Systemic scleroderma is a disease affecting various organs, which is based on changes in connective tissue with a predominance of fibrosis and damage to blood vessels such as obliterating endarteritis.

The incidence of systemic scleroderma is approximately 12 cases per 1 million population. Women get sick seven times more often than men. The disease is most common in the age group of 30-50 years.

Causes of systemic scleroderma

The disease is often preceded by factors such as infections, hypothermia, stress, tooth extraction, tonsillectomy, hormonal changes in a woman’s body (pregnancy, abortion, menopause), contact with toxic chemicals, and vaccination.

The exact cause of the disease has not been established. Currently, one of the main ones is the theory of genetic predisposition. Family cases of the disease have been identified. In addition, relatives of the patient have a higher incidence of other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) compared to the general population. The theory of viral effects is supported by the identification of changes in immunity associated with the activity of viruses (especially retroviruses and herpes viruses). But the specific strain of the virus that causes systemic scleroderma has not yet been found.

Symptoms of systemic scleroderma

The main symptom of the disease is increased fibroblast function. Fibroblasts are the main cells of connective tissue that synthesize collagen and elastin, due to which the connective tissue is very strong and at the same time elastic. With increased function, fibroblasts begin to produce collagen in large quantities, and fibroformation increases. Finally, foci of sclerosis form in various organs and tissues. In addition, fibrotic changes also affect the vascular wall, which thickens. Obstructions to blood flow are created, and as a result, blood clots form. Such changes in blood vessels lead to disruption of normal blood supply to tissues and the development of ischemic processes.

Connective tissue is widely represented in the body, so systemic scleroderma affects almost all organs and tissues. Therefore, the symptoms of the disease are very varied.
In acute, rapidly progressive variants of the disease, sclerotic changes in the skin and fibrosis of internal organs develop within one to two years from the onset of the disease. With this option, a constantly high body temperature and loss of body weight appear very quickly. The mortality rate of patients with the acute rapidly progressing variant is high.

The chronic course of systemic scleroderma is characterized by initial signs of the disease in the form of Raynaud's syndrome, skin or joint damage. These manifestations can be isolated over many years. Subsequently, symptoms of damage to internal organs appear in the clinical picture.

Skin lesions is the most characteristic sign of systemic scleroderma and occurs in most patients. The skin of the face and hands is initially affected. In typical cases, scleroderma changes go through the stages of skin thickening due to edema, then induration (skin thickening due to fibrosis) and partial tissue atrophy occur. At the same time, the skin on the face becomes dense and immobile, due to its tension, purse-shaped wrinkles are formed around the mouth, the face takes on a resemblance to a mask.

Sclerodactyly is also a characteristic feature of the disease. In this case, thickening of the skin of the hands is formed with the development of deformation of the fingers (“sausage-shaped” fingers).

Along with skin thickening, trophic disorders are also detected in the form of ulcerations, suppurations, deformation of the nail plates and the appearance of areas of baldness.

Vascular disorders are the most common initial sign of the disease. The most common are vasospastic crises (Raynaud's syndrome). In this case, under the influence of cold, excitement, or in the absence of external causes, a narrowing of small vessels occurs, usually in the hands. This is accompanied by numbness, paleness or even blue discoloration of the fingertips. As the disease progresses due to tissue ischemia, long-term non-healing ulcers (“rat bites”) form on the fingertips. In severe cases, necrosis of the last phalanges of the fingers develops.

Joint damage manifested by pain in them, morning stiffness, a tendency to flexion deformities due to compaction and atrophy of the tissues around the joint. By palpating the affected joints above them, it is possible to detect tendon friction noise. Systemic scleroderma is characterized by muscle tightening and atrophy. Bone disease is manifested by osteolysis (destruction) of the bones of the fingers with shortening of the phalanx.

Osteolysis of the distal phalanges of the fingers

The most vulnerable organs of the digestive system in systemic sclerodemia are esophagus and intestines. In the esophagus, due to the compaction of its wall, a sclerotic deformation is formed with disruption of the normal passage of food. Patients complain of a feeling of a lump behind the sternum, nausea, heartburn, and vomiting. If the deformity is significant, surgery may be required to widen the lumen of the esophagus. The intestines are affected less frequently, but the symptoms of the disease significantly reduce the quality of life of patients. The clinical picture is dominated by pain, diarrhea, and weight loss. Constipation is characteristic of damage to the colon.

Lung damage currently comes to the forefront among the causes of death in patients with systemic scleroderma. Two types of lung damage are characteristic: interstitial disease - fibrosing alveolitis and diffuse pneumosclerosis, as well as pulmonary hypertension. External manifestations of interstitial damage are nonspecific and include shortness of breath, dry cough, general weakness, and fatigue. Pulmonary hypertension is manifested by progressive shortness of breath, the formation of blood stagnation in the lungs and heart failure. Often thrombosis of the pulmonary vessels and acute right ventricular failure cause death in patients.

Scleroderma is characterized by damage to all layers of the heart. With myocardial fibrosis, the heart increases in size, stagnation of blood forms in the cavities with the development of heart failure. Very often, due to impaired innervation of the enlarged heart, patients experience arrhythmias. Arrhythmias are the main cause of sudden death in patients with scleroderma. With sclerosis of the heart valves, stenotic type defects are formed. And with pericardial fibrosis, adhesive pericarditis develops.

At the core kidney damage lies sclerosis of small blood vessels with the development of ischemia and death of kidney cells. With the progressive version of scleroderma, a renal crisis often develops, which is characterized by a sudden onset, rapid development of renal failure and malignant hypertension. The chronic variant of scleroderma is characterized by moderately pronounced changes in the kidneys, which remain asymptomatic for a long time.

Diagnosis of systemic scleroderma

The diagnosis of systemic scleroderma is reliable if one “major” or two “minor” criteria are met (American College of Rheumatology).

"Big" criterion:
- proximal scleroderma: symmetrical thickening of the skin in the area of ​​the fingers, extending proximally from the metacarpophalangeal and metatarsophalangeal joints. Skin changes can be observed on the face, neck, chest, and abdomen.
"Small" criteria:
- Sclerodactyly: the above skin changes limited to the fingers.
- Digital scars - areas of skin retraction on the distal phalanges of the fingers or loss of substance of the finger pads.
- bilateral basal pneumofibrosis; reticular or linear nodular shadows, most pronounced in the lower parts of the lungs during a standard x-ray examination; There may be “honeycomb lung” type manifestations.

In Russia, the following signs of systemic scleroderma have been proposed.

Treatment of systemic scleroderma

Patients with scleroderma are advised to follow a certain regime: avoid psycho-emotional shocks, prolonged exposure to cold and vibration. It is necessary to wear warm clothing to reduce the frequency and severity of vasospasm attacks. It is recommended to quit smoking, avoid caffeine-containing drinks, as well as drugs that cause vasoconstriction: sympathomimetics (ephedrine), beta-blockers (metoprolol).

The main areas of treatment for scleroderma are:

Vascular therapy for the treatment of Raynaud's syndrome with signs of tissue ischemia, pulmonary hypertension and nephrogenic hypertension. Angiotensin-converting enzyme inhibitors (enalapril), calcium channel blockers (verapamil) and prostaglandin E are used. In addition, antiplatelet agents (chirantil) are used to prevent the formation of blood clots.

It is advisable to prescribe anti-inflammatory drugs in the early stages of the disease. Non-steroidal anti-inflammatory drugs (ibuprofen), hormonal drugs (prednisolone) and cytostatics (cyclophosphamide) are recommended according to a specific regimen.

Penicillamine is used to suppress excess fibroformation.

Surgical treatment of systemic scleroderma consists of eliminating skin defects through plastic surgery, as well as eliminating narrowing of the esophagus and amputating dead areas of the fingers.

Complications of systemic scleroderma and prognosis

With a rapidly progressing form of scleroderma, the prognosis is unfavorable; the disease ends in death 1-2 years after manifestation, even with timely initiation of treatment. In the chronic form, with timely and comprehensive treatment, the five-year survival rate is up to 70%.

General practitioner Sirotkina E.V.

Skin lesions are a common clinical sign of systemic vasculitis affecting small and medium-sized vessels. The nature of dermatological manifestations largely depends on the size of the vessels involved in the pathological process and the immunological specificity of vasculitis. Histological examination of the skin is important to confirm the diagnosis of vyskulitis, helps in early differentiated diagnosis and timely prescription of adequate therapy. An important task for the doctor is to suspect when severe systemic vasculitis with multiple organ damage is hidden with dermatological manifestations. This article presents clinical and histological data on skin lesions in various systemic vasculitis, as well as existing algorithms for differential diagnosis.

Systemic vasculitis is a heterogeneous group of diseases, the main morphological feature of which is inflammation of the vascular wall, and the range of clinical manifestations depends on the type, size and location of the affected vessels and the severity of concomitant inflammatory disorders. The incidence of vasculitis with skin lesions ranges from 15.4 to 29.7 cases per million population per year. Women and adults are more often affected than men, with the exception of hemorrhagic vasculitis, which occurs almost exclusively (90%) in children. Skin manifestations may be the first clinical symptoms of vasculitis, but as a rule they occur against the background of other systemic signs. Clinically, vasculitis with skin involvement can present with a whole arsenal of nonspecific or low-specific dermatological symptoms that include subcutaneous nodules, palpable purpura, vesicles, papules, livedo, ulcers, digital infarcts and gangrene. Skin lesions in patients with systemic vasculitis do not affect the prognosis of the disease, but may have a recurrent course and be difficult to treat. Given the wide range of manifestations of skin lesions in systemic vasculitis and the significant number of diseases that can mimic vasculitis, it is not surprising that in clinical practice there are often difficulties in diagnosing and correctly classifying patients with cutaneous vasculitis. Today, the most acceptable is the pathohistological classification of systemic vasculitis of the International Consensus Conference in Chapel Hill, 2012 (Table 1).

Table 1. Updated classification and nomenclature of systemic vasculitides (Chapel Hill, 2012)

Large vascular vasculitis		Giant cell arteritis (GCA)
		Takayasu arteritis
Medium vascular vasculitis		Polyarteritis nodosa (PA)
		Kawasaki disease
Small vessel vasculitis	ANCA-associated vasculitis	Microscopic polyangiitis (MPA)
		Granulomatosis with polyangiitis (Wegener's granulomatosis) (GPA)
		Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (EGPA)
	Immune complex vasculitis	Cryoglobulinemic vasculitis
		IgA-associated vasculitis (Henoch-Schönlein disease)
		Hypocomplementary urticarial vasculitis
		Vasculitis associated with autoantibodies to the basement membranes of the glomerular capillaries of the kidneys
Vasculitis with variable vascular lesions		Behcet's disease
		Cogan syndrome
Vasculitis affecting one organ		Cutaneous leukocytoclastic vasculitis
		Cutaneous arteritis
		Primary vasculitis of the central nervous system
		Isolated aortitis
Vasculitis associated with systemic diseases		Vasculitis associated with systemic lupus erythematosus (SLE)
		Vasculitis associated with rheumatoid arthritis (RA)
		Vasculitis associated with sarcoidosis
Vasculitis of known (suspected) etiology		HCV-associated cryoglobulinemic vasculitis
		Drug-induced immune complex vasculitis
		Drug-induced ANCA vasculitis
		Paraneoplastic vasculitis

Another commonly used classification of vasculitis is the American College of Rheumatology (ACR) classification, which is based primarily on clinical data. However, both classifications were developed to compare groups of patients with vasculitis, and not as diagnostic criteria for an individual patient.

Only some vasculitis have pathognomonic clinical, instrumental (PET angiography) and laboratory manifestations, which once again confirms the need for skin biopsy as the most accurate method of diagnosis (Fig. 1). On the other hand, histological confirmation of vasculitis cannot stand aside from medical history, clinical and laboratory examinations and/or angiographic features.

Figure 1. Histological classification (selection of the optimal biopsy method) of vasculitis with skin lesions (according to Carlson J.A., 2010)

Henoch-Schönlein disease and cutaneous leukocytoclastic vasculitis affect the superficial vessels of the skin, while polyarteritis nodosa and giant cell arteritis affect the deep muscular vessels that are found in the subcutaneous fat. Most other forms of vasculitis, such as cryoglobulinemic and ANCA-associated vasculitis, can affect both small and large vessels. The diagnostic value of a skin biopsy depends largely on the depth of the biopsy. For an accurate diagnosis of all vasculitis, with the exception of leukocytoclastic and Henoch-Schönlein disease, it is necessary to perform an incisional (cutting of tissue) or excisional (cutting out a piece of tissue) biopsy of subcutaneous fat.

A characteristic sign of skin lesions in patients with vasculitis of small-caliber vessels is purpura, which is palpable. This element of the skin rash is the result of extravasation of red blood cells through the vascular wall into the dermis. The predominant localization of purpura is symmetrical areas of the lower extremities and back (photo 1). With leukocytoclastic vasculitis, aseptic pustular elements may form at the apex of the purpura (photo 2), due to a large number of destroyed leukocytes. Purpura can be asymptomatic, sometimes causes itching or burning, and leaves behind hyperpigmentation.

Photo 1. Purpura of varying duration on the legs with hemorrhagic vasculitis

Photo 2. Purpura with pustular elements on the lower leg with leukocytoclastic vasculitis

Data on the association of certain types of skin rashes with different types of vasculitis are shown in Table 2.

Table 2. Elements of skin rash in patients with systemic vasculitis (according toXu L.Y.et al., 2009)

Type of vasculitis	Purpura that is palpable	Papules	Vesicles	Subcutaneous nodules	Livedo	Ulcers	Digital necrosis
Henoch-Schönlein disease	++++
Cryoglobulinemic vasculitis	++++
Hypocomplementary urticarial vasculitis
Cutaneous leukocytoclastic vasculitis	++++
Polyarteritis nodosa				++++	++++
Microscopic polyangiitis	++++
Granulomatosis with polyangiitis	++++

In 2009, Japanese dermatologist T. Kawakami created a diagnostic algorithm for cutaneous vasculitis, which is based on immunological (ANCA, cryoglobulin, IgA) and histological data (Fig. 2).

Figure 2. Diagnostic algorithm for primary cutaneous vasculitis (according to T. Kawakami, 2010)

The disadvantages of this algorithm are that the clinical picture of the disease and known immunological features are not taken into account (24% of patients with GPA are positive for MPO-ANCA, 26% of patients with MPA and less than 5% of patients with EGPA are positive for PR-3-ANCA), which once again proves the importance of an integrated approach to the diagnosis of systemic vasculitis.

Polyarteritis nodosa

Polyarteritis nodosa(UP) is a systemic necrotizing vasculitis, which is characterized by damage to medium and small arteries with the formation of microaneurysms, which leads to the development of tissue ischemia and infarction.

According to the literature, skin manifestations are observed in 26-60% of patients with polyarteritis nodosa. Skin lesions are usually accompanied by other systemic manifestations of UP (fever, weight loss, myalgia, arthralgia, peripheral neuropathy). According to research by Agard C. et al, skin lesions (purpura, subcutaneous nodes) were the first symptoms in 11% of patients with polyarteritis nodosa. Systemic manifestations may not appear until 1-20 years after the onset of the skin rash. The most common dermatologic manifestations of polyarthritis nodosa are infarcts, ulcers, livedo reticularis, subcutaneous nodules, and ischemic changes in the distal phalanges of the fingers (Figure 3). The most common location of skin rash is the lower extremities (95%). Subcutaneous nodes from bright red to cyanotic color have dimensions of 0.5-2 cm, usually bilateral, localized on the legs and thighs, less often - the arms, torso, head, neck, buttocks. Due to ischemia of the nodes, ulcers appear (photo 4). Livedo reticularis can occur independently or simultaneously with subcutaneous nodules. The most common localization of livedo is the lower and upper extremities, less often - the torso. Livedo is a macular ring-shaped rash of cyanotic color that forms a mesh. The pathognomonic symptom of UP is the appearance of the so-called “stellate” or livedo tree, which differs from livedo reticularis in the shape of the rash (livedo tree consists of torn or irregular rings) (photo 5). Despite the clinical differences, in the literature the term “livedo reticularis” is very often used to refer to any livedo. Some patients with polyarteritis nodosa develop atrophic, star-shaped scars (white skin atrophy).

Photo 3. Gangrene of the distal phalanges of the fingers in a patient with polyarteritis nodosa

Photo 4. Leg ulcers in a patient with polyarteritis nodosa

Photo 5. Livedo tree in a patient with polyarteritis nodosa

Other manifestations of polyarthritis nodosa may include urticaria, transient erythema, superficial phlebitis, Raynaud's phenomenon, and subungual hemorrhages. Pustular changes are characteristic of UP and usually arise as a result of secondary infection of necrotic changes.

According to one retrospective study, skin lesions were observed in half (52%) of patients with polyarteritis nodosa (n=112). Typical manifestations were subcutaneous nodules and ulcerative-necrotic changes (in 20.7% of patients), livedo (in 15.5% of patients) and polymorphic rash (13.8%). Other elements of skin lesions were less common (Figure 3).

Figure 3. Structure of skin manifestations in patients with polyarteritis nodosa at the onset of the disease

The classic histological sign of polyarteritis nodosa is the presence of necrotic inflammation of medium-diameter vessels (Figure 6). There are four histoligic stages in the development of polyarteritis nodosa: degenerative, stage of acute inflammation, development of granulation tissue and terminal. The degenerative stage includes coagulative necrosis of the medial layer of vessels, fibrinous exudates around the outer elastic membrane, neutrophil infiltration and partial destruction of the outer and inner elastic membrane. The stage of acute inflammation is characterized by neutrophilic, lymphocytic and eosinophilic infiltration, complete destruction of the internal elastic membrane, fibrinous exudates of the entire vascular wall with complete destruction of the tunica media, proliferation of fibroblasts, edematous changes in the surrounding connective tissue and total obliteration of the lumen of blood vessels with the formation of a fibrin thrombus. During the development of granulation tissue, lymphocytes replace neutrophils, separating granulation tissue, which covers the middle and outer lining of the vessel and can penetrate through defects in the internal elastic membrane into the lumen of the vessels and contribute to intimal thickening. The terminal stage includes the formation of scar tissue in the vascular wall and perivascular proliferation of fibroblasts.

Photo 6. Polyarteritis nodosa. Necrotizing vasculitis of medium-sized vessels (according to Carlson J.A., 2010)

In ulcerative lesions, histological examination reveals vyskulitis of medium-diameter vessels of subcutaneous fat with neutrophilic infiltration, leukocytoclasia, endothelial edema and fibrosis with necrosis of the dermis and ulcerative defect of the epidermis. Subcutaneous nodes are histologically represented by neutrophilic vasculitis of muscular type vessels with predominant localization in the areas of bifurcations.

Microscopic polyangiitis

Microscopic polyangiitis(MPA) - systemic vasculitis with damage to small vessels (arterioles, capillaries and venules) without the formation of extravascular granulomas. Microscopic polyangiitis is characterized by the development of segmental necrotic glomerulonephritis, hemoptysis and association with ANCA (26% of patients are positive for antibodies to PR-3 and 58% of patients are positive for antibodies to MPO). In most patients with microscopic polyangiitis, the development of pulmonary and nephrological symptoms is preceded by arthralgia, myalgia and constitutional symptoms (fever, weight loss).

Dermatological manifestations are detected in 15% of patients at the onset of MPA and up to 65% of patients at the height of the disease. The most characteristic dermatological sign of microscopic polyangiitis is purpura, which is palpable and found in approximately 50% of patients, and is localized on the lower extremities. Other dermatologic manifestations include subungual hemorrhages, subcutaneous nodules, palmar erythema, livedo, hemorrhagic bullae, vesicles, infarctions, erythema annulare, ulcers, and telangiectasias. According to some data, among the skin manifestations of microscopic polyangiitis (n=14), palpable purpura, ulcerative necrotic changes, and livedo are more common.

The classic histological signs of MPA according to skin biopsy are neutrophilic vasculitis of small vessels of the dermis and subcutaneous fat. Involvement of medium-diameter vessels in the pathological process is rare. Other histologic features include lymphocytic perivascular infiltration of the upper dermis, mixed lymphocytic and neutrophilic perivascular infiltration of the middle and deep dermis, and mixed lymphocytic and histiocytic infiltration of the middle dermis. Livedo tree is histologically represented by vasculitis of the vessels of the deep layers of the dermis and subcutaneous fat. Involvement of small vessels is a diagnostic criterion for MPA, which includes the diagnosis of polyarteritis nodosa. The histological differentiated feature between GPA and MPA is the absence of granuloma formation in MPA.

Granulomatosis with polyangiitis (Wegener's granulomatosis)

Granulomatosis with polyangiitis(GPA) is a systemic vasculitis, which, according to the classification of the International Consensus Conference in Chapel Hill, includes the following triad: granulomatous inflammation of the respiratory tract, necrotic vasculitis of medium and small diameter vessels, necrotic glomerulonephritis. However, only 16% of patients with GPA meet all three classification criteria. Characteristic laboratory manifestations of GPA are positivity for antibodies to PR-3 (66%) and antibodies to MPO (24%). The clinical course of GPA is often accompanied by constitutional manifestations (fever, weight loss), arthralgia, myalgia and damage to the upper respiratory tract (rhinitis, sinusitis, ulcers of the nasal and oral mucosa, perforation of the nasal septum, saddle-shaped deformation of the nose, granulomatous inflammation of the trachea with the formation of subpharyngeal stenosis ).

Skin lesions in patients with GPA occur, according to various studies, with a frequency of 14 to 77% and in 10% of patients they are the first symptoms of the disease. The most common element of a skin rash in GPA is purpura, which is palpable, localized on the lower extremities.

Papulo-necrotic changes occur less frequently in patients with GPA, but are a more specific symptom compared to palpable purpura. Cutaneous extravascular necrotic granulomas or papulo-necrotic changes may appear in areas typical of rheumatoid nodes (Figure 7). Considering that one third of patients are positive for GPA according to the rheumatoid factor and the presence of articular syndrome at the onset, such patients are often diagnosed with rheumatoid arthritis. In such cases, the determination of antibodies to cyclic citrullinated protein, which are not detected in patients with GPA, is important in carrying out a differentiated diagnosis.

Photo 7. Papulo-necrotic rash on the elbow in a patient with GPA

Other manifestations of skin lesions in patients with GPA include subcutaneous nodules, vesicles, digital infarcts, subungual hemorrhages, ulcers that resemble pyoderma gangrenosum, and polymorphic rash. Unlike polyarteritis nodosa, GPA is not characterized by the presence of livedo. In patients with GPA who were under observation (n=25), skin lesions occurred in 52% of cases, including necrotic papules - in 28%, digital infarctions - in 16%, polymorphic rash - in 12%.

There are four histological changes in skin biopsies in patients with GPA:

1. Necrotic neutrophilic vasculitis of small and medium-sized dermal vessels.
2. Palisade granuloma with a central core of basophilic collagen surrounded by histiocytes and neutrophils (the so-called “blue” granuloma).
3. Granulomatous vasculitis with perivascular lymphohistiocytic infiltrates and the presence of infiltration of the walls of muscle-type vessels of subcutaneous fatty tissue with giant cells.
4. Perivascular infiltration with atypical lymphocytes.

Biopsy of skin lesions in patients with GPA often demonstrates granulomatous changes and rarely reveals evidence of vasculitis.

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)

Eosinophilic granulomatosis with polyangiitis(EGPA) is a systemic vasculitis, which is characterized by the presence of bronchial asthma (usually with a late onset), allergic symptoms (allergic rhinitis, nasal polyps), peripheral and tissue eosinophilia and necrotic vasculitis of small and medium-sized vessels. Antibodies to MPO are found in 40% of patients with EGPA, and antibodies to PR-3 are found in 5% of patients. Skin lesions that are accompanied by peripheral neuropathy are a characteristic sign of Churg-Strauss syndrome. Other clinical signs include pulmonary infiltrates, abdominal pain, intestinal obstruction, arthralgias, myalgias, and constitutional symptoms. Skin lesions are observed in 40-75% of patients with EGPA and in 6% of patients they are the first symptoms of the disease. As with other ANCA-associated vasculitides, the characteristic skin lesion for EGPA is palpable purpura, with a typical localization on the lower extremities, which is detected in half of patients with cutaneous manifestations. Subcutaneous nodules and papulo-necrotic changes in the lower extremities, extensor ulnar surface, fingers and scalp are detected in a third of patients. Other dermatologic manifestations of EGPA include livedo reticularis, ulcers, vesicles, erythema multiforme, digital arteritis, panniculitis, and facial edema. Among patients with EGPA, skin lesions were found in 36% of cases, mainly ulcerative-necrotic changes, digital arteritis, palpable purpura, and panniculitis. The relatively low frequency of dermatological manifestations may be due to the fact that most patients with this vasculitis came to the attention of a rheumatologist, already receiving glucocorticoid treatment prescribed by a pulmonologist.

Skin biopsy shows three main histological features of EGPA:

1. Eosinophilic and neutrophilic vasculitis of small and medium-sized vessels of the superficial and middle layers of the dermis.
2. Interstitial infiltration of the dermis with eosinophils.
3. Formation of a “red” granuloma (photo 8). The “red” granuloma consists of a central core, represented by eosinophil breakdown products and collagen fibers, and histiocytes located along the periphery.

Photo 8. Eosinophilic granulomatosis with polyangiitis. Vasculitis of medium-diameter vessels with eosinophilic infiltrates (according to Carlson J.A., 2010)

Skin lesions in patients with systemic vasculitis are common clinical signs of this disease. The range of skin lesions is quite wide, while some variants of dermatological changes are specific to certain forms of systemic vasculitis (for example, for polyarthritis nodosa - livedo tree, gangrene of the distal parts of the fingers, for GPA and EGPA - papulo-necrotic changes). For early diagnosis and prescription of adequate treatment for systemic vasculitis with dermatological manifestations, in addition to clinical symptoms and immunological data, it is important to conduct a histological examination of the skin and subcutaneous tissue.

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:

1. 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.
2. 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.
3. 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

1. 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 quickly ended in death. With the use of modern adequate therapy, the prognosis has improved somewhat.
2. 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.
3. 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

1. Initial - the presence of 1 to 3 localizations of the disease.
2. The stage of generalization, reflecting the systemic nature of the lesions with the polysyndromic nature of the manifestations of the process.
3. 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:

1. Damage to the skin in the form of dense swelling.
2. Vascular disorders and Raynaud's syndrome.
3. Damage to the musculoskeletal system.
4. 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:

1. 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).
2. 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 scleroderma, 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:

1. Sclerodermic nature of skin lesions.
2. Raynaud's syndrome and digital ulcers and/or scars.
3. Musculo-articular lesions with the development of contractures.
4. Calcification of the skin.
5. Osteolysis.
6. Fibrosis of the basal regions of the lungs.
7. Lesions of the gastrointestinal tract of a sclerodermic nature.
8. Development of large-focal cardiosclerosis with conduction and heart rhythm disturbances.
9. Scleroderma acute nephropathy.
10. Typical results of video capillaroscopy of the nail bed.
11. 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.

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. Antiplatelet agents (Curantil, Trental) and anticoagulants (small doses of acetylsalicylic acid, Fraxiparine).
7. 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.

ULCERS OF THE STOMACH AND DUODENUM.

Peptic ulcer --- chronic recurrent disease, prone to progression, involving in the pathological process along with stomach (AND)and duodenum (duodenum) other organs of the digestive system, leading to the development of complications that threaten the patient’s life.
This disease mainly affects the working age population.

Etiology.

• Hereditary predisposition(if there is more congenital HCI or IgA, the protective reaction is less).
• Psycho-social factor
• Nutritional factor. Systematic eating disorders. Very hot food is equivalent to 96% alcohol in its effect on the gastric mucosa. The volume of food taken also matters. You need to eat often, in small portions.
• Bad habits. Smoking weak risk factor, but annoying.
• There is a controversial version of the influence among scientists Alcohol on the gastric mucosa.
  It is believed that constant use Alcohol in very small quantities, no more than 20-30g, of high quality (mulberry vodka, whiskey, gin) contribute to scarring of ulcers, if there is no concomitant gastritis and duodenitis; and wine, cognac, on the contrary, have a negative effect on peptic ulcers. But we must remember that even the highest quality alcohol in large quantities is detrimental to the gastric mucosa.
• Coffee and tea has an irritating effect on the stomach and increases acidity.
• Vascular factor. In the elderly, vascular atherosclerosis leads to ischemia, the protective barrier is disrupted, and an ulcer forms. It is believed that an ulcer is a stomach infarction.
• Infectious factor, Helicobacter Pilory.

Pathogenesis.

There are 3 major pathogenetic mechanisms:

• Nervous mechanism
• Hormonal or humoral
• Local, most important

1.Nervous mechanism.
Small constant stresses are much more dangerous than rare violent ones. The cerebral cortex is exposed, foci of unextinguished, stagnant excitation develop, the subcortex is activated, the hypothalamus, pituitary gland, adrenal glands are activated, the vagus, and gastroduodenal zone are activated.
That is, the nervous mechanism of regulation of the gastroduodenal zone is disrupted.
Motor skills are lost, there may be a spasm, hypertonicity, etc.

2. Hormonal mechanism.
Pituitary gland - Hypothalamus - Adrenal gland.
Under the influence of corticosteroids, the barrier and blood supply to the mucosa are disrupted.

3. Local factor.
The most important factor. Without it, the above factors will not lead to an ulcer. The local factor is the interaction of aggressive factors and protective factors.
A healthy person has a balance between these factors.

Factors of aggression:

• HCI,
• pepsin,
• bile,
• duodeno-gastric reflux,
• motor impairment
• spasm,
• hypertonicity.

Protective factors:

• a layer of mucus covering the mucous membrane, if of normal consistency, viscosity composition;
• mucous membrane, normal trophism;
• level of regeneration (if regeneration is normal, then this is a protective factor);
• normal blood supply;
• bicarbonates.

In young people, aggression factors and their increase play an important role. And in the elderly, a decrease in protective factors plays an important role.
In the pathogenesis of duodenal ulcers, a special role is played by hypermotility and hypersecretion under the influence of activation of n.vagus (factors of aggression). In the clinic there are clear, rhythmic pains, heartburn, increased acidity. In the pathogenesis of peptic ulcer disease, the state of the mucous membrane (barrier) plays an important role, the state of the protective factors, hypersecretion does not matter. Since a stomach ulcer occurs against the background of gastritis, malignancy occurs frequently; with duodenal ulcers, this occurs rarely.

In women of childbearing age, complications occur 10-15 times less than in men. In women, ulcers also recur less frequently, heal more smoothly, and the scars are more tender than in men. With the onset of pregnancy, relapses stop and exacerbation subsides. With the onset of menopause, the frequency and course of peptic ulcers equalizes with men.

Clinical symptoms.

1. Pain syndrome --- Cardiac, central peptic ulcer syndrome (not because it is strong, but specific to peptic ulcer disease).The pain can be dull, burning, aching, paroxysmal, sharp, and also accompanied by vomiting.In some cases, patients may experience flatulence and bloating as an equivalent pain symptom.

A) Diurnal rhythm of pain associated with food intake - - during the day there is a clear alternation in time for a given patient. For example:
Eating --- rest, after 1, 2, 3 hours -- pain --- this happens in patients with peptic ulcer of the pyloroduodenal zone.
Eating --- pain -- then rest after a while--- this is typical with ulcers of the entrance to the stomach.
At the same time, they distinguish early (after 30–60 minutes), late (after 1.5–2 hours), hungry (6–7 hours after eating) and night pain.

b) The presence of seasonal frequency of the disease.
In most cases, 90% of the disease worsens in the autumn-spring period. Moreover, this patient is often observed in certain months (for example: always in September and May, in rare cases in the winter-summer period) .

V) Localization of pain – pain is localized in a certain limited area in the epigastric region, mainly to the right of the midline.

• Patients often point at the dot with their finger.
• With a duodenal ulcer, if the ulcer is on the posterior wall, then the pain may be on the left - this is an atypical localization of pain.
• With soft superficial palpation, local sensitivity and pain correspond to the location of the ulcer.
• Percussion according to Mendel (Mendel's sm) - along the rectus abdominis muscles from top to bottom, we alternately tap on the right, then on the left to the navel. Pain is detected at one point. This point approximately corresponds to the projection of ulcers, the point localization of pain.

2. Heartburn.
Typically, heartburn precedes peptic ulcer disease for several months, years, in the pre-ulcer period. Heartburn occurs in the same way as pain, depending on the location of the ulcer.

3. Vomit.
Just like heartburn depends on impaired motor skills. This is gastroesophageal reflux, just like heartburn.
Vomit in patients with ulcer usually occurs at the peak of pain and brings relief. In some patients, the equivalent of vomiting may be nausea and excessive salivation.
Vomiting immediately after eating indicates damage to the cardiac part of the stomach, after 2–3 hours - an ulcer of the body of the stomach, 4–6 hours after eating - an ulcer of the pylorus or duodenum. Vomiting in the form of “coffee grounds” indicates a bleeding gastric ulcer (rarely duodenal ulcer). And young people often, during an exacerbation of the disease, have very persistent constipation, colitis.

Features of peptic ulcer disease in adolescents.

Gastric ulcers are practically not found in them; duodenal ulcers are 16-20 times more common.

It occurs in 2 forms:

• Latent
• Painful

1. Latent occurs in the form of gastric dyspepsia syndrome (belching, nausea, hypersalivation). Children with this pathology are physically poorly developed, neurotic, capricious, have poor appetite, and poor academic performance. It can last from 2-5 years and turn into a painful form.
2. Painful form.
Extremely pronounced pain syndrome, in children it is stronger than in adults, the pain is persistent. In adolescence, complications often occur - perforation, bleeding.

Features of peptic ulcer in adults.

In elderly and elderly people, patients over 50 years of age, stomach ulcers are 2-3 times more common than duodenal ulcers.
Localization of stomach ulcers.
Localization is more common in the area of ​​the inlet (cardial) part of the stomach, the lesser curvature and the outlet (pyloric) part. Ulcers can be large, often gigantic, wrinkled, and difficult to treat. The pain syndrome is mild, dyspepsia is pronounced, and the acidity level is reduced. Ulcers develop against the background of atrophic gastritis (atrophic hypertrophic gastritis). Complications occur 2-3 times more often than in young people. And malignancy of ulcers at this age occurs very often.
Localization of duodenal ulcers.
90% of duodenal ulcers are localized in the bulb (bulbar, initial section), 8-10% are postbulbar ulcers (area of ​​the large duodenal nipple).
Complications of ulcers:
Bleeding, perforation, covered perforation, penetration (towards the pancreas, lesser omentum), cicatricial disease, pyloric stenosis, malignancy.

TYPES OF ULCERS.

Ulcers located in the inlet (cardiac) part of the stomach.

The cardiac section is the upper section of the stomach, adjacent to the esophagus through the cardial opening. With cardiac ulcers, the following symptoms are observed.
1. Pain localized at the xiphoid process, behind the sternum.
2. The pain radiates in the left half of the chest, left arm, left half of the torso, paroxysmal pain (very reminiscent of ischemic heart disease), not relieved by nitroglycerin. More often these ulcers occur in men over 40 years of age.
3. Heartburn.

Differential diagnosis of gastric ulcer and
The patient is given validol and antacid. For peptic ulcers, the antacid immediately calms down. In case of ischemic disease, validol relieves pain within 2 minutes, and if after 20-30 minutes, then it is not ischemic heart disease. These ulcers are difficult to detect because the endoscope quickly passes through this area and is more difficult to detect. Malignancy and bleeding often occur.

Ulcers on the lesser curvature of the stomach.

Classic peptic ulcer of the stomach, if there is an infectionH. Pilory, usually located at the small curvature.
This is characterized by:
1. Early, aching, moderate pain in the epigastric region (epigastric region), lasting 1–1.5 hours and stopping after the evacuation of food from the stomach.
2. Dyspepsia.
3. Weight loss in 20-30% of patients.

Ulcers of the antrum of the stomach.

For ulcers antrum (vestibule) The following symptoms appear in the pyloric part of the stomach:
1. Pain most often occurs on an empty stomach, at night and 1.5–2 hours after eating (late). The pain usually subsides after eating.
2. Often observed Heartburn.

Ulcers of the pyloric canal of the gastric pylorus.

Pyloric canal - the excretory section of the stomach, which passes into the duodenum. This is a very sensitive neuromuscular area of ​​the stomach., therefore, with ulcers located in this section, the symptoms are quite pronounced.
The typical symptoms here arePyloric Triad:
1. Pain syndrome, quite stubborn. Painradiates to the right hypochondrium, back.
2. Frequent vomiting and, against this background
3. Weight loss.

Pain There are several types. On the one side, classic version -- During the day after eating, pain occurs 1 hour later.
Sometimes the occurrence of pain does not depend on food intake, it occurs paroxysmal or wave-like pain.
Along with pain there is vomit, up to 5-10 times during an exacerbation, the first 10 days. These ulcers are very difficult to treat. In 50% of these patients, after a long period of treatment, the ulcers do not close. In 1/3 of patients, after healing, the ulcers soon open again.

Bulbar ulcers of the duodenum.

When localizing ulcers in the duodenal bulb (bulbar area) characteristic:
1. Pain nocturnal, hungry. At the location of the ulcer on the posterior wall of the duodenal bulb the pain radiates to the lumbar region. The pain disappears immediately after eating.
2. Heartburn.

Postbulbar ulcers of the duodenum.

The pain is localizednot in the epigastrium, but in right hypochondrium, in the right upper quadrant of the abdomen,radiates to the back, under the right shoulder blade.The pain may be paroxysmal, reminiscent of hepatic or renal colic.
Jaundice may appear if the ulcer is located in the area of ​​the nipple of Vater, since the pathological process involvesbiliary tract, pancreas. All this gives a picture of cholecystitis and hepatitis.

Very often, 70% of these ulcers bleed. With ulcers in other areas, only 10% bleed. After scarring of the ulcers, there may be compression of the portal vein, followed by ascites. If ascites of unknown etiology in women, one must think about either adnexal cancer or scarring of ulcers in the area of ​​the portal vein. If the pain subsides immediately after eating, then these are bulbar ulcers, and if 20-30 minutes after eating the pain does not go away, then these are postbulbar ulcers.

Diagnosis of Peptic Ulcer.

• Esophagogastroduodenoscopy (EGD) with biopsy
• X-ray
• Testing for Helicobacter Pylori (stool, vomit, blood or endoscopy biopsy).
• Palpation.

TREATMENT OF ULCER DISEASE.

Conservative treatment is used in the majority who do not have a complicated course (no, etc.)
A conservative approach is not only the correct medicinal approach, but also dietary nutrition, the elimination of bad habits, the correct organization of work and rest, taking into account age, duration of the course, the effectiveness of previous treatment, as well as the location and size of the ulcer, the nature of HCI secretion, the state of gastric motility and duodenum and associated diseases.

Diet.

• Frequent, small meals, 3-4 times a day.
• Food must have buffering and antacid properties. Food should be soft, gentle, easily digestible, be a buffer - protein-fat, less carbohydrates.
• 100-120g protein, 100-120g fat, no more than 400g carbohydrates per day.
• Vitamins: rosehip juice, sea buckthorn oil, but not recommended for concomitant calculous cholecystitis, bacterial cholecystitis, gastritis, duodenitis, since bile enters the duodenum and stomach, causing excessive irritation of the mucous membrane.
• Milk, bread, and meat have antacid buffering properties from products. Table No. 1 is recommended, but depending on the condition it is adjusted by the doctor

Drug therapy.

• Antacids -- the purpose is to buffer the environment, that is, HCI binding.
  Non-absorbable Long-acting antacids do not disturb the electrolyte balance; they contain Al and Mg salts. Long-acting antacids are prescribed during inter-digestive periods, 2.5 hours after meals or 30 minutes before meals.
  Antacids --- Almagel, Maalox, Mailanta, Gastal, Phospholugel, Polysilane, Bedelix, Supralox, Mutesa, Rogel, Normogastrin, Gelusil-varnish, Riopan-plas.
• H2 blockers:
  1st generation drugs:
  Cimetidine, 200 mg 3 times a day, immediately after meals and 2 tablets. at night It works well for patients with bleeding.
  The solution can be administered intravenously to achieve a hemostatic effect. Antacids have the same hemostatic effect.

  2nd generation drugs:
  Group Zantac or A-Zantac. Synonyms - Pectoran, Ranisa, Raniplex, Ranitidine.

  3rd generation drugs (most purified group):
  GroupFamotidina - Axid, Kvamatel. All these drugs are prescribed 1 tablet 2 times a day, 1 tablet in the morning, 2 tablets at night. If the patient is especially restless at night, then you can immediately give 2 tablets at night.
  Group Thiotidine- also an H2 blocker.
• Sucralfate group -Venter, Ulkar, Keal, block the reverse diffusion of hydrogen ions into the mucosa, form a good protective membrane, and have an affinity for granulation tissue.
  A special indication for the use of sucralfate is hyperphosphatemia in patients with uremia who are on dialysis.
• Bismuth preparations - Vikair, Vikalin, Denol.
  Vikair, vikalin nare prescribed 40 minutes after meals if the patient eats 3 times a day. For the first 1-2 weeks, it is advisable to take antacids and bismuth preparations together. These drugs can cause stones to form.
  Denol -- forms a protective film, has cytoprotective properties, and also suppresses Helikobakter Pilory; antacids should not be prescribed at the same time as De-Nol, and it should not be washed down with milk.

• Drugs regulating motor-evacuation activity.
  Raglan, Cerucal.
  Also prescribed Motilium, Perinorm, Debridat, Peridis, Duspatalin, Dicetel.
  Nauzekam, Nausein, Eglanil (Dogmatil, Sulpiil).
  Most cause drowsiness, lethargy, and act at the level of the central structures of the brain, the reticular formation.
  Eglonil-- solution, in the form of injections at night, 2 ml. for 10 days (during exacerbations and severe pain), then 1 tablet. 2-3 times a day.
• Anticholinergics -- Atropine, Platiphylline, Metacin, Gastrocepin. Gastrocepin -- injections 1 amp 1-2 times a day IM or 10-50 mg 1 tablet 2 times a day, prescribed more often in older age groups.
• Solcoseryl group or Actovegin - - act on blood microcirculation.
• Cytoprotectors - -Misoprastol, Cytotec. They increase the cytoprotective properties of the gastric and duodenal mucosa, increase the barrier function,improve blood flow in the gastric mucosa and also have fairly high antisecretory activity. Prescribed auxiliary for difficult-to-heal ulcers or treatment and prevention of gastroduodenal erosive and ulcerative lesions caused by NSAIDs.
• Antibiotics - prescribed for inflammation, deformation, infiltration, and in the presence of Helicobacter Pilory.

TREATMENT SCHEME FOR STOMACH AND DUODENAL ULCERS.

HelicobacterРylori ,
used before 2000

• Colloidal Bismuth subcitrate (De-nol, Ventrixol, Pilocid) 120 mg 4 times a day, 14 days + Metronidazole(trichopolum and other synonyms) 250 mg 4 times a day, 14 days + Tetracycline 0.5 g 4 times a day, 14 days + Gastrocepin 50 mg 2 times a day, 8 weeks for PUD and 16 weeks for PUD.
• K colloidal bismuth subcitrate (De-nol) 108 mg 5 times a day, 10 days + Metronidazole 200 mg 5 times a day, 10 days + Tetracycline 250 mg 5 times a day, 10 days (the combination corresponds to the drug "gastrostat") + Losec (Omeprazole) 20 mg 2 times a day, 10 days and 20 mg 1 time a day, 4 weeks for PUD and 6 weeks for PUD.
• Losec (omeprazole) 20 mg 2 times a day, 7 days and 20 mg 1 time a day for 4 weeks for PUD and 6 weeks for PUD + + Amoxicillin 0.5 g 4 times a day or Klacid 250 mg 4 times a day, 7 days
• Zantac (ranitidine, raniberl) 150 mg 2 times a day, 7 days and 300 mg 1 time a day, 8 weeks for PUD and 16 weeks for PUD + Metronidazole (Trichopolum, etc.) 250 mg 4 times a day, 7 days + Amoxicillin 0.5 g 4 times a day or Klacid 250 mg 2 times a day, 7 days.
• Famotidine (quamatel, ulfamid and other synonyms) 20 mg 2 times a day, 7 days and 40 mg 1 time a day, 8 weeks for PUD and 16 weeks for PUD + Metronidazole (Trichopolum, etc.) 250 mg 4 times a day, 7 days + Amoxicillin 0.5 g 4 times a day or Klacid 250 mg 2 times a day, 7 days.

With the first combination, infection of the mucous membrane is eliminated on average in 80% of cases, and with the rest - up to 90% or more.

Treatment regimens for ulcer associated with Helicobacter pylori,
according to the Maastricht Agreement.

Duration of treatment is 7-14 days.
1st line therapy.
Triple therapy

• Omeprazole 20 mg 2 times a day or Lansoprazole 30 mg 2 times a day or Pantoprazole 40 mg 2 times a day + Clarithromycin 500 mg 2 times a day + Amoxicillin 1000 mg 2 times a day
• Omeprazole 20 mg 2 times a day or Lansoprazole 30 mg 2 times a day or Pantoprazole 40 mg 2 times a day + Clarithromycin 500 mg 2 times a day + Metronidazole 500 mg 2 times a day.
• Ranitidine bismuth citrate 400 mg 2 times a day + Clarithromycin 500 mg 2 times a day + Amoxicillin 1000 mg 2 times a day.
• Ranitidine bismuth citrate 400 mg 2 times a day + Clarithromycin 500 mg 2 times a day + Metronidazole 500 mg 2 times a day.

2nd line therapy.
Quad therapy

• Omeprazole 20 mg 2 times a day 1 20 mg 4 times a day + Metronidazole 500 mg 3 times a day + Tetracycline 500 mg 4 times a day.
• Lansoprazole 30 mg 2 times a day + Bismuth subsalicylate/subcitrate 120 mg 4 times a day + Metronidazole 500 mg 3 times a day + Tetracycline 500 mg 4 times a day.
• Pantoprazole 40 mg 2 times a day + Bismuth subsalicylate/subcitrate 120 mg 4 times a day + Metronidazole 500 mg 3 times a day + Tetracycline 500 mg 4 times a day.

Triple therapy regimens based on De-nol (Colloidal Bismuth Subcitrate).

• De-nol 240 mg 2 times a day + Tetracycline 2000mg per day + Metronidazole 1000-1600 mg per day.
• De-nol 240 mg 2 times a day + Amoxicillin 2000 mg per day + Metronidazole 1000-1600 mg per day.
• De-nol 240 mg 2 times a day + Amoxicillin 2000 mg per day + Clarithromycin 500 mg per day.
• De-nol 240 mg 2 times a day + Clarithromycin 500 mg per day + Metronidazole 1000-1600 mg per day.
• De-nol 240 mg 2 times a day + Amoxicillin 2000 mg per day + Furozolidone 400 mg per day.
• De-nol 240 mg 2 times a day + Clarithromycin 500 mg per day + Furozolidone 400 mg per day.

After completing a 7- or 14-day course of eradication therapy, treatment continues with one Antisecretory drug, included in the combination.
Accept half the daily dose once(For example, De-Nol 240 mg 1 time per day or Omeprazole 20 mg per day) for 8 weeks for PU and 5 weeks for DU.

Occasionally used as a symptomatic remedy for a short period Antacids(phosphalugel, Maalox, etc.) and
Prokinetics (Motilium, Coordinax, etc.) with impaired motor skills accompanying peptic ulcer disease.

Russian doctors often use bismuth-based triple therapy regimens as first-line treatment.
For example: Colloidal bismuth subcitrate + Amoxicillin + Furazolidone.

To prevent exacerbations of ulcerative disease, 2 types of treatment are recommended.

• Carry out long-term (months and even years) maintenance therapy with an antisecretory drug at half the dose, e.g. famotodine-- 20 mg each, or omeprazole-- 10 mg or gastrocepin-- 50 mg each.
• If symptoms characteristic of ulcer appear, resume antiulcer therapy with one of the antisecretory drugs during the first 3-4 days at the full daily dose, and for the next 2 weeks at a maintenance dose.

Indications for continuous maintenance therapy for ulcerative disease are:
1. Unsuccessful use of intermittent course of antiulcer treatment, after which 3 or more exacerbations occur per year.
2. Complicated course of ulcer (history of bleeding or perforation).
3. The presence of concomitant diseases requiring the use of non-steroidal anti-inflammatory and other drugs.
4. Concomitant ulcerative reflux esophagitis.
5. In the presence of gross cicatricial changes in the walls of the affected organ.
6. Patients over 60 years of age.
7. The presence of gastroduodenitis and HP in the mucus.

Indications for the use of intermittent “on demand” treatment are:
1. Newly diagnosed DU.
2. Uncomplicated course of PUD with a short history (no more than 4 years).
3. The recurrence rate of duodenal ulcers is no more than 2 per year.
4. The presence of typical pain and a benign ulcerative defect at the last exacerbation without gross deformation of the wall of the affected organ.
5. Absence of active gastroduodenitis and HP in the mucus.

Table 1. SCHEMES FOR ERADICATION THERAPY OF Helicobacter pylori INFECTION
under the Maastricht Agreement (2000)

First line therapy Triple therapy
Pantoprazole 40 mg 2 times a day + clarithromycin 500 mg 2 times a day +	Ranitidine bismuth citrate 400 mg 2 times a day + clarithromycin 500 mg 2 times a day + amoxicillin 1000 mg 2 times a day or + clarithromycin 500 mg 2 times a day + metronidazole 500 mg 2 times a day
Second line therapy Quad therapy
Omeprazole 20 mg 2 times a day or Lansoprazole 30 mg 2 times a day or Pantoprazole 40 mg 2 times a day + Bismuth subsalicylate/subcitrate 120 mg 4 times a day + metronidazole 500 mg 3 times a day + tetracycline 500 mg 4 times a day

is a disease of the stomach of a chronic, recurrent nature, accompanied by the formation of a defect in the gastric mucosa and the tissues located underneath it. The main symptom is epigastric pain on an empty stomach or after eating, often radiating to the back and chest. Vomiting, belching, heartburn, and nausea are often observed. The most dangerous complications are bleeding, perforation of the stomach wall, pyloric stenosis, and malignant degeneration of an ulcer. Diagnosed by gastroscopy and x-ray of the stomach, tests for Helicobacter pylori infection. Uncomplicated gastric ulcers are treated conservatively; in complicated cases, surgery is used.

General information

Drug-induced ulcers

Gastric ulcer has the same development mechanisms as duodenal ulcer and is also classified.

Symptoms of a stomach ulcer

Unlike duodenal ulcers, gastric ulcers are characterized by pain that occurs and intensifies immediately after eating. Vomiting with a stomach ulcer brings relief. A common symptom is heartburn, as well as heaviness in the stomach (associated with impaired emptying), flatulence. Appetite is usually reduced. However, sometimes an ulcer localized in the antrum of the stomach can manifest itself as hunger pain and night pain.

Just like a duodenal ulcer, a gastric ulcer is dangerous due to complications such as bleeding and gastric perforation. If the ulcer is localized in the pyloric region, stenosis of the pyloroduodenal region may develop. Ulcers localized in the stomach also have a high risk of malignancy, unlike duodenal ulcers.

Diagnostics

Gastroscopy, an endoscopic examination of the stomach, provides the main information for accurately diagnosing gastric ulcers. Also, severe ulceration can be detected with contrast radiography of the stomach. When examining gastric contents, a bacterial culture is performed to identify Helicobacter. For the same purpose, a breath test and Helicobacter detection using PCR and ELISA are used. A general and biochemical blood test may show signs of anemia if there is bleeding from the ulcerated wall; laboratory tests cannot identify specific signs of an ulcer. Stool may also be tested to look for hidden bleeding (fecal occult blood test).

Treatment of stomach ulcers

In the treatment of gastric ulcers, strict adherence to the diet is of great importance - avoidance of foods that irritate the stomach wall and increase the production of gastric juice. Patients suffering from stomach ulcers should exclude spicy, salty, sour, fried and smoked foods, and foods rich in coarse fiber from their diet. It is recommended to consume food boiled or steamed. Drug therapy includes:

• proton pump inhibitors (omeprazole, rebeprazole, esomeprazole and analogues) or H2-histamine receptor blockers to suppress gastric secretion (ranitidine group drugs);
• gastroprotective (bismuth, sucralfate) and antacids;
• antibacterial drugs to suppress Helicobacter pylori infection (metronidazole). Drug therapy aimed at eradicating H. Pylori is usually carried out for 10-14 days, after which maintenance therapy with acid-lowering drugs is continued.

An uncomplicated gastric ulcer does not require surgical treatment. Surgical removal of part of the stomach (resection) is prescribed only in case of severe complications: perforation, obstruction, malignancy of the ulcer with the development of stomach cancer. Surgical treatment is rarely used for persistent, often relapsing disease that is refractory to conservative therapy.

Treatment of symptomatic gastric ulcers requires, first of all, removal of the factor that provoked the ulcer. As a rule, this is enough for a positive effect. As additional therapy, agents that reduce the secretion of hydrochloric acid (proton pump inhibitors, H2-gastroprotectors) are used. A decrease in secretory activity in gastric ulcers can be achieved surgically - by performing vagotomy.

Prognosis and prevention

Prevention of gastric ulcer, as well as duodenal ulcer, is the timely detection and treatment of Helicobacter pylori infection of the gastrointestinal tract, avoidance of stressful situations, uncontrolled use of medications and regular balanced nutrition. Uncomplicated gastric ulcers can be successfully cured if detected early and adequately treated. Poor prognosis if complications develop.