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

general information

Short description

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.

Protocol code:

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

Date of development of the protocol: year 2012

Protocol users: rheumatologists, therapists, general practitioners.

Indication that there is no conflict of interest.

Classification

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

1. An acute, rapidly progressive course is characterized by the development of generalized fibrosis of the skin (diffuse form) and internal organs (heart, lungs, kidneys) in the first 2 years from the onset of the disease; previously it often ended in death; modern adequate therapy has improved the prognosis of this category of patients.
2. In a subacute, moderately progressive course, clinically and laboratory tests indicate a predominance of signs of immune inflammation (dense swelling of the skin, arthritis, myositis); overlap syndromes are not uncommon.
3. The chronic, slowly progressive course is characterized by a predominance of vascular pathology: at the onset of the disease - long-term Raynaud's syndrome with the gradual development of moderate skin changes (limited form), an increase in vascular ischemic disorders, visceral pathology (damage to the gastrointestinal tract, pulmonary hypertension). The prognostic differences in the course options are illustrated by 5- and 10-year survival rates, which in acute cases are 4 and 0%, in subacute cases 75 and 61%, and in chronic cases 88 and 84%, respectively. Currently, with earlier diagnosis and modern therapy, the prognosis of patients with SSc has improved, but differences in onset, main clinical manifestations and evolution remain.

Stages of SSD:
- initial, when 1-3 localizations of the disease are identified.
- stage of generalization, reflecting the systemic, polysyndromic nature of the process.
- late (terminal), when there is already failure of one or more organs (heart, lungs, kidneys).
All 3 parameters of the classification of SSc are recommended to be used when making a diagnosis, determining the prognosis and choosing adequate therapy.

Diagnostics

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 (<60% от должной величины).
Heart damage:
Symptoms of heart damage are a feeling of discomfort or prolonged dull pain in the precordial region, palpitations and arrhythmias, shortness of breath at rest or during exercise. Chest pain can also be caused by damage to the esophagus or the muscles of the chest wall. In many cases, cardiac damage in SSc is asymptomatic and is detected during instrumental examination.
Fibrosis of the ventricular myocardium is a characteristic pathomorphological sign of scleroderma heart disease and is the cause of systolic and diastolic dysfunction of the left ventricle with a decrease in ejection fraction.
Arrhythmias and cardiac conduction disorders are detected in 70% of patients and are very diverse. Frequent rhythm disturbances are supraventricular tachycardia, polytopic and group extrasystoles. The severity of arrhythmias correlates with the severity of cardiac damage and significantly worsens the prognosis, especially in patients with simultaneous involvement of skeletal muscles, and can cause sudden death. Cardiac conduction disorders are manifested mainly by prolongation of the P-Q interval, intraventricular conduction defects, and left anterior bundle branch block. Signs of myocarditis are observed almost exclusively in patients with symptoms of polymyositis; myocarditis is associated with poor patient survival. Damage to the pericardium in the form of adhesive and, less commonly, exudative pericarditis is detected in 70-80% of patients during a special study and is often asymptomatic. In rare cases, there is significant pericardial effusion, which can lead to cardiac tamponade. Heart failure develops rarely, but when it does occur, it is refractory to therapy and has a poor prognosis.
Changes in the heart can develop secondarily, due to pathology of the lungs (pulmonary hypertension) or kidneys (scleroderma renal crisis).
Kidney damage:
In clinical studies, on average, 50% of patients show certain signs of renal dysfunction: proteinuria, hematuria, a slight increase in blood creatinine levels, arterial hypertension. It should be borne in mind that these changes can be caused by other reasons, such as heart failure, pulmonary hypertension, nephrotoxic effects of drugs, etc.
- Severe kidney damage - scleroderma renal crisis, develops in 5-10% of patients, mainly in patients with a diffuse form of SSc. Characteristic manifestations of scleroderma renal crisis are: acutely developed and rapidly progressive renal failure, usually in the absence of previous kidney disease; malignant arterial hypertension associated with high renin levels; normal urinary sediment or minor changes (microscopic hematuria and proteinuria). Proteinuria can be detected long before the development of a renal crisis and intensifies with the development of this complication, but is usually not significant.
- Changes associated with renal vascular damage and arterial hypertension, including microangiopathic (non-immune) hemolytic anemia, thrombocytopenia, hypertensive encephalopathy and retinopathy.
A feature of scleroderma renal crisis is its sudden onset, without previous warning signs. In approximately 10% of patients, no increase in blood pressure is observed - the so-called normotensive scleroderma renal crisis. Without treatment (usually within 1-2 months), end-stage renal failure develops. Risk factors for scleroderma renal crisis are the diffuse form, taking high doses of GC (more than 15 mg/day), and AT to RNA polymerase III.
Damage to the nervous system: Polyneuritic syndrome, which may be associated with Raynaud's phenomenon or primary damage to peripheral nerves. Trigeminal sensory neuropathy occurs in 10% of patients and is manifested by unilateral or bilateral facial numbness, sometimes in combination with pain or paresthesia. Patients with the diffuse form of SSc often develop carpal tunnel syndrome. Other manifestations of SSc include Sjogren's syndrome (20%), damage to the thyroid gland (Hashimoto's thyroiditis, de Quervain's thyroiditis), leading to the development of hypothyroidism; primary biliary cirrhosis in patients with a limited form of SSc.

Laboratory research:

- General blood analysis: hypochromic anemia, moderate increase in ESR (in approximately half of the patients), decrease in hematocrit; an increase in ESR does not correlate with the clinical activity of SSc and may be associated with a latent infection (usually bronchopulmonary).
- General urine analysis: hyposthenuria, microhematuria, proteinuria, cylindruria, leukocyturia. The severity of urinary syndrome varies depending on the clinical form of kidney damage.
- Blood chemistry: no characteristic changes.
- IMMUNOLOGICAL STUDIES. ANF ​​is detected in 95% of patients with SSc, usually in a moderate titer. The determination of so-called scleroderma-specific autoantibodies is important.
- ATScl-70, or AT to topoisomer-ze-1, is more often detected in diffuse than in limited form of SSc. The presence of AT in combination with carriage of - - - HLA-DR3/DRw52 increases the risk of developing pulmonary fibrosis in SSc by 17 times. AT titer correlates with the extent of skin lesions and disease activity. Detection of ATScl-70 in patients with isolated Raynaud's phenomenon is associated with the subsequent development of the clinical picture of SSc.
- Anticentromere AT (ACA) are found in 20% of patients with SSc, mainly in the limited form. Also detected in 12% of patients with primary biliary cirrhosis (half of whom have signs of SSc), very rarely in chronic active hepatitis and primary pulmonary hypertension. - ACAs are considered as a marker of the development of SSD in isolated Raynaud's phenomenon.
- AT to RNA polymerase III are detected in 20-25% of patients, mainly with a diffuse form and kidney damage, and are associated with a poor prognosis.
In addition to the listed autoantibodies, other antinucleolar antibodies are detected with less frequency in SSc, including:
- AT to Pm-Scl are detected in approximately 3-5% of patients with SSc in combination with polymyositis (SSD-po-lymyositis cross syndrome);
- AT to iZ-RNP are detected in 7% of patients and are associated with a diffuse form of the disease, primary pulmonary hypertension, damage to skeletal muscles and early onset of the disease;
- AT to U1-RNP are detected on average in 6% of patients with SSc and are associated with SSc-SLE crossover syndrome, arthritis, isolated pulmonary hypertension and early onset of the disease.
RF is detected in 45% of patients, mainly when combined with Sjögren's syndrome.

Instrumental studies
Capillaroscopy of the nail bed reveals changes characteristic of SSc (dilatation and reduction of capillaries) at an early stage of the disease, and has high sensitivity and specificity.
Since SSc is characterized by damage to many visceral systems, which can be asymptomatic (especially at an early stage of the disease), for their timely detection and assessment of the extent of damage, it is necessary to conduct appropriate instrumental studies, the nature and frequency of which are determined by the clinical form, course of the disease and the need to monitor the effectiveness of therapy (Table 1).
Table 1. Special studies of internal organs in systemic scleroderma.

Organ being examined	Type of lesion	Diagnostic
Esophagus	Hypotension	Manometry
	Reflux esophagitis	Endoscopy/pH-metry
	Stricture	X-ray/endoscopy
Stomach	Paresis	Scintigraphy
	NSAID-induced ulcer	Endoscopy
Small intestine	Hypotension	X-ray contrast study
	Excessive growth of microflora	Hydrogen breath test
	Pseudo-obstruction, NSAID-induced ulcer, pneumatosis	Survey radiography
Colon	Hypotony, pseudodiverticula	Barium enema
	Pseudo-obstruction	Survey radiography
Anorectal department	Sphincter lesion	Manometry
Lungs	Interstitial fibrosis	X-ray, high-resolution computed tomography, pulmonary function, bronchoalveolar lavage, scintigraphy, thoracoscopic lung biopsy
	Pulmonary hypertension	Doppler-ECHO-CG, ECG, radiography
Heart	Arrhythmias	Choletr-ECG monitoring
	Focal myocardial fibrosis	ECG, ECHO-CG, scintigraphy
	Myocardial dysfunction	Doppler-ECHO-KG
	Perikadite	Echo-CG, radiography
Kidneys	Scleroderma renal crisis	Blood pressure monitoring, creatinine content, reninia in the blood, CBC (hemoglobin, schistocytes, platelets), ophthalmoscopy, kidney biopsy

Indications for consultation with specialists
- If there are signs of kidney damage, the patient should be referred to a nephrologist for a kidney biopsy.
- Consultation with a neurologist is indicated in case of development of neurological symptoms to clarify the nature and extent of damage to the nervous system and select symptomatic therapy.
Patients with visual impairments need to consult an ophthalmologist to clarify the genesis of these disorders (retinal vascular pathology within the framework of SSD, manifestations of side effects of GCs or Sjögren's syndrome).List of diagnostic measures:
A) Main:

1. Biochemical blood test (creatinine, K+, Na+, ALT, AST, total and direct bilirubin, lipid spectrum, glucose)

B) Additional:

1. Coagulogram
2. Daily proteinuria
3. ECHO-KG
4. Doppler ultrasound of the vessels of the upper and lower extremities, kidney vessels
5. Ultrasound of obstructive kidneys, kidneys
6. FGDS, pH-metry, esophageal manometry
7. X-ray of the esophagus, stomach, duodenum with barium contrast
8. CT lungs
9. Spirography
10. Biopsy of myocutaneous flap, kidney

Consultation with a neurologist, nephrologist, ophthalmologist, gynecologist.

Differential diagnosis

Differential diagnosis:
Differential diagnosis of SSc is carried out with other diseases of the scleroderma group, most of which do not have Raynaud's phenomenon or damage to internal organs.
· Diffuse eosinophilic fasciitis - skin induration begins with the forearms and/or lower legs with possible spread to the proximal limbs and trunk; fingers and face remain intact. It is characterized by “orange peel” skin lesions, flexion contractures, eosinophilia, hypergammaglobulinemia and increased ESR. In approximately 1/3 of cases, there is a connection with previous excessive physical activity or injury. The development of aplastic anemia is possible.
· Buschke's sclerodrema - severe induration in the face, neck, and shoulder girdle. Often associated with a previous upper respiratory tract infection.
· Limited scleroderma - focal (plaque) and linear (“saber strike”, hemiform) damage to the skin and underlying tissues.
· Multifocal fibrosis. Main localizations: retroperitoneal, intraperitoneal and mediastinal fibrosis; less often - foci of fibrosis in the lungs, orbit (orbital pseudotumor), thyroid gland (Riedel's thyroiditis), etc. Minor forms also include Dupuytren's contractures and keloids. Often a combination of 2-3 or more localizations of the process.
· Tumor-associated (paraneoplastic) scleroderma is a variant of paraneoplastic syndrome, which is manifested by the predominant development of fibrosis in periarticular tissues, contractures, or a type of SSD that is torpid to therapy with a predominance of peripheral symptoms.
· Pseudoscleroderma - skin changes observed with congenital or acquired metabolic disorders: porphyria, phenylketonuria, amyloidosis, Werner syndrome, Rothmund syndrome; diabetic pseudoscleroderma; scleromyxedema, etc.
· Werner's syndrome (adult progeria, lamin gene defect) is manifested by scleroderma-like changes in the skin (especially extremities) and skeletal muscles, the development of cataracts, hypogenitalism, premature arteriosclerosis, insular failure, and an increased risk of developing osteosarcoma; observed more often in men aged 20-30 years. Rothmund-Thomson syndrome (atrophic poikiloderma). Clinically: poikiloderma of the face and extremities, bilateral cataracts, hair dystrophy (nails and teeth), hypogonadism, endochondral ossification disorders, arteriosclerosis and dwarfism, skin hyperpigmentation, telangiectasia, atrophic dermatosis, anemia, increased risk of osteogenic sarcoma . Synonyms: cataract, Rothmund's dystrophy.
. Raynaud's phenomenon is one of the main symptoms that determine the need for differential diagnosis of SSc with other systemic connective tissue diseases: mixed connective tissue disease, antisynthetase syndrome within poly/dermatomyositis.

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Treatment

Treatment goals:
- prevention and treatment of vascular complications
- suppression of fibrosis progression
- prevention and treatment of damage to internal organs.
Treatment tactics:
. Early diagnosis and adequate therapy largely determine the effectiveness of treatment and prognosis, especially in rapidly progressive diffuse SSc. Treatment should be individualized as much as possible depending on the clinical manifestations and disease activity.

Non-drug treatment:
Avoid psycho-emotional stress, prolonged exposure to cold and vibration, and reduce exposure to the sun. To reduce the frequency and intensity of vasospasm attacks, it is recommended to wear warm clothing, including heat-preserving underwear, hats, woolen socks and mittens instead of gloves. For the same purpose, recommend that the patient stop smoking, stop drinking coffee and caffeine-containing drinks, and avoid taking sympathomimetics (ephedrine, amphetamine, ergotamine), beta-blockers.

Drug treatment:
The main directions of drug treatment are vascular, anti-inflammatory and antifibrotic therapy, as well as treatment of visceral manifestations of SSc.
1. Vascular therapy is aimed primarily at treating Raynaud's phenomenon. In addition, the following drugs are used for SSD:
Sildenafil, a phosphodiesterase inhibitor, at a dose of 50 mg per day promotes the healing of digital ulcers in patients with SSc who have not had an effect when using calcium channel blockers.
Bosentan is a non-selective endothelin-1 receptor antagonist used to treat pulmonary hypertension; at a dose of 125 mg/day reduces the likelihood of new digital ulcers by 2 times.
2. Anti-inflammatory and cytotoxic drugs are used at the early (inflammatory) stage of SSc and the rapidly progressive course of the disease:
· NSAIDs in standard therapeutic doses are indicated for the treatment of muscular and joint manifestations of SSc, persistent low-grade fever (high fever is not typical for SSD).
· Glucocorticoids are indicated for progressive diffuse skin lesions and obvious clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory arthritis, tenosynovitis) in small (no more than 15-20 mg/day) doses. Taking higher doses increases the risk of developing normotensive scleroderma renal crisis.
· Cyclophosphamide in combination with GC is used to treat ILD (see below Lung damage).
· Methotrexate is able to reduce the prevalence and severity of skin thickening, but does not affect visceral pathology. The indication for methotrexate is the combination of SSc with RA or polymyositis.
· Cyclosporine has a positive effect on the dynamics of skin changes, however, nephrotoxicity and the high likelihood of developing acute renal crisis during treatment seriously limits the use of the drug in SSc

1. Antifibrotic therapy is indicated at an early stage (during the first 5 years of the disease) or when the severity and prevalence of skin thickening increases in patients with diffuse systemic scleroderma. D-penicillamine is the main drug that suppresses the development of fibrosis. The effective dose of the drug is 250-500 mg/day.

TREATMENT OF VISCERAL MANIFESTATIONS OF SSc
1. Damage to the esophagus and stomach. Treatment is aimed at reducing symptoms associated with gastroesophageal reflux and impaired peristalsis. For this purpose, patients are recommended to eat frequent small meals, not lie down for 3 hours after eating, sleep on a bed with the head end elevated, and give up smoking and alcohol.
2. It should be borne in mind that calcium channel blockers can increase the manifestations of reflux esophagitis. Drug therapy includes the prescription of antisecretory drugs and prokinetics.
Omeprazole, a proton pump inhibitor, is the most effective antisecretory drug for the treatment of gastrointestinal reflux.
In most cases, a single dose of 20 mg stops the manifestations of esophagitis within 24 hours; if necessary, the dose of the drug is increased to 40 mg per day.
Famotidine is a histamine H2 receptor blocker, reduces the manifestations of gastroesophageal reflux
Ranitidine is a blocker of histamine H2 receptors, reduces the manifestations of gastroesophageal reflux, but is inferior in effectiveness to proton pump inhibitors.
Metoclopramide is a prokinetic agent; long-term administration of metoclopramide is unacceptable, since the development of neurological disorders (parkinsonism) caused by the effect on dopaminergic structures of the brain is possible.
Erythromycin also has a prokinetic effect, the use of which in a dose of 100-150 mg 2 times a day or azithromycin 400 mg 1 time a day for 4 weeks reduces nausea, vomiting and attacks of pain in the epigastric region. A combination of prokinetics and antisecretory drugs improves the condition of patients with reflux esophagitis.
Severe esophageal stricture is an indication for endoscopic dilatation. If the evacuation function of the stomach is impaired, it is recommended to take semi-liquid food.
2. Intestinal damage. Disturbances in intestinal motility contribute to excessive growth of microflora and the development of malabsorption syndrome, for the treatment of which the following antibacterial drugs are used: tetracycline - 250 mg per day, amoxicillin + clavulanic acid 500 mg per day, ciprofloxacin 250 mg per day, cephalosporins. Antibiotics should be alternated to prevent the development of microflora resistance. The duration of taking antibiotics depends on the severity of diarrhea and steatorrhea (usually 7 - 10 days per month). If diarrhea appears while taking antibiotics, metronidazole is additionally prescribed (7-10 days) to suppress the anaerobic flora. Prescribing prokinetics (metoclopramide) is not advisable, since they do not have the expected effect. Improvement in peristalsis in intestinal pseudo-obstruction is observed with the use of a long-acting somatostatin analogue, octreotide 50 mg per day subcutaneously.
3. Lung damage.
· Interstitial lung disease. Combination therapy with GC and cyclophosphamide is most effective. The effectiveness of D-penicillamine has not been proven. Prednisolone is prescribed at a dose of 20-30 mg per day for 1 month with a gradual reduction to a maintenance dose of 10-15 mg per day; Large doses of GC should be avoided due to the risk of scleroderma renal crisis. Cyclophosphamide is prescribed intravenously in doses of 500 mg/m2 - 750 mg/m2 per month or orally in doses of 1 mg/kg/day - 2 mg/kg/day, depending on the effectiveness and tolerability of the drug. IV administration is considered preferable, as there is a lower incidence of side effects (including hemorrhagic cystitis) compared to oral administration. Pulse therapy with cyclophosphamide is continued at this dose for at least 6 months (in the absence of side effects). If the dynamics of pulmonary function tests and radiological changes are positive, the interval between pulse therapy with cyclophosphamide is increased to 2 months, and if the positive dynamics are maintained - to 3 months. Pulse therapy with cyclophosphamide must be continued for at least 2 years. The effectiveness of therapy is evidenced by the stabilization of the forced vital capacity of the lungs, since improvement in the function of external respiration at the stage of reticular changes in the lungs is unlikely.
· MMF can be prescribed to patients with SSc and IPD in case of intolerance or ineffectiveness (including secondary) of CP in combination with GC. MMF is prescribed at a dose of 1000 mg/day. (in two doses), increasing it to 2000 mg/day. (in two doses) if well tolerated. The duration of the MMF course must be at least 6 months.
· In case of ineffectiveness of drug therapy and progressive respiratory failure, transplantation of one lung is indicated (efficacy is comparable to transplantation of both lungs).
. Pulmonary hypertension. Treatment of pulmonary hypertension should begin as early as possible (at the latent stage) due to the high mortality of patients (3-year survival rate less than 50%). To treat pulmonary hypertension, vasodilators (calcium channel blockers, synthetic prostacyclin analogues or endothelin receptor antagonists) and anticoagulants are used.
- Nifedipine. Before prescribing long-term therapy for pulmonary hypertension with nifedipine, it is necessary to carry out catheterization of the right ventricle with a test sample (measurement of pressure in the pulmonary artery before and after a single dose of nifedipine), since nifedipine causes a decrease in pressure in the pulmonary artery in only 25% of patients and does not affect the resistance of the pulmonary vessels in the remaining patients. Calcium channel blockers have no effect on patient survival.
- Warfarin. Long-term use of the drug improves survival of patients with primary pulmonary hypertension. The daily dose is determined by the MHO value, which should be kept within 2-3.
- Iloprost and epoprostenol are synthetic analogues of prostacyclin, used for infusion therapy, and effectively reduce pressure in the pulmonary artery. Prostacyclin preparations have also been developed for subcutaneous and inhalation administration.
- Kidney damage. Adequate blood pressure control is central to the treatment of scleroderma renal crisis. Aggressive treatment of arterial hypertension can stabilize or even improve renal function if therapy is initiated promptly, before irreversible changes in the renal vessels develop. The drugs of choice are angiotensin-converting enzyme inhibitors (lisinopril, captopril, enalapril, etc.). The drug dose is selected in such a way as to maintain diastolic pressure at the level of 85-90 mm Hg. Angiotensin-converting enzyme (ACE) inhibitors may also improve the outcome of normotensive scleroderma renal crisis. It is recommended to start treatment with captopril, prescribing 6.25-12.5 mg every 8 hours, and gradually increase the dose to the maximum (50 mg 3 times a day). At the beginning of treatment, a daily increase in the dose of ACEI should reduce the level of systolic blood pressure by 10-20 mmHg, since too rapid a decrease in blood pressure (as well as hypovolemia) can lead to an undesirable decrease in renal perfusion (worsening ischemia). When blood pressure stabilizes, you can switch to taking a longer-acting ACE inhibitor. Captopril is not discontinued even if kidney function continues to deteriorate. If the maximum dose of captopril does not normalize blood pressure within 72 hours, add calcium channel blockers, nitrates (especially if congestion occurs in the lungs) or other vasodilating agents. If the oliguric stage of acute renal failure persists, the issue of hemodialysis is considered. Recovery or improvement of kidney function after SKC occurs slowly over 2 years. If after this period the need for hemodialysis continues, the question should be raised about
- kidney transplantation.
· Heart damage. Manifestations of primary scleroderma heart disease (i.e. lesions that are not a consequence of systemic or pulmonary hypertension) can be pericarditis, arrhythmia, myocarditis, myocardial fibrosis. Treatment of pericarditis is carried out in clinically manifest forms and includes the use of NSAIDs and GK (15 - 30 mg/day). If the effusion is significant, pericardiocentesis or pericardiotomy is performed. Myocarditis is usually observed in patients with inflammatory lesions of skeletal muscles; treatment with GC often results in an increase in left ventricular ejection fraction. Rhythm disturbances usually do not require treatment. For severe arrhythmias (group and polytopic extrasystoles, ventricular tachycardia, etc.), the drug of choice is amiodarone. Taking beta-blockers can increase the manifestations of Raynaud's phenomenon.
· SSD and pregnancy. Most patients with SSc have a history of one or more pregnancies and births. The limited form and chronic course of SSc are not a contraindication for pregnancy. However, during pregnancy organ pathology may develop, which requires regular examination. Contraindications to pregnancy: diffuse form of SSD, severe dysfunction of internal organs (heart, lungs and kidneys). In cases of SSc detection during pregnancy, careful monitoring of renal and cardiac functions is necessary.
List of essential medications:
Nonsteroidal anti-inflammatory drugs
Glucocorticoids

1. Prednisolone, 5 mg, tab
2. Methylprednisolone 4 mg, 16 mg, tab.
3. Methylprednisolone 250 mg, 500 mg, vial.
4. Prednisolone, 30 mg, amp

Basic antifibrotic drugs

1. D-penicillamine (cuprenil) 250 mg, tab.

Immunosuppressive drugs

1. Cyclosporine 25 mg, 100 mg, caps
2. Cyclophosphamide 50 mg, tablets
3. Cyclophosphamide 200 mg, vial
4. Methotrexate 2.5 mg, tablet

List of additional medications:
Vascular therapy:

1. Pentoxifylline 2%, 5 ml, amp
2. Vazaprostan 20 mg/5ml

Anticoagulants:

1. Heparin 5000 IU, bottle
2. Clexane 0.4 ml, syringe
3. Fraxiparine 0.3 ml, 0.4 ml, syringe
4. Warfarin

Gastroprotectors(omeprazole)
Prokinetics(domperidone, metoclopramide)
Antihypertensive drugs(nifedipine, amlodipine, enalapril)
Antibacterial agents (macrolides, cephalosporins, combination a/b)

Patient management: patients with SSc are subject to clinical observation in order to assess the current activity of the disease, timely detection of organ pathology and, if indicated, correction of therapy. A medical examination is carried out every 3-6 months, depending on the course of the disease, the presence and severity of visceral lesions. At the same time, general and biochemical blood and urine tests are carried out. During repeated visits to the doctor, it is necessary to actively question the patient in order to assess the dynamics of Raynaud's phenomenon, increased manifestations of esophageal reflux, shortness of breath, cardiac arrhythmia, etc. When examining the patient, you should pay attention to the prevalence and severity of skin thickening, basal crepitus of the lungs, increased blood pressure, the presence of digital ulcers and edema. Pulmonary function testing and echocardiography are recommended. In patients taking warfarin, the prothrombin index and MHO should be monitored, and when treated with cyclophosphamide, general blood and urine tests should be examined every 1-3 months.

Indicators of treatment effectiveness and safety of diagnostic and treatment methods described in the protocol: Reducing the activity of the inflammatory process.

Hospitalization

Indications for hospitalization:
- Newly diagnosed SSD, especially the early stage of the diffuse form.
- Multiple recurrent ulcerative skin lesions and gangrene of the fingers and toes.
- Progressive damage to the lungs (fibrosing alveolitis, pulmonary hypertension), heart (exudative pericarditis), gastrointestinal tract (abdominal pain, pseudo-ileus, malabsorption syndrome).
- Development of scleroderma renal crisis (malignant hypertension, increased blood creatinine).

Prevention

Preventive actions: The etiology of SSc is unknown, and therefore primary prevention of the disease is not carried out. Preventive measures are reduced to preventing exacerbation of the disease and the development of side effects of drug therapy.

Information

Sources and literature

1. Minutes of meetings of the Expert Commission on Health Development of the Ministry of Health of the Republic of Kazakhstan, 2013
   1. List of used literature: 1. Rheumatic diseases. Ed. J.H. Klippela, J.H. Stone, L.J. Crofford, P.H. White, 2012 2. Rheumatology, Ed. ON THE. Shostak, 2012 3. Diagnosis and treatment in rheumatology. Problematic approach, Pyle K., Kennedy L. Translation from English. / Ed. ON THE. Shostak, 2011 4. Rheumatology: Clinical guidelines / ed. Academician RAMS E.L. Nasonova. – 2nd ed., rev. and additional - M.: GEOTAR-Media, 2010. – 752 p. 5. Smolen J.S., Landewe R., Breedveld F.C. et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. AnnRheumDis, 2010; 69:964–75. 6. Diffuse connective tissue diseases: a guide for doctors / ed. prof. IN AND. Mazurova. – St. Petersburg: SpetsLit, 2009. 192 p. 7. West S.J. - Secrets of rheumatology, 2008 8. Rheumatology: national guide / ed. E.L. Nasonova, V.A. Nasonova. - M.: GEOTAR-Media, 2008 - 720 9. Federal guidelines for the use of medicines (formulary system). Issue VIII. Moscow, 2007. 10. Belousov Yu.B. - Rational pharmacotherapy of rheumatic diseases, 2005. 11. Differential diagnosis of internal diseases: algorithmic approach. P.M. Healy, E.J. Jacobson. Binom, Moscow, 2003. 12. Vasculitis. Grinshtein Yu.I., Krasnoyarsk: IPK "Platina", 2003., 224 p. 13. Systemic lupus erythematosus - Donetsk: KP Region, 2003 - 464 p.. 14. Rational pharmacotherapy of rheumatic diseases. Guide for practicing physicians. Edited by V.A. Nasonova, E.L. Nasonova. Litterra, Moscow, 2003. 15. Rheumatic diseases: nomenclature, classification, standards of diagnosis and treatment - V.N. Kovalenko, N.M. Shuba - K.: Katran Group LLC, 2002. - 214 p. 16. Vasculitis and vasculopathies. E.L. Nasonov, A.A. Baranov, N.P. Shilkina. Upper Volga, Yaroslavl, 1999. 17. Rare and atypical syndromes and diseases in the clinic of internal diseases - Ganja I.M., Decik Yu.I., Peleshchuk A.P. et al.; Ed. I. M. Gandzhi. - Kyiv: Zdorov, 1983. - 544 p.

Information

Evaluation criteria for monitoring and auditing the effectiveness of protocol implementation

Reviewer: Kushekbaeva A.E., Ph.D., Associate Professor, Department of Rheumatology, ASIUV

External review results: positive rating, recommended for use

List of protocol developers with qualification information
1. Togizbaev G.A. - Doctor of Medical Sciences, chief freelance rheumatologist of the Ministry of Health of the Republic of Kazakhstan, head of the Department of Rheumatology, AGIUV
2. Seisenbaev A.Sh. - Doctor of Medical Sciences, Professor
3. Aubakirova B.A. - chief freelance rheumatologist in Astana
4. Sarsenbayuly M.S. - chief freelance rheumatologist of the East Kazakhstan region
5. Omarbekova Zh.E. - chief freelance rheumatologist of Semey
6. Nurgalieva S.M. - chief freelance rheumatologist of the West Kazakhstan region
7. Kuanyshbaeva Z.T. - chief freelance rheumatologist of Pavlodar region

Indication of the conditions for reviewing the protocol: the presence of new diagnostic and treatment methods, deterioration of treatment results associated with the use of this protocol.

Attached files

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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.

Etiology of chronic recurrent aphthous stomatitis

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

Pathogenesis of chronic recurrent aphthous stomatitis

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.

Histology of the fibrinous form of CRAS

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 or erosion, or ulcer. 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.

HRAS classification

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.

Fibrinous form of HRAS

More often in women.

– 10-30 years.

Relapse rate– 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.

Amount of elements– from 1 to 100. In most cases, 1-6 elements.

Size– from 2-3 mm to 1 cm.

Localization– the mucous membrane of the oral cavity, covered with stratified squamous non-keratinizing epithelium.

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

Afta Settona

More often in women.

Age of onset of initial attack– 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- constantly; There is no period when there is not at least one ulcer in the mouth.

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

Clinical course– wavy, long-term course, leads to significant deformation of the mucous membrane.

Amount of elements– 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– mucous membrane covered with stratified squamous non-keratinizing epithelium, however, as the ulcer grows, it can spread to areas with keratinizing epithelium.

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

Herpetiform form of HRAS

More often in women.

Age of onset of initial attack– 10-30 years.

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

Clinical course– 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– elements of the lesion can be located in any part of the oral cavity.

Behçet's disease

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 prognosis, however, due to the lack of specificity for making a diagnosis, they are of secondary importance

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

Differential diagnosis of HRAS

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

Treatment for HRAS

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.

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.

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 a peptic ulcer 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 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

1. Raynaud's syndrome represents episodes of transient digital ischemia due to vasoconstriction of the digital arteries, precapillary arterioles and cutaneous arteriovenous shunts under the influence of cold temperature and emotional stress.

3. The nature and extent of therapy depends on the intensity of Raynaud's attacks (frequency, duration and prevalence of episodes of vasospasm) and complications.

4. Treatment is considered successful when the severity of vasospasm decreases and there is no appearance of new ischemic lesions.

5. For Raynaud's syndrome associated with SSc, all patients should undergo long-term drug therapy.

7. Calcium channel blockers (calcium antagonists) of the dihydropyridine group, mainly nifedipine, are the first-line drug for the treatment of Raynaud's syndrome associated with systemic scleroderma. ( Level of evidence A).

8. Prostanoids for intravenous use ( iloprost, alprostadil) are prescribed for the treatment of severe Raynaud's syndrome when calcium antagonists are ineffective. ( Level of evidence B).

9. Prostanoids (and loprost And alprostadil) effective in healing digital ulcers and reducing the number of relapses. ( Level of evidence B).

10. Bosentan at a dose of 125 mg/day, it halves the frequency and duration of Raynaud’s attacks, and the frequency of new or recurrent digital ulcers, but does not affect the healing of existing ulcers. ( Level of evidence B/A). Bosentan is recommended for the treatment of multiple and recurrent digital ulcers in patients with diffuse SSc when calcium channel blockers and prostanoids are ineffective.

11.Sildenafil- phosphodiesterase inhibitor (25-100 mg per day) is used in the treatment of severe Raynaud's syndrome and digital ulcers when calcium antagonists and prostanoids are ineffective. ( Level of evidence B).

13. Infected digital ulcers require local and/or systemic use of broad-spectrum antibiotics.

Anti-inflammatory and cytotoxic drugs.

Used at the early (inflammatory) stage of SSc and rapidly progressing course of the disease:

NSAIDs in standard therapeutic doses are indicated for the treatment of muscular and joint manifestations of SSc, persistent low-grade fever (high fever is not typical for SSD).

Glucocorticoids indicated for progressive diffuse skin lesions and obvious clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory arthritis, tenosynovitis) in small (no more than 15-20 mg/day) doses. Taking higher doses increases the risk of developing normotensive scleroderma renal crisis.

Cyclophosphamide at a dose of up to 2 mg/kg per day for 12 months. Reduces skin itching only in patients with the diffuse form of SSc. Pulse therapy in combination with high doses of glucocorticosteroids for a combination of diffuse skin lesions and fibrosing alveolitis.

Methotrexate is able to reduce the prevalence and severity of skin compaction, but does not affect visceral pathology. The indication for methotrexate is the combination of SSc with RA or polymyositis.

CELLSEPT(mycophenolate mofetil) – a modern cytostatic immunosuppressant that helps suppress immune mechanisms that induce the development of systemic fibrosis in SSc.

Used in an initial dose of 2000 mg per day; maintenance dose of 1000 mg per day under the dynamic supervision of a physician.

Mycophenolate mofetil significantly reduces skin itching in patients with early diffuse SSc after induction of immunosuppression with antithymocyte immunoglobulin.

Cyclosporine has a positive effect on the dynamics of skin changes, however, nephrotoxicity and the high likelihood of acute renal crisis during treatment seriously limits the use of the drug in SSc

Antifibrotic therapy indicated at the early stage of the diffuse form of SSc.

D-penicillamine- the main drug that suppresses the development of fibrosis. The effective dose of the drug is 250-500 mg/day. Treatment with penicillamine leads to a significantly greater reduction in the severity and prevalence of skin thickening and increases 5-year survival compared to patients who did not receive this treatment. Taking high doses of the drug (750-1000 mg/day) does not lead to a significant increase in the effectiveness of therapy, but much more often causes side effects that require interruption of treatment.

Treatment of visceral manifestations of SSc.

Damage to the esophagus and stomach. Treatment is aimed at reducing symptoms associated with gastroesophageal reflux and impaired peristalsis. For this purpose, patients are recommended to eat frequent small meals, not lie down for 3 hours after eating, sleep on a bed with the head end elevated, and give up smoking and alcohol. It should be borne in mind that calcium channel blockers may increase the manifestations of reflux esophagitis. Drug therapy includes the prescription of antisecretory drugs and prokinetics.

Pantoprazole- a proton pump inhibitor, is the most effective antisecretory drug for the treatment of gastrointestinal reflux. In most cases, a single dose of 20 mg stops the manifestations of esophagitis within 24 hours; if necessary, the dose of the drug is increased to 40 mg per day.

Metoclopramide- prokinetic; long-term administration of metoclopramide is unacceptable, since the development of neurological disorders (parkinsonism) caused by the effect on dopaminergic structures of the brain is possible.

Severe esophageal stricture is an indication for endoscopic dilatation. If the evacuation function of the stomach is impaired, it is recommended to take semi-liquid food.