Diagnosis and treatment of scleroderma. Recommendations. Systemic scleroderma: forms and signs, treatment and prognosis Juvenile scleroderma in children clinical recommendations

Systemic scleroderma, or progressive systemic sclerosis, belongs to a group of autoimmune systemic inflammatory diseases of connective tissue. It is characterized by a staged course and a large polymorphism of clinical manifestations associated with characteristic damage to the skin, some internal organs and the musculoskeletal system.

These lesions are based on a widespread cascade of microcirculatory disturbances, inflammation, and generalized fibrosis. Life expectancy with systemic scleroderma depends on the nature of the course, stage and predominant damage to organs and body systems.

Age-related morbidity and survival of patients

In accordance with average statistical data, the primary incidence per year per 1,000,000 population ranges from 2.7 to 12 cases, and the overall prevalence of this pathology ranges from 30 to 450 cases per year per 1,000,000 population. The development of the disease is possible in various age groups, including young people (juvenile scleroderma).

However, its onset is most often noted between the ages of 30 and 50, although upon detailed study, the initial signs are often identified at earlier ages. The disease affects women (according to various sources) 3-7 times more often than men. A smaller gender difference is noted in morbidity statistics among children and among adults over 45 years of age.

Retrospective data from studies of patient survival (how long they live), depending on the course of the disease and its natural development, show the following differences:

in an acute, rapidly progressive course with a predominance of tissue fibrosis and initial symptoms in the form of skin lesions, life expectancy does not exceed 5 years, while the survival rate is only 4%;
in a subacute, moderately progressive course, damage to the immune system predominates with initial symptoms in the form of articular syndrome; life expectancy can be up to 15 years, with survival rate in the first 5 years - 75%, 10 years - about 61%, 15 years - on average 50%;
in a chronic, slowly progressive course, vascular pathology predominates with initial signs in the form of Raynaud's syndrome; survival rate in the first 5 years of the disease is on average 93%, 10 years - about 87%, and 15 years - 85%.

Etiology and pathogenesis of the disease

The reasons for the development of systemic scleroderma are not well understood. It is currently believed to be a multifactorial disease caused by:

1. Genetic predisposition, the individual mechanisms of which have already been deciphered. An association of the disease with certain histocompatibility antigens, a connection of clinical manifestations with specific autoantibodies, etc. Previously, genetic predisposition was argued by the presence of cases of systemic scleroderma or other pathology close to it or immune disorders in family members or relatives.

2. The influence of viruses, among which the main influence of cytomegalovirus and retroviruses is considered. Attention is also paid to studying the role of activated latent (latent) viral infection, the phenomenon of molecular mimicry, etc. The latter is manifested in the production of humoral antibodies by the immune system, which destroy antigens with the formation of immune complexes, as well as in the reproduction of cell-toxic T-lymphocytes. They destroy body cells that contain viruses.

3. The influence of exogenous and endogenous risk factors. Particular importance is attached to:

hypothermia and frequent and prolonged exposure to sunlight;
vibrations;
industrial silicon dust;
chemical agents of industrial and household origin - vapors from petroleum products processing, vinyl chloride, pesticides, organic solvents;
some foods containing rapeseed oil and L-tryptophan supplements;
implants and certain medications, for example, bleomycin (antitumor antibiotic), vaccines;
neuroendocrine disorders, frequent stressful conditions, a tendency to vascular spastic reactions.

Schematic presentation of the complex mechanism of disease development

A characteristic feature of systemic scleroderma is the excessive production of collagen protein by fibroblasts. Normally, this promotes the restoration of damaged connective tissue and leads to its replacement with scar (sclerosation, fibrosis).

In autoimmune connective tissue diseases, physiological changes under normal conditions are excessively intensified, acquiring pathological forms. As a result of this disorder, normal connective tissue is replaced by scar tissue, thickening of the skin and changes in joints and organs occur. The general scheme for the development of this process is as follows.

Viruses and risk factors against the background of genetic predisposition affect:

Connective tissue structures, which leads to defective cell membranes and increased fibroblast function. The result of this is excess production of collagen, fibrokinetin (a large glycoprotein of the intercellular matrix), proteoglycans and glycosaminoglycans, which are complex proteins that include immunoglobulins (antibodies), most protein hormones, interferon, etc.
Microvasculature, resulting in damage to the endothelium (epithelium of the inner wall of blood vessels). This, in turn, leads to the proliferation of myofibroblasts (cells similar to both fibroblasts and smooth muscle cells), sedimentation of platelets in small vessels and their adhesion (sticking) to the vascular walls, deposition of fibrin threads on the inner lining of small vessels, edema and impairment permeability of the latter.
The body's immune system, leading to an imbalance of T- and B-lymphocytes involved in the formation of the immune response, as a result of which the function of the former is disrupted and the latter are activated.

All these factors, in turn, cause the further development of the following disorders:

Excessive formation of collagen fibers with subsequent progressive generalized fibrosis in the dermis, musculoskeletal system and internal organs. Fibrosis is an overgrowth of connective tissue.
Excessive production of collagen proteins in the walls of small vessels, thickening of the basement membranes and vascular fibrosis, increased blood clotting and thrombosis in small vessels, narrowing of their lumen. All this leads to damage to small vessels with the development of vascular spasms like Raynaud's syndrome and disruption of the structure and function of internal organs.
Increased formation of cytokines (specific peptide information molecules), immune complexes and autoantibodies, also leading to inflammation of the inner lining of small vessels (vasculitis) and, accordingly, also to damage to internal organs.

Thus, the main links in the pathogenetic chain are:

violation of the mechanisms of cellular and humoral immunity;
damage to small vessels with destruction and dysfunction of the endothelium of the vascular wall, with thickening of its inner membrane and microthrombosis, with narrowing of the lumen of the blood microcirculation channel and disruption of the microcirculation itself;
disruption of the formation of collagen proteins with increased formation of smooth muscle fibers and collagen, which is manifested by fibrous restructuring of the connective tissue of organs and systems with disruption of their function.

Classification of systemic scleroderma and brief characteristics of individual forms

When formulating a diagnosis, the signs of systemic scleroderma are specified in accordance with such characteristics as the clinical form of the disease, the variant of its course and the stage of development of the pathology.

The following clinical forms are distinguished:

Diffuse

It develops suddenly and already after 3-6 months manifests itself with a multiplicity of syndromes. Within 1 year, extensive, generalized damage to the skin of the upper and lower extremities, face, and torso occurs. At the same time or somewhat later, Raynaud's syndrome develops. Damage to the tissues of the lungs, kidneys, gastrointestinal tract, and heart muscles occurs early. Videocapillaroscopy of the nail bed reveals a pronounced desolation (reduction) of small vessels with the formation of avascular areas (avascular zones) of the nail bed. Blood tests detect antibodies to an enzyme (topoisomerase 1) that affects the continuity of the cellular DNA molecule.

Limited

It is characterized by less common indurative skin changes, later and slower development of pathology, a long period of presence of only Raynaud's syndrome, late development of hypertension in the pulmonary artery, limitation of skin lesions to the areas of the face, hands and feet, late development of calcification of the skin, telangiectasia and damage to the digestive tract . When performing capillaroscopy, dilated small vessels without the presence of pronounced avascular zones are determined. Venous blood tests reveal specific anticentromere (antinuclear) autoantibodies against various components of the cell nucleus.

Cross

Characteristic of this form is a combination of symptoms of systemic scleroderma with symptoms of one or more other systemic connective tissue pathologies - rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis or polymyositis, etc.

Scleroderma without scleroderma

Or the visceral form, which occurs without thickening of the skin, but with Raynaud's syndrome and signs of damage to internal organs - with pulmonary fibrosis, the development of acute scleroderma kidney, damage to the heart, and the digestive tract. Autoimmune antibodies to Scl-70 (nuclear topoisomerase) are detected in the blood.

Juvenile systemic scleroderma

Development begins before the age of 16 according to the type of linear (usually asymmetric) or focal scleroderma. With linear - areas of skin with scar changes (usually on the scalp, bridge of the nose, forehead and face, less often on the lower extremities and chest) are linear in nature. With this form, there is a tendency to form contractures (limitation of movements in the joints) and the possibility of abnormal development of the limbs. Pathological changes in internal organs are quite insignificant and are detected mainly during instrumental studies.

Induced

The development of which is clearly related in time to the influence of environmental factors (chemical, cold, etc.). Skin thickening is widespread, often diffuse, sometimes in combination with vascular lesions.

Prescleroderma

Clinically manifested by isolated Raynaud's syndrome, combined with a capillaroscopic picture and/or immunological changes characteristic of the disease.

Variants of systemic scleroderma, depending on the nature of the course and rate of progression

Acute, rapidly progressing variant - during the first 2 years from the onset of the disease, generalized diffuse fibrosis of the skin and internal organs, mainly the lungs, heart and kidneys, develops. Previously, in most cases the disease was quickly fatal. With the use of modern adequate therapy, the prognosis has improved somewhat.
Subacute, moderately progressive. According to clinical symptoms and laboratory data, it is characterized by a predominance of signs of an immune inflammatory process - dense skin edema, myositis, arthritis. Cross syndromes are common cases.
Chronic, slowly progressive. This variant of systemic scleroderma is distinguished by: the predominance of vascular lesions - the long-term (for many years) existence of Raynaud's syndrome in the first stages of the disease, which is accompanied by the slow development of moderately pronounced skin changes; gradual increase in disorders associated with ischemia (malnutrition) of tissues; gradual development of pulmonary hypertension and damage to the digestive tract.

Stages of the disease

Initial - the presence of 1 to 3 localizations of the disease.
The stage of generalization, reflecting the systemic nature of the lesions with the polysyndromic nature of the manifestations of the process.
Terminal, or late, which is characterized by insufficiency of the function of one or more organs - respiratory, cardiac or renal failure.

The use of the three listed parameters when formulating a diagnosis of a disease allows you to navigate in relation to drawing up a treatment program for the patient.

Main symptoms

Based on the mechanism of development of systemic scleroderma and the prevalence of lesions, the large number and variety of symptoms of this disease are understandable. However, taking into account the staged development of the process, there are certain possibilities for diagnosing pathology in the early stages of its development, predicting and influencing the life expectancy of patients.

Diagnosis is carried out taking into account the main characteristic initial and more distant signs:

Damage to the skin in the form of dense swelling.
Vascular disorders and Raynaud's syndrome.
Damage to the musculoskeletal system.
Changes in internal organs.

Complaints of patients in the early stages

Patients note general weakness, fatigue, malaise, often elevated temperature not exceeding 38 °, decreased appetite, body weight, etc. These manifestations occur mainly in diffuse forms of systemic scleroderma, are not specific and do not allow one to suspect the onset of pathology before the appearance characteristic symptoms.

Skin and mucous membranes

Skin lesions are one of the main diagnostic symptoms of the disease and develop in most patients with systemic scleroderma. The process of characteristic skin changes, localized mainly in the area of the face and hands, goes through the following stages in its development:

dense swelling;
inductive;
atrophic.

They lead to impoverishment of facial expressions (“hypomimia”). The face of a sick person takes on a characteristic “mask-like” appearance - the facial skin is thickened, compacted and stretched, the tip of the nose becomes pointed, vertical folds and wrinkles appear around the mouth, collected like a pouch (the “pouch” symptom), the diameter of the entrance to the oral cavity decreases. Systemic scleroderma can be combined with Sjögren's syndrome.

Changes in the hands are expressed in sclerodactyly, which is also characterized by dense swelling, fibrosis and induration of the skin, leading to a feeling of stiffness, especially in the morning, an increase in limited range of motion, and a change in the appearance of the fingers, taking on the shape of “sausages”.

These symptoms allow an unmistakable diagnosis to be made even with the first cursory visual examination of the patient.

In the diffuse form of the disease, swelling, induration and atrophy of the skin extend beyond the face and hands. They spread to the skin of the trunk, lower and upper extremities. Along with these signs, areas of skin with limited or diffusely widespread reduced pigmentation or completely depigmented, as well as with focal or diffuse hyperpigmentation, are often observed.

Under the skin, as a later manifestation, calcifications (accumulations of calcium salts) are formed, which can lead to cheesy necrosis, tissue destruction and the formation of ulcers with the release of a mass of cheesy (in the form of crumbs) character.

To establish an early diagnosis, the 4-point “skin count” technique is important, allowing one to assess such early manifestations as the initial degrees of skin thickening due to its swelling. The method is based on palpation of the skin in 17 areas - in the face, chest, abdomen and symmetrical areas of the upper and lower extremities. The inspection results are assessed in points:

absence of any changes - 0 points;
the density of the skin is insignificant, if the skin is relatively easy, but more difficult than usual, to be folded - 1 point;
moderate density, if the skin is difficult to fold - 2 points;
pronounced density, “board-shaped” - 3 points.

When examining a skin biopsy, intense fibrosis is determined.

Can systemic scleroderma cause a persistent runny nose?

The mucous membranes are affected quite often simultaneously with the skin. This is manifested by subatrophic or atrophic rhinitis, accompanied by difficult-to-correct constant dryness and nasal congestion, pharyngitis, stomatitis, increased thickness, atrophy and shortening of the frenulum of the tongue, which is a characteristic sign of involvement of the mucous membranes in the process.

Vascular pathology

Often combined with skin disorders. It is an early and frequent manifestation of systemic scleroderma, which reflects the generalized (widespread) nature of the disease. The most characteristic sign of vascular pathology is Raynaud's syndrome. It represents symmetrical vascular spastic crises of the terminal arteries and arterioles, as a result of which the flow of blood into the tissues is disrupted (ischemia).

Attacks are accompanied by a successive two- or three-phase change in color (pallor - cyanotic - redness) of the skin of the fingers, less often the toes, with the simultaneous occurrence of pain, paresthesia, and numbness. Although the main localization is the fingers, these symptoms tend to spread directly to the entire hand, feet, and sometimes to the tips of the nose, tongue and chin, causing dysarthria (speech articulation disorder).

Due to the fact that spasms occur in vessels with already changed walls, attacks are prolonged. Raynaud's syndrome attacks can occur spontaneously, but more often they develop under the influence of cold or psychogenic factors.

Their severity is assessed in degrees or points:

I degree - the presence of only changes in skin color without subjective sensations and trophic changes.
II degree - a feeling of pain, tingling or numbness in the fingers during an attack of the syndrome. There may be single scars on the skin of the fingers.
III degree - severe pain during an attack and/or unhealed single ulcers.
IV degree - multiple ulcers or areas of gangrene.

Vascular spasms and changes in their walls lead to disruption of tissue nutrition and trophic disorders - development, dryness and disruption of skin texture, deformation of nails, painful, long-term non-healing and recurrent ulcerations and suppuration.

Trophic ulcers are located mainly on the terminal phalanges of the fingers (“digital ulcers”), as well as in places of greatest mechanical impact - in the area of the elbow and knee joints, heel bones and ankles. On the distal phalanges of the fingers, pinpoint scars (a “rat bite” symptom) are often found, formed as a result of atrophic processes.

The fingertips decrease in volume and become thinner due to the resorption of the bones of the nail phalanges (acroosteolysis). In addition, skin necrosis and gangrene may develop, followed by self-amputation in the area of the distal and even middle phalanges.

In the chronic course of the process on the face, anterior and posterior surfaces of the chest, on the extremities, on the mucous membranes of the lips, hard palate, and on the tongue, telangiectasia can often be found, occurring several months or even years after the onset of the disease and, like calcifications, being late manifestations of systemic scleroderma.

Musculoskeletal system

Lesions of joints and periarticular tissues

The most common, and sometimes the first, manifestations of systemic scleroderma are joint damage, manifested by:

a symptom of “tendon friction”, which often precedes skin thickening; it occurs as a result of sclerosis of the tissue of the tendon sheaths and the tendons themselves and is defined as a “crunch” when palpating the joints during active movements in them;
polyarthralgia, less often rheumatoid-type polyarthritis, but without pronounced destructive changes in the joints; at the same time, erosive changes in the articular surfaces are found in 20% of patients;
stiffness in the joints, especially the hands, mainly after a night's sleep;
development of flexion contracture in joints, caused mainly by changes in the synovial membranes, periarticular ligaments, tendons and muscles;
osteolysis (resorption) of bones in the area of the distal parts of the terminal phalanges of the fingers, manifested by deformation and shortening of the latter, as well as sometimes osteolysis of the mandibular processes and the distal third of the radial bones.

The onset of the disease with arthritis is most characteristic of the cross-sectional form of systemic scleroderma and its subacute course.

Muscle tissue involvement

It is expressed by one of the forms of myopathy (muscular dystrophy):

non-progressive fibrous myopathy of a non-inflammatory nature is the most common form of this disease; manifested by moderate muscle weakness in proximal muscle groups and a slight increase in the level of creatine phosphokinase (an enzyme contained in muscle tissue) in the blood;
inflammatory, accompanied by weakness and pain in the muscles, an increase in creatine phosphokinase in the blood by 2 times or more, as well as inflammatory changes in the results of the study of muscle biopsies and in the results of electromyography.

In addition, the diffuse form of the disease is accompanied by the development of muscle atrophy caused by contractures and impaired joint mobility.

Internal organs

Gastrointestinal tract (GIT)

Systemic scleroderma with gastrointestinal involvement occurs among 70% of patients. Any part of the digestive tract can be affected, but in 70-85% it is the esophagus (scleroderma esophagitis) and intestines.

Esophagus

Hypotension (decreased tone) of the esophagus is the most common form of damage not only to the latter, but also to the entire gastrointestinal tract. Its morphological basis is fibrosis and widespread atrophy of the smooth muscles of the walls of the esophagus. Characteristic symptoms are difficulty swallowing, constant heartburn, a feeling of a lump of food behind the sternum, which intensifies after eating and/or in a horizontal position.

When carrying out esophagogastroscopy and x-ray examination, narrowed lower sections of the esophagus are determined, which makes eating solid and dry food much more difficult, and dilated upper (2/3) sections, the absence of waves of peristalsis and lack of elasticity of the walls (rigidity), sometimes the presence of a hiatal hernia is possible diaphragm holes. Due to the low tone of the lower esophageal sphincter, acidic gastric contents reflux into the esophagus (gastroesophageal reflux) and the formation of erosions, ulcers and cicatricial narrowing in it, accompanied by painful heartburn and severe chest pain.

With a long course of gastroesophageal reflux disease, some patients may experience replacement of the esophageal epithelium of the mucous membrane with cells identical to the epithelium of the mucous membranes of the stomach or even the small intestine (metaplasia), which predisposes to the development of esophageal cancer.

Stomach and duodenum

Hypotension of the stomach and duodenum is the cause of impaired evacuation of food mass and its retention in the stomach. This causes a feeling of rapid satiety while eating, frequent belching, pain and a feeling of heaviness in the epigastric region, sometimes gastric bleeding due to the formation of multiple telangiectasias, erosions and ulcers in the mucous membrane.

Changes in the intestines

They occur much less frequently compared to the esophagus, with the exception of the large intestine, the frequency of which is almost the same. However, the symptoms of intestinal pathology in the entire clinical picture of systemic scleroderma often become the leading one. The most characteristic are:

signs of duodenitis resembling a peptic ulcer;
with the predominant development of pathology in the small intestine, absorption is impaired, manifested by bloating, symptoms of partial paralytic small intestinal obstruction (rarely), malabsorption syndrome - frequent diarrhea with a large amount of fat in the stool (steatorrhea), alternating with constipation and leading to a significant decrease in body weight ;
when the large intestine is damaged, persistent and frequent constipation occurs (less than 2 independent bowel movements per week), fecal incontinence, and partial recurrent intestinal obstruction may develop.

Respiratory system

They are affected in more than 70% of cases and in recent decades have become the main cause of death among patients with systemic scleroderma. Lung damage is accompanied by repeated perifocal pneumonia, the formation of emphysema, subpleural cysts, abscesses, pleurisy, the occurrence of repeated spontaneous pneumothorax, lung cancer, which occurs 3-5 times more often than in the corresponding age groups without systemic scleroderma, gradual (within 2-10 years) development of pulmonary failure. Changes in the lungs occur in the form of two clinical and morphological options:

According to the interstitial type of lesion (interstitial lung disease), characterized by pulmonary fibrosis and diffuse pneumosclerosis, most pronounced in the lower parts of the lungs. Pathological changes develop within the first five years of the disease and are most pronounced in people with a diffuse form of the disease. The clinical symptoms of systemic scleroderma are not specific - a dry cough, often hacking, shortness of breath with difficulty exhaling, fatigue and the presence of crepitant wheezing, reminiscent of “cellophane crackling” (during auscultation) in the posterior lower parts of the lungs.
The examination reveals a decrease in the vital capacity of the lungs, an enhanced and deformed pulmonary pattern in the lower sections (on an x-ray), and a computed tomography scan reveals uneven darkening of the lung tissue (ground glass symptom) and a picture of “honeycomb lungs” (at later stages).
Isolated (primary) pulmonary hypertension, resulting from vascular lesions of the lungs, or secondary (in 10%), developing as a result of interstitial pathology in the later stages of systemic scleroderma. Pulmonary hypertension of both types often develops 10 years after the onset of the disease in 10-40%. Its main symptom is rapidly progressing (over several months) shortness of breath. The main complications of pulmonary hypertension are cor pulmonale with right ventricular failure, as well as thrombosis of the pulmonary arteries, which is usually fatal.

Changes in the heart

They represent one of the most unfavorable and frequent (16-90%) localizations of the disease and are in first place among the causes of sudden death in patients with systemic scleroderma. The changes are:

conduction disorders and heart rhythm disturbances (in 70%), which especially worsen the prognosis of the disease;
the development of myocarditis (in this case, the survival rate is the lowest), especially among people with polymyositis;
damage to the inner lining of the heart (endocardium) with the development of valve defects, mainly the bicuspid valve;
the development of adhesive or (less commonly) exudative pericarditis, which can cause cardiac tamponade;
heart failure, which develops very rarely, but is characterized by resistance to the use of corrective drugs.

The main symptoms are shortness of breath with minor physical exertion or at rest, a feeling of discomfort and dull long-term pain in the sternum and to the left of it, palpitations and cardiac arrest, a feeling of tremors in the heart.

Kidney damage

Thanks to the availability of modern effective drugs, it is relatively rare. They are based on changes in the arterioles of the kidneys, which cause limited necrosis of the renal tissue due to a violation of its adequate blood supply.

More often, these changes occur latently, with minor functional disorders determined only by urine and blood tests. Less commonly, glomerulonephritis or latent chronic nephropathy develops.

Pronounced changes in the form of scleroderma renal crisis (acute nephropathy) develop among 5-10% (mainly in the diffuse form of systemic scleroderma). It is characterized by sudden onset and rapidly progressive renal arterial hypertension, increased protein content in the urine and renal failure. Only 23% of patients with acute nephropathy survive for more than 5 years. In general, with kidney damage, only 13% survive longer than 15 years, while without this complication - about 72%.

The latest methods for diagnosing systemic scleroderma

Relatively new laboratory tests include methods for determining antinuclear antibodies (ANA):

antibodies to topoisomerase-1 (Scl-70), which, in the presence of isolated Raynaud's syndrome, are harbingers of the development of systemic scleroderma (usually diffuse);
immunogenetic markers HLA-DR3/DRw52; their presence in combination with antibodies to Scl-70 represents a 17-fold increase in the risk of pulmonary fibrosis;
anticentromere antibodies - present in 20% of patients, usually with a limited form of pathology; also considered a marker of the disease in the presence of isolated Raynaud's syndrome;
antibodies to RNA polymerase III - found in 20-25%, mainly in diffuse form and kidney damage; they are associated with a poor prognosis.

The presence of other autoantibodies, the frequency of which in the disease is much less, is determined less often. These include antibodies to Pm-Scl (3-5%), to U 3 -RNP (7%), to U 1 -RNP (6%) and some others.

Clinical recommendations for systemic scleroderma, proposed by the Association of Rheumatologists of Russia, include additional instrumental examination methods that make it possible to clarify the nature and extent of lesions of various organs:

for the digestive tract - esophagogastroduodenoscopy, contrast radiography, pressure manometry in the esophagus, endoscopic gastric pH-metry, biopsy of the metaplastic area of the esophagus;
for the respiratory system - body plethysmography, high-resolution computed tomography, determination of external respiration and pulmonary diffusion capacity through spirometry and the technique of a single breath with breath holding;
to determine pulmonary hypertension and heart damage - Doppler echocardiography, electrocardiography and catheterization of the right heart, Holter electrocardiographic monitoring, radioisotope scintigraphy;
for skin, muscles, synovial membrane of joints and tissues of internal organs - biopsy studies;
wide-field video capillaroscopy of the nail bed, “skin counting” (described above).

Differential diagnosis

Differential diagnosis of systemic scleroderma is carried out with such connective tissue diseases and syndromes as systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, Raynaud's disease, limited scleroderma, Buschke's scleredema, pseudoscleroderma, multifocal fibrosis, tumor-associated scleroderma, Werner and Rothmund-Thomson syndromes.

Diagnosis of systemic scleroderma is carried out on the basis of a combination of clinical symptoms (preference is given), instrumental and laboratory methods. For these purposes, the “Association of Rheumatologists of Russia” recommends using criteria such as basic and additional signs that allow differential diagnosis. To establish a reliable diagnosis, it is sufficient to have 3 of the main signs listed below or one of the main ones (scleroderma skin changes, characteristic changes in the digestive organs, osteolysis of the nail phalanges) in combination with three or more additional ones.

The main features include:

Sclerodermic nature of skin lesions.
Raynaud's syndrome and digital ulcers and/or scars.
Musculo-articular lesions with the development of contractures.
Calcification of the skin.
Osteolysis.
Fibrosis of the basal regions of the lungs.
Lesions of the gastrointestinal tract of a sclerodermic nature.
Development of large-focal cardiosclerosis with conduction and heart rhythm disturbances.
Scleroderma acute nephropathy.
Typical results of video capillaroscopy of the nail bed.
Detection of specific antinuclear antibodies, mainly to Scl-70, anticentromere antibodies and antibodies to RNA polymerase III.

Additional signs:

Loss of body weight by more than 10 kg.
Disorders of tissue trophism.
The presence of polyserosite, usually of an adhesive (sticky) form.
Telangiectasia.
Chronic course of nephropathy.
Polyarthralgia.
Trigeminal neuralgia (trigymenitis), polyneuritis.
An increase in ESR values of more than 20 mm/hour.
Increased levels of gammaglobulins in the blood, exceeding 23%.
Presence of antinuclear factor (ANF) or autoantibodies to DNA.
Detection of rheumatoid factor.

Treatment of systemic scleroderma

Treatment of the disease is long-term, usually lifelong. It should be carried out comprehensively, depending on the form of the pathology, the nature of the course and the involvement of certain organs and systems in the process.

The effectiveness of therapy is significantly reduced due to the presence of the above risk factors, as well as the presence of such provoking factors as unhealthy diet, smoking (!), consumption of alcohol and energy (!) drinks, coffee and strong brewed tea, physical and neuropsychic stress, insufficient rest.

Is it possible to sunbathe with systemic scleroderma?

Ultraviolet radiation is one of the fairly high risk factors that can lead to an exacerbation of the disease. Therefore, staying in places unprotected from sunlight, especially during periods of increased solar activity, is undesirable. Holidays on the sea coast are not contraindicated, but only in the autumn months and subject to staying in the shade. It is also necessary to always use creams with the maximum degree of protection against ultraviolet rays.

Nutritional Features

Nutrition for systemic scleroderma is of particular importance, which should be multiple meals with short breaks between meals in small volumes, especially if the esophagus is affected. It is recommended to exclude allergenic dishes and consume foods with sufficient protein content (milk and fermented milk products, mild cheeses, meat and fish), micro- and macroelements, especially calcium salts.

In case of impaired renal function (nephropathy, renal failure), protein consumption should be strictly dosed, and if various parts of the digestive tract are affected, a diet and food processing should be followed that correspond to the disorders of these organs, taking into account the specific nutrition in scleroderma.

It is also desirable to limit the consumption of carbohydrates, especially when taking glucocorticosteroid drugs, and a sufficient amount of vegetables, berries and fruits with a low sugar content.

Principles of drug treatment and rehabilitation

The main goals of therapy are:

achieving the stage of remission or the maximum possible suppression of the activity of the process;
stabilization of the functional state;
prevention of complications associated with changes in blood vessels and progression of fibrosis;
prevention of damage to internal organs or correction of existing dysfunctions.

Therapy should be especially active in the first years after detection of the disease, when the main and most significant changes in the systems and organs of the body intensively occur. During this period, it is still possible to reduce the severity of inflammatory processes and reduce the consequences in the form of fibrotic changes. Moreover, it is still possible to influence already formed fibrotic changes in terms of their partial reverse development.

Cuprenil (D-penicillamine) in tablets, which has an anti-inflammatory effect, an effect on metabolic processes in connective tissues and a pronounced anti-fibrotic effect. The latter is realized only after application for six months to a year. Cuprenil is the drug of choice for rapid progression of pathology, diffuse skin indurative process and active fibrosis. It is prescribed in gradually increasing and then decreasing dosages. Maintenance doses are taken for 2 to 5 years. Due to possible side effects (toxic effects on the kidneys, impaired intestinal function, dermatitis, effects on the hematopoietic organs, etc.) observed in approximately 30% of patients, the drug is taken under constant medical supervision.
Immunosuppressants Methotrexate, Azathioprine, Cyclophosphamide and others. Methotrexate has an effective effect against skin syndrome, with damage to muscles and joints, especially in the early, inflammatory stage of the disease. Cyclophosphamide is used in cases of high activity of the process, interstitial lung damage with the formation of pulmonary fibrosis (an absolute indication for use), the presence of pronounced immunological changes and in cases where there is no noticeable effect from the previously used treatment.
Enzyme agents (Lidase and Ronidase) - break down mucopolysaccharides and reduce the viscosity of hyaluronic acid. Prescribed for the chronic process in courses of subcutaneous or intramuscular injections, as well as in the form of iontophoresis and applications in the area of tissue induration or contractures.
Glucocorticosteroids (Dexamethasone, Metipred, Prednisolone, Triamcinolone) are prescribed for the activity of the II or III degree process, as well as in cases of acute or subacute course. Their use is carried out with constant monitoring of renal function.
Vascular drugs - the main ones are calcium channel blockers (Corinfar, Nifedipine, Cordaflex, Foridon), angiotensin-converting enzyme inhibitors (Captopril, Capoten, etc.), prescribed already in the initial stages of the disease, prostanoids (Iloprost, Vazaprostan), endothelin receptor antagonists (Traklir, Bosentan), which reduces resistance in both systemic and pulmonary vessels.
Antiplatelet agents (Curantil, Trental) and anticoagulants (small doses of acetylsalicylic acid, Fraxiparine).
Nonsteroidal anti-inflammatory drugs (Ibuprofen, Nurofen, Piroxicam, Indomethacin) and aminoquinoline drugs (Plaquenil).

A new method is the use of genetically engineered biological products for systemic scleroderma. Currently, the study of their effectiveness and prospects for use in severe forms of systemic scleroderma continues. They represent a relatively new direction in the therapy of other systemic connective tissue diseases.

These drugs include Etarnecept and Inflixicamb, which suppress autoimmune reactions, the immunosuppressant Rituximab, which is a monoclonal antibody to B-lymphocyte receptors (in combination with low doses of glucocorticosteroids), antibodies to transforming growth factor beta-I, antimonocyte immunoglobulin, the cytostatic Imatinib, which suppresses excess synthesis of the intercellular matrix, as a result of which skin syndrome is reduced and lung function is improved in the diffuse form of systemic scleroderma, gama- and alpha-interferons.

Treatment with traditional medicine

It is advisable to include traditional medicine in the treatment complex. However, it is always necessary to remember that treatment of systemic scleroderma with folk remedies should never be the only one or used as the main one. It can only serve as a minor addition (!) to the main therapy prescribed by specialists.

For these purposes, you can use vegetable oils, as well as infusions of medicinal plants (St. John's wort, calendula) in vegetable oil, which must be lubricated several times a day on the affected areas of the skin to soften them, improve nutrition and reduce the severity of inflammatory processes. It is beneficial for joints, skin and blood vessels to take warm baths with infusions of geranium, wavy rhubarb, pine buds or needles, birch leaves, and oat straw.

Alcohol tinctures or infusions (for oral administration) of saponaria officinalis, Sakhalin buckwheat, harpagophytum root tea, infusions of horsetail, lungwort and knotweed herbs have anti-inflammatory and immunosuppressive properties. An infusion of the following mixture of plants has anti-inflammatory and vasodilating effects: immortelle, St. John's wort, sweet clover, meadow geranium, meadow clover, yarrow, bird's eye knotweed, mint leaves, plantain and oregano, raspberries and lingonberries, dandelion roots. There are many other combinations of medicinal plants in the form of herbs.

Massage and exercises, physiotherapy

The system of complex therapy and rehabilitation also includes (in the absence of activity or insignificant activity of the process): massage and a set of exercises for systemic scleroderma, improving respiratory and cardiac function, regulating vascular tone, improving joint mobility, etc.; physiotherapy courses - iontophoresis with anti-inflammatory, vascular and enzyme drugs (Lidaza), thermal procedures (paraffin, ozokerite), applications with Dimethyl sulfoxide on the most affected joints; spa treatment (mud therapy and balneotherapy).

Is pregnancy possible and is there a chance of carrying a child?

Pregnancy is accompanied by significant hormonal changes in the body, which is a fairly high risk for a woman in terms of exacerbation of the disease, as well as a risk for the fetus and unborn child. However, it is possible. Systemic scleroderma is not an absolute contraindication for pregnancy and childbirth, even naturally. There is a particularly high chance of bearing a child in the initial stages of the disease with a subacute or chronic course in the absence of process activity and pronounced pathological changes in the internal organs, especially the kidneys and heart.

However, pregnancy planning must be coordinated with the treating specialist to resolve the issue of the possibility of discontinuing certain medications and correcting treatment in general with the use of hormonal, cytostatic, vascular, antiplatelet drugs, drugs that help improve tissue metabolism, etc. In addition, in During pregnancy, it is necessary to be observed and examined at least once a trimester not only by an obstetrician-gynecologist, but also by a rheumatologist.

In order to decide the possibility of prolonging pregnancy, a woman should be hospitalized in a hospital in the first trimester, and in the future - if there is a suspicion of intensification of the disease or complications of the pregnancy.

Implementation of timely adequate treatment, proper employment, patient compliance with the rules of constant dispensary observation, elimination or minimization of provoking factors, the influence of risk factors can slow down the progression of the disease, significantly reduce the degree of aggressiveness of its course, improve the survival prognosis and improve the quality of life.

It is characterized by a staged course and a large polymorphism of clinical manifestations associated with characteristic damage to the skin, some internal organs and the musculoskeletal system.

Age-related morbidity and survival of patients

In accordance with average statistical data, the primary incidence per year per population ranges from 2.7 to 12 cases, and the overall prevalence of this pathology ranges from 30 to 450 cases per year per population. The development of the disease is possible in various age groups, including young people (juvenile scleroderma).

Retrospective data from studies of patient survival (how long they live), depending on the course of the disease and its natural development, show the following differences:

in an acute, rapidly progressive course with a predominance of tissue fibrosis and initial symptoms in the form of skin lesions, life expectancy does not exceed 5 years, while the survival rate is only 4%;
in a subacute, moderately progressive course, damage to the immune system predominates with initial symptoms in the form of articular syndrome; life expectancy can be up to 15 years, with survival rate in the first 5 years - 75%, 10 years - about 61%, 15 years - on average 50%;
in a chronic, slowly progressive course, vascular pathology predominates with initial signs in the form of Raynaud's syndrome; survival rate in the first 5 years of the disease is on average 93%, 10 years - about 87%, and 15 years - 85%.

Etiology and pathogenesis of the disease

The reasons for the development of systemic scleroderma are not well understood. It is currently believed to be a multifactorial disease caused by:

3. The influence of exogenous and endogenous risk factors. Particular importance is attached to:

hypothermia and frequent and prolonged exposure to sunlight;
vibrations;
industrial silicon dust;
chemical agents of industrial and household origin - vapors from petroleum products processing, vinyl chloride, pesticides, organic solvents;
some foods containing rapeseed oil and L-tryptophan supplements;
implants and certain medications, for example, bleomycin (antitumor antibiotic), vaccines;
neuroendocrine disorders, frequent stressful conditions, a tendency to vascular spastic reactions.

Schematic presentation of the complex mechanism of disease development

Viruses and risk factors against the background of genetic predisposition affect:

Connective tissue structures, which leads to defective cell membranes and increased fibroblast function. The result of this is excess production of collagen, fibrokinetin (a large glycoprotein of the intercellular matrix), proteoglycans and glycosaminoglycans, which are complex proteins that include immunoglobulins (antibodies), most protein hormones, interferon, etc.
Microvasculature, resulting in damage to the endothelium (epithelium of the inner wall of blood vessels). This, in turn, leads to the proliferation of myofibroblasts (cells similar to both fibroblasts and smooth muscle cells), sedimentation of platelets in small vessels and their adhesion (sticking) to the vascular walls, deposition of fibrin threads on the inner lining of small vessels, edema and impairment permeability of the latter.
The body's immune system, leading to an imbalance of T- and B-lymphocytes involved in the formation of the immune response, as a result of which the function of the former is disrupted and the latter are activated.

All these factors, in turn, cause the further development of the following disorders:

Excessive formation of collagen fibers with subsequent progressive generalized fibrosis in the dermis, musculoskeletal system and internal organs. Fibrosis is an overgrowth of connective tissue.
Excessive production of collagen proteins in the walls of small vessels, thickening of the basement membranes and vascular fibrosis, increased blood clotting and thrombosis in small vessels, narrowing of their lumen. All this leads to damage to small vessels with the development of vascular spasms like Raynaud's syndrome and disruption of the structure and function of internal organs.
Increased formation of cytokines (specific peptide information molecules), immune complexes and autoantibodies, also leading to inflammation of the inner lining of small vessels (vasculitis) and, accordingly, also to damage to internal organs.

Thus, the main links in the pathogenetic chain are:

violation of the mechanisms of cellular and humoral immunity;
damage to small vessels with destruction and dysfunction of the endothelium of the vascular wall, with thickening of its inner membrane and microthrombosis, with narrowing of the lumen of the blood microcirculation channel and disruption of the microcirculation itself;
disruption of the formation of collagen proteins with increased formation of smooth muscle fibers and collagen, which is manifested by fibrous restructuring of the connective tissue of organs and systems with disruption of their function.

Classification of systemic scleroderma and brief characteristics of individual forms

The following clinical forms are distinguished:

Scleroderma without scleroderma

Juvenile systemic scleroderma

Clinically manifested by isolated Raynaud's syndrome, combined with a capillaroscopic picture and/or immunological changes characteristic of the disease.

Variants of systemic scleroderma, depending on the nature of the course and rate of progression

Acute, rapidly progressing variant - during the first 2 years from the onset of the disease, generalized diffuse fibrosis of the skin and internal organs, mainly the lungs, heart and kidneys, develops. Previously, in most cases the disease was quickly fatal. With the use of modern adequate therapy, the prognosis has improved somewhat.
Subacute, moderately progressive. According to clinical symptoms and laboratory data, it is characterized by a predominance of signs of an immune inflammatory process - dense skin edema, myositis, arthritis. Cross syndromes are common cases.
Chronic, slowly progressive. This variant of systemic scleroderma is distinguished by: the predominance of vascular lesions - the long-term (for many years) existence of Raynaud's syndrome in the first stages of the disease, which is accompanied by the slow development of moderately pronounced skin changes; gradual increase in disorders associated with ischemia (malnutrition) of tissues; gradual development of pulmonary hypertension and damage to the digestive tract.

Initial - the presence of 1 to 3 localizations of the disease.
The stage of generalization, reflecting the systemic nature of the lesions with the polysyndromic nature of the manifestations of the process.
Terminal, or late, which is characterized by insufficiency of the function of one or more organs - respiratory, cardiac or renal failure.

The use of the three listed parameters when formulating a diagnosis of a disease allows you to navigate in relation to drawing up a treatment program for the patient.

Main symptoms

Diagnosis is carried out taking into account the main characteristic initial and more distant signs:

Damage to the skin in the form of dense swelling.
Vascular disorders and Raynaud's syndrome.
Damage to the musculoskeletal system.
Changes in internal organs.

Complaints of patients in the early stages

Skin and mucous membranes

These symptoms allow an unmistakable diagnosis to be made even with the first cursory visual examination of the patient.

absence of any changes - 0 points;
the density of the skin is insignificant, if the skin is relatively easy, but more difficult than usual, to be folded - 1 point;
moderate density, if the skin is difficult to fold - 2 points;
pronounced density, “board-shaped” - 3 points.

When examining a skin biopsy, intense fibrosis is determined.

Can systemic scleroderma cause a persistent runny nose?

Vascular pathology

Their severity is assessed in degrees or points:

I degree - the presence of only changes in skin color without subjective sensations and trophic changes.
II degree - a feeling of pain, tingling or numbness in the fingers during an attack of the syndrome. There may be single scars on the skin of the fingers.
III degree - severe pain during an attack and/or unhealed single ulcers.
IV degree - multiple ulcers or areas of gangrene.

Vascular spasms and changes in their walls lead to disruption of tissue nutrition and trophic disorders - the development of diffuse baldness, dryness and disruption of skin texture, deformation of nails, painful, long-term non-healing and recurrent ulcerations and suppuration.

Musculoskeletal system

Lesions of joints and periarticular tissues

The most common, and sometimes the first, manifestations of systemic scleroderma are joint damage, manifested by:

a symptom of “tendon friction”, which often precedes skin thickening; it occurs as a result of sclerosis of the tissue of the tendon sheaths and the tendons themselves and is defined as a “crunch” when palpating the joints during active movements in them;
polyarthralgia, less often rheumatoid-type polyarthritis, but without pronounced destructive changes in the joints; at the same time, erosive changes in the articular surfaces are found in 20% of patients;
stiffness in the joints, especially the hands, mainly after a night's sleep;
development of flexion contracture in joints, caused mainly by changes in the synovial membranes, periarticular ligaments, tendons and muscles;
osteolysis (resorption) of bones in the area of the distal parts of the terminal phalanges of the fingers, manifested by deformation and shortening of the latter, as well as sometimes osteolysis of the mandibular processes and the distal third of the radial bones.

The onset of the disease with arthritis is most characteristic of the cross-sectional form of systemic scleroderma and its subacute course.

Muscle tissue involvement

It is expressed by one of the forms of myopathy (muscular dystrophy):

non-progressive fibrous myopathy of a non-inflammatory nature is the most common form of this disease; manifested by moderate muscle weakness in proximal muscle groups and a slight increase in the level of creatine phosphokinase (an enzyme contained in muscle tissue) in the blood;
inflammatory, accompanied by weakness and pain in the muscles, an increase in creatine phosphokinase in the blood by 2 times or more, as well as inflammatory changes in the results of the study of muscle biopsies and in the results of electromyography.

In addition, the diffuse form of the disease is accompanied by the development of muscle atrophy caused by contractures and impaired joint mobility.

Internal organs

Gastrointestinal tract (GIT)

Stomach and duodenum

signs of duodenitis resembling a peptic ulcer;
with the predominant development of pathology in the small intestine, absorption is impaired, manifested by bloating, symptoms of partial paralytic small intestinal obstruction (rarely), malabsorption syndrome - frequent diarrhea with a large amount of fat in the stool (steatorrhea), alternating with constipation and leading to a significant decrease in body weight ;
when the large intestine is damaged, persistent and frequent constipation occurs (less than 2 independent bowel movements per week), fecal incontinence, and partial recurrent intestinal obstruction may develop.

Respiratory system

According to the interstitial type of lesion (interstitial lung disease), characterized by pulmonary fibrosis and diffuse pneumosclerosis, most pronounced in the lower parts of the lungs. Pathological changes develop within the first five years of the disease and are most pronounced in people with a diffuse form of the disease. The clinical symptoms of systemic scleroderma are not specific - a dry cough, often hacking, shortness of breath with difficulty exhaling, fatigue and the presence of crepitant wheezing, reminiscent of “cellophane crackling” (during auscultation) in the posterior lower parts of the lungs.

The examination reveals a decrease in the vital capacity of the lungs, an enhanced and deformed pulmonary pattern in the lower sections (on an x-ray), and a computed tomography scan reveals uneven darkening of the lung tissue (ground glass symptom) and a picture of “honeycomb lungs” (at later stages).

Isolated (primary) pulmonary hypertension, resulting from vascular lesions of the lungs, or secondary (in 10%), developing as a result of interstitial pathology in the later stages of systemic scleroderma. Pulmonary hypertension of both types often develops 10 years after the onset of the disease in 10-40%. Its main symptom is rapidly progressing (over several months) shortness of breath. The main complications of pulmonary hypertension are cor pulmonale with right ventricular failure, as well as thrombosis of the pulmonary arteries, which is usually fatal.

Changes in the heart

conduction disorders and heart rhythm disturbances (in 70%), which especially worsen the prognosis of the disease;
the development of myocarditis (in this case, the survival rate is the lowest), especially among people with polymyositis;
damage to the inner lining of the heart (endocardium) with the development of valve defects, mainly the bicuspid valve;
the development of adhesive or (less commonly) exudative pericarditis, which can cause cardiac tamponade;
heart failure, which develops very rarely, but is characterized by resistance to the use of corrective drugs.

Kidney damage

More often, these changes occur latently, with minor functional disorders determined only by urine and blood tests. Less commonly, glomerulonephritis or latent chronic nephropathy develops.

The latest methods for diagnosing systemic scleroderma

Relatively new laboratory tests include methods for determining antinuclear antibodies (ANA):

antibodies to topoisomerase-1 (Scl-70), which, in the presence of isolated Raynaud's syndrome, are harbingers of the development of systemic scleroderma (usually diffuse);
immunogenetic markers HLA-DR3/DRw52; their presence in combination with antibodies to Scl-70 represents a 17-fold increase in the risk of pulmonary fibrosis;
anticentromere antibodies - present in 20% of patients, usually with a limited form of pathology; also considered a marker of the disease in the presence of isolated Raynaud's syndrome;
antibodies to RNA polymerase III - found in 20-25%, mainly in diffuse form and kidney damage; they are associated with a poor prognosis.

for the digestive tract - esophagogastroduodenoscopy, contrast radiography, pressure manometry in the esophagus, endoscopic gastric pH-metry, biopsy of the metaplastic area of the esophagus;
for the respiratory system - body plethysmography, high-resolution computed tomography, determination of external respiration and pulmonary diffusion capacity through spirometry and the technique of a single breath with breath holding;
to determine pulmonary hypertension and heart damage - Doppler echocardiography, electrocardiography and catheterization of the right heart, Holter electrocardiographic monitoring, radioisotope scintigraphy;
for skin, muscles, synovial membrane of joints and tissues of internal organs - biopsy studies;
wide-field video capillaroscopy of the nail bed, “skin counting” (described above).

Differential diagnosis

Diagnosis of systemic scleroderma is carried out on the basis of a combination of clinical symptoms (preference is given), instrumental and laboratory methods. For these purposes, the “Association of Rheumatologists of Russia” recommends using criteria such as basic and additional signs that allow differential diagnosis. To establish a reliable diagnosis, it is sufficient to have 3 of the main signs listed below or one of the main ones (scleroderma skin changes, characteristic changes in the digestive organs, osteolysis of the nail phalanges) in combination with three or more additional ones.

The main features include:

Sclerodermic nature of skin lesions.
Raynaud's syndrome and digital ulcers and/or scars.
Musculo-articular lesions with the development of contractures.
Calcification of the skin.
Osteolysis.
Fibrosis of the basal regions of the lungs.
Lesions of the gastrointestinal tract of a sclerodermic nature.
Development of large-focal cardiosclerosis with conduction and heart rhythm disturbances.
Scleroderma acute nephropathy.
Typical results of video capillaroscopy of the nail bed.
Detection of specific antinuclear antibodies, mainly to Scl-70, anticentromere antibodies and antibodies to RNA polymerase III.

Loss of body weight by more than 10 kg.
Disorders of tissue trophism.
The presence of polyserosite, usually of an adhesive (sticky) form.
Telangiectasia.
Chronic course of nephropathy.
Polyarthralgia.
Trigeminal neuralgia (trigymenitis), polyneuritis.
An increase in ESR values of more than 20 mm/hour.
Increased levels of gammaglobulins in the blood, exceeding 23%.
Presence of antinuclear factor (ANF) or autoantibodies to DNA.
Detection of rheumatoid factor.

Treatment of systemic scleroderma

Is it possible to sunbathe with systemic scleroderma?

Nutritional Features

It is also desirable to limit the consumption of carbohydrates, especially when taking glucocorticosteroid drugs, and a sufficient amount of vegetables, berries and fruits with a low sugar content.

Principles of drug treatment and rehabilitation

The main goals of therapy are:

achieving the stage of remission or the maximum possible suppression of the activity of the process;
stabilization of the functional state;
prevention of complications associated with changes in blood vessels and progression of fibrosis;
prevention of damage to internal organs or correction of existing dysfunctions.

Cuprenil (D-penicillamine) in tablets, which has an anti-inflammatory effect, an effect on metabolic processes in connective tissues and a pronounced anti-fibrotic effect. The latter is realized only after application for six months to a year. Cuprenil is the drug of choice for rapid progression of pathology, diffuse skin indurative process and active fibrosis. It is prescribed in gradually increasing and then decreasing dosages. Maintenance doses are taken for 2 to 5 years. Due to possible side effects (toxic effects on the kidneys, impaired intestinal function, dermatitis, effects on the hematopoietic organs, etc.) observed in approximately 30% of patients, the drug is taken under constant medical supervision.
Immunosuppressants Methotrexate, Azathioprine, Cyclophosphamide and others. Methotrexate has an effective effect against skin syndrome, with damage to muscles and joints, especially in the early, inflammatory stage of the disease. Cyclophosphamide is used in cases of high activity of the process, interstitial lung damage with the formation of pulmonary fibrosis (an absolute indication for use), the presence of pronounced immunological changes and in cases where there is no noticeable effect from the previously used treatment.
Enzyme agents (Lidase and Ronidase) - break down mucopolysaccharides and reduce the viscosity of hyaluronic acid. Prescribed for the chronic process in courses of subcutaneous or intramuscular injections, as well as in the form of iontophoresis and applications in the area of tissue induration or contractures.
Glucocorticosteroids (Dexamethasone, Metipred, Prednisolone, Triamcinolone) are prescribed for the activity of the II or III degree process, as well as in cases of acute or subacute course. Their use is carried out with constant monitoring of renal function.
Vascular drugs - the main ones are calcium channel blockers (Corinfar, Nifedipine, Cordaflex, Foridon), angiotensin-converting enzyme inhibitors (Captopril, Capoten, etc.), prescribed already in the initial stages of the disease, prostanoids (Iloprost, Vazaprostan), endothelin receptor antagonists (Traklir, Bosentan), which reduces resistance in both systemic and pulmonary vessels.
Antiplatelet agents (Curantil, Trental) and anticoagulants (small doses of acetylsalicylic acid, Fraxiparine).
Nonsteroidal anti-inflammatory drugs (Ibuprofen, Nurofen, Piroxicam, Indomethacin) and aminoquinoline drugs (Plaquenil).

Treatment with traditional medicine

Massage and exercises, physiotherapy

Is pregnancy possible and is there a chance of carrying a child?

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What is scleroderma?

The term "scleroderma" means "tight skin." The extensive scleroderma group of diseases includes diseases whose main symptom is skin thickening, but they all differ in the range of clinical manifestations, course and prognosis.

At focal scleroderma There is limited skin thickening, but subcutaneous tissue and bone may be involved. There are two main forms of focal scleroderma - plaque (morphea) and linear. In the first case, the skin lesion has the appearance of round-shaped compactions (“Plaques”), with a purple rim along the periphery at the onset of the disease. These lesions, single or multiple, can appear on the trunk, face and limbs. In the linear form of focal scleroderma, the affected areas have the appearance of stripes of skin compaction, often involving the underlying muscles and bones, and are localized mainly on the limbs and face. This form of focal scleroderma, if developed in childhood and adolescence, can lead to limitation of movements (muscle and joint contractures) and developmental disorders of the affected areas. Internal organs are not affected by focal scleroderma.

Systemic scleroderma (SSc)- a form of scleroderma, in which, along with skin thickening, various lesions of the joints, blood vessels and internal organs (heart, lungs, gastrointestinal tract, kidneys) are detected. In rare cases, only internal organs are affected, without skin changes. The disease can develop in all age groups, but the peak incidence is observed at the age of 30-50 years. Women get sick 3-5 times more often than men. SSD is divided into limited and diffuse forms, which differ in the prevalence and severity of damage to the skin and internal organs.

Reason for development(etiology) SSc remains unknown. The disease is caused by the overproduction of a protein called collagen by certain cells. Excess collagen accumulates in the skin and internal organs, leading to thickening and hardening of the skin and dysfunction of the affected organs. Damage to small blood vessels and activation of the immune system are also observed. All this together gradually leads to sclerosis of the affected tissues.

Limited form of SSD characterized by less widespread skin thickening, inconspicuous onset and gradual development of the disease. For a long time, the disease may manifest itself only as Raynaud's phenomenon and slight swelling of the fingers. Skin thickening is limited to the face and hands. The most common damage to internal organs is a decrease in esophageal peristalsis, which is manifested by difficulty swallowing solid food and persistent heartburn. With a long course of the disease, serious damage to the lungs and intestines is possible.

Diffuse form of SSD usually develops suddenly and is characterized by more widespread thickening of the skin, involving both the face and extremities, as well as the trunk. Already in the early stages of the disease, signs of damage to internal organs are revealed.

Symptoms of the disease

Clinical symptoms of SSc can vary significantly between individual patients, depending on the form of the disease.

Raynaud's phenomenon - vasospasm in response to exposure to cold or emotional stress is one of the characteristic and early signs of SSc.

Signs of Raynaud's phenomenon in systemic scleroderma are the following:

whitening and/or blue discoloration of the fingers, sometimes the tip of the nose, ears, in the cold or with excitement;
tingling, numbness or pain in the fingers during episodes of vasospasm;
the appearance of sores or cracks in the skin on the tips of the fingers or around the nails.

Swelling of the fingers: At first it may be transient and appear only in the morning. At the same time, the skin becomes tense and shiny, and the person experiences difficulty clenching his fingers into a fist;

Hardening and thickening of the skin, especially on the fingers and face;

Limitation of movements in the fingers;

Skin color changes which becomes darker or, conversely, areas of clearing (depigmentation) appear;

The appearance of calcifications(subcutaneous deposits of calcium salts in the form of small compactions, usually on the fingers and around the joints, which can open to release a white crumbly mass);

The appearance of telangiectasia "spider veins" are a consequence of the expansion of small blood vessels in the skin and are visible in the form of small, several millimeters in diameter, round red spots that disappear with pressure;

Joint inflammation(arthritis) and muscle weakness.

Along with skin and muscle-joint symptoms, patients with SSc already in the early stages of the disease develop signs involvement of internal organs.

Damage to the gastrointestinal tract

Manifested by the following complaints:

difficulty swallowing (dysphagia), as a result of which patients are forced to wash down solid food with water;

persistent heartburn, which worsens when lying down, bending the body forward, or lifting heavy objects;

a feeling of rapid satiety and fullness in the stomach;

bloating and constipation.

Lung damage

It can cause varying degrees of severe shortness of breath (from moderate during physical activity, greater than usual, to significant - which is disturbing even at rest) and persistent dry cough.

Heart damage

In this case, patients often feel interruptions in the heart, palpitations, and less often - pain in the heart area.

Kidney damage

The most serious complication of the disease remains scleroderma renal crisis. It is characterized by sudden development and rapid progression, leading in a short period to irreversible impairment of renal function. Scleroderma renal crisis is almost always associated with the development of arterial hypertension, which becomes malignant. As a result, patients begin to complain of headaches, visual disturbances, and severe weakness. If the above complaints occur, you must immediately contact a rheumatologist who will prescribe the necessary tests!

Why do you need to consult a rheumatologist?

It has been proven that with an early diagnosis of the disease, treatment results are always better than in advanced cases.

During the appointment, the rheumatologist will carefully collect an anamnesis of the disease, study the available medical documentation, conduct an examination and answer all questions regarding this disease. Since complications from various internal organs with predominant damage to one of them are possible in SSc, it is necessary to conduct a comprehensive examination, including laboratory (blood and urine tests) and instrumental (ECG, Echo-CG, chest x-ray, spirography, etc.) studies . Once the diagnosis is confirmed, your doctor will discuss available treatment options with you.

Can scleroderma be cured?

Unfortunately, a complete cure for the disease is impossible. With focal scleroderma, it is possible to achieve long-term remission. In SSc, it is more difficult to completely suppress the activity of the disease, but with early treatment it is possible to significantly slow down the rate of progression and maintain the stability of the functions of vital organs for a long time. Only a strong alliance between the patient and the doctor will allow success in solving this difficult problem.

Treatment

All patients with SSc should avoid hypothermia and prolonged stay in a cold room. Nicotine and caffeine contribute to peripheral vasospasm; patients with SSc should stop smoking and limit the consumption of coffee and caffeine-containing products. All questions related to drug treatment should be resolved only with the attending physician.

All questions related to drug treatment, which is prescribed depending on the clinical form, severity and nature of damage to internal organs should only be discussed with your doctor.

It is mandatory to take vasodilating and antiplatelet (preventing blood clotting) drugs, since vascular lesions occur in all patients and are generalized in nature. The need for treatment with anti-inflammatory and anti-fibrotic drugs is decided in each case individually. The Institute has developed unique approaches to the treatment of SSc, including the use of modern innovative genetically engineered biological drugs.

Diagnosis and treatment of systemic scleroderma at the Federal State Budgetary Institution NIIR named after. V.A. Leading experts in this field are working with Nasonova:

Make an appointment with a specialist by phone: +7 495 109-29-10; +7 495 109-39-99

Treatment of patients with SSc should be as early as possible, comprehensive and determined depending on the clinical form, rate of progression and severity of organ pathology. Long-term treatment is required, which can be lifelong. Treatment of SSc includes vascular medications and anti-inflammatory and immunosuppressive drugs. The goal of treatment is to restore vascular homeostasis and reduce damage due to inflammation and fibrotic changes.

3.1 Conservative treatment.

reduction of activity and suppression of disease progression;
prevention and treatment of Raynaud's syndrome and vascular complications;
prevention and treatment of visceral manifestations of the disease.
The main place in the treatment of SSc is occupied by vascular, anti-inflammatory and immunosuppressive drugs.
Taking into account international experience and in accordance with EULAR versions, recommendations are grouped by organ systems or the most severe clinical syndromes.
For Raynaud's syndrome associated with SSc, long-term drug therapy is recommended for all patients. Treatment is considered successful when the severity of vasospasm decreases and there is no emergence of new ischemic lesions.
The choice of specific therapy depends on the clinical condition and severity, which are classified according to the WHO functional scale. Functional class 1 includes asymptomatic patients or those with symptoms that minimally limit normal physical activity, and functional class 4 includes patients with the greatest limitations in physical activity that occur even at rest. In patients with functional classes I, II and III, the first-line drugs are bosentan and sildenafil. In addition to these drugs, inhaled iloprost can be used in patients with functional class III. With the development of functional class IV, combination therapy with these drugs is usually prescribed.
Recommended as first-line drugs (reduce the frequency and severity of Raynaud's syndrome attacks compared to placebo and for the treatment of Raynaud's syndrome associated with systemic scleroderma) - calcium channel blockers (calcium antagonists) of the dihydropyridine group (mainly nifedipine** orally).

Comments. Long-acting calcium antagonists are preferred;
Prostanoids for intravenous use (iloprost, alprostadil**) are recommended if calcium antagonists are ineffective for the treatment of severe Raynaud's syndrome.
Convincing level of recommendations A.
Prostanoids (mainly iloprost IV) not only reduce the frequency and severity of Raynaud's syndrome attacks compared to placebo, but also have a positive effect on healing, and are therefore recommended for the treatment of active digital ulcers.
Convincing level of recommendations A.
Iloprost is prescribed 20-50 mcg per infusion in 3-5 day courses several times a year at a rate of 0.5-2 ng/kg per minute IV for at least 6 hours a day. Alprostadil** is prescribed in courses of 10-15 administrations 2-3 times a year, 20-60 mcg per IV infusion (at least 3 hours a day).

Comments. Calcium antagonists and prostanoids may cause similar hemodynamic effects, requiring increased attention to monitoring for possible side effects when these classes of drugs are used in combination. Patients treated with prostanoids are more likely to experience ischemic cardiovascular complications, therefore, before starting treatment with prostanoids, cardiovascular risk should be carefully assessed in all patients.
If calcium antagonists and prostanoids are ineffective, non-selective type I endothelin receptor blockers (ET-1) are recommended for the treatment of multiple and recurrent digital ulcers in the diffuse form of the disease: bosentan** reduces the frequency and duration of Raynaud's attacks, and the incidence of new or recurrent digital ulcers.

Recommended for the treatment of severe Raynaud's syndrome and digital ulcers, including when calcium antagonists and prostanoids are ineffective - phosphodiesterase type 5 inhibitors sildenafil and tadalafil.
Convincing level of recommendations B/ A.
It is recommended to take drugs that suppress platelet aggregation simultaneously with vasodilators.

It is recommended to reduce pain from digital ulcers - taking NSAIDs, paracetamol and weak opioids (tramadol**) in adequate doses.
Convincing level of recommendations C.
For the treatment of infected digital ulcers, it is recommended to use local and/or systemic use of broad-spectrum antibiotics, which are advisable to prescribe after culture of the wound contents for flora and sensitivity to antibiotics.
Convincing level of recommendations C.
The main goal of pharmacotherapy for skin lesions in SSc is to reduce the severity and prevalence of skin thickening. The effectiveness of drugs against skin fibrosis can be assessed by the dynamics of the skin count (after 6 and 12 months).
It is recommended at an early stage (during the first 3-5 years of the disease) or when the severity and prevalence of skin thickening increases in patients with diffuse systemic scleroderma D-penicillamine** (250-500 mg per day). .
Level of strength of recommendations C).
Recommended for the treatment of early diffuse SSc - Methotrexate** in doses of 10-15 mg/day.

Recommended for reducing skin count - Mycophenolate Mofetil** (MMF) at a therapeutic dose of 2 g/day. .
Strength of recommendation: B/C.
Recommended for progressive diffuse skin lesions as monotherapy or in combination with the above drugs - Glucocorticoids (GC).
Comments. In addition to skin lesions, GCs are also recommended for obvious clinical signs of inflammatory activity (serositis, myositis, IPL, refractory synovitis and/or tenosynovitis) in small doses - up to 15-20 mg per day, etc.; taking GCs increases the risk of scleroderma renal crisis (SRC).
In many patients with SSc, lung damage is relatively benign, without obvious progression, so not all patients with IPD need to be treated. The choice of whom and how to treat is made taking into account the initial severity of IPD and the obvious risk of progression. Treatment is indicated for patients with shortness of breath in the first 5-7 years from the onset of the disease, if.
according to HRCT of the chest, the volume of lung damage exceeds 20% and/or;
FVC ≤ 70% and/or;
there was a decrease in FVC by ≥ 10% over the previous 3-12 months.
The effectiveness of therapy is monitored by the level of forced vital capacity, which must be determined at least once every 6 months.
Convincing level of recommendations B.
Comments. The effectiveness of therapy is indicated by stabilization or increase in FVC levels.
It is recommended to use GCs orally in doses of 10-15 mg/day for the treatment of IPL in SSc. In combination with immunosuppressants.
Convincing level of recommendations C.
A comment. There was no significant association between improvement in pulmonary function parameters and the use of high doses of GCs. It must be remembered that the administration of high doses of glucocorticoids increases the risk of scleroderma renal crisis;
Recommended as induction therapy for interstitial lung disease (ILD) in SSc - Cyclophosphamide** (CP) in combination with small doses of GC. CP is prescribed intravenously in doses of 500 mg/m2 - 750 mg/m2 per month or orally in doses of 1 mg/kg/day - 2 mg/kg/day, depending on the effectiveness and tolerability of the drug.
Strength of recommendation A.
Comments. The method of administration of CP (oral or intravenous) does not significantly affect the level of changes in pulmonary function tests and the frequency of adverse reactions. The duration of the course of CP should be at least 6 months (Conviction level of recommendations C), however, if the drug is well tolerated, the duration of therapy can be 12 months or more until the IPL stabilizes.
MMF is recommended both as induction therapy for IPL (in case of intolerance or ineffectiveness, including secondary, of cyclophosphamide in combination with GC), and as a maintenance therapy after stabilization of the pulmonary process during cyclic phosphatase therapy.
Strength of recommendation A.
Comments. MMF is prescribed at a dose of 1000 mg/day. (in two doses), increasing it to 2000-3000 mg/day. (in two doses) if well tolerated.
It is recommended that in case of ineffectiveness or intolerance of therapy with CP and/or MMF, the use of Azathioprine** (100 mg/day) or Cyclosporine A** (in doses not exceeding 2.5 mg/kg/day) for 12-18 months.
Convincing level of recommendations C.
Tactics for managing a patient with interstitial lung disease.
Treatment of PAH includes traditional therapy: diuretics, cardiac glycosides (if supraventricular arrhythmias occur).
Recommended for severe hypoxemia (saturation less than 90%) - oxygen therapy;
Anticoagulants are recommended only for thrombotic complications;
It is not recommended for PAH to prescribe beta-blockers, ACE inhibitors, angiotensin-2 receptor antagonists, ivabradine, unless taking these drugs is necessary.
In recent years, PAH-specific therapy has been introduced into practice, which is prescribed to improve exercise tolerance, slow the progression of the disease, it causes regression of changes in the pulmonary vessels, improves quality of life and survival prognosis. PAH-specific drugs promote vasodilation and decrease pulmonary artery pressure through different mechanisms.
Endothelin-1 receptor antagonists (ET-1). Bosentan** is recommended at a starting dose of 62.5 mg 2 times a day. After 4 weeks, if well tolerated, increase the dose to 125 mg 2 times a day. It is recommended to monitor transaminase and bilirubin levels monthly. Women taking bosentan require reliable contraception due to the possible teratogenic effects.
Convincing level of recommendations C.
Comments. ET-1 receptor antagonists suppress the vasoconstrictive effect of ET-1 by binding to type A and B receptors (non-selective ET-1 antagonists) or only to type A receptors (selective ET-1 antagonists). The former include bosentan and macitentan, and a representative of the selective ET-1 antagonists is ambrisentan and loprost.
Prostacyclin analogues. It is recommended from 6 to 12 inhalations of iloprost per day to maintain a stable effect. Inhaled iloprost effectively reduces pulmonary artery pressure.
Convincing level of recommendations C.
Comments. Iloprost is a chemically stable prostacyclin analogue that is available as an intravenous infusion, oral administration, and aerosol. The half-life of iloprost is 20-25 minutes, duration of action is 45-60 minutes. When using an ultrasonic nebulizer, the duration of inhalation is 5 minutes. Analogs of prostacyclin are also epoprostenol (in infusion form) and treprostenil (for intravenous and subcutaneous administration and in the form of an aerosol).
Prostacyclin receptor agonists: Selexipag 10 mg once daily is recommended. Selexipag is an oral, selective prostacyclin IP receptor agonist;
Phosphodiesterase type 5 (PDE5) inhibitors suppress the inactivation of cyclic GMP in cells. It is recommended to use Sildenafil at a dose of 20 mg x 3 times a day; if ineffective, the dose may be increased to 200 mg per day. It is recommended to take Tadalafil (selective PDE5 inhibitor) once a day (2.5-40 mg). Vardenafil (selective PDE-5 inhibitor) is recommended at a dose of 20 mg 2 times a day;
Stimulators of soluble guanylate cyclase increase the synthesis of GMP. Riociguat is recommended orally 3 times a day, 1 mg (maximum daily dose 7.5 mg).
Convincing level of recommendations C.
Comments. The combination of guanylate cyclase stimulators and PDE5 inhibitors is contraindicated due to hypotension and other serious side effects.
Scheme for determining the treatment of pulmonary arterial hypertension.
The most unfavorable prognostic manifestation of SSc is acute nephropathy (scleroderma renal crisis (SRC) or “acute scleroderma kidney”), the mortality rate of which exceeds 40-50%. The main manifestations of SKC are the sudden development of acute kidney injury and arterial hypertension, which quickly becomes malignant. In 10-20% of cases, normotensive SBS is diagnosed, which can be suspected in patients with SSc who are at risk of developing SBS. Renal function should be regularly assessed in patients with SSc. To assess renal function in patients with SSc, as in the general population, it is advisable to determine the glomerular filtration rate using the CKD-EPI calculation formula. Risk factors for SPC: diffuse form of the disease, early stage of the disease (especially 1-3 years), rapid progression of skin syndrome, rapid formation of joint contractures, male gender, old age, the presence of antibodies to ribonucleoprotease III, taking large doses of CS.
Criteria for acute kidney injury: increase in creatinine level ≥26.5 mmol/L (≥0.3 mg/dL) within 48 hours or increase in serum creatinine level ≥1.5 times the initial level, definitely or suspected to have increased within 7 days .
It is not recommended to prescribe GCs more than 15 mg per day and potentially nephrotoxic drugs (D-penicillamine**, Cyclosporine A**) to patients with risk factors for SBS due to the possibility of provoking SCS.
Convincing level of recommendations C.
Angiotensin-converting enzyme inhibitors (ACEIs) are recommended as first-line drugs in the treatment of SPC. Aggressive antihypertensive therapy may stabilize or improve renal function. It is recommended to start treatment with captopril** 12.5-25 mg with dose titration to the maximum (50 mg 3 times a day).
Convincing level of recommendations C.

Synonym: sclerodermia systemica, diffuse scleroderma, universal scleroderma, progressive systemic sclerosis.

Systemic scleroderma - diffuse connective tissue disease with a predominance of fibrosis and obliterating microangiopathy, characterized by indurative changes in the skin, damage to the musculoskeletal system, internal organs (lungs, heart, digestive tract, kidneys), generalized vasospastic Raynaud's syndrome.

Etiology systemic scleroderma has not been clarified. Viral and hereditary origins of the disease are assumed. Systemic scleroderma is preceded by infectious diseases or a moderate fever of unknown cause, chilliness, sweating, repeated sore throats, increased sensitivity of the hands to cold, paresthesia of the fingers (Raynaud's syndrome), pain in muscles and joints, dyspepsia, headaches.

Systemic scleroderma is diagnosed predominantly in women (3:1) aged 35 to 64 years. The disease rarely occurs in children, as well as in adults under 30 years of age. The incidence of systemic scleroderma is 6.3-12 cases per 1 million population.

Pathogenesis systemic scleroderma includes changes in connective tissue metabolism (increased collagen biosynthesis and neofibrillogenesis, tissue fibrosis), immune disorders (decrease in the level of T-suppressors with normal levels of B-lymphocytes in the blood, the appearance of antibodies to collagen, sometimes antinuclear antibodies) and damage to the microvasculature (cytotoxic lymphocytes damage the endothelium, which is accompanied by adhesion and aggregation of platelets, activation of coagulation, release of inflammatory mediators, increased permeability of the vascular wall with plasma impregnation and fibrin deposition, narrowing of the lumen). Cytokines and growth factors secreted by lymphocytes, monocytes and platelets play an important role in the development of fibrosis. They cause hyperproduction of collagen and macromolecules of the main substance of connective tissue with the subsequent development of areas of fibrosis.

Clinic . Systemic scleroderma includes cutaneous and extracutaneous syndromes. Skin syndrome: sclerodactyly; acrosclerosis; diffuse - generalized type; Tibierge-Weissenbach syndrome. Extracutaneous syndromes: muscular-articular, gastrointestinal, pulmonary, cardiovascular, renal, neurological.

Systemic or diffuse scleroderma (universal, generalized, progressive) begins more often in women in childhood or adolescence, affecting the skin of the hands, face, and then the limbs and torso. At diffuse scleroderma Skin fibrosis is localized proximal to the elbow or knee joints, including the neck and trunk. Patients may experience Raynaud's phenomenon during the first year of the disease; internal organs are more often affected: lungs, kidneys, heart. Also distinguished limited scleroderma, in which fibrosis of the skin of the hands, forearms and feet develops, but the face and neck can be affected. In patients in this group, Raynaud's phenomenon has been observed for years; they develop telangiectasia, calcifications in the skin, and later pulmonary hypertension develops.

Skin lesions is the leading sign of the disease. The appearance of acrosclerosis is possible, sometimes numerous numerous subcutaneous calcareous nodules are formed with further ulceration. Skin thickening develops due to abnormal production of type I collagen by skin fibroblasts, as well as excessive deposits of glycosaminoglycans and fibronectin in the extracellular matrix. Externally, the patient has affected and unaffected areas of skin. However, studies have shown the presence of procollagen-1 and adhesive molecules in all areas of the dermis, which indicates a generalized pathological process.

Dense swelling appears on the skin of the face, neck, and hands, then thickening and sclerosis of the skin develop. Subsequently, its atrophy occurs and the face takes on a mask-like appearance: the folds are smoothed out, there are no facial movements, the lips become thinner, radial deep folds form around them, similar to a semi-tightened pouch, the mouth does not close, the tongue does not protrude from the edges of the teeth, the eyelids often do not close; the nose becomes thinner, the skin on its wings becomes smooth, taut, and shiny. The voice weakens, it becomes as if from the depths. The ears also noticeably atrophy and become thinner. Hair gradually falls out, nails become thinner and then separate from the nail bed. There is severe dry skin, hyperkeratosis of the palms and soles. The secretion of sweat and sebaceous glands decreases and then stops. The process often involves the mucous membrane of the mouth, tongue, soft palate, larynx, esophagus, lungs and other internal organs, as well as muscles, joints, and bones. Subsequently, the lesion can spread to the entire skin: forearms, shoulders, torso, thighs, legs and feet. The skin becomes waxy-yellow in color, with areas of pronounced hyperpigmentation alternating with depigmented lesions; multiple telangiectasias are noted. Subcutaneous fat gradually disappears, the skin grows to the underlying fascia and becomes motionless over the bones, and does not fold. As a result, woodiness of the whole body occurs. With total damage to the skin of the trunk and limbs, cachexia and mummification (“living relics”) develop. Movements in the joints and even breathing are sharply limited, the patient experiences difficulty in eating.

Sometimes calcium salts are deposited (calcification) in the subcutaneous tissue in the form of nodules of a rocky consistency, which opens with the formation of fistulas and white crumbly discharge. Calcinosis is deposits of hydroxyapatites in the skin, which are localized mainly on the hands in the area of the proximal interphalangeal joints and nail phalanges, around the joints and over bone protrusions (especially on the extensor surface of the elbow and knee joints). Periarticular calcium deposition in the form of white foci translucent through the skin is called Tibierge-Weissenbach syndrome. Calcium deposits are not always determined visually; in this case, they are detected by radiography. Calcification persists for years and is difficult to treat.

There are multiple telangiectasias (dilated venules, capillaries, arterioles), which look like oval or irregularly shaped spots 2-7 mm in diameter and are located on the hands, face, lips and oral mucosa. Telangiectasias disappear spontaneously over time.

Condition manifested To alcinosis, syndrome R eino, uh zophagopathy, With clerodactyly and T eleangiectasia is called CREST-syndrome (according to the first letters of the symptoms). This syndrome is considered a favorable variant of the disease and belongs to limited scleroderma.

The earliest sign of systemic scleroderma is Raynaud's syndrome, which is characterized by the sudden appearance of paresthesia (feeling of numbness, crawling) in the area of the II-IV fingers, feet, and their sharp blanching. At the end of the attack, pain appears, a feeling of heat in the fingers, and the skin becomes hyperemic. Raynaud's syndrome in systemic scleroderma affects not only the fingers and toes, but also the lips, the tip of the tongue, and parts of the face. In patients with Raynaud's syndrome, it is possible to confirm the presence of systemic scleroderma at an early stage using the following signs (studies): the presence of antinuclear antibodies, anti-centromere antibodies or antibodies to topoisomerase 1 (anti-Scl-70 antibodies); changes in the capillary bed of the nail bed - a decrease in the number of capillaries or their dilatation; phenomena of tenosynovitis (thickening along the tendons and friction noise in the area of the tendon sheath); severe swelling of the fingers or toes; concomitant reflux esophagitis.

Osteoarticular syndrome may be one of the early signs of systemic scleroderma. There are three main types of articular syndrome: polyarthralgia; scleroderma polyarthritis with a predominance of exudative-proliferative or fibrous-indurative changes; periarthritis with the development of contractures due to the involvement of periarticular tissues in the pathological process. Bone lesions are characterized by acrosclerosis with osteolysis, usually of the nail phalanges, shortening and deformation of the fingers and toes. Bone damage is mainly due to bone resection. Arthralgia and morning stiffness often occur, and ankylosis is observed.

Muscle syndrome characterized by different types of muscle damage, which can be in the form of interstitial myositis or polymyositis; manifested by muscle pain, muscle weakness, and a feeling of stiffness in the muscles. The first type of lesion is characterized by moderate weakness of the proximal muscles due to benign myopathy of non-inflammatory origin. Histological examination reveals type 2 muscle fiber atrophy, which is associated with immobility and corticosteroid use. The concentration of muscle enzymes is within normal limits. The second type of lesion is characterized by a moderate increase in the concentration of muscle fibers and the presence of a symptom of “waxy” muscle weakness. Biopsy reveals interstitial fibrosis and muscle fiber atrophy. A moderate infiltration of inflammatory cells is detected. The third type of lesion is manifested by myopathy of inflammatory origin with an increase in the concentration of enzymes.

Gastrointestinal syndrome manifests itself as duodenitis, enteritis (with the development of malabsorption syndrome), colitis (with severe constipation, symptoms of intestinal obstruction). Damage to the esophagus (esophagitis) is considered characteristic, which is manifested by dysphagia, diffuse dilation of the esophagus, narrowing in the lower third, weakening of peristalsis and rigidity of the walls, reflux esophagitis, and sometimes the development of peptic ulcers and strictures.

Pulmonary syndrome manifested by the clinic of fibrosing alveolitis and diffuse pneumofibrosis with predominant localization in the basal parts of the lungs. Some patients develop pulmonary hypertension due to damage to the blood vessels of the lungs. Severe pneumosclerosis is sometimes combined with the development of bronchiectasis, emphysema, and possibly pneumonia.

Cardiovascular syndrome characterized by cardiosclerosis with an increase in heart size, arrhythmias, cardiac rhythm and conduction disturbances, and the development of circulatory failure. Large-focal cardiosclerosis can imitate “infarction-like changes” on the ECG. The development of interstitial myocarditis leads to the appearance of clinical symptoms that are actually similar to cardiosclerosis. Damage to the endocardium in the area of the valve apparatus leads to the formation of scleroderma heart disease, most often mitral valve insufficiency. Some patients develop mitral valve prolapse. Pericarditis may develop.

Renal syndrome manifested by the involvement of the kidneys in the pathological process. There are two forms - acute and chronic nephropathy. Acute nephropathy (true scleroderma kidney) is manifested by the following symptoms: oligoanuria, arterial hypertension, increasing proteinuria, microhematuria, cylindruria, retinopathy, encephalopathy. Acute nephropathy is based on generalized damage to renal arterioles and the development of cortical necrosis, which leads to acute renal failure. The most common kidney damage in systemic scleroderma is chronic nephropathy. The morphological substrate of this type of kidney pathology is considered to be damage to the vessels and glomeruli of the kidneys, as well as tubules and interstitium. Clinical symptoms correspond to those of chronic glomerulonephritis (proteinuria, cylindruria, microhematuria, decreased glomerular filtration, arterial hypertension, development of chronic renal failure).

Neurological syndrome characterized by damage to the peripheral nervous system in the form of polyneuropathy (pain in the arms and legs, impaired sensitivity in the form of hyperesthesia with the subsequent development of distal hypoesthesia, decreased tendon reflexes). Polyneuropathy acquires a long, persistent course. Persistent, recurrent trigeminitis (inflammation of the trigeminal nerve) is also characteristic. Damage to the central nervous system is rare; encephalitis, meningoencephalitis, ischemic strokes, and cerebral hemorrhages are described.

Endocrinological syndrome is marked by dysfunction of the thyroid gland (hypothyroidism, possible autoimmune thyroiditis, rarely hyperthyroidism), adrenal insufficiency, decreased function of the gonads. A combination of systemic scleroderma and diabetes mellitus is possible. Damage to the endocrine glands is primarily due to damage to their vascular system.

Systemic scleroderma is characterized by loss of body weight, up to cachexia, especially pronounced with a rapidly progressive course of the disease and with its severe exacerbation.

There are three variants of the course of systemic scleroderma: acute, subacute and chronic.

Acute course characterized by rapid (within a year) development of diffuse symptoms, steady progression of damage to internal organs, increasing fibrosis of organs and tissues, and development of a sclerotic kidney. The acute course is marked by pronounced changes in laboratory parameters, which reflect the activity of the inflammatory process.

For subacute course The clinical picture of the disease is characterized by damage to the skin, joints, muscles, and internal organs against the background of mildly expressed vasomotor trophic disorders; there is an increase in ESR, fibrinogen,  2 - and -globulins in the blood, the presence of rheumatoid factor, antinuclear factor.

Chronic course It is characterized by a slowly progressive process over several years and is characterized by pronounced vascular and trophic disorders, thickening of the skin and periarticular tissue with the formation of contractures, osteolysis, and slowly developing lesions of the esophagus, lungs, and heart. Typical skin changes can be focal in nature and remain the only manifestation of the disease for a long time.

initial stage scleroderma is manifested by Raynaud's syndrome, arthralgia, tachycardia, and frequent respiratory tract infections. Complex treatment at this stage leads to long-term remission and even recovery.

Generalized stage occurs with all the previously mentioned symptoms and is characterized by a detailed picture of the disease.

Terminal stage occurs with advanced changes and is accompanied by severe loss of body weight, insufficiency of the functions of one or more organs. Treatment at this stage has no effect.

According to the degree of activity of systemic scleroderma, the following are distinguished: minimum(I) degree - vasospastic and trophic disorders, ESR less than 20 mm/h; moderate(II) degree - arthralgia, arthritis, adhesive pleurisy, cardiosclerosis, ESR within 20-35 mm/h; high(III) degree - fever, polyarthritis, myocardiosclerosis, nephropathy, ESR more than 35 mm/h.

Laboratory and instrumental methods . General blood analysis: signs of hypochromic anemia, leukopenia, sometimes leukocytosis, increased ESR. Analysis of urine: increased excretion of hydroxyproline, proteinuria. Blood chemistry: hyperproteinemia, increased levels of  2 - and -globulins, fibrin, seromucoid, C-reactive protein, haptoglobin, hydroxyproline (collagen metabolism disorder).

Immunological blood test : antibodies to the endothelium, antinuclear antibodies to the SCL-70 antigen, decreased number of suppressor T-lymphocytes, hyper- and disimmunoglobulinemia; detection of rheumatoid factor (40-45%), antinuclear antibodies (30-90%). Musculocutaneous flap biopsy: fibrous transformation of tissues, vascular pathology. Pathomorphology of the skin: in the early stages, small infiltrates are detected around the vessels of the dermis and merocrine sweat glands, as well as infiltration of the subcutaneous tissue; in the later stages, the disappearance of the interpapillary wedges of the epidermis is noted; thickened homogeneous bundles of collagen fibers, brightly stained with eosin; fusion of bundles, obliteration and disappearance of the interfascicular space; thickening of the dermis, replacement of adipose tissue (upper layers or all) with collagen, hyalinosis; reduction in the number of vessels, thickening of the walls and narrowing of the lumen, hyalinosis; atrophy of skin appendages; sweat glands are located in the upper layers of the dermis; deposits of calcium salts in sclerotic subcutaneous tissue. Electrocardiogram: diffuse changes in the myocardium, sometimes bundle branch block and atrioventricular block. X-ray examination: areas of calcification in the subcutaneous tissue, mainly at the ends of the fingers, less often in the feet, in the area of the elbows, knees and other joints. Osteolysis in the nail phalanges of the fingers, toes, distal parts of the radius and ulna, and posterior parts of the ribs. Periarticular osteoporosis, narrowing of joint spaces, sometimes single erosions on the surface of the articular cartilage, bone ankylosis. Decreased tone and weakened peristalsis of the gastrointestinal tract, which leads to expansion of the esophagus and duodenum. Diffuse and cystic pneumosclerosis in the basal regions and an increase in the size of the heart.

Diagnostics . The American Institute of Rheumatology has developed diagnostic criteria for systemic scleroderma:

Main (big) criterion- scleroderma lesions of the skin of the body (proximal to the metacarpophalangeal or metatarsophalangeal joints - proximal scleroderma).

Small criteria- sclerodactyly, scars on the distal phalanges of the fingers, bilateral basal pulmonary fibrosis.

To establish a diagnosis of systemic scleroderma, the presence of a major and two minor criteria is required.

Diagnostic signs (main and additional) of systemic scleroderma [N.G. Guseva, 1993, 1997].

Main features

Scleroderma skin lesions, passing through the stages of “dense” edema, induration and atrophy, with a predominant localization on the face (mask-like) and in the area of the hands (sclerodactyly), a total lesion is possible. Usually the syndrome is combined with pigmentation.

Raynaud's syndrome.

Articular-muscular syndrome with the development of persistent contractures, which is based on rheumatoid-like arthritis, periarticular changes and fibrosing myositis.

Osteolysis of the nails, and sometimes the middle and main phalanges of the fingers, less often of the toes, which is manifested by shortening and deformation of the fingers.

Tibierge-Weissenbach syndrome is the deposition of calcium salts mainly in the area of the fingers and periarticularly - around the elbow, shoulder and hip joints, in the subcutaneous tissue, sometimes along the fascia and muscle tendons.

Damage to the digestive tract (scleroderma esophagitis with physphagia, dilation of the esophagus, gastritis, duodenitis, impaired intestinal motility up to intestinal obstruction, development of malabsorption syndrome).

Heart damage of the type of primary macrofocal cardiosclerosis.

Damage to the lungs such as basal pneumosclerosis, cystic lung (on the radiograph - “honeycomb”).

True scleroderma kidney is diagnosed clinically on the basis of a sudden increase in blood pressure and the development of acute renal failure.

The presence of specific antinuclear antibodies (anti-Scl-70 and anticentromere antibodies).

Capillaroscopic signs (according to wide-field capillaroscopy).

Additional (minor) signs

Peripheral: skin hyperpigmentation, telangiectasia, trophic disorders, Sjogren's syndrome, polyarthralgia, polymyalgia, polymyositis.

Visceral: polyserositis (usually adhesive), chronic nephropathy, polyneuritis, trigeminitis.

General: weight loss (more than 10 kg).

Laboratory: increased ESR (more than 20 mm/h), hyperproteinemia (more than 85 g/l), hypergammaglobulinemia (more than 23%), antibodies to DNA or antinuclear factor, rheumatoid factor.

For a reliable diagnosis of systemic scleroderma, the presence of any three main signs or one of the main ones is sufficient if it is scleroderma skin lesions, osteolysis of the nail phalanges or a characteristic lesion of the digestive tract, in combination with three or more auxiliary signs. With fewer symptoms, only a “probable” diagnosis is made.

Treatment. To treat patients with systemic scleroderma, antifibrotic agents, nonsteroidal anti-inflammatory drugs, and immunosuppressants are used; microcirculation-improving agents, local therapy, massage.

Antifibrotic agents . The main basic drug in the treatment of systemic scleroderma is D-penicillinamine(cuprenil), which suppresses excess collagen synthesis by fibroblasts; binds and removes copper from the body, which leads to activation of collagenase and causes collagen breakdown; disrupts collagen maturation and accelerates its breakdown; suppresses autoimmune inflammation. The effect of using the drug is manifested by a decrease in dense swelling and pigmentation of the skin, a decrease in arthralgia and myalgia, and a decrease in the manifestations of Raynaud's syndrome. Initially, the drug is prescribed at 150-300 mg per day for 2 weeks, then the dose is increased every 2 weeks by 300 mg to a maximum of 1800 mg. This dose is prescribed for 2 months, and then slowly reduced to a maintenance dose of 300-600 mg per day. The effect of the drug is observed no earlier than two months from the start of treatment. Side effects of cuprenil: dermatitis, hair loss, dyspepsia, leukopenia, thrombocytopenia, kidney damage. If side effects develop, it is necessary to reduce the dose of the drug or discontinue it. Cuprenil is contraindicated in cases of renal and hepatic pathology, leukopenia, thrombocytopenia.

Madecassol - a preparation from the extract of the plant Centella asiatica, contains asiatic and madecassolic acids. Madecassol inhibits collagen synthesis and stabilizes lysosomal membranes. Prescribed 10 mg orally 3 times a day for 3-6 months.

Diuciphone - an antilepromatous drug that also has moderate antifibrotic and immunomodulatory effects. Prescribed 0.1-0.2 g 3 times a day orally.

Lidaza - an enzymatic drug that affects the hyaluronic acid - hyaluronidase system, slows down fibrosis formation. the drug is used for chronic scleroderma and focal scleroderma. A contraindication to the use of enzymatic drugs is the high activity of the process and sharply increased vascular permeability. Lidaza is a drug containing hyaluronidase; causes the breakdown of hyaluronic acid into glucosamine and glucuronic acid and reduces its viscosity. Lidase is administered subcutaneously or intramuscularly at 64 UE (in 1 ml of 0.5% novocaine solution), 12-14 injections per course of treatment. The drug is contraindicated for peptic ulcers, a tendency to hemorrhage, and renal failure.

Nonsteroidal anti-inflammatory drugs . Prescribed for severe articular syndrome, as well as for contraindications to glucocorticoids. Nonsteroidal anti-inflammatory drugs are used for systemic scleroderma in combination with aminoquinolone compounds or when the dose of glucocorticoids is reduced. Non-steroidal anti-inflammatory drugs inhibit the synthesis of pro-inflammatory prostaglandins, reduce the energy supply to the site of inflammation, reduce platelet aggregation, and have a mild immunosuppressive effect. The most commonly used drugs are: voltaren (diclofenac sodium, ortofen) 0.25 g 3-4 times a day; Voltaren-retard 0.075 g 1-2 times a day; Brufen (ibuprofen) 0.2-0.4 g 3 times a day.

Immunosuppressants (glucocorticoids, cytostatics, aminoquinolines) suppress the autoimmune inflammatory process in connective tissue and inhibit excessive fibrosis formation.

Glucocorticoids prescribed for subacute and acute course of systemic scleroderma. The chronic course of systemic scleroderma and stage I activity do not require glucocorticoids. Prednisolone is predominantly prescribed. The initial dose of the drug for grade III activity is on average 30 mg for 1.5-2 months until a clinical effect is achieved, followed by a reduction in the maintenance dose of 20-10 mg. In case of II degree of activity, the initial daily dose of prednisolone is 20 mg for 2 months, followed by a dose reduction. Glucocorticoids have a positive effect on fever, polyarthritis, skin syndrome, visceral manifestations, and myositis. To prevent osteoporosis, it is recommended to use anabolic drugs (retabolil, methandrostenolone) and calcium gluconate against the background of glucocorticoid therapy.

Cytostatics prescribed for acute and subacute course of the disease with significant immune disorders and high activity of the process, for polymyositis, glomerulonephritis. Imuran (azathioprine) or cyclophosphamide 100-150 mg per day, methotrexate 7.5-10 mg per week are used. Treatment with cytostatics is combined with the use of glucocorticoids. Treatment with cytostatics lasts 2-3 months.

Aminoquinoline drugs have a weak immunosuppressant and anti-inflammatory effect, stabilize lysosomal membranes and inhibit the release of proteolytic enzymes from lysosomes. Aminoquinoline drugs are indicated for any course of systemic scleroderma in combination with basic drugs. Prescribe delagil 0.25 g per day or plaquenil 0.2-0.4 g per day continuously for a year, after which they switch to taking the drugs with a break in the summer. Side effects of aminoquinoline drugs: headaches, dizziness, dyspepsia, damage to the retina and cornea.

Products that improve microcirculation prescribed at the very beginning of the disease (calcium antagonists, antiplatelet agents, acetylsalicylic acid, rheopolyglucin, captopril, prostaglandins, andecalin, dilminal, solcoseryl, angioprotectors, nicotinic acid).

Local therapy . The goal of local therapy is to reduce the severity and prevent the progression of fibrotic changes in the skin, musculoskeletal system and vascular disorders. Applications of dimethyl sulfoxide (DMSO) are used, which has an analgesic and anti-inflammatory effect, penetrates well through the skin and carries various drugs through it, and is also able to inhibit the proliferation of fibroblasts and inhibit the development of connective tissue. It is recommended to use applications of a 50-70% DMSO solution on the affected areas for 30-40 minutes, the course of treatment is from 10 to 30 procedures. Local physiotherapeutic treatment is carried out in the absence or minimal activity of the process: electrophoresis with lidase or ronidase, phonophoresis of madecassol, electrophoresis with nicotinic acid, dimexide, laser therapy, EHF therapy; acupuncture; phonopuncture; applications of paraffin, ozokerite.

The complex treatment of patients with systemic scleroderma includes the use of physical therapy and therapeutic massage, which are prescribed during the period of minimal activity of the process under the control of the general condition and cardiovascular system.

Forecast . The disease progresses steadily, leading to sclerosis of the skin and internal organs. Ten-year survival rate exceeds 50%. The main cause of death is kidney failure; less often - damage to the heart and lungs. Spontaneous remissions are sometimes observed. The prognosis for CREST syndrome is more favorable.