeutic researches, for creation of classifications, the generalizing works of the monographic plan, from to-rykh the greatest attention E. M. Tareeea, N. G. Guseva, G. Ya. Vysotsky, S. I. Dov-zhansky, Yablonskaya's works deserve (St. Jablon-ska), G. P. Rodnan, E. C. LeRoy, etc.

the Aetiology

the Aetiology is not found out; the probability of a virus and hereditary origin of a disease is discussed. Indirectly confirm detection of virus-like particles in the struck fabrics possible participation of a viral infection in system S.'s etiology, virusospetsifichesky enzyme (the return transcriptase) in marrow, increase in a caption of antiviral antibodies in blood serum of patients. The possibility of transplacental «vertical» and «horizontal» transmission of a virus, integration of a virus with a genome of a cell, activation of a latent viral infection is discussed.

The concept of hereditary transfer of system S. is based hl. obr. on existence of family cases, frequent detection immunol. disturbances at a klinncheska of healthy relatives of the diseased, the big frequency of aberation chromosomes (see. Mutation ) at patients system Page.

Cooling, vibration, an injury, contact with nek-ry chemical agents (silicon dust, chlorvinyl, etc.), infections, the neuroendocrinal disturbances preceding at a number of patients to system S.'s development can be considered as provocative factors. They keep the value in the theory of polygenic multifactorial inheritance of system S.

the Pathogeny

the Pathogeny is difficult, it includes characteristic changes of metabolism connecting fabric (see) with increase in biosynthesis collagen (see) and a neofibrillogenesis as a basis of generalized fibrosis, immune disturbances and defeat of a vascular, microcirculator bed with development of a peculiar sklerodermichesky angiopatiya (obliterating eidarteriolit, a reduction of capillaries, widespread vasospastic reactions).

The hyperactivity of fibroblasts with an excess kollageno-and fibrillation at disturbance of intercellular and interstitial interaction of components of connecting fabric is characteristic of system S. Are observed increase in content of oxyproline (see. Prolin ) in urine and a blood plasma of patients, substantial increase of speed of biosynthesis of collagen in skin, increase in soluble fraction of collagen and enzyme of a protocollagen-proline-hydroxylase at a part of patients, ultrastructural signs of the increased functional activity of fibroblasts of skin and the strengthened neofibrillogenesis. The Sklerodermopodobny syndrome at treatment by Bleomycinum is also connected with excess products of collagen owing to the stimulating impact of drug on fibroblasts. At a research of monolayer culture of fibroblasts of skin of patients of system S. steady hyperproduction of components of connecting fabric, hl is found phenotypical. obr. collagen, disturbance of functional properties of a membrane of fibroblasts is revealed (abnormal reaction to adrenaline, etc.). Change of functions of collagen-producing cells with reduced or «defective» perception of a signal from regulatory systems of an organism can lead to anomaly of processes of fibrillation (aggregation of collagenic fibers, assembly of fibrilla, etc.) and to fibrosing of fabrics, characteristic of system S.

Also disturbances humoral and cellular are inherent to system S. immunity (see) what the combination to various autoimmune diseases and syndromes testifies to — hemolitic anemia (see), Hashimoto's thyroiditis (see. Hashimoto disease ), Shegren's syndrome (see. Shegrena syndrome ), etc. At it quite often come to light: anti-nukleolyarnye and antinuclear antibodies, including antibodies to Scleroderma-70 antigen, anti-centromere (to centromere chromatin) autoantibodies; antibodies and cellular immune responses on collagen; decrease in maintenance of T-suppressors at the normal content V-lim-fotsitov in blood; cytopathic effect of lymphocytes; similarity of skin and vascular changes at system S. with the reactions observed at transplantation of marrow, etc.

Disturbances of microcirculation (see) and actually skleroder-michesky angiopatiya which is playing the leading role in an origin of many a wedge, system S.'s manifestations and quite often defining the forecast, in particular at development of a so-called true sklerodermichesky kidney have important pathogenetic value.

Blood serum of patients of system S. has cytotoxic activity concerning an endothelium, damage to-rogo is followed by adhesion and aggregation of thrombocytes (see), activation coagulations (see), fibrinolysis (see), release of mediators of an inflammation (see), increase in permeability of a vascular wall with the subsequent its plasmatic treatment and adjournment of fibrin. Mediators of an inflammation strengthen destruction of an endothelium, microfibrinferments and intravascular coagulation, supporting damage. The subsequent reparation of a vascular wall is followed by reduplication of basal membranes, intimalny migration and proliferation of smooth muscle cells. The last, being, a kind of fibroblasts, are capable to synthesize collagen preferential the III type and are responsible substantially (in the specified conditions) for development of vascular and perivascular fibrosis.

Thus, the microcirculator bed plays a role of a target organ where the contact with the hypothetical damaging agent is made, and it actively participates, along with connecting fabric and immune system, in development characteristic of a system scleroderma patol. process.

The pathological anatomy

System S. is morphologically characterized by the expressed fibrosis of various bodies and fabrics. Defeat of vessels and excess products of collagen is the cornerstone of fabric damages (see).

The most characteristic changes are noted in skin. Both at system, and at limited S. allocate three stages of skin changes: 1) stage of dense hypostasis; 2) stage of an induration; 3) stage of an atrophy. In a stage of dense hypostasis signs of the increased vascular permeability prevail (see). Come to light gidropichesky dystrophy of cells of a basal layer of epidermis (see. Vacuolar dystrophy), expansion limf, cracks, an insignificant razvolokneniye of collagenic bunches of a derma at the expense of hypostasis, vasculites (see), teleangiectasias (see), inflammatory infiltration around vessels, appendages of skin and in hypodermic cellulose. Among cells of inflammatory infiltrate in the struck fabrics sharp dominance of T lymphocytes and macrophages with signs of intensively proceeding phagocytosis is noted (see). The reinforced hyalinized bunches of collagenic fibers meet in a stage of dense hypostasis only in deep departments of a mesh (reticular) layer of a derma. By R. Fleischmajer et al. (1980) by means of an immunofluorescence (see) and a submicroscopy (see) it is established that the sclerosis begins around capillaries and near hypodermic cellulose. Fibroblasts in sites of fibrosis have the developed rough endoplasmic reticulum (see), are surrounded with accumulations of thin fibrilla (to dia. 10 — 30 nanometers); increase in amount of fine collagenic fibers, unripe bunches is noted to-rykh are similar to those, to-rye come to light in skin during the embryonal period.

Fig. 1. Microdrug of skin at a system scleroderma (a stage of an induration): 1 — a sclerosis and a hyalinosis of papillary and mesh layers of a derma and hypodermic cellulose, 2 — scanty limfondno-histiocytic infiltration on the course of the remained capillaries, 3 — an atrophy of epidermis, 4 — an atrophy of a follicle of a hair; coloring hematoxylin-eosine; X 120.

The stage of an induration (fig. 1) is characterized by a sclerosis of papillary and Mesh layers of a derma with a zapustevaniye of capillaries, a sclerosis of walls of vessels, reduction of quantity of cells, a thickening of collagenic bunches of a mesh layer and hyaline (see), an atrophy of epidermis and appendages of skin, a sclerosis and a hyalinosis of hypodermic cellulose. Vasculites at this stage come to light seldom. Cellular infiltrates usually scanty, are presented by 3 — 5 cells of lymphoid type.

The stage of an atrophy develops in many years after the beginning of a disease. At gistol. a research of skin and hypodermic cellulose fields of the hyalinized fabric with a diffusion atrophy of epidermis, alignment of nipples, sharp for-pustevaniyem vessels to microcircus-lyatornogo of a bed, reduction of quantity of cells, an atrophy of appendages of skin come to light. These changes of skin are followed by necroses (see) and trophic ulcers (see). At a syndrome of Tibyerzha — Veyssenbakh (see below) in hypodermic cellulose deposits of lime come to light. In sites of externally not changed skin the thickening of collagenic bunches of deep department of a mesh layer of a derma is noted.

Fig. 2. Microdrug of a synovial membrane of a knee joint at a system scleroderma: 1 — a chronic productive vasculitis, 2 — proliferation of an internal cover of a vessel; coloring hematoxylin-eosine; X 200.

At an active current patol. process vasculites of arterioles and small arteries have proliferative character with circular growth of an internal cover (fig. 2). At a submicroscopy in capillaries of the struck fabrics vacuolation and destruction of an endothelium, and also a multilayer basal membrane is found. By data To a meadow (N. K of lug) et al. (1977), etc., at an immunoflyuo-restsentny research of the material received at a biopsy of kidneys, muscles and skin in walls of small arteries and capillaries and also under a sarcolemma of muscle fibers found the deposits IgM and a complement.

Fig. 3. Microdrug of a skeletal muscle at a system scleroderma: 1 — lipomatoz a perimysium, 2 — thinning of muscle fibers, 3 — proliferation of kernels of a sarcolemma, 4 — a sclerosis of a perimysium; coloring hematoxylin-eosine; X 160.

Damage of skin at system S. is often combined with damage of joints, bones and muscles. At damage of joints it is found exudative and proliferative synovitis (see) with fibrinous imposings on a surface of a synovial layer of the joint capsule, the focal proliferations of sinoviotsit, single productive vasculites which are moderately expressed by an angiomatosis, lymphoid and macrophagic infiltration in subsynovial and fibrous layers. The joint cartilage at system S. loses elasticity, becomes fragile and quickly wears out; osteoporosis is noted circumarticular (see). In the absence of symptoms of arthritis in a joint cavity actually there is no synovial fluid, macroscopically synovial layer of the joint capsule becomes dense, deprived of fibers. At gistol. a research hardly it is possible to find its organospetsifichesky features: sinoviotsita on a bigger extent are absent, the synovial layer is covered with gialinopodobny masses, the subsynovial layer is presented by fibrous connecting fabric poor in vessels with extensive fields of a hyalinosis. At the system S. which is followed by a myopathic syndrome, gistol. the research of skeletal muscles reveals a picture hron. a miositis (see) with a raznokalibernost of muscle fibers, gidropichesky dystrophy and a myolysis of a part them, perivascular infiltrates from lymphocytes, macrophages, polinuklear, vasculites, growth of granulyatsionny and fibrous connecting fabric in endo-and perimysiums. The fibroziruyushchy intersticial miositis (fig. 3) with the expressed sclerosis, lipomatozy, a hyalinosis of Epi - and a perimysium, a sclerosis of walls of vessels, a zapustevaniye of a capillary bed, melkoochagovy perivascular lymphoid and macrophagic infiltration, single vasculites, focal perifastsikulyarnon or a diffusion atrophy of muscle fibers is more characteristic.

In went. - kish. a path the sclerosis and a hyalinosis of a submucosa and a serous cover sometimes with development of erosion and ulcers are noted a mucosal atrophy and unstriated muscles. The atrophy of unstriated muscles of a circular layer is especially sharply expressed. At a subacute current of system S. find an esophagitis (see), enteritis (see. Enteritis , Coloenteritis ), colitis (see) with proliferative, more rare destructive and proliferative vasculites of arteries of a mesentery and walls of a gullet and intestines. In a liver it is noted periduktalny, perivascular, intra lobular fibrosis, a sclerosis and a hyalinosis of walls of vessels, fatty dystrophy of hepatocytes is more rare. Meet hron less often. active hepatitis (see), primary biliary and macronodular cirrhosis (see).

In lungs the picture intersticial is noted pneumonia (see) and basal pneumosclerosis (see). Subpleural localization patol prevails. process; at the same time the centers of a sclerosis alternate with emphysematous sites and small cysts.

Damage of heart is morphologically characterized diffusion melkoochagovy or macrofocal cardiosclerosis (see), hypertrophy of a myocardium of both the right, and left ventricles, adhesive pericardis (see). In 1/3 cases the diffusion thickening of an endocardium, both pristenochny, and valve, sometimes meets development of heart diseases. At a subacute current of system S. find a peculiar interstitial myocarditis (see) with hypostasis and growth of connecting fabric, proliferative, is more rare destructive and proliferative in and sk than an ulitama of small branches of coronary (coronal) arteries and arterioles. Occasionally the hyalinosis of internal and outside covers of the main trunks of coronary arteries comes to light.

At a so-called true skleroder-michesky kidney thrombosis, heart attacks, necroses of its cortical substance are noted. At gistol. a research proliferation of an intima, mucoid hypostasis, thrombovasculites of interlobular arteries, a fibrinoid necrosis of the bringing arterioles, inflammatory infiltration, dystrophy and a necrosis of an epithelium of tubules are defined. Occasionally the fibrinoid necrosis and «wire loops» in balls of renal little bodies meet. However, is more often at system S., in kidneys the picture of a focal or chronic intracapillary proliferative and hymenoid glomerulonephritis is noted (see). In the outcome of the last secondary wrinkling of kidneys can develop.

Connect defeat of c with vasculites, a sclerosis and a hyalinosis of walls of vessels. N of page. In vegetative nerve terminations, nodes of a sympathetic trunk and the vegetative centers of a brain trunk reveal dystrophic changes. In case of development at system S. of a polyneuritis (see) or polyneuropathies (see the Neuropathy, in neurology) it is noted as a vasculitis of the small vessels feeding nerves, and a sclerosis of an epineurium, a perineurium of nervous trunks and destruction of axons.

The clinical picture

the Clinical picture of a polisindromn, reflects the system, progressing nature of a disease. System S. begins gradually with the vascular disorders characteristic of a Raynaud's disease more often (see. Reynaud disease ), than moderate arthralgias (see), is more rare from arthritis (see. Arthritises ), dense hypostasis of fingers of hands with restriction of movements and tendency to formation of contractures (see); in some cases — from damage of internals (the alimentary system, heart, lungs). The acute polysyndromic beginning of a disease is much less often observed, above, quickly progressing course and generalization of process in the first 3 — 6 months from an onset of the illness is frequent with fervescence to 38 °. From the general displays of a disease the catastrophic lose of weight which is observed during generalization or bystry progressing of a disease is most characteristic considerable, sometimes. At a half of patients subfebrile temperature is noted.

Fig. 7. A brush of the patient with a sclerodactylia: sites of a depigmentation and a hyperpegmentation of skin, deformation and shortening of fingers of a brush at the expense of ossifluence. Fig. 8. The Maskoobraznost of the person at a sick system scleroderma. Fig. 9. Person sick system scleroderma: pallor of face skin, teleangiectasia. Fig. 10. Fingers of a brush of the patient with a system scleroderma: thinning, a focal hyperpegmentation, stiffness of skin that adds it gloss ("the sucked round fingers"); hem on site the former necrosis at the basis of the II finger and a fresh necrosis in the field of an interphalangeal joint of the II finger. Fig. 11. Distal part of foot of the patient with a system scleroderma: partial amputation And finger, dystrophic changes of nails. Fig. 12. Hip sick blyashechny scleroderma: the center of damage of skin in the form of the site of consolidation of color of ivory with a brilliant surface and a lilac rim.

One of important diagnostic characters of system S. is the characteristic damage of skin changing appearance at 80 — 90% of patients, but which at the beginning of a disease is observed only in 1/3 cases. The hl is localized. obr. on brushes — a sclerodactylia (tsvetn. fig. 7), on a face — a maskoobraznost (tsvetn. fig. 8), upper half of a trunk, feet; less often (it is preferential at the rapid progressing current) diffusion damage of skin is observed. Along with the characteristic sklerodermichesky changes of skin which are taking place stages of dense hypostasis induration (see) and atrophies (see), teleangiectasias are noted the hyperpegmentation which is quite often alternating with sites of a depigmentation (see Dyschromias of skin) (tsvetn. fig. 9), trophic disturbances (deformation of nails, baldness). At certain patients damage of skin as narrow S. Neredko is observed damage of mucous membranes — hron is noted. conjunctivitis (see), atrophic and subatrophic rhinitis (see), stomatitis (see), pharyngitis (see) and defeat of sialadens, in some cases Shegren's syndrome (see Shegren a syndrome).

Reynaud's syndrome — a precursory and frequent symptom of system S., occurs, according to various researchers, at 70 — 90% of patients. Unlike a Raynaud's disease, Reynaud's syndrome at system S. more widespread: change of vessels is noted on brushes, feet, sometimes in a face, similar changes — in lungs and kidneys. Quite often Reynaud's syndrome precedes joint and skin manifestations long before or develops along with them. Such factors as cooling, vibration, emotional lability, aggravate already available disturbances of microcirculation, promote progressing of a syndrome of Reynaud and emergence vascular trofiche-skikh changes (tsvetn. fig. 10) — repeated ulcerations of fabrics of finger-tips up to a gangrenosis (see).

Defeat of a musculoskeletal system is noted at all patients of system S. and is one of the reasons of disability of these patients. The joint syndrome is often observed; it is one of initial symptoms of a disease. Allocate three of its the main of option: 1) polyarthralgia; 2) polyarthritis with dominance exudative and proliferative (revmato-idopodobny) or to fibrous Indus - rativnykh changes; 3-) a periarthritis with deformation of joints and development of contractures, it is preferential due to defeat of periartikulyarny fabrics. Damage of muscles at system S. is shown more often by an interstitial intersticial myositis with development of contractures, is more rare — a true miositis with the progressing muscular weakness and disturbances of movements, as at a dermatomyositis (see).

Changes of bones in the form of ossifluence are characteristic (see), is more often than distal (nail) phalanxes that is shown clinically in the form of shortening (tsvetn. fig. 11) and deformations of fingers of hands and legs. The calcification of soft tissues known as a syndrome of Tibyerzha — Veyssenbakh is characteristic of system S. Deposits of salts of calcium are localized preferential in fingers of hands and periartikulyarno — around elbow, shoulder and hip joints, in hypodermic cellulose, sometimes on the course of fastion and sinews of muscles. Calcification of fabrics develops gradually, as a rule, not earlier than in 5 years from an onset of the illness. More often calcification of fabrics does not cause unpleasant feelings and comes to light only radiological, and at its localization in fingers — on deformation of the last. At more rough, is more often as separate aggravations, development of process infiltration of fabrics with the expressed pain syndrome, deterioration in the general state and sometimes feverish reaction comes to light. At a superficial arrangement the centers of calcification can be opened with allocation of a white kroshkovaty or light body.

Damage of a digestive tract, especially a gullet and intestines, is observed in 60 — 70% of cases and has a characteristic clinicoradiological picture. Changes from a gullet can be noted at early stages of a disease; they are shown by a dysphagy (see), weakening of a vermicular movement (see), expansion of an upper third and narrowing of the lower third of a gullet, rigidity of its walls. Later the phenomena ref (((((((((((((((join (see the Esophagitis) that is followed in a number of cases by development of round ulcers (see), strictures, hernia of an esophageal opening of a diaphragm (see). Sklerodermiches-koye damage of intestines is shown by dilatation of a duodenum, a duodenitis (see), Saky-kulyatsiyey of a large intestine, a syndrome of disturbance of absorption (see Maljabsorbtion a syndrome) and persistent locks, sometimes with the phenomena of partial obstruction of intestines (see).

Damage of a liver is shown by its increase, in some cases — a skin itch, periodically arising jaundice that testifies about hron. hepatitis (see) or cirrhosis. Changes of a pancreas come to light seldom, preferential at functional researches.

Damage of lungs is observed approximately at 2/3 patients; it is characterized by gradual development of a diffusion piyevmoskleroz (compact, is more rare — cystous) with preferential localization in basal departments, and also existence of commissural process and a thickening (fibrosis) of a pleura. A wedge, signs of a pneumosclerosis (see) in an initial stage are insignificant or are absent while functional disturbances and rentgenol. changes are already available. Therefore use of these methods of a research for early diagnosis of a sklerodermichesky pneumofibrosis is recommended. Degree of manifestation and weights of a pneumofibrosis is caused, first of all, by activity of sklerodermichesky process. At patients from subacute S. intersticial pneumonia is observed (see). At the expressed pneumofibrosis bronchiectasias, emphysema, perifocal pneumonia, the phenomena of respiratory insufficiency develop.

Damage of heart, in particular a myocardium, the leading sign of damage of internals at system S. both on frequency, and on the importance since in some cases leads to death. Increase in the sizes of heart, disturbance of a rhythm (is more often — premature ventricular contraction) and conductivity is characteristic of the sklerodermichesky cardiosclerosis (see) which is the cornerstone of damage of a myocardium, weakening of sokratitelny function with the zones of an adynamia revealed at rents-genokimografii (see) and is especially distinct at an echocardiography (see). Macrofocal fibrosis of a myocardium is followed infarktopodobnymn by changes on an ECG and in some cases can lead to development of a peculiar «calloused» aneurism of heart. At system S. defeat of an endocardium of valves with formation of heart disease is possible, is more often than the left atrioventricular — mitral (see the Heart diseases acquired), K-ry differs in relative high quality of a current with rare development of a decompensation. Wedge, and rentgenol. the picture of heart disease is not always clear in connection with simultaneous damage of a myocardium and a pericardium. The Sklerodermichesky pericardis (see) has preferential adhesive character though on section increase in liquid in a pericardiac cavity (disturbance of transudation) quite often is registered.

At 1/3 patients, usually at a subacute and chronic current of system S., the subkli-npchesky form of damage of kidneys revealed during the carrying out functional researches, napr, re-nografiya with use of 131 I gpp-puran (see Renog a raffia radio iso-topiaya), and also signs latent and, rather seldom, the gtsher-tenzivny, nephrotic or mixed type (are found at a subacute current) a glomerulonephritis (see).

The so-called true skle-rodermichesky kidney — the state which is characterized by catastrophic sharpness of a course of a disease (2 — 4 weeks) and a lethal outcome is described. Symptoms of quickly accruing renal failure (see) — an azotemia (see), an oliguria (see) and a terminal anury (see), arterial hypertension (see arterial hypertension), a retinopathy (see) and encephalopathy are characteristic of it a proteinuria (see), (see). Similarity of nek-ry pathogenetic lines and morfol is noted. signs of a true sklerodermichesky kidney with malignant arterial hypertension. At heavy arterial hypertension the high level of a renin in a blood plasma is found. The true sklerodermnchesky kidney develops, as a rule, at the acute quickly progressing system S. and is the main cause of death of patients at this option of a course of a disease.

Defeat of a nervous system at system S. meets often. The leading syndrome is neurocirculatory dystonia (see). Already at early stages of a disease secretion of sweat glands is broken: at first the hyperhidrosis of palms p axillary areas (see the Hyperhidrosis), and then decrease in sweating in places of an atrophy of skin is noted. Vegeto-vascular and related trophic frustration are shown by a peeling of skin, a hyperkeratosis (see), a hair loss and eyelashes, a growth disorder of nails, hypersensitivity by cold, decrease in skin temperature on 1 — 2 °, absence local and reflex dermographism (see).

At system S. the polyneuropathic syndrome quite often meets (see the Polyneuritis). According to N. G. Guseva, it is observed in 1/3 cases. Generally polyneuropathic syndrome is shown by disturbances of sensitivity, patients complain of paresthesias (see) in hands and legs, sometimes on bolp. At a research morbidity on the course of nervous trunks, a hyperesthesia, and sometimes a hypesthesia or a hyperpathia in distal departments of extremities in the form of «gloves» and «socks» comes to light. Motive frustration at S. are not characteristic though, according to V. V. Mikheyev, development of atrophic paresis of brushes and paralyzes of feet is possible. Despite frequent absence of rough paresis and disorders of sensitivity, quite typically early fading of tendon jerks on hands and legs, up to full areflexias (see). Existence of symptoms of a tension of Lasega is characteristic (see. Radiculitis ).

Defeat of c. the N of page meets seldom. It is shown meningo-entsefaliticheskpm by a syndrome (see Encephalitis) or vascular disorders of hemorrhagic or ischemic character. The acute disorder of cerebral circulation (see) can lead to a lethal outcome. The Meningoentsefalitichesky syndrome is characterized by headaches, dizzinesses and is slight-nymp focal symptoms. Change of mentality with alarming and depressive reactions, sometimes development of an acute psychotic state with a delirium, auditory and olfactory hallucinations, amnesia is rather typical. Pressure of cerebrospinal liquid is increased, in it protein content is increased. The papilledema can develop (an optic disk, T.).

The spinal cord is surprised seldom, there are single descriptions of development of symptoms of a myelitis (see) and a miye-lopoliradikulonevrita (see). These phenomena are caused by the vascular disorders connected with a basic disease.

Distinguish three main options of a current of system S.: acute (quickly progressing), subacute and chronic, to-rye differ from each other in activity and speed of progressing patol. process, degree of manifestation and character peripheral (skin, joint, etc.) and visceral manifestations. For the most frequent hron. currents are characteristic the progressing vasculomotor disturbances (Reynaud's syndrome) and the expressed trophic frustration caused by them. They quite often are the only display of a disease for a row of years and further prevail in a picture of a disease. At hron. a current laboratory tests remain usually within norm or are close to them, except for a moderate hyperproteinemia and a hypergammaglobulinemia at V3 of patients.

The subacute current is characterized by existence of a dense cutaneous dropsy with the subsequent its induration, recurrent polyarthritis (sometimes as rhematoid), is more rare — a miositis with a myasthenic syndrome, a polyserositis (see), than visceral pathology — intersticial pneumonia with the subsequent development of a pneumosclerosis, cardiosclerosis, sklerodermichesky esophagitis (see), a duodenitis (see), hron. glomerulonephritis, and also vasculomotor and trophic disturbances.

The acute quickly progressing current differs extraordinary bystry (in the first year of a disease) in diffusion S.'s development, steady progressing of damages of internals, quickly accruing fibrosis of bodies and fabrics and heavy vascular pathology with frequent damage of kidneys as a true sklerodermichesky kidney.

The diagnosis

the Diagnosis at the developed picture of a disease does not cause difficulties; it is based hl. obr. on a wedge, S.'s manifestations in combination with laboratory, radiological and morphological (a biopsy of skin) data.

According to criteria of the American rheumatological association (1979) a «certain» system S.'s diagnosis can be established in the presence «big» criterion what are considered proximal (in relation to fingers) sklerodermi-chesky changes of skin, or — two of three «small» criteria — a sclerodactylia, trophic ulcers of finger-tips of hands, bilateral basal pulmonary fibrosis.

The early diagnosis of system S. is based on existence of a syndrome of Reynaud in combination with persistent arthralgias (more rare — arthritis) and (or) moderate flexion contractures, dense hypostasis of fingers of hands, persons, are more rare — characteristic damages of internals (a gullet, lungs, heart).

Blood at system S. is changed a little, only at certain patients hypochromia anemia is noted (see), the leukopenia (see), is slightly more often — a leukocytosis (see). The accelerated ROE along with increase in content of fibrinogen (see), an alpha of 2 globulins (see. Globulins ), ceruloplasmin, emergence of S-reactive protein (see) reflects activity patol. process. In red marrow plazmotsitarny and reticulocytic reaction quite often comes to light. Approximately at a half of patients of system S. it is observed hyper-gammaglobuliiyemiya, causing a tendency to a hyperproteinemia; in some cases — a monoclonal gammapathy. According to various researchers, in 40 — 60% of cases in blood serum of patients a rhematoid factor (see), antinuclear antibodies (in 36 — 91%) and LE cells (in 2 — 7% of cases) are found out that this disease pulls together with a pseudorheumatism (see) and a system lupus erythematosus (see). Existence of special antinuclear antibodies to so-called Scleroderma-70 antigen and anti-cent-romernykh of antibodies is characteristic of system S. (the last come to light hl. obr. at CREST-sind-rum, i.e. hron. course of a disease). At a part of patients the cryoglobulinemia is noted. At 40 — 60% of patients of sistekhmny S. increase in content of oxyproline in a blood plasma and urine comes to light that demonstrates the expressed disturbances of metabolism of collagen.


Rentgenol. the research at system S. has important a wedge, value since, specifying a picture of a disease, promotes the solution of a question of the diagnosis. Use various rentgenol. techniques depends on what bodies and systems are subject to studying.

Fig. 4. The roentgenogram of a brush at a system scleroderma: 1 — ossifluence of nail phalanxes of I and II fingers, 2 — the osteoporosis moderated circumarticular, 3 — the centers of calcification in soft tissues III, IV and V fingers.

Changes, typical for system S., from soft tissues, bones and joints (fig. 4) are sites of calcification (see) in hypodermic cellulose, preferential trailer departments of fingers of hands, is more rare — stop, areas of elbow, knee and other joints. Ossifluence (see) is observed in nail phalanxes of fingers of hands, feet, coronal shoots of branches of a mandible, distal departments of beam and elbow bones, back departments of edges and nek-ry other bones. Narrowing of joint cracks, sometimes single erosion on the surfaces of a joint cartilage and bone ankiloza are noted circumarticular osteoporosis (see), (see), is more often in joints of a wrist.

Fig. 5. The roentgenogram of a duodenum and initial department of a jejunum at a system scleroderma: expansion of the lower horizontal part of a duodenum and initial department of a jejunum, a delay in them a baric suspension (it is specified by shooters) owing to decrease in a tone of walls of guts and weakening of a vermicular movement.

Is of great importance for system S.'s diagnosis rentgenol. a research went. - kish. a path as allows to reveal one of the most specific symptoms of a disease — decrease in a tone and weakening of a vermicular movement that leads to expansion of a gleam of body and a long staz of a baric suspension. Most often such changes meet in a gullet, duodenal and a jejunum (fig. 5), is more rare — in a stomach and a large intestine.

At damage of lungs radiological in basal departments the diffusion and cystous pneumosclerosis (see) which is often combined with moderate emphysema of lungs (see) and also symptoms of adhesive (commissural) pleurisy is defined (see).

Fig. 6. Rentgenokimogramma of heart sick system scleroderma: in the bottom of a contour of the left departments of heart — the lack of rentgenokimografichesky teeth testimonial of falloff of amplitude of a pulsation (a zone of an adynamia).

Rentgenol. symptoms of damage of heart come to light almost in 100% of observations and are characterized by changes of its configuration due to increase in the sizes of a left ventricle and the right departments (owing to development of a pneumosclerosis and pulmonary hypertensia). The reduction of amplitude of a pulsation up to zones of an adynamia (fig. 6) which is well revealed at a rentgenokimografiya (see) is typical. Signs of defeat of the valve device can be observed, it is preferential in the form of insufficiency of the left atrioventricular (mitral) valve, in some cases — a stenosis of the left atrioventricular opening and aortic incompetence (change of a configuration, the sizes of cardial cavities, as well as character of a heartbeat).

System S. should be differentiated with diseases of so-called sklerodermichesky group (limited S., an eosinophilic fasciitis, a scleredema of B an ear), with other diffusion diseases of connecting fabric, a pseudorheumatism (see), with group of psevdosklerodermi-chesky states.

Features a wedge, pictures allow to differentiate rather easily system and limited S., however it must be kept in mind a vozkhmozhnost of focal damage of skin at system Page. Differential diagnosis with an eosinophilic fasciitis is based on inherent to the last (established by a biopsy) a diffusion induration of deep layers of a fascia and hypodermic cellulose, is preferential in forearms, is more rare — shins, a trunk, an eosinophilia of blood and quite often than fabrics, and also absence at an eosinophilic fasciitis of a syndrome of Reynaud and damage of internals. At a scleredema of B an ear unlike system S. initial localization of process is noted in a neck and a face; preferential hypodermic cellulose is surprised.

At a pseudorheumatism, especially at a juvenile pseudorheumatism, emergence of a syndrome of Reynaud, thinning and trophic changes of skin of fingers of hands are possible. On the other hand, in some cases at system S. the polyarthritis reminding damage of joints at a pseudorheumatism develops. Difficulties at differential diagnosis in these cases can be resolved at the accounting of characteristic symptoms and dynamics of process.

The nature of a disease in general, and also features of vasospastic disturbances and porazheshsh internals usually allow to distinguish system S. from a dermatomyositis (see) and a poikilodermatomyositis (see) even with similar lines (flexion contractures of extremities, a maskoobraznost of the person, a dysphagy). The polymiositis (see the Miositis) can be system S.'s manifestation, but unlike defeat of skeletal muscles at a dermatomyositis it seldom and only short term prevails in a picture of a disease. Differential diagnosis with a system lupus erythematosus (see) usually not difficult. It is necessary to consider that an antinuclear factor, antibodies to DNA (is more often in a small caption), single LE cells can be observed at system S. more often than a subacute current.

Psevdosklerodermichesky syndromes at primary amiloidsz, inborn disturbances of metabolism — porphyrias (see), fenilketonu-riya (see), hepatocerebral dystrophy (see), at separate endocrinopathies, napr, Verner's syndrome (see Verner a syndrome) and paraneopla-stichesky syndromes (see), are characterized by hl. obr. skin sustavnomyshechnoy, is more rare — the vascular symptomatology reminding, but not identical to manifestations system S. Atipizm peripheral and lack of damages of internals, characteristic of S., along with a wedge, features of isevdosklerodermiche-sky syndromes, are a basis of differential diagnosis.

System S. it is necessary to differentiate with such Dermatolum. diseases, as hron. an atrophic acrodermatitis (see) and scleroatrophic lichenins with preferential damage of mucous membranes and the secondary progressing their sclerosis that can be followed by narrowing of a gleam of a gullet, vaginas. Full wedge, inspection of the patient, specification of nature of local defeat and dynamics patol. process allow to differentiate these diseases.

Treatment

Treatment of patients of system S. is carried out is long (for years). At the choice of a complex to lay down. actions it is necessary to consider character of a current, activity and a stage of a disease. From pharmaceuticals D-penitsggalamin, Unithiolum, corticosteroids, amshyukhino-linovy drugs, immunodepressants, the nonsteroid anti-inflammatory, vasodilating and disaggregating drugs, a lidaza, a dimethyl sulfoxide are applied, is more rare — muscle relaxants of the central action, colchicine, heparin, grpzeofulvin, etc.

D-penitsillamnn inhibits maturing and, partially, biosynthesis of collagen. The hl is applied. obr. at the acute and subacute course of a disease in gradually increasing doses: since 300 mg to 1 — 2 g a day with the subsequent transition to a maintenance dose (300 mg a day). Treatment is carried out is long — within 2 — 3 years (sometimes to 5). At 1/3 patients side reactions are observed: dermatitis, dispeptic frustration, loss of taste, fever, leukopenia and thrombocytopenia, medicinal nephropathy. At prolonged treatment of D - ne-nitsil of l amine clearly decrease indurative changes of skin, joint and vascular syndromes. Influence of drug on visceral pathology is less distinct. In separate observations under the influence of treatment crossing of the acute current in subacute and even chronic is noted.

Unithiolum, just as D - penntsill-amine, contains sulphhydryl groups and makes impact on metabolism of collagen; it can be applied in complex treatment of S. Naznachayut repeated courses of treatment ugshtioly; enter on 5 ml 5% of solution intramusculary, on a course 10 — 12 injections.

Glucocorticosteroids (preferential Prednisolonum) appoint in the presence a wedge, and a lab. signs of activity patol. process, at an acute and subacute current and it is rare (short courses lasting 1 — 2 month) at an aggravation chronic Page. The initial dose makes 30 — 40 mg a day (in combination with D-Penicillaminum — 20 mg); it is applied within 1 — 2 month before achievement a wedge, effect. In the subsequent, at stabilization of process, gradually the dose of drug is reduced to supporting (20 — 15 — 10 mg a day). Glucocorticosteroids apply is long; side reactions at the same time arise seldom. Glucocorticosteroids are effective at joint, skin and vascular syndromes, nek-ry visceral manifestations (myocarditis, intersticial pneumonia). They are not shown at development of a true sklerodermichesky kidney.

Derivatives of aminoquinoline (chloroquine, Resochinum, plaquenil) apply as a main type of treatment at subacute and especially hron. system S. Naznachayut's current on 0,25 g of chloroquine or 0,4 g of plaquenil a day it is long (2 — 3 years) under control of blood tests and observation of the oculist. These drugs make positive impact preferential at a joint syndrome.

Non-steroidal anti-inflammatory drugs (acetilsalicylic to - that, Brufenum, Voltarenum, indometacin, etc.) appoint system S.'s patient most often at a joint syndrome. Cytostatic pmmu-nodepressant (Azathioprinum, cyclophosphamide, Chlorbutinum, etc.) apply at system S. rather seldom, hl. obr. at high activity patol. the process which is not giving in to influence of corticosteroids or in case of contraindications to treatment by them. Azathioprinum is preferable at damage of kidneys as a glomerulonephritis. It is appointed on 1 — 3 mg to 1 kg of the weight (weight) of a body of the patient (50 — 200 mg a day) within 2 — 3 months under control of blood tests. From vazodilatator and dezagregant at system S. apply komplamin, anginin, ande-guelder-roses, drugs nicotinic to - you, grizeofulvp, curantyl, a low-molecular dextran, etc. Improve peripheric circulation hyper baric oxygenation (see), a balneoterapiya and physical therapy.

At a polyneuropathy, in addition to the specified drugs, appoint vitamins of group B and repeated rates of adenil on 1 ml 2 times a day within 1 month, and also massage and LFK.

At development of a true sklerodermichesky kidney the massive hypotensive therapy including inhibitors of system a renin — angiotensin, repeated is necessary hemodialysis (see), it is in some cases shown renal transplantation (see).

Lidaza is applied at hron. system S.'s current repeated courses in the form of subcutaneous injections on 64 — 128 PIECES (on a course 12 — 14 injections) or an electrophoresis on affected areas of skin.

The dimethyl sulfoxide is appointed in the form of applications to affected areas of skin, it can be combined with drugs nicotinic to - you, Trilonum In, analgetics.

In the presence of calcification treatment of Na2 EDTA possessing chelating action is shown.

Dignity. - hens. treatment using a balneoterapiya (radonic, hydrosulphuric, carbonic bathtubs), mud cures, etc. is shown to hl. obr. at hron. current system Page. In the absence of contraindications perhaps early inclusion in a therapeutic complex of massage and to lay down. physical cultures.

The forecast and Prevention

the Forecast define character of a current, timeliness of diagnosis and adequacy of therapy. At hron. a current the forecast favorable, at subacute — satisfactory, at acute — adverse, especially in cases of development of a true sklerodermichesky kidney.

Prevention consists in elimination of the external factors provoking system S.'s development in the persons «threatened» concerning development of a disease: coolings, vibrations, influences of chemical substances, including silicon dust, allergenic influences, etc. Persons with tendency to vasospastic reactions, from limited S. or recuring a polyart-ral gpyamp, relatives of patients with collagenic diseases concern group «threatened» concerning system S.'s development. The secondary prevention expected the prevention of aggravations and progressing of a disease includes early diagnosis and timely adequate treatment of exacerbations of a disease in a hospital and out-patient conditions, medical examination, carrying out rehabilitation measures, including a stage of a resort therapy (it is preferential at hron. current). The correct employment of patients and exception of the factors provoking S.'s development and its aggravations stated above is necessary. At an acute and subacute current of system S. patients are, as a rule, disabled and shall be transferred to disability, and at chronic — restrictedly are able-bodied.

The correct timely treatment and employment allow to improve the forecast and to keep working capacity of a part of patients of system S.

Features of a system scleroderma

System S. at children occurs at children seldom. The disease begins usually aged from 5 up to 10 years. Girls get sick 5 times more often. Provocative factors, in addition to those, to-rye cause a disease in adults, acute children's infections, introduction of vaccines and serums are.

Changes of skin, typical for system S., as the first symptom of a disease are noted only at a half of patients. Consecutive change of stages of skin changes manages to be tracked not always. At the same patient the combination of a dense cutaneous dropsy to an in-duration, induration with an atrophy or presence at the same time of all three stages is possible. As well as at adults, changes of skin in the form of limited S. and trophic disorders, disturbances of pigmentation occur at children in addition to typical. Teleangiectasias at children are rare. The vascular syndrome in the form of vasospastic crises (Reynaud's syndrome) as the first symptom of a disease meets approximately by 3 times less than at adults, but further the frequency of vascular manifestations increases. At the progressing process formation of trophic ulcers is possible (at 20% of patients). The joint syndrome is similar to that at adults. Already at early stages of a disease heavy joint and muscular contractures quite often appear. Clinic of muscular defeats, and also frequency of a true miositis same, as at adults. Ossifluence and calcification meet twice less than at adults, however, unlike adults, at children their emergence of century earlier periods — on 2 — the 3rd year of a disease is possible.

Damages of internals at children are, as a rule, a little expressed, progress slowly. However by means of tool methods of a research reveal the big frequency and prevalence of visceral pathology. Changes from heart are most often observed. The myocardium is surprised at all patients, the pericardium — is slightly more rare, but by 4 times more often than at adults, an endocardium — at V3 of sick children. Damage of lungs on frequency is on the second place (approximately at 70% of patients). Precursory symptom of damage of lungs are functional disturbances, in particular the regional decrease in vital capacity of lungs revealed by means of radio pneumography (see. Lung ventilation). Damage of a gullet in the form of disturbance of motility is diagnosed rentgenol. by method at a half of children. Damage of kidneys clinically comes to light approximately at 40% of patients and is more often characterized by poorly expressed changes in urine (a passing albuminuria, minor changes of a deposit).

At children the same options of a current of system S., as well as at adults are observed. The subacute and chronic current meets approximately identical frequency. Perhaps acute current with a lethal outcome in the first three years of a disease. Hron. forms of a disease, it is long proceeding with the isolated Reynaud's syndrome, at children are rare.

Complications are most often connected with accession of consecutive infection — infection of ulcers, pyelonephritis (see), pneumonia (see), sepsis is more rare (see). As a rare complication meet patol. the fractures of bones of the lower extremities which are not connected with hormonal treatment.

The differential diagnosis should be carried out with a scleredema (see) and a fenilketonuriya (see). Staging of emergence of an induratspa, absence of fibrosis and atrophy of soft tissues, joint and vasospastic manifestations are characteristic of the first; patol. processes in internals proceed is good-quality and abate in process of disappearance of a skin pnduration. At the fenilketonu-riya which is followed by consolidation of skin and muscles lag of mental and physical development, and also increase in content of phenylalanine in blood and its detection in urine is noted.

The principles of therapy of system S. at children the same, as at adults.

The forecast is most serious at a course of a disease at early age and depends on speed of development and weight of damage of muscles and joints, depth and prevalence of vascular frustration, accession of consecutive infection. During the progressing of visceral defeats the forecast is burdened.

Prevention is similar to S.'s prevention at adults; it is necessary to carry out careful and adequate treatment of children's infections, to follow rules of carrying out planned inoculations.

Limited scleroderma

Limited scleroderma (sclerodermia circumscripta; synonym: focal S., the localized S., keloidopodobny S., Addison's keloid). As well as at system S., patol. process at limited S. takes place three stages in skin: dense hypostasis, indura-tion and atrophy. In nek-ry cases in addition to skin the subject muscles with development of a limited myosclerosis are surprised. On the nature of skin defeats allocate several options of narrow S.

Blyashechnaya S. (sclerodermia placata) it is observed most often. It develops usually gradually, without the visible reasons, gshet a long current with the periods of aggravations and remissions. It is characterized by education on a side surface of a trunk, a back, a waist or proximal departments of extremities of one or several spots of various size, oval or irregular shape of pinkish color with various shades (lilac, lilac). Spots gradually increase in sizes, and in several weeks in their central part sclerous changes develop, owing to what it is formed smooth dense as a cardboard, brilliant, colors of ivory the plaque which is a little acting over the level of surrounding skin (tsvetn. fig. 12). On the periphery of a plaque there is violet color a zone in the form of a ring which is gradually passing into normal skin. This zone demonstrates progressing of process. The created plaque slowly increases in sizes, on it sites of pigmentation and a teleangiectasia can be formed. The multiple centers of defeat (the generalized or disseminated blyashechny S.) are in rare instances noted. In several years the center of defeat imperceptibly resolves and exposed to an atrophy, leaving slightly pigmented retraction of skin. The atrophied skin reminding the crumpled tissue paper easily gathers pleated. Extremely seldom in the field of plaques there are bubbles with hemorrhagic contents (violent and hemorrhagic blyashechny S.) or sites of a superficial ulceration. Blyashechny S.'s kinds are superficial limited S., at a cut on skin small phaeochrous spots with l a silty shade without signs of consolidation and infiltration, and also a knotty form (tuberous, keloidopodobny) in the form of speakers of nodes develop. In a zone of sklerodermichesky plaques hair drop out, secretion grease and sweat glands decreases.

Tape-like, or polosovidny, S. (sclerodermia striata) differs in a linear form of the centers of damage of skin and is frequent involvement in patol. process of the subject fabrics (hypodermic cellulose, muscles). S.'s centers are located along one of extremities, sometimes on the course of nerves (sclerodermia zoniformis) or tsir-kulyarno, surrounding a trunk, all extremity or a finger (sclerodermia anularis). At damage of sinews, sheaves and muscles the retractions and contractures limiting the volume of movements in joints are formed. Tape-like S.'s localization on a face (in a nose bridge and a forehead) and a pilar part of the head is possible (reminds a hem from blow by a saber). Nek-ry researchers carry to limited S. the progressing atrophy of the person — Parri's disease — Romberg (see the Hemiatrophy).

The scleroderma tear-shaped is characterized by emergence small, several millimeters in the diameter, whitish color of the spots, a round or polygonal form sometimes surrounded with a narrow pink border. Spots quite often are located with groups, can merge, forming the large centers of scalloped outlines. In several years on places of spots the atrophy of skin develops (see). Rashes are localized on a neck, an upper part of a breast or a back, is more rare on extremities. Though most of researchers considers a disease of white spots limited S.'s kind, there is an opinion on its possible communication with red flat is deprived (see. Deprive red flat).

The diagnosis is made on the basis a wedge, data.

For limited S.'s treatment widely use a lidaza, to-ruyu enter subcutaneously or intramusculary 64 PIECES every other day, on a course 12 — 15 injections. Repeated courses are conducted after 2 — a 3-month break. Also the electrophoresis of a lidaza and compresses from skin, roni-dazy on the center of defeat, are effective. Apply intradermal or hypodermic introduction to the centers of defeat of suspension of a hydrocortisone on 1 — 2 ml from 0,25% solution of novocaine, 2 times a week, 6 — 8 obkalyvaniye; fonofo-cut of suspension of a hydrocortisone; greasing of the centers dimethyl sulfoxide in pure form or obkalyvaniye of the centers of 1 — 5% solution of a dimethyl sulfoxide. Improvement can be reached by also repeated novocainic blockade of nodes of a sympathetic trunk, reception of ganglioblo-kiruyushchy substances (Pachycarpinum). Fortifying treatment is carried out (vitamins of group B, A, PP, C). In a stage of consolidation of skin thermal procedures (bathtubs, mud cure, a paraffinotherapy), light massage, sea and hydrosulphuric bathtubs (Sochi-Matsesta, Pyatigorsk) are effective, to lay down. physical culture.

The forecast at limited S. favorable, reliable cases of its transition to system S. it is not described.

Patients with limited S. are subject to the dispensary account and observation. At the same time carry out sanitation of the centers hron. infections, treatment of associated diseases. Work in cold rooms, and also the work connected from travkhmatizatsiy skin, vibration is contraindicated to patients with a limited scleroderma.



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H. G. Guseva; T. H. Kopyeva (stalemate. An.), V. V. Mikheyev, N. A. Ilyina (not BP.), H. N. Uvarova (features of a system scleroderma at children), Yu. S. Homyakov (rents.), O. K. Shaposhnikov (limited scleroderma)

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