Digital ulcers in scleroderma. Ulcers of the stomach and duodenum. Causes, symptoms and treatment of peptic ulcer. Schematic presentation of the complex mechanism of disease development

Chronic recurrent aphthous stomatitis is a common disease of the oral mucosa and is characterized by the development of painful recurrent single or multiple ulcerations of the oral mucosa. The disease was first described in 1884 by Miculicz Kummel, and then in 1888 by Ya.I. Trusevich.

Chronic recurrent aphthous stomatitis (CRAS):

HRAS, fibrinous form. Third day after occurrence.

Bacterial infection (L-form of α-hemolytic streptococcus Streptococcus Sangvis)

This microorganism is always isolated from lesions in patients with typical aphthous lesions. Its administration to experimental animals causes the appearance of lesion elements. There is an increase in skin sensitivity to the introduction of streptococcal antigen.

Autoimmune reaction

Considered as a manifestation of an autoimmune reaction of the oral epithelium. However, normal levels of antinuclear antibodies and complement do not allow us to consider CRAS as an autoimmune disease associated with central immune mechanisms. With HRAS, a local immune response occurs to the antigenically altered oral mucosa.

Predisposing factors:

Ulcerative colitis

Crohn's disease

Reiter's syndrome

Cyclic neutropenia

Megaloblastic anemia

Iron-deficiency anemia

T-immunodeficiency

Local trauma

Hormonal disorders

Psychogenic factors

Allergic reactions

The L-form of the α-hemolytic streptococcus Streptococcus Sangvis infects the epithelium of the ducts of the small salivary glands, leading to the development of chronic inflammation. When microorganisms multiply, an excess amount of antigens accumulates and the humoral component of immunity is stimulated. In an excess of antigen, an antigen-antibody complex is formed, which precipitates on the walls of blood vessels, activates the complement system, the blood coagulation system, which leads to the formation of thrombosis, ischemia and necrosis (Arthus reaction - an immunocomplex type of damage that occurs in an excess of antigen, with the formation of soluble immune complexes , which can spread through the bloodstream, leading to vasculitis and damage to various organs and systems).

The process is complicated by the addition of autoimmune reactions to antigens released as a result of tissue necrosis. The resulting autoantibodies adhere to the epithelial cells of the spinous layer and stimulate autoimmune complex damage.

Shallow ulcer covered with fibrinous plaque. Intensive infiltration of neutrophils in the lamina propria of the mucous membrane under the zone of superficial necrosis. Deeper in, mononuclear cells, predominantly lymphocytes, dominate. At the base of the lesion, growth of granulation tissue is noted.

Small salivary glands with symptoms of perialveolar and peritubular fibrosis, chronic inflammation, dilation of the salivary gland ducts. (Acute inflammation is preceded by chronic inflammation. Such changes in the salivary glands are also observed in the absence of ulcers). Damage to the epithelium of the ducts of the small salivary glands.

The element of damage in HRAS is either erosion or ulceration. Superficial erosion, which is a round-shaped defect in the epithelium, measuring from 2 to 10 mm, covered with fibrinous plaque, surrounded by a bright red rim of hyperemia, is called AFTA.

There are many classifications of HRAS. There are large and small forms of HRAS; by severity - mild, moderate and severe.

THEM. Rabinovich (1998) identifies the following forms:

Fibrinous

Necrotic

Glandular

Deforming

The disadvantage of these classifications is the identification of non-independent forms that do not clinically differ from each other.

Fibrinous form of HRAS (Mikulich's aphtha);

Necrotizing periadenitis (Setton's aphthae) (recurrent scarring deep aphthae, deforming aphthae, creeping aphthae);

Aphthous stomatitis herpetiformis;

Symptom of Behçet's disease.

More often in women.

– 10-30 years.

The frequency of relapses ranges from 1-2 attacks per year, to several relapses within a month, up to a permanent course.

Harbingers

Clinical course – single or multiple ulcerations (aphthae), sharply painful. The appearance may be preceded by nodules and inflammation of the small salivary glands.

The number of elements is from 1 to 100. In most cases, 1-6 elements.

Size – from 2-3 mm to 1 cm.

Localization – oral mucosa, covered with stratified squamous non-keratinizing epithelium.

Course – healing occurs within 7-14 days. Healing occurs with the formation of a gentle scar or without visible scarring.

More often in women.

The age of onset of the primary attack is 10-30 years. The disease can begin as a deep ulcer, but more often it is preceded by a fibrinous form of CRAS.

Relapse rate is constant; There is no period when there is not at least one ulcer in the mouth.

Precursors are often paresthesia of the mucous membrane, sometimes low-grade fever, localized lymphadenopathy, swelling of the mucous membrane, often of the tongue.

The clinical course is wavy, long-lasting, leading to significant deformation of the mucous membrane.

The number of elements is from 2 to 10, rarely more. A creeping ulcer is characterized by healing at one pole, with growth at the other.

Size - from 1 cm up to damage to large areas of the mucous membrane.

Localization is the mucous membrane, covered with stratified squamous non-keratinizing epithelium, however, as the ulcer grows, it can spread to areas with keratinizing epithelium.

Duration - up to one and a half months. Healing occurs with the formation of a deforming scar.

More often in women.

The age of onset of the primary attack is 10-30 years.

Recurrence rate - lesions are almost constant for 1-3 years with relatively short remissions.

The clinical course is multiple small shallow ulcerations (aphthae), sharply painful. It begins as small erosions (1-2 mm), which then increase and merge to form extensive erosive surfaces.

Localization - lesions can be located in any part of the oral cavity.

The basis of the disease is systemic vascular damage - vasculitis.

Main symptoms:

Recurrent aphthous stomatitis;

Damage to the genitals;

Eye damage (photophobia, iritis, conjunctivitis, hypopyon)

The fundus is affected much more often than is diagnosed.

Minor symptoms

Skin lesions (pyoderma, pustular rashes, papular rashes, erythema nodosum, erythema multiforme exudative);

Artalgia, monoarthritis of large joints;

Damage to the central nervous system;

Kidney damage;

Defeat of the SSS.

Minor symptoms, which are crucial for the prognosis, however, due to the lack of specificity for making a diagnosis, are of a secondary nature

Laboratory diagnostics – hypergammaglobulinemia, increased ESR, leukocytosis, eosinophilia.

Differential diagnosis of fibrinous form of CRAS

With traumatic erosion(presence of a traumatic factor, irregular outlines of erosion, slight pain);

With secondary syphilis(papules are located on any areas of the mucus, including those with keratinizing epithelium, are painless, have an infiltrated base, when scraped, the plaque is easily removed with the formation of flesh-red erosion, regional scleradenitis, pathogens are always found in the lesions, the serological reaction is positive).

With herpetic stomatitis(accompanied by gingivitis, damage to the red border of the lips; the mucous membrane, covered with keratinizing epithelium, is affected predominantly; the primary element of the lesion is a vesicle, with a herpetiform arrangement, with a tendency to merge to form polycyclic outlines)

With exudative erythema multiforme(polymorphism of rashes, general intoxication)

Differential diagnosis of Setton's aphthae:

With Vincent's ulcerative-necrotizing stomatitis(crater-shaped ulcers covered with abundant necrotic plaque, the ulcer bleeds heavily, has a fetid odor, occurs against the background of intoxication, pathogens are identified in the lesion).

With mucosynechial bullous dermatitis of Lort-Jacob(primary element is a bubble, secondary is erosion, there is no infiltration, often there is eye damage).

With traumatic ulcer

With a cancerous ulcer

With specific ulcers

Local treatment:

Elimination of traumatic factors;

Rinse with tetracycline solution (250 mg per 5 ml of water 4 times a day for 5-7 days);

Applications of corticosteroids and antibiotics;

Painkillers according to indications.

For deep ulcers - the use of proteolytic enzymes.

General treatment:

Antibiotics by mouth

Tetracycline

Rifampicin (2 capsules, 2 times a day)

Tarivid (1 table. 2 r/s 20 days)

Sodium thiosulfate (10 ml of 30% solution IV 1 time per day or 1.5-3 g orally)

Prodigiosan (according to the regimen starting with 15 mcg once every 5 days, increasing the dose to 100 mcg).

Pyrogenal according to the scheme

Levamisole (50 mg x 3 times a day 2 days in a row per week or 150 mg once)

Delagil (1 tablet 1 time per day)

Colchicine (1 tablet x 2 times a day for 2 months)

Aevit (1 ml once a day IM for 20 days)

Histaglobulin (2.0 ml s.c. once every 3 days)

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.

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.

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 are the most characteristic sign of systemic scleroderma and occur 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.

Damage to the joints is manifested by pain in them, morning stiffness, and 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 the 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 is currently the leading cause 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.

The basis of kidney damage is 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.

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.

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.

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).

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.

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 (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 (MPA) is a 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 (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:

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

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis, which is characterized by the presence of bronchial asthma (usually with 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 detected 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:

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.

01.10.2017

Systemic scleroderma (SSc) is a systemic connective tissue disease characterized by fibrosis, vascular damage and immunological abnormalities with varying degrees of involvement of internal organs. Despite the fact that SSc is often clinically divided into two subtypes based on the degree of skin damage—diffuse and localized (limited), Raynaud's phenomenon and its complications are universal signs of the disease that occur in more than 95% of patients. It is well known that angiopathy in SSc causes microcirculatory disorders with organ ischemia, activation of fibroblasts and the subsequent development of extensive fibrosis. In this regard, Raynaud's phenomenon is a potentially dangerous symptom, since it quite often progresses to ulceration (in 50% of patients), leading to gangrene of the limb.

The seriousness of the situation is associated with the formation of structural disorders and functional vascular abnormalities in Raynaud's phenomenon within the framework of SSc, in contrast to the primary (idiopathic) forms of this phenomenon, when vascular abnormalities are completely reversible and never progress to irreversible tissue injury. Thus, digital vasculopathy is one of the factors leading to chronic ischemic pain and disability in patients with SSc.

Primary Raynaud's phenomenon is a temporary, reversible vasospastic phenomenon. Raynaud's phenomenon is episodes of transient ischemia due to vasospasm of arteries, precapillary arterioles and cutaneous arteriovenous anastomoses under the influence of cold and emotional stress. It most often affects the fingers and toes, tips of the ears, nose and nipples. Typically, changes in skin color undergo three phases: initial pallor, cyanosis and erythema as an expression of compensatory vasodilation. Clinical manifestations of Raynaud's phenomenon can be grouped as follows:

• most often, color changes are observed on the fingers;
• changes begin on one finger, then spread to other fingers and become symmetrical on both hands;
• the II-IV fingers of the hands are most often involved, the thumb usually remains intact;
• changes in skin color may also be observed in other areas - the ears, tip of the nose, face, above the knees;
• during Raynaud's attacks, livedo reticularis may appear on the extremities, which disappears after the completion of vasospasm;
• in rare cases, damage to the tongue is observed, which is manifested by numbness and transient speech disorders (speech becomes slurred, blurred);
• a significant proportion of patients complain of sensory disturbances (numbness, tingling, pain) during the attack.

The prevalence of Raynaud's phenomenon is less than 10% in the general population. N.A. Flavahan (2015) in a recent review emphasizes thermoregulatory mechanisms as the basis for understanding Raynaud's phenomenon, emphasizing the role of arteriovenous anastomoses and increased activity of α2-blockers in reducing blood flow.

Raynaud's phenomenon in SSc is a consequence of structural and functional vascular disorders with pronounced proliferation of the intima of the distal arteries of the extremities (digital arteries). Vascular changes are of a twofold nature. On the one hand, significant proliferation and fibrosis of the intima and endothelial damage lead to increased release of vasoconstrictor mediators and a simultaneous decrease in the levels of vasodilator molecules. On the other hand, frequent episodes of vasospasm ultimately lead to progressive tissue ischemia, the production of free superoxide radicals and further enhance pathological changes in tissues. The pathophysiology of Raynaud's phenomenon involves complex mechanisms and involves interactions between vascular, intravascular, and neural control factors.

The diagnosis of Raynaud's phenomenon is established primarily on the basis of complaints and clinical symptoms and is considered reliable if the answer is positive to the following three questions:

If the answer to all three questions is positive, the diagnosis of Raynaud's phenomenon is reliable.

Secondary Raynaud's phenomenon is most common in systemic connective tissue diseases with the highest prevalence in SSc (up to 95% of cases), as well as in systemic lupus erythematosus (about 40%), dermatomyositis as part of antisynthetase syndrome (about 25%), rheumatoid arthritis (10 %). Diagnostic criteria for primary and secondary Raynaud's phenomenon are presented in Table 1.

It is generally accepted that ulceration of the tips (pads) of the fingers is a consequence of ischemia, while ulceration on the extensor surface of the fingers is “traumatic” in nature. Until today, we did not have sufficient evidence for this theory. However, a study by B. Ruaro et al. (2015), which included 20 patients with SSc and finger ulcers, demonstrated a significant decrease in blood flow at the site of finger ulcer formation and its improvement during healing. Tissue ischemia also underlies the development of osteolysis, mainly of the nail phalanges.

The ability to predict the development of digital ulcers is of great clinical importance, since this will allow us to identify a group of patients requiring targeted preventive interventions. Recently, several studies have described predictors and prognostic factors for ulceration in SSc. In a large prospective study (n=623) of patients with SSc, the strongest risk factors for the development of new digital ulcers over the next 6 months were: capillary density on the middle finger of the dominant hand (abnormal capillaroscopic pattern), number of digestive ulcers tract and the presence of initial critical ischemia. Other predictors of fingertip ulceration include the presence of antibodies to topoisomerase (anti-Scl-70), the presence of antibodies to the endothelin-1 receptor type A (ET-1), increased circulating levels of ET-1, and the severity of thermography changes. In a systematic review by PRISMA I. Silva et al. (2015) summarized the risk factors for the development of digital ulcers, which are: the subtype of diffuse skin lesions in SSc, early onset of Raynaud's phenomenon, the presence of antibodies to topoisomerase (anti-Scl-70), an abnormal capillaroscopy pattern, increased ET-1 levels and low factor levels vascular endothelial growth factor (VEGF).

At the same time, it is recognized that the presence of digital ulcers is associated with a severe course of the disease and even increased mortality. In a multivariate analysis of 3196 patients from the EUSTAR database, a history of digital ulcers was a significant predictor of death.

The mechanism of development of digital ulcers in SSc is explained by several factors, which include repeated microtrauma, thinning of the skin, dryness and the presence of calcification. It is believed that 8-12% of ulcers arise from calcification of the skin and subcutaneous tissue. However, prolonged ischemia due to Raynaud's phenomenon is the most important mechanism. Digital ulcers vary in size and borders, the presence of exposed tissue (bone, tendon), and tissue calcification. Ulcers are considered acute for up to 3 months, chronic for more than 6 months. The clinical outcome of ulcers depends on numerous factors. Soft tissue and bone loss occurs in approximately 30% of patients with SSc and digital ulcers. During a 7-year monitoring of complications in patients with ulcers, gangrene was detected in 11% of cases; in case of ineffectiveness or lack of treatment, or the presence of recurrent ischemic attacks, the development of gangrene was subsequently observed in 100% of patients; 12% of patients with digital ulcers required hospitalization and surgery.

Critical limb ischemia in SSc is an urgent condition and requires urgent measures. Since the development of critical ischemia is based on irreversible ischemia (as opposed to Raynaud's phenomenon), this process can quickly lead to gangrene of the limb and possible loss of fingers. Figure 1 (a, b, c) shows photographs of patients with digital ulcers and developed critical ischemia against the background of SSc.

The occurrence of critical ischemia is accompanied by severe pain, which sometimes even requires the use of narcotic analgesics. The slightest touch and movement causes pain. The appearance of critical ischemia is preceded by changes in the color of the fingers, persistent whitening, later turning blue, and a border appears between the “blue” and “white” zones of the fingers. Regular hand warming does not have any beneficial effect (which may have been effective in the past). Typically, critical ischemia develops in the II-IV fingers. Although the underlying vasculopathy in SSc is vaso-occlusive disease, prompt and decisive action has reversal potential and can prevent loss of soft tissue and even fingers.

Management of patients with Raynaud's phenomenon, digital ulcers/necrosis in SSc includes non-pharmacological, pharmacological approaches and surgical intervention (Table 2). Non-pharmacological modalities used include avoidance of triggers that precipitate ischemic episodes, including cold exposure, emotional stress, or drugs that promote vasoconstriction, including beta-blockers, antimigraine drugs (such as sumatriptan and ergotamine), oral contraceptives, certain chemotherapy agents (such as cisplatin, vinblastine, targeted tyrosine kinase blockers, etc.) and amphetamines. Smoking cessation is absolutely necessary to prevent further vascular damage to already vulnerable ischemic tissue.

Vasoactive therapies are central to the pharmacological treatment of vascular complications of SSc. E. Hachulla et al. (2007) reported that vasodilation therapy significantly delayed the development of distal ulcerations (odds ratio, RR 0.17; 95% confidence interval, CI 0.09–0.32).

Calcium channel blockers (CCBs) have received little study in the treatment/prevention of digital ulcers, although many clinicians use drugs in this group (most often nifedipine) in the treatment of severe Raynaud's phenomenon. A randomized, double-blind study compared oral nifedipine (30 mg daily for 4 weeks followed by 60 mg daily for 12 weeks) and intravenous iloprost for the treatment of severe Raynaud's phenomenon. According to the results obtained, the average number of digital ulcers was reduced from 4.3 to 1.4 after 16 weeks of treatment with nifedipine. When using iloprost, the number of digital injuries decreased from 3.5 to 0.6. An increase in hand temperature and improvement in microcirculation was noted only with the use of iloprost.

Although there is a strong therapeutic rationale for the role of angiotensin-converting enzyme (ACE) inhibitors in SSc and vascular complications as agents of vascular remodeling (as in patients with coronary artery disease), there is currently a lack of evidence supporting the effectiveness of this intervention. In a multicenter, double-blind, randomized clinical trial of 210 patients with limited SSc or autoimmune Raynaud's phenomenon (scleroderma-specific autoantibodies), three years of quinapril treatment was not associated with a significant reduction in the number of new digital ulcers (RR -0.08; 95% CI - 0.23 to 0.06) .

Phosphodiesterase type 5 (PDE5) inhibitors inhibit the degradation (and therefore increase the bioavailability) of cyclic guanosine monophosphate (GMP) with subsequent vasodilation. In a meta-analysis of digital ulcer therapy that included 31 randomized controlled trials, PDE5 inhibitors (based on three randomized clinical trials, n=85) were associated with ulcer healing and patient improvement.

In a recent multicenter, double-blind, randomized controlled trial of 84 patients, treatment with sildenafil for 12 weeks was associated with a significant reduction in the number of new digital ulcers (0.86 vs. 1.51). However, the healing time of these ulcers (the study's primary endpoint) was not reduced. Three commercially available PDE5 inhibitors include sildenafil, vardenafil, and tadalafil. Sildenafil and vardenafil have a shorter half-life of about 4 hours, while tadalafil has a much longer half-life of 18 hours. The doses of oral vasodilating drugs that are most often used in the treatment of Raynaud's phenomenon and its complications are presented in Table 3.

Prostanoids are potent vasodilators and also inhibit platelet aggregation and proliferation of vascular smooth muscle cells. Iloprost, approved in Europe for the treatment of digital ulcers associated with SSc, is a chemically stable prostacyclin analogue with dual vasodilator and platelet effects. Iloprost is a synthetic analogue of prostacyclin, suppresses platelet aggregation and activation, dilates arterioles and venules, increases capillary density and reduces increased vascular permeability caused by mediators such as serotonin and histamine in the microcirculation system; activates endogenous fibrinolysis, provides an anti-inflammatory effect, suppresses the adhesion and migration of leukocytes after endothelial damage, as well as the accumulation of leukocytes in ischemic tissues.

With intravenous administration of prostanoids, there is a fairly high incidence of side effects and poor tolerability of the drugs, including systemic hypotension, dizziness, hot flashes, gastrointestinal disorders, jaw pain and myalgia, which is observed in 92% of patients.

Intravenous prostanoid therapy should be considered for refractory Raynaud's phenomenon, especially in patients with a generalized form of SSc and in the cold season. The most commonly used are intravenous iloprost (3-5 days of treatment at a rate of 0.5-2 ng/kg/min for 6 hours, repeated courses every 4/6/8 weeks for 52 weeks) and epoprostenol.

Intravenous prostanoid therapy has also been reported to improve healing of digital ulcers and reduce the incidence of new ones. In two multicenter, double-blind, randomized trials, intravenous prostanoid therapy (iloprost 0.5–2.0 ng/kg/min over 6 hours for 5 consecutive days) was associated with significantly greater healing of digital ulcers than placebo.

In severe cases of vasculopathy, with recurrent non-healing ulcers, patients should receive repeated courses of prostanoids; Continuous or extended courses of intravenous therapy should be considered in clinically impasses.

It should be noted that oral prostanoid drugs (iloprost, as well as new drugs - beraprost, cisaprost, treprostinil) have not demonstrated any improvement in the healing of digital ulcers. Other prostaglandin analogues, alprostadil, are less commonly used in the treatment of Raynaud's phenomenon and digital ulcers.

Prazosin, an α1-adrenergic receptor antagonist, has demonstrated beneficial effects on Raynaud's phenomenon in two randomized trials. Prazosin 1 mg three times daily has been reported to improve disease progression and prognosis compared with placebo and to be associated with fewer side effects than higher doses. Unfortunately, there is very little published data on its effect on digital ulcerations.

Topical nitrates have been used to improve local blood flow, but the relatively complex application and potential side effects have reduced enthusiasm for their routine use.

ET-1 is not only a powerful vasoconstrictor, but also has a pronounced proliferative effect on smooth muscle cells and fibroblasts, acting through two receptors (ETA and ETB). In general, ETA and ETB, found on smooth muscle cells, promote vasoconstriction and hyperplasia, while ETB, which is also found on endothelial cells, promotes vasodilation.

Bosentan is a dual ET-1 receptor antagonist licensed in Europe for the treatment of pulmonary arterial hypertension (PAH) and the prevention of recurrent digital ulcers. Two large multicenter, double-blind, randomized controlled trials demonstrated that treatment with bosentan significantly reduced the incidence of new ulcerations. In a randomized, double-blind, placebo-controlled study of the effect of bosentan on the healing and prevention of ischemic digital ulcers in patients with SSc, which included 188 patients with SSc, 24 weeks of bosentan (62.5 mg twice daily for 4 weeks and 125 mg twice daily) day) was associated with a 30% reduction in the number of new digital ulcers. Bosentan is approved in Europe for the prevention of digital ulcers in scleroderma, but was not approved by the US Food and Drug Administration (FDA) after extensive review. Bosentan may be an important treatment option given its oral administration and potentially unique ability to prevent the formation of new digital ulcerations.

In patients with intractable, recalcitrant digital ulcers refractory to PDE5 inhibitor therapy and intravenous prostanoid infusions, ET-1 receptor antagonists may be particularly beneficial.

To date, two new ET-1 receptor antagonists have been approved for the treatment of PAH in Europe: macitentan and ambrisentan, which are being studied in the treatment of digital ulcers in SSc.

Calcification of the tissue surrounding the ulcer may require surgical debridement if other measures to heal it are unsuccessful. Digital (palmar) sympathectomy may provide significant benefit to patients who have not responded to conservative treatment methods. An unconditional limitation is that this technique is performed in separate specialized surgical centers.

Figures 2, 3 and 4 present adapted recommendations for the management of patients with Raynaud's phenomenon, digital ulcerations and critical ischemia. They present a stepwise approach to escalate therapy based on the effectiveness or ineffectiveness of previous interventions, based on best clinical practice.

Thus, SSc-associated vasculopathy is a serious and pressing problem that significantly aggravates the course of SSc. In this regard, the search and development of well-tolerated, inexpensive, accessible therapeutic options for the treatment of Raynaud's phenomenon and its complications in the form of digital ulcers remains a priority. The use of the proposed multifaceted therapeutic approach to optimize the management of patients with Raynaud's phenomenon and digital ulcerations will allow adequate supervision of such patients and prevent the formation of new lesions to provide patients with a decent quality of life.

Literature

Atrial fibrillation (AF) is associated with increased risk of death, stroke and other thromboembolic complications, heart failure and hospitalization, decreased vitality, decreased tolerance physical impairment and dysfunction of the left ventricle (LS) (Camm et al., 2010). FP on Tli transferred to the Gostroy coronary syndrome (GKS) є sewn with a folded clay situation, the co -co -carguna of anticoagulant therapy (kirchhof et al., 2016; Steffel et al., 2018) ....) ....

01/13/2020 Cardiology Rheumatology Myocardial infarction with polyarteritis nodules

Despite the importance of comprehensive treatment strategies for patients with acute myocardial infarction (MI) over the past decade, this disease is still one of the leading causes of morbidity and mortality in som world. More than 80% of cases of IM are inherited from stenotic atherosclerosis of the coronary arteries (CA), and in 5% of cases the cause of fatal IM is a non-atherosclerotic lesion of the coronary artery. However, according to the research data of J. Saw et al., in women with IM age ≤50 years of age, additional coronary angiography (CG) in 28.8% showed unchanged arteries, in 36.4% - atherosclerotic, in 30.3% - non-atherosclerotic urazhennya KA in 4.5% – etiology has not been established. ...

RCHR (Republican Center for Health Development of the Ministry of Health of the Republic of Kazakhstan)
Version: Clinical protocols of the Ministry of Health of the Republic of Kazakhstan - 2013

Progressive systemic sclerosis (M34.0)

Rheumatology

Approved

minutes of the meeting of the expert commission

on health development issues of the Ministry of Health of the Republic of Kazakhstan

Definition: Systemic scleroderma (SSc) is an autoimmune connective tissue disease, the main clinical signs of which are caused by widespread microcirculation disorders, fibrosis of the skin and internal organs.

ICD-10 codes:
M 34.0 Progressive systemic sclerosis
M 34.1 CREST syndrome
M 34.2 Systemic sclerosis caused by drugs and chemical compounds
M 34.8 Other forms of systemic sclerosis
J 99.1 with lung damage
G 73.7 with myopathy
M 34.9 Systemic sclerosis, unspecified
M 35.0 Sicca syndrome (Sjogren's)
M 35.1 Other crossover syndromes

Abbreviations used in the protocol:
AT antibodies
GC-glucocorticosteroids
Gastrointestinal tract - gastrointestinal tract
ILD - interstitial lung disease
CT - computed tomography
ICD - international classification of diseases
NSAIDs - non-steroidal anti-inflammatory drugs
CBC - general blood test
OAM - general urine analysis
RNA - ribonucleic acid
SSc - systemic scleroderma
CREST-calcinosis, Raynaud’s syndrome, esophageal dysmotility, sclerodactyly, telangiectasia.
ESR - erythrocyte sedimentation rate
SLE - systemic lupus erythematosus
Doppler ultrasound
FGDS - fibrogastroduodenoscopy
EMG-electromyography

Protocol development date: 2012

Users of the protocol: rheumatologists, therapists, general practitioners.

Indication that there is no conflict of interest.

Clinical classification (the most common approaches, for example: by etiology, by stage, etc.).

Clinical forms
- Diffuse form. Generalized skin lesions of the extremities, face and trunk during the year; Raynaud's syndrome appears simultaneously or after skin lesions. Early development of visceral pathology (interstitial damage to the lungs, damage to the gastrointestinal tract, myocardium, kidneys). Significant reduction of capillaries of the nail bed with the formation of vascular areas (according to capillaroscopy of the nail bed). Detection of antibodies to topoisomerase-1 (Scl-70).
- Limited form. Long period of isolated Raynaud's phenomenon. Skin involvement is limited to the face and hands/feet. Late development of pulmonary hypertension, gastrointestinal lesions, telangiectasia, calcification (CREST syndrome). Detection of anticentromere antibodies. Dilatation of nail bed capillaries without obvious avascular areas.
- Scleroderma without scleroderma. Scleroderma without scleroderma (sclerodermasines scleroderma) is characterized by: no skin thickening, Raynaud's phenomenon, signs of pulmonary fibrosis, acute scleroderma kidney, damage to the heart and gastrointestinal tract, detection of antinuclear antibodies (Scl-70, ACA, nucleolar).
- Cross shapes. Crossover forms (overlap-syndromes) are characterized by a combination of clinical signs of SSc and one or more systemic connective tissue diseases.
- Juvenile scleroderma. The onset of the disease is before 16 years of age. Skin lesions are often of the type of focal or linear (hemiform) scleroderma. Tendency to form contractures. Abnormalities in the development of the limbs are possible. Moderate visceral pathology (detected mainly by instrumental examination).
- Prescleroderma. There is also the so-called prescleroderma, which includes patients with isolated Raynaud's phenomenon in combination with capillaroscopic changes or immunological disorders characteristic of SSc.
Flow options

Diagnostic criteria:
To verify the diagnosis of SSc, the criteria of the American Rheumatological Association are used.
A. “Big” criterion. Proximal scleroderma: symmetrical thickening, induration, and induration of the skin of the fingers and proximal to the metacarpophalangeal and metatarsophalangeal joints. Changes may affect the face, neck, and torso (chest and abdomen).
B. “Small” criteria.
1. Sclerodactyly: the above skin changes limited to the fingers.
2. Digital scars - areas of skin retraction on the fingertips
or loss of pad substance.
3. Bilateral basal pulmonary fibrosis: bilateral reticular or linear nodular shadows, most pronounced in the basal areas of the lungs during standard x-ray examination; There may be “honeycomb lung” type manifestations. These changes should not be associated with primary lung disease.
The criteria allow us to exclude patients with local forms of scleroderma, eosinophilic fasciitis and various types of pseudoscleroderma. The patient must have either a major criterion or at least 2 minor criteria. Sensitivity - 97%, specificity - 98%. These criteria are suitable for identifying characteristic and quite severe SSc, but do not cover all clinical forms of the disease, including early limited, cross-sectional and visceral SSc.

Complaints: weakness, fatigue, weight loss, low-grade fever, etc. are observed at the onset of the disease (mainly in patients with the diffuse form) and present diagnostic difficulties before the appearance of characteristic skin and visceral signs of SSc.

Physical examination:
Constitutional symptoms - weakness, fatigue, weight loss, low-grade fever, etc. are observed at the onset of the disease (mainly in patients with the diffuse form) and present diagnostic difficulties before the appearance of characteristic skin and visceral signs of SSc.
Vascular damage:
- Raynaud's phenomenon - a symmetrical paroxysmal spasm of the digital arteries, cutaneous arterioles and arteriovenous shunts, induced by cold or emotional stress, characterized by a consistent change in the color of the skin of the fingers (whitening, cyanosis, redness). Vasospasm is often accompanied by numbness of the fingers and pain. In many patients with SSc, Raynaud's attacks are prolonged due to structural changes in blood vessels and permanently reduced blood flow.
- Telangiectasias - dilated capillaries and venules with a characteristic localization on the fingers, palms and face, including the lips, are a late sign of the disease.
- Skin damage:
Skin thickening (scleroderma) always begins in the fingers (sclerodactyly). The severity of skin compaction is assessed by palpation using a 4-point system: 0 - no compaction; 1 - slight compaction; 2 - moderate compaction; 3 - pronounced compaction (impossible to fold). To objectify skin lesions, a skin score is determined, which represents the sum of the scores for the severity of skin compaction in 17 anatomical areas: on the face, chest, abdomen and on symmetrical parts of the limbs - fingers, hands, forearms, shoulders, thighs, legs and feet. In SSD, there are stages of skin damage: edema, induration, atrophy.
The severity of skin thickening varies between individual patients and reaches a maximum in the first 3-4 years of the disease. Skin count correlates with visceral pathology and is one of the predictors of unfavorable outcome of SSc.
· The “pouch-purse” symptom is a decrease in the oral aperture, thinning of the red border of the lips, around which radial folds form.
· Digital ulcers - a characteristic sign of SSc (included in the classification criteria), develops on the distal phalanges of the fingers; can be sharply painful, characterized by torpidity to treatment and recurrent course.
· Ulcerative skin lesions are also observed in areas exposed to mechanical stress - above the elbow and knee joints, in the ankles and heels.
· Dry gangrene - necrosis of the skin and subcutaneous soft tissues begins with the distal phalanges of the fingers and can spread to the middle phalanges, followed by demarcation and self-amputation.
· Hyperpigmentation - limited or diffuse, with areas of hypo- or depigmentation (“salt and pepper”).
- Digital scars are pinpoint areas of skin atrophy of the distal phalanges of the fingers (“rat bite”).
- Due to atrophy of hair follicles, sweat and sebaceous glands, the skin in areas of compaction becomes dry and rough, and hair disappears.
- Calcifications - small subcutaneous deposits of calcium salts, usually appear on the fingers and in areas frequently exposed to injury. Calcifications can open with the release of a curdled mass.
- Damage to the mucous membranes; a characteristic sign of SSD is thickening and shortening of the frenulum of the tongue.
Damage to joints and bones
- Polyarthralgia and morning stiffness are common manifestations of SSc, especially in the early stages of the disease.
- Arthritis is not typical for SSc, but at the same time, erosive arthropathy is detected in 20% of patients.
- Acroosteolysis - resorption of the terminal sections of the distal phalanges of the hands due to prolonged ischemia, manifested by shortening and deformation of the fingers. - In some cases, resorption of the distal radius and processes of the mandible is observed.
- A symptom of tendon friction is crepitus, determined by palpation in patients with a diffuse form of SSD with active flexion and extension movements of the fingers and hands; is a predictor of subsequent diffuse skin lesions.
- Flexion contractures, mainly of the joints of the hands, are the result of local thickening of the skin involving the tendons and their sheaths. - Occur more often in patients with a diffuse form of SSD, in which contractures of large joints of the extremities can be detected. Increased contractures are associated with disease activity and progression.
Muscle damage:
- Muscle involvement manifests itself in two different forms of myopathy:
Non-inflammatory, non-progressive fibrous myopathy is a more common form of muscle damage in SSc, characterized by slight weakness of proximal muscle groups and a minimal increase in CPK levels.
Inflammatory myopathy - manifested by myalgia, proximal muscle weakness, a significant (2 or more times) increase in CPK, inflammatory changes in EMG and biopsy specimens.
- In the diffuse form of SSD, muscle atrophy may develop, associated with impaired mobility and contractures.
Damage to the gastrointestinal tract:
- Esophageal hypotension is the most common form of damage to the esophagus and gastrointestinal tract in general; manifested by dysphagia, a feeling of a lump behind the sternum after eating, persistent heartburn, worsening in a horizontal position.
- Stricture is a narrowing of the lumen of the lower third of the esophagus, as a result of which it becomes impossible to eat solid food. The formation of strictures leads to a significant reduction in the severity of heartburn.
- Erosion and ulcers of the esophagus appear as a result of gastroesophageal reflux, accompanied by severe heartburn and chest pain.
- Gastric hypotension - epigastric pain and a quickly onset feeling of satiety due to impaired evacuation of stomach contents.
- Gastric bleeding is a rare but serious complication that can occur with multiple telangiectasias of the gastric mucosa.
- Malabsorption syndrome - manifested by flatulence, steatorrhea, alternating constipation and diarrhea, weight loss.
- Intestinal pseudo-obstruction is a rare complication, manifested by the symptoms of paralytic ileus.
- Colon damage leads to constipation (less than 2 spontaneous bowel movements per week) and fecal incontinence; occurs with the same frequency as esophageal hypotension.
Lung damage:
Involvement of the lungs is observed in 70% of patients with SSc and is second in frequency only to damage to the esophagus. The main clinical and morphological types of lung damage in SSc are interstitial lung disease (pulmonary fibrosis) and pulmonary hypertension.
- Interstitial lung disease (ILD) develops mainly in the first 5 years of the disease and is more pronounced in the diffuse form of SSc. Clinical manifestations of ILD are nonspecific and include shortness of breath, dry cough, and weakness. The characteristic auscultatory sign of ILD is bilateral basal crepitus, often described as “cellophane crackling.” Risk factors for ILD are: diffuse form of SSc, decreased forced vital capacity at the onset of the disease, and the presence of Scl-70 AT. The progression of pulmonary fibrosis is indicated by a decrease in the forced vital capacity of the lungs and the diffusion capacity of CO over the previous 6-12 months; spread of ground-glass changes and a “honeycomb” appearance of the lung on HRCT; an increase in the number of neutrophils and/or eosinophils in the lavage fluid. The clinical equivalent of progressive ILD is increased dyspnea.
Pulmonary hypertension is defined as an increase in pulmonary artery pressure above 25 mmHg at rest or 30 mmHg during exercise. Pulmonary hypertension can be primary (isolated) - due to vascular damage or secondary - as a result of damage to the interstitial tissue of the lungs; it develops on average in 10% of patients, mainly in the late stages of the disease and with a limited form of SSc. The main clinical sign of pulmonary hypertension, as with ILD, is shortness of breath, which tends to progress rapidly over several months. An auscultatory sign of pulmonary hypertension is the accent and bifurcation of the second tone on the pulmonary artery and tricuspid valve, especially obvious at the height of inspiration. A predictor of pulmonary hypertension is an isolated decrease in the diffusion capacity of CO (