Mixed connective tissue disease is a rare disease characterized by the simultaneous presence of systemic lupus erythematosus, systemic scleroderma, polymyositis or dermatomyositis, and rheumatoid arthritis with very high titers of circulating antinuclear autoantibodies to ribonucleoproteins (RNP). Characterized by the development of edema of the hands, Raynaud's phenomenon, polyarthralgia, inflammatory myopathy, hypotension of the esophagus and impaired lung function. Diagnosis is based on the analysis of the clinical picture of the disease and the detection of antibodies to RNP in the absence of antibodies characteristic of other autoimmune diseases. Treatment is similar to that for systemic lupus erythematosus and involves the use of glucocorticoids for moderate to severe disease.
Mixed connective tissue disease (MCTD) occurs throughout the world, in all races. The maximum incidence occurs in adolescence and the second decade of life.
Clinical manifestations of mixed connective tissue disease
Raynaud's phenomenon can be several years ahead of other manifestations of the disease. Often, the first manifestations of mixed connective tissue disease can resemble the onset of systemic lupus erythematosus, scleroderma, rheumatoid arthritis, polymyositis, or dermatomyositis. However, regardless of the nature of the initial manifestations of the disease, the disease is prone to progression and spread with a change in nature. clinical manifestations.
The most common swelling of the hands, especially the fingers, makes them look like sausages. Skin changes resemble those of lupus or dermatomyositis. Skin lesions similar to those in dermatomyositis, as well as ischemic necrosis and ulceration of the fingertips, are less common.
Almost all patients complain of polyarthralgia, 75% have clear signs of arthritis. Usually arthritis does not lead to anatomical changes, however, erosion and deformations can occur, as in rheumatoid arthritis. Weakness of the proximal muscles, with or without tenderness, is common.
Kidney damage occurs in about 10% of patients and is often mild, but in some cases it can lead to complications and death. In mixed connective tissue disease, sensory neuropathy of the trigeminal nerve develops more often than in other connective tissue diseases.
Diagnosis of mixed connective tissue disease
Mixed connective tissue disease should be suspected in all patients with SLE, scleroderma, polymyositis, or RA, with the development of additional clinical manifestations. First of all, it is necessary to conduct a study for the presence of antinuclear antibodies (ARA), antibodies to the extracted nuclear antigen and RNP. If the results obtained correspond to a possible MCTA (for example, a very high titer of antibodies to RNA is detected), in order to exclude other diseases, studies of the concentration of gamma globulins, complement, rheumatoid factor, antibodies to Jo-1 antigen (histidyl-t-RNA -synthetase), antibodies to the ribonuclease-resistant component of the extracted nuclear antigen (Sm), and the DNA double helix. The plan for further studies depends on the existing symptoms of damage to organs and systems: myositis, kidney and lung damage require appropriate diagnostic methods (in particular, MRI, electromyography, muscle biopsy).
Almost all patients have high titers (often> 1: 1000) of fluorescent antinuclear antibodies. Antibodies to extractable nuclear antigen are usually present in very high titers (> 1: 100,000). The presence of antibodies to RNP is characteristic, while antibodies to the Sm-component of the extracted nuclear antigen are absent.
In sufficiently high titers, rheumatoid factor can be detected. ESR is often increased.
Prognosis and treatment of mixed connective tissue disease
The ten-year survival rate corresponds to 80%, but the prognosis depends on the severity of symptoms. The main causes of death are pulmonary hypertension, renal failure, myocardial infarction, colon perforation, disseminated infections, and cerebral hemorrhage. In some patients, it is possible to maintain long-term remission without any treatment.
The initial and maintenance treatment for mixed connective tissue disease is similar to that for systemic lupus erythematosus. Most patients with moderate to severe illness respond to glucocorticoid treatment, especially if started early enough. Mild disease is successfully controlled by salicylates, other NSAIDs, antimalarial drugs, in some cases - low doses of glucocorticoids. Severe lesions of organs and systems require the administration of high doses of glucocorticoids (for example, prednisolone at a dose of 1 mg / kg 1 time per day, orally) or immunosuppressants. With the development of systemic sclerosis, appropriate treatment is carried out.
DIFFUSIVE CONNECTIVE TISSUE DISEASES
Diffuse connective tissue diseases (DZST) or collagenoses (a term that has historical significance) is a group of diseases characterized by systemic immunoinflammatory damage to connective tissue and its derivatives. This is a group, but not a nosological concept, in connection with which this term should not denote individual nosological forms.
DZST combine a fairly large number of diseases. The most common are SLE, SSD and DM. This group of diseases also includes ARF, traditionally described in the section of diseases of the cardiovascular system. Currently, it has been proven that with DZST, profound disorders of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions immune system, accompanied by the formation of antibodies or sensitized lymphocytes directed against the antigens of their own body.
At the heart of autoimmune disorders is an immunoregulatory imbalance, expressed in suppressive suppression and increased helper activity of T-lymphocytes, followed by activation of B-lymphocytes and overproduction of various specific autoantibodies.
There are a number of common features that unite DZST:
Common pathogenesis - violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of immune complexes "antigen-antibody" circulating in the blood and fixing in tissues with the subsequent development of a severe inflammatory reaction (especially in the microvasculature, kidneys, joints, etc.);
The similarity of morphological changes (fibrinoid changes in the basic substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbation and remission;
Aggravation under the influence of nonspecific influences (infectious diseases, insolation, vaccination, etc.);
Multiple lesions (skin, joints, serous membranes, kidneys, heart, lungs);
The therapeutic effect of immunosuppressive drugs (glucocorticoids, cytostatic drugs).
All diseases included in this group differ in clinical and morphological signs, therefore, in each specific case, one should strive for an accurate nosological diagnosis.
This chapter presents a diagnostic search for SLE, SJS and DM.
SYSTEMIC RED Lupus
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that occurs in young people (mainly in women) and develops against a background of genetically determined imperfection of immunoregulatory processes, which leads to uncontrolled production of antibodies to its own cells and their components and the development of autoimmune and immunocomplex chronic lesions (V.A.Nasonova, 1989). The essence of the disease consists in immuno-inflammatory damage to the connective tissue, microvasculature, skin, joints and internal organs, while visceral lesions are considered leading, which determine the course and prognosis of the disease.
The incidence of SLE is from 4 to 25 cases per 100 thousand population. The disease most often develops in women of childbearing age. During pregnancy and in postpartum period the risk of exacerbation increases significantly. Women suffer from SLE 8-10 times more often than men. The peak incidence occurs at the age of 15-25 years. In children, the ratio of sick girls and boys decreases and is 3: 1. The mortality rate in SLE is 3 times higher than in the population. In men, the disease is as severe as in women.
SLE belongs to genetically determined diseases: studies carried out in the population have shown that the predisposition to SLE is associated with certain genes of class II histocompatibility (HLA), genetically determined deficiency of certain complement components, as well as with gene polymorphism of some receptors and tumor necrosis factor α (TNF-α).
Etiology
The specific etiological factor in SLE has not been established, but a number of clinical symptoms (cytopenic syndrome, erythema and enanthema) and certain patterns of disease development make it possible to associate SLE with diseases of viral etiology. Currently, RNA viruses (slow or latent viruses) are considered to be of importance. The detection of family cases of the disease, the frequent existence in families of other rheumatic or allergic diseases and various immunity disorders allows us to think about the possible significance of the family-genetic predisposition.
The manifestation of SLE is facilitated by a number of nonspecific factors - insolation, nonspecific infection, administration of sera, intake of some medicines(in particular, peripheral vasodilators from the hydralazine group), as well as stress. SLE can start after childbirth or abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis
Due to the effect on the immune system of the virus, and possibly antiviral antibodies, against the background of a hereditary predisposition, dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, there is an uncontrolled production of antibodies to its various tissues, cells and proteins (including various cellular organelles and DNA). It has been established that in SLE, autoantibodies are produced by about forty out of more than two hundred potential antigenic cellular components. Subsequently, the formation of immune complexes and their deposition in various organs and tissues (mainly in the microvasculature) occur. Various defects in immunoregulation are characteristic, accompanied by the overproduction of cytokines (IL-6, IL-4 and IL-10). Then, processes associated with the elimination of fixed immune complexes develop, which leads to the release of lysosomal enzymes, damage to organs and tissues, and the development of immune inflammation. In the process of inflammation and destruction of connective tissue, new antigens are released, causing the formation of antibodies and the formation of new immune complexes. Thus, a vicious circle arises that ensures the chronic course of the disease.
Classification
Currently, our country has adopted a working classification of clinical variants of the course of SLE, taking into account:
The nature of the flow;
The activity of the pathological process;
Clinical and morphological characteristics of damage to organs and systems. The nature of the course of the disease
The acute course is characterized by the rapid development of multi-organ changes (including kidney and central nervous system damage) and high immunological activity.
Subacute course: at the onset of the disease, the main symptoms appear, nonspecific lesions of the skin and joints. The disease proceeds in waves, with periodic exacerbations and the development of multiple organ disorders within 2-3 years from the moment the first symptoms appear.
The chronic course is characterized by a long-term predominance of one or more symptoms: recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Verlhof's syndrome or Sjogren's syndrome. Multiple organ damage occurs by the 5-10th year of the disease.
Phase and degree of activity of the process:
Active (high activity - III, moderate - II, minimal - I);
Inactive (remission).
Clinical and morphological characteristics of the lesions:
Skin (butterfly symptom, capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis - pleurisy, pericarditis and peresplenitis);
Heart (myocarditis, endocarditis, heart failure mitral valve);
Lungs (acute and chronic pneumonitis, pneumosclerosis);
Kidney (nephrotic or mixed lupus nephritis, urinary syndrome);
Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, represented by a clinical and laboratory symptom complex, including venous and (or) arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ damage. A characteristic immunological sign is the formation of antibodies that react with phospholipids and phospholipid-binding proteins (more details on antiphospholipid syndrome will be discussed later).
There are also three degrees of activity of the pathological process, which characterize the severity of potentially reversible immune-inflammatory damage and determine the characteristics of the treatment of each particular patient. Activity should be distinguished from the severity of the disease, which is understood as a set of irreversible changes that are potentially dangerous for the patient.
Clinical picture
The clinical picture of the disease is extremely diverse, which is associated with the multiplicity of damage to organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
They do not receive information on the basis of which an idea can be drawn:
About the variant of the onset of the disease;
The nature of the course of the disease;
The degree of involvement in the pathological process of certain organs and systems;
Previous treatment, its effectiveness and possible complications.
The options for the onset of the disease can be very diverse. Most often it is represented by a combination of various syndromes. Monosymptomatic onset is usually uncommon. In this regard, the assumption of SLE disease arises from the moment such a combination is found in a patient. In this case, the diagnostic value of certain syndromes increases.
V early period SLE is considered the most common syndromes of joints, skin and serous membranes, as well as fever. Thus, the most suspicious in relation to SLE will be the following combinations:
Fever, polyarthritis and trophic skin disorders (in particular, hair loss - alopecia);
Polyarthritis, fever, and pleural involvement (pleurisy);
Fever, trophic skin disorders and pleural lesions.
The diagnostic significance of these combinations increases significantly if the skin lesion is represented by erythema, but in the initial period of the disease it is recorded only in 25% of cases. Nevertheless, this circumstance does not reduce the diagnostic value of the above combinations.
The malosymptomatic onset of the disease is not typical, but the debut of SLE with the onset of massive edema due to the development of diffuse glomerulonephritis (lupus nephritis) of a nephrotic or mixed type from the very beginning was noted.
Involvement of various organs in the pathological process manifests itself with symptoms of their inflammatory lesions (arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.).
Information about previous treatment allows us to judge:
About its optimality;
On the severity of the course of the disease and the degree of activity of the process (initial doses of glucocorticoids, duration of their use, maintenance doses, inclusion in medical complex cytostatics for severe immune disorders, high activity of lupus nephritis, etc.);
On the complications of glucocorticoid and cytostatic treatment.
At the first stage, certain conclusions can be drawn regarding the diagnosis with a long course of the disease, but in its debut, the diagnosis is established at further stages of the study.
You can get a lot of data indicating organ damage and the degree of their functional failure.
The defeat of the musculoskeletal system is manifested by polyarthritis, resembling RA, symmetric lesion of the small joints of the hand (proximal interphalangeal, metacarpophalangeal, radiocarpal) and large joints(less often). With an expanded clinical picture of the disease, defiguration of the joints is determined due to periarticular edema. During the course of the disease, deformities of small joints develop. Articular changes can be accompanied by muscle damage in the form of diffuse myalgias, and very rarely - by true PM with edema and muscle weakness. Sometimes the defeat is represented only by arthralgias.
The defeat of the skin is noted as often as the joints. The most typical erythematous rash on the face in the area of the zygomatic arches and the nasal bridge ("butterfly"). Inflammatory rashes on the nose and cheeks, repeating the shape of the "butterfly", are represented by various options:
Vascular (vasculitic) "butterfly" - unstable, pulsating, diffuse redness of the skin with a cyanotic shade in middle zone faces,
intensifying under the influence of external factors (insolation, wind, cold) or excitement;
... "Butterfly" type of centrifugal erythema (skin changes are localized only in the nose bridge).
In addition to the "butterfly", you can find discoid eruptions - erythematous rising plaques with keratic disorders and the subsequent development of atrophy of the skin of the face, extremities and trunk. Finally, in some patients, nonspecific exudative erythema on the skin of the extremities and chest is noted, as well as signs of photodermatosis on open parts of the body.
Skin lesions include capillaritis - a small-point hemorrhagic rash on the pads of the fingers, nail beds and palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulceration can be found on the mucous membrane of the mouth or nasopharyngeal region.
The defeat of the serous membranes occurs in 90% of patients (the classic diagnostic triad is dermatitis, arthritis, polyserositis). Especially often they find damage to the pleura and pericardium, less often - the peritoneum. The symptoms of pleurisy and pericarditis are described in the previous sections, so only their features in SLE will be listed below:
Dry pleurisy and pericarditis occur more often;
With effusion forms, the amount of exudate is small;
The defeat of the serous membranes is short-term, and usually it is diagnosed retrospectively when pleuropericardial adhesions or thickening of the costal, interlobar and mediastinal pleura are detected on x-ray examination;
A pronounced tendency towards the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities) is noted.
SLE is characterized by damage to the cardiovascular system, which occurs at various stages of the course of the disease.
Most often, pericarditis is found, which is prone to recurrence. Significantly more often than previously thought, endocardial damage is noted in the form of warty endocarditis (lupus endocarditis) on the cusps of the mitral, aortic or tricuspid valve. With a long course of the process, at the second stage of the search, signs of insufficiency of the corresponding valve can be detected (signs of stenosis of the hole are usually absent).
Focal myocarditis is almost never recorded, but diffuse lesions, especially in severe cases, are accompanied by certain symptoms (see "Myocarditis").
Vascular lesions can manifest with Raynaud's syndrome, which is characterized by paroxysmal developing disorders of the arterial blood supply to the hands and (or) feet, arising under the influence of cold or excitement. During an attack, paresthesia is noted; the skin of the fingers becomes pale and / or cyanotic, the fingers are cold. Mostly there is a lesion of the II-V fingers and toes, less often - other distal parts of the body (nose, ears, chin, etc.).
Lung involvement may be due to an underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) is acute or lasts for months and manifests itself with signs of inflammatory infiltration syndrome lung tissue, similar to those in pneumonia. The peculiarity of the process is the occurrence of an unproductive cough in combination with shortness of breath. Another variant of lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), expressed in the development of slowly progressive dyspnea and changes in the lungs on X-ray examination. Typical physical data are practically absent, so it is almost impossible to judge about a similar lesion of the lungs at the second stage of the diagnostic search.
The defeat of the gastrointestinal tract, as a rule, is represented by subjective signs found at the first stage. Physical examination sometimes reveals vague soreness in the epigastric region and at the site of the projection of the pancreas, as well as signs of stomatitis. In some cases, hepatitis develops: an increase and soreness of the liver is noted.
Most often, with SLE, kidney damage occurs (lupus glomerulonephritis or lupus nephritis), on the evolution of which the future fate of the patient depends. Kidney damage in SLE can occur in the form of various variants, therefore, the data of direct examination of the patient can vary widely. With isolated changes in urinary sediment, no abnormalities are found during physical examination. With glomerulonephritis occurring with nephrotic syndrome, determine massive edema and often - hypertension. When forming chronic nephritis with constant hypertension, an increase in the left ventricle and an accent of the II tone in the second intercostal space to the right of the sternum are found.
Autoimmune thrombocytopenia (Werlhof syndrome) manifests itself as typical rashes in the form of hemorrhagic spots of various sizes on the skin of the inner surface of the limbs, the skin of the chest and abdomen, as well as on the mucous membranes. After minor injuries (for example, after tooth extraction), bleeding occurs. Nosebleeds sometimes become profuse and lead to anemia. Skin hemorrhages can have different colors: blue-greenish, brown or yellow. Often, SLE manifests itself for a long time only with Werlhof's syndrome without other typical clinical symptoms.
The defeat of the nervous system is expressed to varying degrees, since almost all of its departments are involved in the pathological process. Patients complain of migraine headaches. Seizures sometimes occur. Cerebral circulation disorders up to the development of a stroke are possible. Examination of the patient reveals signs of polyneuritis with impaired sensitivity, pain along the nerve trunks, decreased tendon reflexes and paresthesias. Organic brain syndrome is characterized by emotional lability, episodes of depression, memory impairment, and dementia.
The defeat of the reticuloendothelial system is represented by an early symptom of generalization of the process - polyadenopathy (an increase in all groups of lymph nodes, not reaching a significant degree), as well as, as a rule, a moderate increase in the spleen and liver.
Damage to the organ of vision manifests itself as dry keratoconjunctivitis, which is caused by pathological changes in the lacrimal glands and a violation of their function. Dry eyes lead to the development of conjunctivitis, corneal erosion, or keratitis with visual impairment.
With antiphospholipid syndrome, venous (in the deep veins of the lower extremities with repeated pulmonary embolism) and arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks) thrombosis can be detected. Record valvular heart disease, intracardiac thrombi mimicking myxoma of the heart, and thrombosis coronary arteries with the development of MI. Skin lesions in antiphospholipid syndrome are varied, but the most common of them is reticular livedo (livedo reticularis).
Thus, after the second stage of the examination, multiple organ lesions are found, and their degree is very different: from hardly clinically noticeable (subclinical) to pronounced, prevailing over the rest, which creates the prerequisites for diagnostic errors - the interpretation of these changes as signs of independent diseases (for example, glomerulonephritis , myocarditis, arthritis).
The third stage of the diagnostic search with SLE has a very great importance, because:
Helps to make a definitive diagnosis;
Demonstrates the severity of immune disorders and the degree of damage to internal organs;
Allows you to determine the degree of activity of the pathological (lupus) process.
At the third stage, the most important is the laboratory blood test. There are two groups of indicators.
Indicators that have direct diagnostic value (indicate severe immunological disorders):
LE cells (lupus erythematosus cells) are mature neutrophils that phagocytose the nuclear proteins of other blood cells that have been degraded by ANF.
ANF is a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in 95% of patients, they are found in a titer of 1:32 and higher). The absence of ANF in the overwhelming majority of cases is against the diagnosis of SLE.
ANA - antibodies to native (i.e. to the whole molecule) DNA. An increase in their concentration correlates with the activity of the disease and the development of lupus nephritis. They are found in 50-90% of patients.
Antibodies to the Sm-nuclear antigen (anti-Sm) are highly specific for SLE. Antibodies to Ro / La ribonucleoprotein are considered specific for SLE (they are detected by immunofluorescence in 30% of cases, by hemagglutination in 20% of patients).
The phenomenon of "rosettes" - altered nuclei (hematoxylin bodies) freely lying in the tissues, surrounded by leukocytes.
Diagnosis of antiphospholipid syndrome in SLE is based on the determination of lupus anticoagulants - specific antibodies to phospholipids, which are detected in the determination of blood clotting using functional tests (determination of increased thromboplastin time) and antibodies to cardiolipin using enzyme immunoassay. The term "lupus anticoagulant" is not correct, since the main clinical sign of the presence of the above antibodies is thrombosis, not bleeding. These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, reticular livedo and autoimmune hemolytic anemia occur.
Nonspecific acute phase indicators, which include:
Dysproteinemia with an increased content of α 2 - and γ-globulins;
CRP detection;
Increased fibrinogen concentration;
Increased ESR.
With pronounced articular lesions in a small titer, you can find RF - an antibody to the Fc-fragment of IgG.
When researching peripheral blood you can find leukopenia (1-1.2x10 9 / l) with a shift in the leukocyte formula to young forms and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Possible moderate hypochromic anemia, in some cases - hemolytic anemia, accompanied by jaundice, reticulocytosis and positive Coombs' test. Thrombocytopenia is sometimes recorded in combination with Werlhof's syndrome.
Changes in the urine are characteristic of kidney damage, which can be classified as follows (I.E. Tareeva, 1983):
Subclinical proteinuria (protein content in urine 0.5 g / day, often in combination with slight leukocyturia and erythrocyturia);
More pronounced proteinuria, which is an expression of the nephrotic syndrome accompanying subacute or active lupus nephritis.
Very high proteinuria (such as with amyloidosis) is rare. Moderate hematuria is noted. Leukocyturia can be a consequence of both a lupus inflammatory process in the kidneys, and the result of the frequent addition of a secondary infectious lesion of the urinary tract.
Puncture biopsy of the kidneys reveals nonspecific mesangiomembranous changes, often with a fibroplastic component. Considered characteristic:
Detection of altered nuclei (hematoxylin bodies) freely lying in the renal tissue in preparations;
Capillary membranes of the glomeruli in the form of wire loops;
Deposition on the basement membrane of fibrin glomeruli and immune complexes in the form of electron-dense deposits.
According to the WHO classification, the following morphological types of lupus nephritis are distinguished:
Class I - no change.
Class II - mesangial type;
Class III - focal proliferative type;
Class IV - diffuse proliferative type;
Class V - membranous type;
Class VI - chronic glomerulosclerosis.
X-ray examination reveals:
Changes in the joints (with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints, with chronic arthritis and deformities - narrowing of the joint space with subluxation);
Changes in the lungs during the development of pneumonitis (with a long course of the disease - disc-shaped atelectasis, strengthening and deformation of the pulmonary pattern in combination with a high standing of the diaphragm);
Changes in the heart with the development of lupus disease or exudative pericarditis.
The ECG allows you to detect nonspecific changes in the end part of the ventricular complex (tooth T and segment ST), similar to those described earlier for myocarditis and pericarditis.
CT and MRI of the brain reveal pathological changes with damage to the central nervous system.
When conducting a diagnostic search, it is also necessary to determine the degree of activity of the lupus process (Table 7-1).
Table 7-1. Criteria for the activity of the pathological process in systemic lupus erythematosus (Nasonova V.A., 1989)
Expansion of the table. 7-1
Diagnostics
In cases of the classical course of SLE-diagnosis is simple and is based on the detection of a "butterfly", recurrent polyarthritis and polyserositis, which make up the clinical diagnostic triad, supplemented by the presence of LE-cells or ANF in diagnostic titers. The young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation and infectious diseases are of secondary importance. It is much more difficult to establish a diagnosis in other cases, especially if the above classical diagnostic signs are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 (Table 7-2) help.
Table 7-2. Diagnostic criteria for systemic lupus erythematosus (ARA)
The end of the table. 7-2
The diagnosis is reliable when four or more criteria are met. If less than four criteria are present, then the diagnosis of SLE is doubtful, and follow-up of the patient is required. This approach has a clear rationale: it warns against prescribing glucocorticoids to such patients, since other diseases (including paraneoplastic syndrome) can occur with the same symptoms, in which their use is contraindicated.
Differential diagnosis
SLE must be differentiated from a variety of diseases. The list of organs and systems involved in the pathological process in SLE is as large as the list of diseases that can be mistakenly diagnosed in a patient. SLE can more closely mimic various pathological conditions. This happens especially often at the onset of the disease, as well as with a dominant lesion of one or two organs (systems). For example, detection of pleural lesions at the onset of the disease can be regarded as pleurisy of tuberculous etiology; myocarditis can be interpreted as rheumatic or nonspecific. Especially many mistakes are made if SLE debuts with glomerulonephritis. In such cases, only glomerulonephritis is diagnosed.
SLE most often has to be differentiated from ARF (rheumatism), IE, chronic active hepatitis (CAH), hemorrhagic diathesis (thrombocytopenic purpura) and other diseases from the DZST group.
The need for differential diagnosis with rheumatism arises, as a rule, in adolescents and young men at the onset of the disease - with the onset of arthritis and fever. Rheumatoid arthritis differs from lupus in greater severity of symptoms, predominant involvement of large joints and transience. One should not attach a differential diagnostic value to a previous infectious lesion (sore throat), since it can serve as a nonspecific factor causing the development of clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic heart disease) appear. Subsequent dynamic observation makes it possible to detect an emerging heart defect, whereas in SLE, if mitral valve insufficiency is formed, then it is expressed insignificantly and is not accompanied by distinct
hemodynamic disorders. Mitral regurgitation is insignificant. Unlike SLE, leukocytosis is noted in the acute stage of rheumatism. ANF is not detected.
Differential diagnosis between SLE and RA is difficult in the initial stage of the disease, which is due to the similarity of the clinical picture: a symmetrical lesion of the small joints of the hand occurs, new joints are involved in the process, morning stiffness is characteristic. Differential diagnosis is based on the predominance of a proliferative component in the affected joints in RA in the affected joints, the early development of muscle wasting, which sets the affected joints in motion, and the persistence of joint lesions. Erosion of the articular surfaces in SLE is absent, but is a characteristic feature of RA. A high titer of RF is characteristic of RA. In SLE, it is rarely found and in a low titer. Differential diagnosis of SLE and visceral RA is extremely difficult. Refined diagnosis in both cases does not affect the nature of the treatment (the appointment of glucocorticoids).
With CAH, systemic disorders can occur in the form of fever, arthritis, pleurisy, skin rashes, and glomerulonephritis. Leukopenia, thrombocytopenia, LE cells and ANF can be detected. When carrying out differential diagnostics, one should take into account:
CAH develops more often in middle age;
The history of CAH patients has indications of the transferred viral hepatitis;
With CAH, pronounced changes in the structure and function of the liver are found (cytolytic and cholestatic syndrome, signs of liver failure, hypersplenism, portal hypertension);
In SLE, liver damage does not always occur and proceeds as hepatitis easy flow(with moderate signs of cytolytic syndrome);
In CAH, various markers of viral liver damage (antiviral antibodies and viral antigen) are detected.
In primary IE, heart damage (aortic or mitral valve insufficiency) quickly occurs, and antibiotic therapy has a distinct effect. LE cells, antibodies to DNA, ANF are usually absent. With the timely conduct of bacteriological research, the growth of pathogenic microflora is detected.
In thrombocytopenic purpura (idiopathic or symptomatic), many of the syndromes seen in SLE, typical laboratory signs (LE cells, ANP, antibodies to DNA) and fever are absent.
Differential diagnosis with other diseases from the DZST group is the most difficult. Conditions such as STS and DM can share many similarities with SLE. This circumstance aggravates the possibility of detecting ANF and LE cells in these diseases, albeit in a lower titer. The main differential diagnostic signs are more frequent and pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin lesions in SJS and a clear myopathic syndrome in DM. In some cases, only a long-term
dynamic observation of the patient. Sometimes it takes many months or even years (especially in the chronic course of SLE with minimal activity).
The formulation of a detailed clinical diagnosis of SLE should take into account all the headings given in the working classification of the disease. The diagnosis should reflect:
The nature of the course of the disease (acute, subacute, chronic), and in the case of a chronic course (usually mono or oligosyndromic), the leading clinical syndrome should be indicated;
Process activity;
Clinical and morphological characteristics of damage to organs and systems, indicating the stage of functional failure (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the existence or absence of heart failure, with lung damage - the existence or absence respiratory failure and etc.);
Indication of treatment (eg, glucocorticoids);
Complications of treatment (if any).
Treatment
Taking into account the pathogenesis of the disease, complex pathogenetic treatment is recommended for SLE patients. Its tasks:
Suppression of immune inflammation and immune complex disorders (uncontrolled immune response);
Prevention of complications of immunosuppressive therapy;
Treatment of complications arising in the course of immunosuppressive therapy;
Impact on individual, pronounced syndromes;
Removal of CEC and antibodies from the body.
First of all, it is necessary to exclude psychoemotional stress, insolation, actively treat concomitant infectious diseases, consume low-fat food with a high content of polyunsaturated fatty acids, calcium and vitamin D. During the period of exacerbation of the disease and against the background of treatment with cytostatic drugs, active contraception is required. Contraceptives with a high estrogen content should not be taken as they will aggravate the disease.
To suppress immune inflammation and immunocomplex disorders in the treatment of SLE, the main immunosuppressants are used: short-acting glucocorticoids, cytostatic drugs and aminoquinoline derivatives. The duration of treatment, the choice of the drug, as well as the maintenance doses are determined by:
The degree of disease activity;
The nature of the flow (sharpness);
Extensive involvement in the pathological process of internal organs;
Tolerance to glucocorticoids or cytostatics, as well as the existence or absence of complications of immunosuppressive therapy;
The existence of contraindications.
In the initial stages of the disease, with minimal activity of the process and the predominance of joint damage in the clinical picture, glucocorticoids should be prescribed in small doses (prednisone at a dose of less than 10 mg / day). Patients should be registered with the dispensary, so that when the first signs of an exacerbation of the disease appear, the doctor can promptly prescribe glucocorticoid treatment in the optimal dose.
In the chronic course of the disease with a predominant skin lesion, chloroquine (at a dose of 0.25 g / day) or hydroxychloroquine can be used for many months.
If signs of high activity and generalization of the process with the involvement of internal organs appear, it is necessary to immediately switch to a more effective immunosuppressive treatment with glucocorticoids: prednisolone is prescribed at a dose of 1 mg / day or more. The duration of high dose administration ranges from 4 to 12 weeks. The dose reduction should be carried out gradually, under close clinical and laboratory control. Patients should take maintenance doses (5-10 mg / day) for many years.
Thus, the main treatment for SLE is the use of glucocorticoids. When using them, you should adhere to the following principles:
Start treatment only when the diagnosis of SLE is confirmed (if suspected, these drugs should not be used);
The dose of glucocorticoids should be sufficient to suppress the activity of the pathological process;
Suppressive dose treatment should be carried out until a pronounced clinical effect is achieved (improvement general condition, normalization of body temperature, improvement of laboratory parameters, positive dynamics of organ changes);
After achieving the effect, you should gradually switch to maintenance doses;
Prevention of complications of glucocorticoid treatment is mandatory. For warning side effects glucocorticoids are used:
Potassium preparations (orotic acid, potassium chloride, potassium and magnesium asparaginate);
Anabolic agents (methandienone at a dose of 5-10 mg);
Diuretics (saluretics);
Antihypertensive drugs (ACE inhibitors);
Antacids.
With the development of severe complications, the following are prescribed:
Antibiotics (for secondary infection);
Anti-tuberculosis drugs (with the development of tuberculosis, more often - pulmonary localization);
Insulin preparations, diet food (for diabetes mellitus);
Antifungal agents (for candidiasis);
Antiulcer treatment (with the formation of a steroid ulcer).
During treatment with glucocorticoids, situations arise when it is necessary to administer extra-high doses of prednisolone (intravenous drip at a dose of 1000 mg for 30 minutes for three days):
A sharp increase (surge) in the activity of the process (III degree), despite the seemingly optimal treatment;
Resistance to doses that have previously achieved a positive effect;
Severe organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).
Such pulse therapy stops the formation of immune complexes due to inhibition of the synthesis of antibodies to DNA. A decrease in the concentration of the latter, caused by glucocorticoids, leads to the formation of immune complexes of smaller sizes (as a result of the dissociation of larger ones).
A significant suppression of the activity of the process after pulsotherapy allows in the future to prescribe small maintenance doses of glucocorticoids. Pulse therapy is most effective in young patients with a short duration of the disease.
Treatment with glucocorticoids is not always successful due to:
The need to reduce the dose with the development of complications, despite the fact that such therapy is effective in a particular patient;
Intolerance to glucocorticoids;
Resistance to glucocorticoid treatment (usually detected early enough).
In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (monthly intravenous bolus administration at a dose of 0.5-1 g / m2 for at least 6 months, and then every 3 months for 2 years) in combination with prednisone at a dose of 10-30 mg / day. In the future, you can return to treatment with glucocorticoids, since resistance to them usually disappears.
For the treatment of less severe, but glucocorticoid-resistant symptoms of the disease, azathioprine (1-4 mg / kg per day) or methotrexate (15 mg / week) and cyclosporine (at a dose of less than 5 mg / kg per day) are prescribed in combination with low doses of prednisolone (10-30 mg / day).
Criteria for evaluating the effectiveness of the use of cytostatics:
Reduction or disappearance of clinical signs;
Disappearance of steroid resistance;
Persistent decrease in the activity of the process;
Prevention of the progression of lupus nephritis. Complications of cytostatic therapy:
Leukopenia;
Anemia and thrombocytopenia;
Dyspeptic symptoms;
Infectious complications.
With a decrease in the number of leukocytes less than 3.0x10 9 / l, the dose of the drug should be reduced to 1 mg / kg of body weight. With a further increase in leukopenia, the drug is canceled and the dose of prednisolone is increased by 50%.
Extracorporeal methods of treatment - plasmapheresis and hemosorption - are widely used. They allow you to remove the CIC from the body, increase the sensitivity of cellular receptors to glucocorticoids and reduce intoxication. They are used for generalized vasculitis, severe organ damage (lupus nephritis, pneumonitis, cerebrovasculitis), as well as for severe immune disorders that are difficult to treat with glucocorticoids.
Usually, extracorporeal methods are used in combination with pulse therapy or, if it is ineffective, independently. It should be noted that in case of cytopenic syndrome, extracorporeal methods are not used.
Patients with a high titer of antiphospholipid antibodies in the blood, but without clinical signs of antiphospholipid syndrome, are prescribed small doses of acetylsalicylic acid (75 mg / day). With a confirmed antiphospholipid syndrome, accompanied by clinical signs, sodium heparin and small doses of acetylsalicylic acid are used.
For the treatment of musculoskeletal disorders (arthritis, arthralgia, myalgia) and moderate serositis, conventional doses of NSAIDs can be used.
Forecast
In recent years, in connection with the use of effective methods of treatment, the prognosis has improved: 10 years after diagnosis, the survival rate is 80%, and after 20 years - 60%. In 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or cerebrovasculitis, the prognosis remains poor.
Prophylaxis
Since the etiology of SLE is unknown, primary prophylaxis is not given. Nevertheless, a risk group is distinguished, which includes, first of all, relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). They should avoid sun exposure, hypothermia, vaccinations, mud therapy and other balneological procedures.
SYSTEMIC SCLERODERMIA
SJS is a systemic disease of the connective tissue and small vessels, characterized by inflammation and widespread fibrosclerotic changes in the skin and internal organs. This definition of the disease reflects the essence of SJS - fibrous transformation of connective tissue, which serves as a skeleton of internal organs, a constituent element of the skin and blood vessels. The unrestrained development of fibrosis is associated with excessive collagen formation due to dysfunction of fibroblasts.
The prevalence of SJS is different in different geographic areas and ethnic groups, including those living in the same region. The primary incidence ranges from 3.7 to 19.0 cases per million population per year. SJS is more often recorded among women (ratio 5: 7.1) at the age of 30-60 years.
Etiology
The cause of the development of the disease is unknown. They attach importance to viruses, since there is indirect evidence of their role in the occurrence of SJS: virus-like inclusions and an increased titer of antiviral antibodies were found in the affected tissues. A family-genetic predisposition to SJS was established, since the relatives of patients show changes in protein metabolism in the form of hypergammaglobulinemia, Raynaud's syndrome, and sometimes SJS.
The unfavorable factors contributing to the manifestation of the disease and its exacerbations include factors external environment(prolonged contact with polyvinyl chloride, silicon dust), the use of drugs (bleomycin, tryptophan), as well as cooling, trauma, impaired neuroendocrine functions and exposure to occupational hazards in the form of vibration.
Pathogenesis
At the heart of the pathogenesis is a violation of the interaction process different cells(endothelial, smooth muscle cells vascular wall, fibroblasts, T- and B-lymphocytes, monocytes, mast cells, eosinophils) with each other and the components of the connective tissue matrix. The result of all of the above is the selection of a population of fibroblasts resistant to apoptosis and functioning in an autonomous mode of maximum synthetic activity, which activates neofibrillogenesis and contributes to a change in glycoproteins of the main substance of connective tissue. As a result, fibrosclerotic changes in the connective tissue develop. At the same time, the body's immune response to the introduction of the virus is dysregulated, which is expressed in the overproduction of antibodies to its own tissues (autoantibodies). Then, immune complexes are formed, which are deposited in the microvasculature and internal organs, which leads to the development of immune inflammation. The severity of immune and autoimmune disorders in SJS is not as great as in SLE.
Fibrosclerotic changes in connective tissue, damage to blood vessels and internal organs as a result of immune inflammation cause a variety of clinical signs of the disease (Fig. 7-1).
Classification
In our country, a working classification of SJS has been adopted, taking into account the nature of the course, the stage of development of the disease and the clinical and morphological characteristics of damage to organs and systems.
The nature of the flow:
Rapidly progressing;
Chronic.
Stage:
Initial;
Generalized;
Terminal.
Rice. 7-1. Pathogenesis of systemic scleroderma
Clinical and morphological characteristics of the lesion:
Skin and peripheral vessels - dense edema, induration, hyperpigmentation, telangiectasia, Raynaud's syndrome;
Musculoskeletal system - arthralgia, polyarthritis, pseudoarthritis, PM, calcification, osteolysis;
Heart - myocardial dystrophy, cardiosclerosis, heart disease (most often - valve insufficiency);
Lungs - interstitial pneumonia, sclerosis, adhesive pleurisy;
Digestive system - esophagitis, duodenitis, spruce-like syndrome;
Kidney - true sclerodermic kidney, chronic diffuse glomerulonephritis, focal glomerulonephritis;
Nervous system - polyneuritis, neuropsychiatric disorders, autonomic shifts.
The severity of skin tightening is assessed by palpation using a 4-point system:
0 - no seal;
1 - slight compaction;
2 - moderate compaction;
3 - pronounced compaction (inability to fold).
In recent years, prescleroderma, diffuse cutaneous scleroderma, limited (limited) scleroderma, including the syndrome CREST(this syndrome will be discussed below), and scleroderma without scleroderma (this option is very rare and accounts for no more than 5% of all patients with SJS).
The chronic course, which is most characteristic of SJS, is characterized by gradually developing vasomotor disorders like Raynaud's syndrome and the trophic disorders caused by them, which serves as the only symptom of the disease for many years. Subsequently, the thickening of the skin and periarticular tissues joins with the development of osteolysis and slowly progressive sclerotic changes in the internal organs (esophagus, heart, lungs).
A rapidly progressive course is characterized by the occurrence of severe fibrous peripheral and visceral lesions in the first year of the disease and frequent kidney damage of the type of true scleroderma kidney (the most common cause of death in patients).
Given the progressive nature of the disease, three stages of the course are distinguished to assess the evolution and the degree of growth of the pathological process:
Stage I - initial manifestations - mainly articular changes in subacute, and vasospastic changes in chronic course;
Stage II - generalization of the process - polysyndromic and polysystemic lesions of many organs and systems;
Stage III - terminal - the predominance of severe sclerotic, dystrophic or vascular-necrotic processes (often - with clear dysfunctions of one or more organs).
Clinical picture
The clinical picture of the disease is characterized by polymorphism and polysyndromism, reflecting its generalized nature. There is practically no organ or system that could not be involved in the pathological process.
On the first stage of the diagnostic search receive information on the basis of which it is possible to form an idea of the diagnosis and the variant of the onset of the disease, the nature of the course of the process, the involvement of various organs in the pathological process, the previously carried out treatment and its effectiveness, as well as complications.
More often, the disease begins with skin lesions, and then organ damage gradually joins (typical form). In other cases (atypical form) in the clinical picture, from the very beginning, the lesion of the internal organs with minimal skin changes predominates, which complicates the diagnosis. As the disease progresses, you can get an idea of the nature of its course (acute, subacute and chronic).
Complaints of patients with the involvement of internal organs in the pathological process correspond to subjective symptoms with one or another of their lesions (pleurisy, arthritis, Raynaud's syndrome, duodenitis, etc.). At the same time, patients may present complaints that are most characteristic of SJS: difficulty in swallowing and choking when swallowing as a result of damage to the upper
parts of the esophagus. Vasospastic disorders in Raynaud's syndrome are not limited to the fingers, but to the hands and feet. It is not uncommon for patients to experience a feeling of numbness in the lips, any part of the face, and the tip of the tongue. They complain of dryness of the mucous membrane of the mouth and conjunctiva, as well as the inability to cry (no tears). Facial skin lesions are expressed in a feeling of tightness in the skin and mouth (it is difficult to open the mouth). As a rule, the body temperature is not elevated. Weight loss (sometimes significant) is usually noted with the progression and generalization of the disease.
After the first stage (with a long course of the disease), you can make a definite conclusion about the diagnosis. It can be extremely difficult to do this at the very beginning, since the symptoms of SJS in many ways resemble other conditions from the DZST group (SLE, RA, DM), and with mono or oligosyndromism, other diseases characterized by damage to only one organ (heart, lungs, etc.) ...
Ha second stage of diagnostic search receive data indicating damage to organs and systems and their functional failure. With a detailed clinical picture of the disease, skin lesions are noted in the vast majority of patients. It is expressed in the sequential development of edema, induration, and then atrophy with predominant localization on the face and hands. Trophic changes in the skin are also possible in the form of depigmentation, accentuated vascular pattern and telangiectasias. The defeat of the mucous membranes is expressed in increased dryness. Ulceration and pustular rash may occur on the skin; hair falls out, nails are deformed. In the final stage of the disease, the skin of the face becomes dense, it is impossible to take it into a fold. The face is amimic, mask-like. The shape of the mouth is characteristic: the lips are thin, collected in non-expanding folds, the ability to open the mouth wide is gradually lost (symptom of "pouch").
Vasospastic changes in Raynaud's syndrome in the form of whitening of the skin surface are found in the face, lips, hands and feet.
The defeat of the joints is expressed in their defiguration due to the predominant damage to the periarticular tissues, as well as true sclerodermic polyarthritis with a predominance of exudative-proliferative or fibro-indurative changes. The development of the scleroderma hand is characteristic: shortening of the fingers due to osteolysis of the nail phalanges, thinning of their tips, deformation of the nails and mild flexion contractures. Such a brush is compared to a bird's paw (sclerodactyly).
Muscle damage, morphologically representing fibrous interstitial myositis or myositis with dystrophic and necrotic changes, is expressed in myasthenic syndrome, atrophy, muscle mass and movement disorders. The formation of painful seals (calcifications) in the muscles is possible. Especially often, calcium salt deposits are found in the soft tissues of the fingers.
The defeat of the gastrointestinal tract (esophagitis, duodenitis, malabsorption syndrome or persistent constipation) is mainly found at the first and third stages of the diagnostic search.
The defeat of the respiratory system is expressed in the form of pneumonitis, acute or chronic, sluggish. Physical data are extremely scarce, in severe cases, only emphysema of the lungs is detected. Significantly more information is provided by X-ray examination, which provides significant assistance in identifying bilateral basal pneumosclerosis, characteristic of SJS.
With severe pneumosclerosis and its long-term existence, pulmonary hypertension develops, leading first to hypertrophy of the right ventricle, and then to its failure. Pulmonary hypertension manifests itself with cyanosis, an accent of the II tone in the second intercostal space to the left of the sternum, shortness of breath, a sharp decrease in exercise tolerance and a pronounced increase in pulsation in the epigastric region due to right ventricular hypertrophy.
Heart disease occupies the main place among the visceral symptoms of SJS both in frequency and in influence on the outcome of the disease. SS is characterized by the so-called primary cardiosclerosis, which is not associated with previous necrotic or inflammatory changes in the myocardium. An increase in the heart (sometimes significant) is noted, as well as violations heart rate in the form of extrasystole or MA. The defeat of the endocardium leads to the development of heart disease, almost always - to mitral insufficiency. The combination of the latter with cardiosclerosis in some cases can lead to the development of heart failure with all of its characteristic features... Pericarditis with SS is rarely observed and more often it proceeds as dry.
Lesion of small vessels - scleroderma angiopathy - manifests vasomotor disorders (Raynaud's syndrome) and is characterized by paroxysmal vasospasm with a characteristic sequence of changes in the color of the skin of the fingers (whitening, cyanosis, redness), a feeling of tension and soreness. In severe cases, Raynaud's syndrome leads to hemorrhages, tissue necrosis of the fingers and telangiectasias.
Kidney damage in SJS (in 80% of patients) is caused by pathological changes in blood vessels, but not by the development of fibrosis. The most severe symptom is scleroderma renal crisis, usually developing in the first five years of the disease in patients with diffuse SJS and manifesting malignant hypertension (BP more than 170/130 mm Hg), rapidly progressing renal failure, hyperreninemia (in 90% of cases) and nonspecific signs. The latter are represented by shortness of breath, headache and seizures. With kidney damage in the form of isolated changes in urinary sediment, no significant pathological signs are found during physical examination.
The damage to the nervous system is based on vascular, dystrophic and fibrotic changes, represented by symptoms of polyneuritis with impaired reflexes and sensitivity.
Thus, after the second stage, multiple organ lesions are found with a predominant lesion of the skin and its derivatives. The degree of change is very different - from subclinical to significantly pronounced. The possibility of establishing the diagnosis of SJS with predominantly skin lesions
higher than with the predominance of visceral disorders. In the latter case, if the defeat of any one organ (kidney, heart) comes to the fore, there are prerequisites for making diagnostic errors.
You can:
Determine the degree of activity of the process;
Clarify the severity of damage to internal organs;
Conduct differential diagnostics with other diseases from the group of chronic DZST.
In determining the degree of disease activity, the most important are nonspecific acute phase indicators, which include:
Dysproteinemia with an increase in the concentration of a 2 -and γ-globulins;
Increasing the content of CRP;
Increased fibrinogen concentration;
Increased ESR.
The existence and severity of immune disorders can be judged by the definition of RF (found in 40-50% of cases), antinuclear antibodies (in 95%) and LE-cells (in 2-7% of patients). In contrast to SLE, all these indicators with SKD are found in a significantly lower titer and less often.
The greatest diagnostic value is attached to the so-called sclerodermic antibodies.
Scl-70 antibodies are more often found in diffuse forms of SJS (40%). Their presence in combination with the carriage of HLA-DR3 / DRw52 is a prognostically unfavorable factor in patients with Raynaud's syndrome, increasing the risk of developing pulmonary fibrosis in SS by 17 times.
Antibodies to the centromere (chromosome element) are found in 20-30% of patients (most of them have signs of CREST syndrome).
Antibodies to RNA polymerase I and III are highly specific for SJS. They are present mainly in patients with a diffuse form and are associated with kidney damage and poor prognosis.
In case of kidney damage, proteinuria is expressed to one degree or another in combination with minimal changes in urinary sediment (microhematuria, cylindruria). With true scleroderma kidney (development of renal tissue necrosis due to damage to renal vessels), acute renal failure may develop with an increase in creatinine in the blood.
With SJS, a dissociation is noted between the pronounced morphological changes in the renal tissue and blood vessels found during puncture biopsy and relatively moderate clinical (including laboratory) signs of kidney damage. If hypertension develops as a result of kidney damage, then changes in the fundus are noted (narrowing of the arteries and varicose veins).
With heart damage, the ECG determines nonspecific changes in the terminal part of the ventricular complex (decrease in amplitude and inversion of the T), and sometimes - violations of intraventricular conduction. Radiographically visualize the enlargement of the heart. X-rays help
to detect calcification of the muscles and soft tissues of the fingers of the hand, as well as to differentiate joint changes in SS with disorders in RA (with SS there is no erosion of the articular surfaces). In 60-70% of cases, X-ray shows damage to the gastrointestinal tract (especially the esophagus and intestines). Changes in the esophagus are represented by its diffuse expansion in combination with narrowing in the lower third, weakening of peristalsis and some rigidity of the walls.
Biopsy of the skin, synovium and muscles reveals fibrotic changes characteristic of SS, as well as vascular lesions. The data of morphological research are not decisive in establishing the diagnosis.
Diagnostics
Diagnosis of the disease is based on the detection of large and small diagnostic criteria.
Large criteria include proximal scleroderma - symmetrical thickening, induration and induration of the skin of the fingers and skin located proximal to the metacarpophalangeal and metatarsophalangeal joints. Changes can affect the face, neck, and torso (chest and abdomen).
Small criteria:
Sclerodactyly - the above skin changes, limited by the involvement of fingers in the pathological process;
Scars on the tips of the fingers or loss of material from the pads of the fingers;
Bilateral basal pulmonary fibrosis.
A patient with SJS must have either a major criterion (large), or at least two minor criteria. Sensitivity - 97%, specificity - 98%.
The combination of calcification, Raynaud's syndrome, esophagitis, sclerodactyly and telangiectasias (syndrome CREST- by the first letters of the English names of the listed symptoms).
Diagnosis of SJS in the early stages is based on the detection of a triad of initial signs (arising most early): Raynaud's syndrome, articular syndrome (more often polyarthralgia) and dense skin edema. Significantly less often at an early stage, one of the visceral localizations of the process is detected.
Significant difficulties in the diagnosis of SJS are associated with the absence of a characteristic skin syndrome in patients with severe polysyndromic lesions of internal organs (the so-called SJS without scleroderma). In these cases, an X-ray examination provides significant help, allowing to detect a violation of the motility of the esophagus and its expansion, as well as dilatation of the duodenum and colon.
Differential diagnosis
SJS should be differentiated from a number of diseases and, first of all, from other DZST, as well as from diseases, the clinical picture of which is very similar to that of a lesion of any organ in SJS (subject to its additional
mining). For example, with sclerodermic heart disease, differential diagnosis is carried out with atherosclerotic cardiosclerosis, rheumatic heart disease and nonspecific myocarditis; with pulmonary disease - with chronic pneumonia, tuberculosis and occupational lung diseases (pneumoconiosis); if the esophagus is damaged, its cancer should be excluded.
The basis for differential diagnosis is the detection of symptoms typical of SJS.
The predominance of peculiar skin lesions in combination with Raynaud's syndrome and slightly pronounced laboratory data in SJS, in contrast to skin changes in SLE, combined with a higher activity of the pathological process (according to laboratory studies).
In contrast to SLE, with SJS, damage to internal organs is not combined with pronounced immune disorders (ANF, RF and antibodies to DNA are found in a lower titer, the frequency of detection and the number of LE cells are also low).
Articular syndrome in SS, in contrast to RA, is combined with muscle contractures, calcium deposition in soft tissues and muscles, fibrous ankylosis and osteolysis of the terminal phalanges. There are no destructive changes in bone tissue with SS; damage to periarticular tissues predominates.
Unlike IHD, heart disease in SS is not accompanied by anginal pain. There are no signs of a previous MI on the ECG. Unlike rheumatic lesions hearts, with SS, stenosis never develops (mitral, orifice of the aorta); there is usually mild, isolated mitral regurgitation.
The dominant lesion of any system or organ in SJS is always combined with skin and muscle changes and Raynaud's syndrome. For the clinical picture of other diseases (chronic pneumonia, atherosclerotic cardiosclerosis, bowel disease, peptic ulcer), from which it is necessary to differentiate SJS, monosyndromism is characteristic.
In SJS, skin changes and Raynaud's syndrome dominate, while in DM, muscle damage in combination with a kind of lilac paraorbital edema ("glasses symptom") comes to the fore.
Glucocorticoids in SLE do not give such a striking positive effect as in SLE.
In a number of cases, when SJS manifests with articular, skin and asthenovegetative syndrome, only long-term follow-up allows a correct diagnosis to be made.
The formulation of a detailed clinical diagnosis should take into account the headings given in the working classification. The diagnosis should reflect:
The nature of the flow;
Stage;
Clinical and morphological characteristics of damage to organs and systems of the body, indicating the stage of functional failure (for example,
measures, with pneumosclerosis - stages of pulmonary failure, with kidney damage - stages of renal failure, etc.).
Treatment
SJS treatment should be comprehensive and take into account the following aspects:
Impact on vascular complications and, first of all, on Raynaud's syndrome;
Impact on the development of fibrotic changes;
Immunosuppression and anti-inflammatory action;
Impact on local symptoms of the disease.
Avoid the influence of cold, smoking, local impact vibration, stressful situations and taking drugs that cause peripheral vascular spasm (β-blockers without vasodilating action).
Drug treatment of Raynaud's syndrome involves the appointment of blockers of slow calcium channels - amlodipine (5-20 mg / day), long-acting nifedipine (30-90 mg / day), felodipine (5-10 mg / day), as well as prolonged verapamil actions (240-480 mg / day) or diltiazem (120-360 mg / day).
Oral ingestion of pentoxifylline (400 mg 3 times a day) has a good effect. Antiplatelet agents are also prescribed - dipyridamole (300-400 mg / day) or ticlopidine (500 mg / day).
In critical situations (pulmonary hypertension, gangrene, renal crisis), synthetic prostaglandins are injected intravenously for 6-24 hours for 2-5 days: alprostadil (0.1-0.4 μg / kg per minute) or iloprost (0 , 5-2 ng / kg per minute).
A drug that destroys internal bonds in the collagen molecule and inhibits excess collagen formation is penicillamine. It is prescribed for subacute course, rapidly growing inductive skin changes and symptoms of progressive generalized fibrosis on an empty stomach every other day at a dose of 250-500 mg / day. Previously recommended high doses (750-1000 mg / day) do not increase the effectiveness of treatment, but the incidence of side effects significantly increases. When treating with penicillamine, it is necessary to monitor the laboratory parameters of urine, since proteinuria may develop at 6-12 months from the start of treatment. When it increases to 0.2 g / day, the drug is canceled. For severe skin lesions, enzyme therapy is recommended. Assign subcutaneous administration of hyaluronidase near the affected areas or electrophoresis with this drug.
Anti-inflammatory and cytotoxic drugs are used at the early (inflammatory) stage of SJS and in the rapidly progressing course of the disease.
Glucocorticoids in small doses (15-20 mg / day) are used for progressive diffuse skin lesions and clear clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory
arthritis and tendosynovitis). Taking large doses is not recommended (risk of developing scleroderma renal crisis).
When administered at a dose of 2 mg / kg per day for 12 months, cyclophosphamide reduces pruritus only in patients with diffuse SJS.
Methotrexate is prescribed when SSD is combined with RA or PM.
In case of sclerodermic renal crisis, ACE inhibitors (captopril 100-150 mg / day, enalapril 10-40 mg / day) are used under the control of blood pressure to eliminate vascular spasms and prevent the development of scleroderma kidney.
In case of damage to the esophagus, in order to prevent dysphagia, frequent fractional meals are recommended and the exclusion of food intake later than 18 hours. Treatment of dysphagia involves the appointment of prokinetics (metoclopramide at a dose of 10 mg 3-4 times a day). With reflux esophagitis, omeprazole is prescribed (by mouth, 20 mg / day).
The impact on the local symptoms of the disease involves the application of a 25-50% solution of dimethyl sulfoxide. In periods of inactivity of the pathological process, exercise therapy and massage can be recommended.
Forecast
With SJS, the prognosis is determined by the course and stage of development. It is noted that the more time separates the developed stage from the appearance of the first signs of the disease (in particular, Raynaud's syndrome), the more favorable the prognosis. The five-year survival rate ranges from 34 to 73%, averaging 68%. The risk of death with SJS is 4.7 times higher than in the population.
Poor prognosis predictors:
Diffuse form of the disease;
Age of disease onset is over 47 years old;
Male;
Pulmonary fibrosis, pulmonary hypertension, arrhythmias, kidney damage in the first three years of illness;
Anemia, high ESR, proteinuria at the onset of the disease.
Prophylaxis
The risk group includes persons with a tendency to vasospastic reactions, polyarthralgias, as well as relatives of patients suffering from various diffuse connective tissue diseases. They should not be exposed to provoking factors (cooling, vibration, injury, exposure to chemicals, infectious agents, etc.). Patients with SJS are put on dispensary registration. Systematic treatment (in particular, properly selected supportive therapy) is the best way to prevent exacerbations.
DERMATOMYOSITIS (POLYMYOSITIS)
DM is a systemic inflammatory disease of skeletal, smooth muscles and skin. Less often, the involvement of internal organs in the pathological process is noted. In the absence of skin lesions use the term "polymyositis" PM.
The main symptom of the disease is severe muscle weakness due to progressive severe necrotizing myositis with a predominant lesion of the muscles of the proximal extremities. As the disease progresses, muscle tissue atrophies and is replaced by fibrous tissue. Similar processes occur in the myocardium. Dystrophic changes develop in the parenchymal organs. The pathological process also involves the vessels of muscles, internal organs and skin.
DM (PM) is a rare disease. The frequency of its occurrence in the population ranges from 2 to 10 cases per 1 million population per year. The disease affects people of mature age (40-60 years), more often men than women (ratio 2: 1).
Etiology
There are two forms of DM (PM) - idiopathic and secondary (tumor). The etiology of idiopathic DM is unclear, but there are known factors contributing to the manifestation, and further exacerbation of this disease:
Insolation;
Hypothermia;
Infectious disease (acute respiratory infections, flu, tonsillitis, etc.);
Hormonal changes (menopause, pregnancy, childbirth);
Emotional stress;
Physical trauma, surgery;
Sensitization with drugs (chlorpromazine, insulin preparations, antibiotics, penicillamine);
Vaccination;
Contact with epoxy resins, photo solvents;
Physiotherapy procedures.
Probably, the hereditary and genetic predisposition is important: the patients are found to have B-8 / DR3, B14 and B40 antigens of the HLA system. This is closely related not to the disease itself, but to certain immune disorders and, first of all, to the overproduction of myosin-specific autoantibodies.
Tumor (secondary) DM accounts for 25% of all cases of the disease and develops in patients with malignant tumors. Most often, DM occurs in cancer of the lung, intestine, prostate, ovary, as well as in hematological malignancies. The occurrence of DM in persons over the age of 60 almost always indicates its neoplastic origin.
Pathogenesis
Under the influence of a virus and a genetic predisposition or tumor antigens, a violation (dysregulation) of the immune response occurs, expressing
in the imbalance of the B- and T-systems of lymphocytes: the body produces antibodies to skeletal muscles and the sensitization of T-lymphocytes to them develops. The "antigen-antibody" reaction and the cytotoxic effect of muscle-sensitized T-lymphocytes promote the formation and deposition of immune complexes in the muscles and microvasculature of various organs. Their elimination leads to the release of lysosomal enzymes and the development of immune inflammation in muscles and internal organs. With inflammation, new antigens are released, which contribute to the further formation of immune complexes, which leads to the chronicity of the disease and the involvement of previously healthy muscles in the pathological process. The main links in the pathogenesis of DM are shown in Fig. 7-2.
Rice. 7-2. Pathogenesis of dermatomyositis
Clinical picture
The clinical picture of the disease is systemic and polysyndromic.
Major syndromes:
Muscular (myositis, muscle atrophy, calcification);
Cutaneous (erythema, skin edema, dermatitis, pigmentation and depigmentation, telangiectasia, hyperkeratosis, urticaria);
Articular (arthralgia, damage to the periarticular tissues, rarely true arthritis);
Visceral (myocarditis, cardiosclerosis, pneumonitis, aspiration pneumonia, pulmonary fibrosis, gastrointestinal bleeding, myoglo-
bulinuric kidney with the development of acute renal failure, polyneuropathy). Allocate next periods course of the disease:
Period I (initial) - lasts from several days to 1 month or more, manifests only muscle and (or) skin changes;
II period (manifest) - a detailed picture of the disease;
III period (terminal) - represented by dystrophic changes in internal organs and signs of their pronounced functional failure (complications may develop).
There are three forms of the course of the disease:
Acute form, when generalized damage to skeletal muscles rapidly grows, leading to complete immobility of the patient. The lesion of the muscles of the pharyngeal ring and esophagus progresses (dysphagia, dysarthria). Damage to internal organs (especially the heart) develops rapidly with a lethal outcome 2-6 months after the onset of the disease;
Subacute form with slower, gradual onset of symptoms. Severe muscle damage and visceritis occur after 1-2 years;
Chronic form with a long cyclic course. The processes of atrophy and sclerosis predominate. Local muscle damage is possible.
On the first stage of the diagnostic search receive information about the nature of the onset of the disease - acute (an increase in body temperature up to 38-39 ° C, skin erythema and muscle pain) or gradual (moderate weakness, unsharp myalgia and arthralgia, aggravated after physical exertion, insolation or other adverse effects).
The most typical complaints are due to muscle damage: patients note weakness, cannot sit or stand on their own, it is extremely difficult for them to climb stairs, and muscle pain is not uncommon. Muscle weakness and soreness are localized symmetrically in the proximal extremities, back and neck.
When the pharyngeal muscles are affected, patients complain of choking when swallowing, liquid food is poured out through the nose. The nasal tone of the voice and hoarseness are caused by damage to the muscles of the larynx.
With skin lesions, patients note a persistent change in its color in places exposed to the sun (décolleté, face, hands), as well as on the outer surfaces of the thighs and legs. Characterized by the appearance of paraorbital edema lilac ("glasses symptom"). When the mucous membranes are affected, patients complain of dryness, burning in the eyes and the absence of tears ("dry" syndrome).
Involvement of various organs in the pathological process is expressed by symptoms characteristic of myocarditis, cardiosclerosis, pneumonitis, glomerulonephritis, polyneuritis, arthritis, etc.
Information about the treatment carried out allows us to judge about its correct selection, and indirectly about the nature of the course: the use of aminoquinoline drugs indicates a chronic course, the use of prednisolone and cytostatics is more acute.
On second stage of diagnostic search with a detailed clinical picture of the disease, first of all, symmetrical muscle damage is noted: dense, doughy to the touch, they are enlarged and painful on palpation. With the defeat of the mimic muscles, a certain mask-like face is noticeable. In the future, muscle atrophy occurs, especially pronounced from the side of the shoulder girdle. The respiratory muscles and diaphragm are also affected. On palpation of the muscles, local seals can be found - calcifications, which are also located in the subcutaneous fatty tissue. Calcification often develops in young people with widespread muscle damage during the transition of an acute course to a subacute or chronic one. Often, a decrease in body weight by 10-20 kg is noted.
Skin lesion is not an obligatory sign of DM, but when it exists on open parts of the body, edema, erythema are noted (over the joints - supra-articular erythema, in the periungual zones in combination with micronecrosis in the form of dark dots - Gottron's syndrome), capillaritis, petechial rashes and telangiectasias. Erythema is very persistent, cyanotic, accompanied by itching and desquamation. A typical "eyeglass symptom" is erythema around the eyes. Redness, peeling and cracking of the skin of the palms ("the hand of a mechanic or artisan"), brittle nails and increased hair loss are often noted.
Quite often, pronounced Raynaud's syndrome is recorded.
Signs of visceral lesions in DM, as well as in SJS, are not too bright, in contrast to SLE. We can note the well-known dissociation between the severity of pathomorphological changes in organs and their clinical manifestation. Damage to the heart (myocarditis, cardiosclerosis) is represented by such nonspecific signs as an increase in its size, deafness, tachycardia and arrhythmias in the form of extrasystole. Severe changes in the myocardium can lead to symptoms of heart failure.
The defeat of the lungs in the form of pneumonitis is accompanied by extremely meager symptoms. Developing fibrosis is detected by signs of pulmonary emphysema and respiratory failure. Aspiration pneumonia is characterized by all the typical symptoms.
Dysphagia is characteristic of lesions of the gastrointestinal tract: solid food is regurgitated and liquid food is poured out through the nose. Pathological changes in the vessels of the stomach and intestines can lead to gastrointestinal bleeding... Sometimes there is a moderate increase in the liver, less often - hepatolienal syndrome with an increase in lymph nodes.
Neurological disorders are represented by changes in sensitivity: hyperesthesia of a peripheral or radicular nature, hyperalgesia, paresthesia and areflexia.
On third stage of diagnostic search significant help is provided by research methods that allow assessing the severity of the inflammatory process and the prevalence of muscle damage.
The severity of the process can be judged by nonspecific acute phase indicators (increased ESR, increased content of fibrinogen and CRP,
hyper-a 2 -globulinemia) and signs of immune changes (low titer of RF, an increase in the content of γ-globulins, antibodies to nucleoprotein and soluble nuclear antigens, antibodies to Mi2, Jol, SRP, and in the case of idiopathic DM, an increase in IgG concentration).
In a chronic, sluggish course of the disease, changes in acute phase indicators may be absent (ESR is often normal).
The prevalence of muscle damage is characterized by a number of biochemical changes. The creatine / creatinine index increases, which is associated with the presence of creatine in the urine with a decrease in creatinuria. With significant muscle damage, myoglobinuria may occur. An increase in transaminase activity is not typical of skeletal muscle lesions. In some patients with myopathic syndrome, this suggests hepatitis.
During immunological research, myositis-specific antibodies are detected. These include antibodies to the aminoacyl synthetases of the transport RNA (antisynthetase antibodies) and, first of all, antibodies to histidyl-tRNA synthetase (Jo1). Antibodies Jo1 are found in half of patients with DM (PM), while other anti-synthetase antibodies are extremely rare (5%). The production of antisynthetase antibodies is associated with the development of the so-called antisynthetase syndrome, characterized by acute onset, fever, symmetric arthritis, interstitial lung disease, Raynaud's syndrome, and hand-mechanic damage to the hands.
For DM tumor origin in men, the detection of a prostate-specific antigen is characteristic, in women - CA-125 (ovarian tumor antigen). In addition, other tumor-specific antigens can be detected at other tumor localization.
Electromyography, which makes it possible to detect normal electrical activity muscles in a state of their voluntary relaxation and low-amplitude - with voluntary contractions.
On biopsies of skin and muscles, a picture of severe myositis with loss of transverse striation is noted. muscle fibers, fragmentation, granular and waxy degeneration, as well as foci of necrosis, lymphoid-plasma cell infiltration and fibrosis phenomena. Muscle biopsy is performed to confirm the diagnosis of DM even in the presence of characteristic clinical, laboratory and instrumental signs of the disease. The most informative is a biopsy of a muscle involved in the pathological process, but without pronounced atrophy.
Other research methods (ECG, X-ray and endoscopic) are necessary for:
Assessment of the condition of the affected internal organs;
Search for a tumor in case of suspected DM of tumor origin.
Diagnostics
For the diagnosis of DM (PM), the following diagnostic criteria should be used.
Skin lesions:
Heliotrope rash (purple-red rash on the eyelids);
Gottron's sign (purplish-red scaly atrophic erythema or spots on the extensor surface of the hands above the joints);
Erythema on the extensor surface of the limbs above the elbow and knee joints.
Proximal muscle weakness (upper and lower limbs and trunk).
Increased activity of CPK or aldolase in the blood.
Muscle pain on palpation or myalgia.
Myogenic changes in electromyography (short polyphase potentials of motor units with spontaneous fibrillation potentials).
Detection of antibodies Jo1 (antibodies to histidyl-tRNA synthetase).
Non-destructive arthritis or arthralgia.
Signs of systemic inflammation (an increase in body temperature over 37 ° C, an increase in the concentration of CRP or ESR over 20 mm / h).
Morphological changes corresponding to inflammatory myositis (inflammatory infiltrates in skeletal muscles with degeneration or necrosis of muscle fibers, active phagocytosis or signs of active regeneration).
If at least one type of skin lesion and at least four other signs are detected, the diagnosis of DM is reliable (sensitivity - 94.1%, specificity - 90.3%).
The presence of at least four signs corresponds to the diagnosis of PM (sensitivity - 98.9%, specificity - 95.2%).
Differential diagnosis
Despite the high sensitivity and specificity of the criteria, the diagnosis of DM (PM) presents great difficulties, especially in the onset of the disease.
DM (PM) should be differentiated from infectious and neurological diseases, SJS, SLE and RA. Differential diagnosis is based on the following changes:
Persistence of the articular syndrome in RA, detection of erosions of the articular surfaces of the bones during X-ray examination, the absence of changes in the skin and muscles characteristic of DM.
In contrast to SLE, in DM, visceral disturbances are not so pronounced and occur much less frequently. In the clinical picture of DM, muscle damage predominates, and laboratory parameters (especially immunological) are changed to a much lesser extent.
In contrast to SJS, skin changes in DM have a completely different character: there are no typical changes in the hands, and muscle syndrome (including severe muscle weakness) is considered the leading one. Nevertheless, the differential diagnosis of SJS and DM is the most difficult. In difficult cases, it is necessary to use electrophysiological and morphological research methods.
In the acute course of DM, it is necessary to exclude an infectious lesion (septic condition, erysipelas and others), which is possible with dynamic observation of the patient.
With the dominance of adynamia and impaired reflexes, it becomes necessary to carry out differential diagnostics with neurological diseases, which is carried out with the joint observation of the patient by a therapist and a neuropathologist.
The formulation of a detailed clinical diagnosis of DM should reflect:
Period of flow;
Flow shape;
Clinical and morphological characteristics of damage to systems and organs, indicating the leading syndromes and the existence or absence of functional insufficiency of organs (systems).
Treatment
The main task is to suppress the activity of immune reactions and the inflammatory process, as well as normalize the function of individual, most affected organs and systems. An early start of treatment (within the first 3 months after the onset of symptoms) is associated with a better prognosis than later.
The best effect is provided by glucocorticoids: in DM, it is preferable to prescribe prednisolone (1-2 mg / kg per day). During the first weeks daily dose should be divided into three doses, and then take it all once in the morning, since the improvement in the patient's condition develops more slowly than with SLE or SJS (on average, after 1-3 months). In the absence of positive dynamics within 4 weeks, the dose of glucocorticoids should be increased. After the effect is achieved (normalization of muscle strength and CPK activity), the dose of prednisolone is very slowly reduced to a maintenance dose, every month - by 1/4 of the total. Dose reduction must be carried out under strict clinical and laboratory supervision.
Pulse therapy is rarely effective. It is prescribed for the rapid progression of dysphagia (risk of aspiration pneumonia) and the development of systemic lesions (myocarditis, alveolitis).
If treatment with prednisolone is not effective or cannot be prescribed due to intolerance and the development of complications, then cytostatic drugs should be used.
At present, the early appointment of methotrexate is recommended, which allows faster transfer of patients to maintenance doses of prednisolone. Methotrexate is administered orally, subcutaneously or intravenously at a dose of 7.5-25 mg / week. Intravenous administration of the drug is recommended in case of insufficient effectiveness or poor tolerance when taken orally. It should be remembered that the absence of the effect of prednisolone treatment indicates the possibility of the existence of a tumor ANF, therefore, before prescribing cytostatic drugs, an extended oncological search should be carried out to exclude a malignant tumor.
Patients with prednisone-resistant forms of the disease are prescribed oral cyclosporine at 2.5-5.0 mg / kg per day.
Azathioprine is inferior to methotrexate in terms of effectiveness. The maximum effect develops later (on average, after 6-9 months). Prescribe the drug inside at 100-200 mg / day.
Cyclophosphamide is the agent of choice for interstitial pulmonary fibrosis (2 mg / kg per day).
Aminoquinoline drugs (chloroquine, hydroxychloroquine) are used in the following situations:
In the chronic course of the disease without signs of activity of the process (to control skin lesions);
With a decrease in the dose of prednisolone or cytostatics to reduce the risk of a possible exacerbation.
Plasmapheresis should be prescribed to patients with severe, resistant to other methods of treatment of DM (PM) in combination with glucocorticoids and methotrexate or cytostatic drugs.
In recent years, TNF-α inhibitors have been increasingly used for treatment. A promising line of treatment is associated with the use of rituximab. The maximum effect develops 12 weeks after the first injection, which is associated with a decrease in the content of CD20 + B-lymphocytes in the peripheral blood.
Forecast
Currently, in connection with the use of prednisolone and cytostatics in acute and subacute forms, the prognosis has improved significantly: the five-year survival rate is 90%. If the disease acquires a chronic course, the patient's ability to work can be restored.
The prognosis for secondary (tumor) DM depends on the effectiveness of the surgical intervention: with a successful operation, all signs of the disease may disappear. Factors that worsen the prognosis of the disease: old age, late diagnosis, improper treatment at the onset of the disease, severe myositis (fever, dysphagia, damage to the lungs, heart and gastrointestinal tract), antisynthetase syndrome. With tumor DM, the five-year survival rate is only 50%.
Prophylaxis
Prevention of exacerbations (secondary prevention) is achieved by carrying out supportive treatment, sanitizing foci of infection and increasing the body's resistance. The relatives of the patient may have primary prevention(exclusion of overloads, insolation, hypothermia).
What autoimmune diseases? Their list is very wide and includes about 80 diseases that are heterogeneous in the course and clinical signs, which, however, are united by a single development mechanism: for reasons still unknown to medicine, the immune system takes the cells of its own body for "enemies" and begins to destroy them.
One organ can fall into the attack zone - then we are talking about an organ-specific form. If two or more organs are affected, then we are dealing with a systemic disease. Some of them can occur with or without systemic manifestations, such as rheumatoid arthritis. Some diseases are characterized by simultaneous damage to different organs, while in others, systemicity appears only in case of progression.
These are the most unpredictable diseases: they can arise unexpectedly and just as spontaneously pass; appear once in a lifetime and never bother a person again; rapidly progress and end in death ... But most often they take on a chronic form and require treatment throughout life.
Systemic autoimmune diseases. List
What other systemic autoimmune diseases are there? The list can be continued with such pathologies as:
- dermatopolymyositis is a severe, rapidly progressive lesion of the connective tissue with the involvement of transverse smooth muscles, skin, internal organs in the process;
- which is characterized by venous thrombosis;
- sarcoidosis is a multisystem granulomatous disease that most often affects the lungs, as well as the heart, kidneys, liver, brain, spleen, reproductive and endocrine systems, gastrointestinal tract and other organs.
Organ-specific and mixed forms
Organ-specific types include primary myxedema, Hashimoto's thyroiditis, thyrotoxicosis (diffuse goiter), autoimmune gastritis, pernicious anemia, (adrenal cortex insufficiency), and severe myasthenia gravis.
Mixed forms include Crohn's disease, primary biliary cirrhosis, celiac disease, chronic active hepatitis and others.
Autoimmune diseases. List of predominant symptoms
This type of pathology can be divided depending on which organ is predominantly affected. Such a list includes systemic, mixed, and organ-specific forms.
Diagnostics
The diagnosis is based on the clinical picture and laboratory tests for autoimmune diseases. As a rule, they take a general, biochemical and immunological blood test.
Systemic connective tissue diseases
1. General views
Systemic lupus erythematosus, systemic scleroderma, dermatomyositis-polymyositis refer to systemic connective tissue diseases (SCDT) - a group of nosologically independent diseases that have a certain similarity in etiology, pathogenesis, and clinical manifestations. They are treated with similar drugs.
A common point in the etiology of all CTDs is latent infection with various viruses. Taking into account the tissue tropism of viruses, the patient's genetic predisposition, expressed in the carriage of well-defined HLA histocompatibility antigens, various diseases from the group in question.
Triggering or "triggering" mechanisms for the inclusion of pathogenetic processes of SZST are nonspecific. Most often it is hypothermia, physical influences (vibration), vaccination, intercurrent viral infection.
The burst of immunoreactivity arising under the influence of the triggering factor in the organism of the predisposed patient is not able to fade away on its own. As a result of antigenic mimicry of cells affected by the virus, a vicious circle of a self-sustaining inflammatory process is formed, leading to the degradation of the entire system of specialized tissue structures in the patient's body to the level of collagen-rich fibrous connective tissue. Hence the old name of this group of diseases - collagenosis.
For all CFTs, damage to epithelial structures is characteristic - skin, mucous membranes, epithelial glands of external secretion. Therefore, one of the typical clinical manifestations of this group of diseases is Sjogren's dry syndrome.
Muscles, serous and synovial membranes are necessarily involved in one way or another, which is manifested by myalgia, arthralgia, polyserositis.
Systemic damage to organs and tissues in SSTD is facilitated by the obligatory formation of secondary immune complex vasculitis of medium and small vessels, including microscopic ones, involved in microcirculation, in all diseases of this group.
A typical manifestation of immune complex vasculitis is Raynaud's angiospastic syndrome, an essential component of the clinical picture of all diseases from the group under consideration.
Clinical cases with convincing signs of several diseases from this group at once, for example, systemic lupus erythematosus, systemic scleroderma, dermatomyositis-polymyositis, point to the closest connection between all STDs. In such cases, we can talk about a mixed diffuse connective tissue disease - Sharp's syndrome.
... Systemic lupus erythematosus
connective disease lupus polymyositis
Definition
Systemic lupus erythematosus (SLE) is a diffuse disease of connective tissue with the formation of autoantibodies to structural elements of tissues, components of cell nuclei, circulation in the blood of immune complexes conjugated with active complement that can cause direct immune and immune complex damage to cellular structures, blood vessels, and dysfunction of internal organs.
Etiology
The disease is more common in individuals with HLA DR2 and DR3, in families with inherited deficiency of certain complement components. Etiological role infection with RNA-containing retroviruses from the "slow" group can play. The pathogenetic mechanism of SLE can be triggered by intense solar insolation, medicinal, toxic, nonspecific infectious effects, and pregnancy. Women aged 15-35 are prone to the disease.
Pathogenesis
A genetic defect and / or modification by "slow" retroviruses of the genetic base of the immune system causes dysregulation of the immune response to some external influences. Cross-immunoreactivity occurs with the movement of normal tissue and intracellular structures into the category of antigens.
A wide range of autoantibodies is formed that are aggressive to their own tissues. Including autoantibodies against native DNA, short nuclear RNA polypeptides (anti-Sm), ribonucleoprotein polypeptides (anti-RNP), RNA polymerase (anti-Ro), protein in RNA (anti-La), cardiolipin (antiphospholipid antibodies) , histones, neurons, blood cells - lymphocytes, erythrocytes, platelets, etc.
Immune complexes appear in the blood that can combine with complement and activate it. First of all, these are complexes of IgM with native DNA. Conjugates of immune complexes with active complement are fixed on the vessel wall, in the tissues of internal organs. The microphage system consists mainly of neutrophils, which, in the process of destruction of immune complexes, release a large amount of proteases from their cytoplasm, and release atomic oxygen. Together with the proteases of the active complement, these substances damage tissues and blood vessels. At the same time, the processes of fibrinogenesis, followed by collagen synthesis, are activated through the C3 component of the complement.
An immune attack on lymphocytes by autoantibodies that react with the DNA-histone complex and active complement ends with the destruction of lymphocytes, and their nuclei is phagocytosed by neutrophils. Neutrophils containing in the cytoplasm the absorbed nuclear material of lymphocytes, possibly other cells, are called LE cells. It is a classic marker of systemic lupus erythematosus.
Clinical picture
The clinical course of SLE can be acute, subacute, chronic.
In an acute course, characteristic of the youngest patients, the temperature suddenly rises to 38 0From and above, there are joint pains, changes in the skin, serous membranes, and vasculitis characteristic of SLE appear. Combined lesions of internal organs - lungs, kidneys, nervous system, etc. - are quickly formed. Without treatment, after 1-2 years these changes become incompatible with life. In the subacute variant, most typical of SLE, the disease begins with a gradual worsening general well-being, decrease in working capacity. Joint pains appear. Skin changes and other typical manifestations of SLE occur. The disease proceeds in waves with periods of exacerbation and remission. Multiple organ disorders incompatible with life do not appear earlier than in 2-4 years. In a chronic course, the onset of SLE is difficult to establish. The disease remains unrecognized for a long time, as it manifests itself as symptoms of one of the many syndromes characteristic of this disease. Clinical masks of chronic SLE can be local discoid lupus, benign polyarthritis of unknown etiology, polyserositis of unknown etiology, angiospastic Raynaud's syndrome, thrombocytopenic Verlhof syndrome, dry Sjogren's syndrome, etc. In this variant of the disease, the clinical picture typical of SLE appears no earlier than 5 -10 years. The advanced phase of SLE is characterized by multiple symptoms of damage to various tissue structures, blood vessels, and internal organs. The minimum typical deviations are characterized by a triad: dermatitis, polyserositis, arthritis. There are at least 28 variants of skin lesions in SLE. Below are a number of the most common pathological changes in the skin and its appendages, mucous membranes. · Erythematous dermatitis of the face. On the cheeks and bridge of the nose, persistent erythema forms, resembling a butterfly in its shape. · Discoid lesion. On the face, trunk, limbs there are raised rounded foci, similar to coins, with hyperemic edges, depigmentation and atrophic changes in the center. · Nodular (nodular) skin lesions. · Photosensitization - pathological hypersensitivity of the skin to solar insolation. · Alopecia - generalized or patchy baldness. · Vasculitis of skin vessels in the form of urticaria, capillaritis (small-point hemorrhagic rash on the pads of the fingers, palms, nail beds), ulceration at the sites of skin microinfarctions. A vascular "butterfly" may appear on the face - a pulsating redness of the bridge of the nose and cheeks with a cyanotic hue. · Erosion on the mucous membranes, cheilitis (persistent thickening of the lips with the formation of small granulomas in their thickness). Lupus polyserositis includes lesions of the pleura, pericardium, and sometimes the peritoneum. The defeat of the joints in SLE is limited to arthralgias, symmetrical non-erosive arthritis without deformation, ankylosis. Lupus arthritis is characterized by symmetrical lesions of the small joints of the hand, knee joints, severe morning stiffness. Jaccoux syndrome can form - arthropathy with persistent deformities of the joints due to damage to tendons and ligaments, but without erosive arthritis. In connection with vasculitis, often develop aseptic necrosis femoral, humerus, and other bones Concomitant SLE myositis is manifested by myalgias, muscle weakness. The lungs and pleura are often affected. The defeat of the pleura is usually bilateral. Possible adhesive (adhesive), dry, exudative pleurisy. Adhesive pleurisy may not be symptomatic. Dry pleurisy is manifested by pain in the chest, pleural friction noise. Stupidity percussion sound, restriction of the mobility of the diaphragm indicate an accumulation in pleural cavities liquids, usually in small volumes. Aseptic pneumonitis, characteristic of SLE, is manifested by an unproductive cough, shortness of breath. Its objective symptomatology does not differ from pneumonia. Vasculitis of the pulmonary arteries can cause hemoptysis, pulmonary insufficiency, increased pressure in the small circle with overload of the right heart. Possible thrombosis of the branches of the pulmonary artery with the formation of pulmonary infarction. Clinical manifestations of cardiac pathology are caused by pancarditis characteristic of SLE: pericarditis, myocarditis, endocarditis, vasculitis of the coronary arteries. Pericarditis with SLE is usually adhesive (sticky) or dry, and may be manifested by pericardial rubbing noise. Less commonly, pericardial effusion occurs with a small accumulation of fluid in the pericardial cavity. Lupus myocarditis is the main cause of rhythm disturbances, conduction, heart failure. Liebman-Sachs warty endocarditis can be accompanied by multiple thromboembolisms in the vessels of internal organs with subsequent heart attacks, and cause the formation of heart defects. Usually, there is a failure of the aortic valves, mitral valve failure. Valvular stenoses are rare. Lupus vasculitis of the coronary arteries causes ischemic damage to the heart muscle up to myocardial infarction. The range of possible changes in the kidneys is very wide. Focal nephritis can be asymptomatic or with minimal changes in urinary sediment (microhematuria, proteinuria, cylindruria). Diffuse forms of lupus nephritis can cause nephrotic syndrome with edema, hypoproteinemia, proteinuria, hypercholesterolemia. Often, kidney damage occurs with a malignant arterial hypertension... In most cases of diffuse lupus nephritis, renal failure occurs and rapidly decompensates. Lupus hepatitis is benign, manifested by moderate hepatomegaly, moderate impairment liver function. It never leads to liver failure, liver cirrhosis. Abdominal pain, sometimes very intense, muscle tension of the anterior abdominal wall (lupus abdominal crisis) is usually associated with mesenteric vasculitis. Most patients develop focal and diffuse changes in the central nervous system caused by vasculitis, thrombosis of cerebral vessels, and direct immune damage to nerve cells. Typical are headaches, depression, psychosis, epileptiform seizures, polyneuropathies, and motor dysfunctions are possible. With SLE, peripheral lymph nodes increase, splenomegaly appears, which is not associated with impaired portal hemodynamics. SLE patients are anemic. Often there is hypochromic anemia belonging to the group of iron redistribution. In immune complex diseases, which include SLE, macrophages react intensively with hemosiderin bodies, which are iron depots, removing (redistributing) them from the bone marrow. There is a deficiency of iron for hematopoiesis while maintaining the total content of this element in the body within normal limits. Hemolytic anemia in SLE patients occurs when erythrocytes are destroyed during the elimination of immune complexes fixed on their membrane, as well as as a result of hyperreactivity of macrophages of an enlarged spleen (hypersplenism). SLE is characterized by clinical Raynaud's, Sjogren's, Verlhof's, antiphospholipid syndromes. Raynaud's syndrome is caused by immune complex vasculitis. In patients after exposure to cold or emotional stress there is an acute spastic ischemia of certain parts of the body. Fingers of the hands, except for the thumb, suddenly turn pale and become icy, less often - the toes, chin, nose, ears. After a short period of time, pallor is replaced by a purple-cyanotic color, swelling of the skin as a result of postischemic vascular paresis. Sjogren's syndrome is an autoimmune lesion of the salivary, lacrimal and other exocrine glands with the development of dry stomatitis, keratoconjunctivitis, pancreatitis, secretory insufficiency of the gastric mucosa. In patients, the shape of the face may change due to compensatory hypertrophy of the parotid salivary glands. Sjogren's syndrome often occurs with Raynaud's syndrome. Werlhof's syndrome (symptomatic thrombocytopenic purpura) with SLE is caused by autoimmune suppression of platelet formation processes, high consumption of platelets in the process of autoimmune reactions. It is characterized by intradermal petechial hemorrhages - purple. In patients with a chronic variant of the clinical course of SLE, Werlhof syndrome can long time be the only manifestation of this disease. With lupus, often even a deep drop in the level of platelets in the blood is not accompanied by hemorrhages. In the practice of the author of this book, there were cases when in patients in the initial period of SLE, the number of platelets in the peripheral blood did not rise above 8-12 per 1000 leukocytes in the absence of bleeding, while the level below which thrombocytopenic purpura usually begins - 50 per 1000. Antiphospholipid syndrome is formed in connection with the emergence of autoantibodies to phospholipids, cardiolipin. Antiphospholipid antibodies are called lupus anticoagulants. They negatively affect some stages of blood clotting, increasing the thromboplastin time. Paradoxically, the presence of a lupus anticoagulant in the blood is characterized by a tendency to thrombosis and not to bleeding. The syndrome in question is usually manifested by deep vein thrombosis of the lower extremities. Mesh livedo is a treelike vascular pattern on the skin of the lower extremities; it can also form as a result of thrombosis of small veins of the legs. In SLE patients, antiphospholipid syndrome is one of the main causes of cerebral, pulmonary and hepatic vein thrombosis. Often combined with Raynaud's syndrome. Diagnostics Complete blood count: a decrease in the number of erythrocytes, hemoglobin, in some cases simultaneously with a decrease in the values of the color index (CP). In some cases, reticulocytosis is detected - evidence of hemolytic anemia. Leukopenia, often pronounced. Thrombocytopenia, often deep. Increased ESR. General urine analysis: hematuria, proteinuria, cylindruria. Biochemical analysis blood: an increase in the content of fibrinogen, alpha-2- and gamma-globulins, total and indirect bilirubin (with hemolytic anemia). With kidney damage, hypoproteinemia, hypercholesterolemia, an increase in the content of urea, creatinine. Immunological research allows obtaining positive results of a number of reactions that are quite specific for SLE. · LE-cells are neutrophils containing the nucleus of a phagocytosed lymphocyte in the cytoplasm. Detection of more than five LE-cells per thousand leukocytes is of diagnostic value. · Increased levels of circulating immune complexes (CICs). · Antibodies to Sm antigen - short nuclear RNA polypeptides. · Antinuclear factor is a complex of antinuclear autoantibodies specific to various components of the cell nucleus. · Antibodies to native DNA. · The rosette phenomenon is the identification of groups of leukocytes surrounding free-lying cell nuclei. · Antiphospholipid autoantibodies. · Positive Coombs' test in hemolytic anemia. · Rheumatoid factor appears in moderate diagnostic titers only with pronounced articular manifestations of SLE. ECG - signs of left ventricular myocardial hypertrophy with formed defects (insufficiency of the mitral and / or aortic valves), arterial hypertension of renal origin, various rhythm and conduction disturbances, ischemic disorders. Radiography of the lungs - pleural effusion, focal infiltration (pneumonitis), interstitial changes (pulmonary vasculitis), triangular shadows of heart attacks with embolism of the branches of the pulmonary artery. X-ray of the affected joints - moderate osteoporosis without usuration, ankylosis. Ultrasound procedure: pleural effusion, sometimes a small amount of free fluid in abdominal cavity... Determined by moderate hepatomegaly, splenomegaly without disturbance of portal hemodynamics. In some cases, signs of hepatic vein thrombosis are determined - Bad Chiari syndrome. Echocardiography - effusion in the pericardial cavity, often significant (up to cardiac tamponade), dilatation of the heart chambers, a decrease in the ejection fraction of the left ventricle, areas of hypokinesia of the wall of the left ventricle of ischemic origin, defects of the mitral and aortic valves. Ultrasound examination of the kidneys: a diffuse, symmetrical increase in the echogenicity of the parenchyma of both organs, sometimes signs of nephrosclerosis. Puncture biopsy of the kidneys - one of the morphological variants of lupus nephritis is excluded or confirmed. The degree of SLE activity is determined based on the following criteria. · I Art. - minimal activity. Body temperature is normal. A little weight loss. Discoid lesions on the skin. Arthralgia. Adhesive pericarditis. Myocardial dystrophy. Adhesive pleurisy. Polyneuritis. Hemoglobin more than 120 g / l. ESR 16-20 mm / hour. Fibrinogen less than 5 g / l. Gamma globulins 20-23%. LE cells are absent or single. Antinuclear factor less than 1:32. The titer of antibodies to DNA is low. The CEC level is low. · II Art. - moderate activity. Fever up to 38 0C. Moderate weight loss. Nonspecific erythema on the skin. Subacute polyarthritis. Dry pericarditis. Moderately pronounced myocarditis. Dry pleurisy. Diffuse mixed glomerulonephritis with arterial hypertension, hematuria, proteinuria. Encephaloneuritis. Hemoglobin 100-110 g / l. ESR 30-40 mm / hour. Fibrinogen 5-6 g / l. Gamma globulins 24-25%. LE cells 1-4 per 1000 leukocytes. Antinuclear factor 1:64. The titer of antibodies to DNA is average. The CEC level is average. · III Art. - maximum activity. Fever over 38 0C. Expressed weight loss. Skin lesions in the form of erythema lupus, "butterfly" on the face, capillaritis. Acute or subacute polyarthritis. Pericardial effusion. Expressed myocarditis. Lupus endocarditis. Exudative pleurisy. Diffuse glomerulonephritis with nephrotic syndrome. Acute encephaloradiculoneuritis. Hemoglobin less than 100 g / l. ESR more than 45 mm / hour. Fibrinogen more than 6 g / l. Gamma globulins 30-35%. LE-cells are more than 5 per 1000 leukocytes. Antinuclear factor is higher than 1: 128. The titer of antibodies to DNA is high. The CEC level is high. Revised American Rheumatological Association SLE Diagnostic Criteria:
The diagnosis is considered reliable if 4 or more of the criteria listed below are met. If there are fewer criteria, the diagnosis is considered presumptive (not excluded). 1.
Lupoid "butterfly»: Flat or raised, fixed erythema on the cheekbones, with a tendency to spread to the nasolabial area. 2.
Discoid rash:raised erythematous plaques with adjacent scales, follicular plugs, atrophic scars on old foci. 3.
Photodermatitis:rashes on the skin that appear as a result of exposure to sunlight. 4.
Erosions and ulcers in the oral cavity:painful ulceration of the oral mucosa or nasopharynx. 5.
Arthritis:non-erosive arthritis of two or more peripheral joints, manifested by soreness, edema, exudation. 6.
Serositis:pleurisy, manifested by pleural pain, pleural rubbing, or signs of pleural effusion; pericarditis, manifested by pericardial rubbing, intrapericardial effusion detected by echocardiography. 7.
Kidney damage:persistent proteinuria 0.5 g / day or more or hematuria, the presence of cylinders in the urine (erythrocytic, tubular, granular, mixed). 8.
Damage to the central nervous system:convulsions - in the absence of drug or narcotic intoxication, metabolic disorders (ketoacidosis, uremia, electrolyte disturbances); psychosis - in the absence of taking psychotropic drugs, electrolyte disturbances. 9.
Hematological changes:leukopenia 4 10 9/ l and less, registered two or more times; lymphopenia 1.5 10 9/ l and less, registered at least twice; thrombocytopenia less than 100 10 9/ l not due to medication. 10.
Immunological disorders:antibodies against native DNA in an increased titer; antibodies to smooth muscle (anti-Sm); antiphospholipid antibodies (an increased level of IgG or IgM - antibodies to cardiolipin, the presence of lupus coagulant in the blood; false-positive Wasserman reaction in the absence of evidence of syphilitic infection (according to the results of RIT - the reaction of immobilization of treponema or RIF - the reaction of immunofluorescent identification of treponemal antibodies). 11.
Antinuclear antibodies:identifying them in an increased titer in the absence of taking medications that can cause lupus-like syndrome. Differential diagnosis It is carried out primarily with lupoid hepatitis (chronic autoimmune hepatitis with extra-laryngeal manifestations), rheumatoid arthritis, as well as with mixed systemic connective tissue disease (Sharp's syndrome), chronic glomerulonephritis, systemic vasculitis. Chronic autoimmune hepatitis with extrahepatic manifestations is also called lupoid, as it is accompanied by multiple lesions of internal organs, arthralgia, polyserositis, vasculitis, etc., resembling SLE. However, unlike lupoid hepatitis, in SLE, liver damage is benign. There are no massive necrosis of hepatocytes. Lupus hepatitis does not progress to liver cirrhosis. In contrast, in lupoid hepatitis, according to puncture biopsy, there are pronounced and severe necrotic damage to the liver parenchyma, followed by a transition to cirrhosis. During the formation of remission of lupoid hepatitis, the symptoms of extrahepatic lesions first fade away, but at least minimal signs of an inflammatory process in the liver remain. In systemic lupus erythematosus, the opposite is true. Signs of liver damage are the first to fade. At the initial stages of the disease, SLE and rheumatoid arthritis have almost the same clinical manifestations: fever, morning stiffness, arthralgia, symmetric arthritis of the small joints of the hands. However, in rheumatoid arthritis, joint damage is more severe. Erosion of the articular surfaces, proliferative processes followed by ankylosis of the affected joint are typical. For SLE, erosive ankylosing arthritis is not typical. Differential diagnosis of SLE and rheumatoid arthritis with systemic manifestations presents significant difficulties, especially at the initial stages of the disease. A common manifestation of SLE is severe glomerulonephritis, leading to renal failure. Glomerulonephritis is rare in rheumatoid arthritis. In cases where it is not possible to distinguish between SLE and rheumatoid arthritis, one should think of Sharpe's syndrome - a mixed systemic disease of connective tissue that combines signs of SLE, rheumatoid arthritis, systemic sclerosis, polymyositis, etc. Survey plan · Complete blood count with platelet count. · General urine analysis. · Test according to Zimnitsky. · Biochemical blood test: fibrinogen, total protein and fractions, bilirubin, cholesterol, urea, creatinine. · Immunological analysis: LE cells, CEC, rheumatoid factor, antibodies to Sm antigen, antinuclear factor, antibodies to native DNA, antiphospholipid antibodies, Wasserman reaction, direct and indirect Coombs' tests. · Radiography of the lungs. · X-ray of the affected joints. · ECG. · Ultrasound of the pleural, abdominal, liver, spleen, kidneys. · Echocardiography. · Biopsy of the musculocutaneous flap (according to indications - if necessary, differential diagnosis with other systemic diseases of the connective tissue, evidence of mixed connective tissue disease - Sharp's syndrome). · Kidney biopsy (according to indications - if necessary, differential diagnosis with other systemic kidney disease, chronic glomerulonephritis). Treatment SLE treatment tactics include: · Suppression of hyperreactivity of immune mechanisms, immune inflammation, immune complex lesions. · Treatment of selected clinically significant syndromes. In order to reduce the hyperreactivity of immunity, inflammatory processes, glucocorticosteroids, immunodepressants (cytostatics), aminoquinoline drugs, efferent methods (plasmapheresis, hemosorption) are used. The basis for the appointment of glucocorticoid drugs is convincing evidence of the diagnosis of SLE. At the initial stages of the disease with minimal signs of activity, glucocorticosteroid drugs are necessarily used, but not non-steroidal anti-inflammatory drugs. Depending on the course of SLE, the activity of immune-inflammatory processes, various schemes of monotherapy with glucocorticoids, combined with their use with other drugs, are used. Treatment is started with an "overwhelming" dose of glucocorticoids with a gradual transition to a supportive dose when the immune-inflammatory process fades away. Most often, oral prednisolone and parenteral methylprednisolone are used to treat SLE. · In the chronic course of SLE with minimal activity of immune inflammation, oral prednisolone is prescribed in minimal maintenance doses of 5-7.5 mg / day. · In acute and subacute clinical course with II and III st. SLE activity, prednisolone is prescribed at a dose of 1 mg / kg / day. If after 1-2 days the patient's condition does not improve, the dose is increased to 1.2-1.3 mg / kg / day. This treatment is continued for 3-6 weeks. With a decrease in the activity of the immune-inflammatory process, the dose is first reduced by 5 mg per week. Upon reaching the level of 20-50 mg / day, the rate of decline is reduced to 2.5 mg per week until the minimum maintenance dose of 5-7.5 mg / day is reached. · With highly active SLE with severe vasculitis, lupus nephritis, severe anemia, leukopenia, thrombocytopenia, lupus encephaloradiculneuritis with acute mental, movement disorders against the background of systematic treatment with prednisolone, pulse therapy with methylprednisolone is performed. For three consecutive days, 1000 mg of methylprednisolone is injected intravenously over 30 minutes. This procedure can be repeated monthly for 3-6 months. In the following days after pulse therapy, the patient should continue the systematic oral administration of prednisolone in order to avoid renal failure due to a decrease in glomerular filtration. Immunosuppressants (cytostatics) are prescribed for SLE only together with glucocorticosteroid drugs or against the background of their systematic use. Immunosuppressants can enhance the anti-inflammatory effect and, at the same time, reduce the required dose of glucocorticoids, thereby reducing the side effects of their long-term use. Cyclophosphamide, azathioprine are used, less often other cytostatics. · With high SLE activity, systemic vasculitis with widespread ulcerative necrotic skin lesions, severe pathological changes in the lungs, central nervous system, active lupus nephritis, if it is impossible to further increase the dose of glucocorticoids, the following is additionally prescribed: o Cyclophosphamide 1-4 mg / kg / day orally, or: o Azathioprine 2.5 mg / kg / day by mouth. · With active lupus jade: o Azathioprine 0.1 once a day by mouth and cyclophosphamide 1000 mg intravenously 1 time in 3 months. · To increase the effectiveness of three-day pulse therapy with methylprednisolone on the second day, 1000 mg of cyclophosphamide is additionally administered intravenously. Aminoquinoline drugs are of secondary importance. They are intended for long-term use with low activity of the inflammatory process, chronic course of SLE with predominantly skin lesions. · · To eliminate excess autoantibodies, immune complexes, and inflammatory mediators from the blood, the following are used: · Plasmapheresis - 3-5 procedures with a single removal of up to 1000 ml of plasma. · Hemosorption on activated carbons and fiber sorbents - 3-5 procedures. For the treatment of thrombocytopenic syndrome are used: · immunoglobulin preparations at 0.4 g / kg / day for 5 days; · dinazole at 10-15 mg / kg / day. When a tendency to thrombosis appears, low molecular weight heparin is prescribed, 5 thousand units under the skin of the abdomen 4 times a day, antiplatelet agents - 150 mg of chimes a day. If necessary, use broad-spectrum antibiotics, anabolic hormones, diuretics, ACE inhibitors, peripheral vasodilators. Forecast. Adverse. Especially in cases of highly active lupus nephritis, cerebral vasculitis. Relatively favorable prognosis in patients with chronic, inactive course of SLE. In such cases adequate treatment provides patients with a life expectancy of over 10 years. ... Systemic scleroderma
Definition Systemic scleroderma (SS) or systemic sclerosis is a diffuse connective tissue disease with fibrosclerotic changes in the skin and internal organs, vasculitis of small vessels in the form of obliterating endarteritis. ICD 10:M 34 - Systemic sclerosis. M34.0 - Progressive systemic sclerosis. M34.1 - CR (E) ST syndrome. Etiology. The disease is preceded by an infection with an unknown RNA-containing virus, long-term professional contact with polyvinyl chloride, work in conditions of intense vibration. Persons with HLA type B35 and Cw4 histocompatibility antigens are predisposed to the disease. The overwhelming majority of patients with SS have chromosomal aberrations - chromatid ruptures, ring chromosomes, etc. Pathogenesis As a result of exposure to endothelial cells of the etiological factor, an immunopathological reaction occurs. T-lymphocytes sensitized to the antigens of damaged endothelial cells produce lymphokines that stimulate the macrophage system. In turn, the monokines of stimulated macrophages even more damage the endothelium and, at the same time, stimulate the function of fibroblasts. A vicious immune-inflammatory circle ensues. Damaged walls of small vessels of the muscle type become hypersensitive to vasoconstrictor influences. Pathogenetic mechanisms of vasospastic ischemic Raynaud's syndrome are formed. Active fibrogenesis in the vascular wall leads to a decrease in the lumen and obliteration of the affected vessels. As a result of similar immune-inflammatory reactions, circulatory disorders in small vessels, interstitial tissue edema occurs, stimulation of tissue fibroblasts, followed by irreversible sclerosis of the skin and internal organs. Depending on the nature of immune shifts, various variants of the disease are formed. The appearance of antibodies to Scl-70 (Scleroderma-70) in the blood is associated with a diffuse form of CC. Antibodies to centromeres are typical of CREST syndrome. Nuclear antibodies - for scleroderma kidney damage and overlap syndrome with dermatomyositis-polymyositis. Limited and diffuse forms of SS are pathogenetically significantly different: · The limited (limited) form of CC is known as CREST-syndrome. Its signs are calcification ( Calcinosis), Raynaud's syndrome ( Reynaud), disorders of esophageal peristalsis ( Esophageal motility disorders), sclerodactyly ( Sclerodactilya), telangiectasia ( Teleangiectasia). Pathological changes are characteristic mainly of the skin of the face and fingers of the hands distal to the metacarpophalangeal joint. This is a relatively benign variant of the disease. Injuries to internal organs are rare and appear only with a prolonged course of the disease, and if they occur, they proceed more easily than with the diffuse form of SS. · Diffuse form of SS (progressive systemic sclerosis) is characterized by sclerotic skin changes upper limbs proximal to the metacarpophalangeal joints, other parts of the body, up to its entire surface. Lesions of internal organs occur much earlier than with a limited form. More organs and tissue structures are involved in the pathological process. The kidneys and lungs are especially often and severely affected. Clinical picture The disease can occur in acute, subacute, chronic forms. The acute form of diffuse SS is characterized by the rapid development of all stages of skin lesions within less than one year. At the same time, lesions of internal organs, primarily kidneys and lungs, appear and reach their culminating development. During the entire period of the disease, the maximum deviations of the indicators of general, biochemical blood tests are revealed, demonstrating the high activity of the pathological process. In a subacute course, the disease develops at a relatively slow pace, but with the presence of all skin lesions, vasomotor disorders, and internal organ lesions typical of diffuse CVS. Deviations of laboratory and biochemical parameters are noted, reflecting the moderate activity of the pathological process. The chronic course of SS is characterized by a gradual onset, slow progression over a long time. Most often, a limited form of the disease is formed - CREST syndrome. Clinically significant lesions of internal organs, deviations of laboratory and biochemical parameters are usually not observed. Over time, patients may develop symptoms of pulmonary hypertension caused by obliterating endarteritis of the pulmonary artery and its branches, signs of pulmonary fibrosis. In typical cases, SS begins with pathological changes in the skin. Patients notice the appearance of a painful thickening of the skin of the fingers of both hands (edematous phase). Then the skin thickens (inductive phase). The subsequent sclerosis causes its thinning (atrophic phase). Sclerosed skin becomes smooth, shiny, taut, very dry. It cannot be folded, since it is welded to the underlying fascia, periosteum, periarticular structures. The vellus hair disappears. The nails are deformed. On the thinned skin of the hands, traumatic injuries, spontaneous ulceration, and abscesses easily arise and slowly heal. Telangiectasias appear. The lesion of the facial skin, which is very characteristic of SS, cannot be confused with anything. The face becomes amimic, mask-like, unnaturally shiny, unevenly pigmented, often with purple foci of telangiectasias. The nose is pointed in the shape of a bird's beak. A "surprised" look appears, as the sclerotic contraction of the skin of the forehead and cheeks widens the eye slits and makes it difficult to blink. The mouth gap narrows. The skin around the mouth shrinks to form non-expanding radial folds, resembling the shape of a "pouch". In the limited form of CC, the lesions are limited to the skin of the fingers and face. With a diffuse form, edematous, indurative-sclerotic changes gradually spread to the chest, back, legs, and the whole body. The defeat of the skin of the chest and back creates in the patient the sensation of a corset that interferes with the respiratory movements of the chest. Total sclerosis of all skin forms a picture of the patient's pseudo-mummification - the phenomenon of "living relics". Along with the skin, mucous membranes can be affected. Patients often point to dryness, lack of saliva in the mouth, pain in the eyes, and the inability to cry. Often these complaints indicate the formation of a "dry" Sjogren's syndrome in a patient with SS. Together with edematous-indurative changes in the skin, and in some cases up to skin lesions, Raynaud's angiospastic syndrome can form. Patients begin to be bothered by attacks of sudden pallor, numbness of the fingers, less often of the legs, the tips of the nose, ears after exposure to cold, against the background of emotions, and even without obvious reasons... Pallor soon turns into bright hyperemia, moderate edema with the appearance of pain at first, and then sensations of pulsating heat. The absence of Raynaud's syndrome is usually associated with the formation of severe scleroderma kidney damage in the patient. Articular syndrome also refers to the early manifestations of SS. It can be limited to polyarthralgia without affecting the joints and periarticular structures. In some cases, it is symmetrical fibrosing scleroderma polyarthritis of small joints of the hands with complaints of stiffness and pain. It is characterized by first exudative and then proliferative changes as in rheumatoid arthritis. Pseudoarthritis scleroderma can also form, characterized by limited joint mobility caused not by damage to the articular surfaces, but by adhesions of the joint capsule and muscle tendons with induratively altered or sclerosed skin. Often, articular syndrome is combined with osteolysis, shortening of the terminal phalanges of the fingers - sclerodactyly. Carpal tunnel syndrome with parasthesias of the middle and index fingers of the hand, pain extending up the forearm to the elbow, flexion contractures of the hand can form. Muscle weakness is characteristic of the diffuse form of CC. Its causes are diffuse muscle atrophy, non-inflammatory muscle fibrosis. In some cases, this is a manifestation of inflammatory myopathy, which is identical to that in patients with dermatomyositis-polymyositis (cross syndrome). Subcutaneous calcifications are found mainly in limited CV (CREST syndrome), and only in a small number of patients with a diffuse form of the disease. Calcifications are more often located in places of natural trauma - the tips of the fingers of the hands, the outer surface of the elbows, knees - Tibierge-Weissenbach syndrome. Swallowing disorders in SS are caused by disturbances in the structure of the wall and motor function of the esophagus. In patients with SS, the smooth muscles of the lower third of the esophagus are replaced by collagen. The striated muscles of the upper third of the esophagus are usually unaffected. There is a stenosis of the lower esophagus and compensatory expansion of the upper. The structure of the esophageal mucosa changes - Beretta metaplasia. As a result of gastroesophageal reflux, erosive reflux esophagitis often occurs, ulcers of the esophagus, post-ulcerative strictures of the esophageal-gastric junction develop. Possible atony and dilatation of the stomach, duodenum... When diffuse gastric fibrosis occurs, iron absorption may be impaired with the formation of sideropenic syndrome. Atony, dilatation often develops small intestine... Fibrosis of the wall of the small intestine is manifested by malabsorption syndrome. The defeat of the colon leads to diverticulosis, manifested by constipation. In patients with a limited form of the disease in the form of CREST-syndrome, primary biliary cirrhosis of the liver can sometimes form, the first symptom of which may be "causeless" itching of the skin. In patients with diffuse CV, lung damage in the form of basal and then diffuse pulmonary fibrosis is manifested by progressive pulmonary insufficiency. Patients complain of constant shortness of breath, aggravated by physical activity... Dry pleurisy with chest pains, pleural rubbing noise may occur. In patients with limited CV, during the formation of obliterating endarteritis of the pulmonary artery and its branches, pulmonary hypertension occurs with overload of the right heart. The diffuse form of CC is sometimes complicated by heart damage. Myocarditis, myocardial fibrosis, myocardial ischemia caused by obliterating vasculitis of the coronary arteries, fibrosis of the mitral valve leaflets with the formation of its insufficiency can cause hemodynamic decompensation. Kidney damage is characteristic of the diffuse form of CC. Kidney pathology is a kind of alternative to Raynaud's syndrome. The scleroderma kidney is characterized by damage to blood vessels, glomeruli, tubules, interstitial tissues. In terms of clinical manifestations, the sclerodermic kidney does not differ from glomerulonephritis, which occurs with arterial hypertension, urinary syndrome in the form of proteinuria, hematuria. A progressive decrease in glomerular filtration rate leads to chronic renal failure. As a result of obliterating fibrosis of interlobular arteries in combination with any vasoconstrictor effect (hypothermia, blood loss, etc.), cortical necrosis of the kidney can occur with a clinical picture of acute renal failure - sclerodermic renal crisis. Damage to the nervous system due to obliterating vasculitis cerebral arteries... Spastic seizures involving intracranial arteries, as one of the manifestations of Raynaud's syndrome, can cause seizures, psychosis, and transient hemiparesis. The diffuse form of CC is characterized by a lesion thyroid gland in the form of autoimmune thyroiditis, fibrous atrophy of the organ. Diagnostics · Complete blood count: May be normal. Sometimes signs of mild hypochromic anemia, mild leukocytosis, or leukopenia. There is an increased ESR. · General urine analysis: proteinuria, cylinduria, microhematuria, leukocyturia, with chronic renal failure - a decrease in the specific gravity of urine. Increased excretion of oskiproline is a sign of impaired collagen metabolism. · Biochemical blood test: may be normal. The active process is accompanied by an increase in the content of fibrinogen, alpha-2- and gamma-globulins, seromucoid, haptoglobins, oxyproline. · Immunological analysis: specific autoantibodies to Scl-70 in diffuse form of CC, autoantibodies to centromeres in a limited form of the disease, nuclear antibodies in renal damage, cross syndrome of CC-dermatomyositis-polymyositis. In most patients, rheumatoid factor is detected, in some cases, single LE-cells. · Biopsy of the musculocutaneous flap: obliterating vasculitis of small vessels, fibrosclerotic changes. · Puncture biopsy of the thyroid gland: identification of morphological signs of autoimmune thyroiditis, vasculitis of small vessels, fibrous arthrophy of the organ. · X-ray examination: calcifications in the tissues of the terminal phalanges of the fingers, elbow, knee joints; osteolysis of the distal phalanges of the fingers; osteoporosis, narrowing of the joint space, sometimes ankylosis of the affected joints. Chest - interpleural adhesions, basal, diffuse, often cystic (cellular lung) pulmonary fibrosis. · ECG: signs of myocardial dystrophy, ischemia, large-focal cardiosclerosis with impaired conduction, excitability, hypertrophy of the left ventricular and atrial myocardium with formed mitral valve insufficiency. · Echocardiography: verification of mitral defect, abnormalities contractile function myocardium, dilatation of the heart chambers, signs of pericarditis may be detected. · Ultrasound examination: identification of structural signs of bilateral diffuse kidney damage, characteristic of nephritis, evidence of autoimmune thyroiditis, fibrous atrophy of the thyroid gland, in some cases, signs of biliary cirrhosis. American Rheumatological Association clinical criteria for the recognition of systemic scleroderma: · "Large" criteria: o Proximal scleroderma - bilateral, symmetrical thickening, induration, induration, sclerosis of the dermis of the fingers, skin of the extremities proximally from the metacarpophalangeal and metatarsophalangeal joints, involvement of the skin of the face, neck, chest, abdomen in the pathological process. · "Small" criteria: o Sclerodactyly - induration, sclerosis, osteolysis of the terminal phalanges, deformation of the fingers; o Scars, tissue defects on the pads of the fingers of the hands; o Basal pulmonary fibrosis on both sides. To be diagnosed with CC, a patient must have either a “major” or at least two “minor” criteria. Clinical and laboratory signs of the activity of the inductive-sclerotic process in patients with SS: · 0 tbsp. - lack of activity. · I Art. - minimal activity. Moderate trophic disorders, arthralgia, vasospastic Raynaud's syndrome, ESR up to 20 mm / hour. · II Art. - moderate activity. Arthralgia and / or arthritis, adhesive pleurisy, symptoms of cardiosclerosis, ESR - 20-35 mm / hour. · III Art. - high activity. Fever, polyarthritis with erosive lesions, large focal or diffuse cardiosclerosis, mitral valve insufficiency, sclerodermic kidney. ESR exceeds 35 mm / hour. Differential diagnosis It is carried out primarily with focal scleroderma, other diffuse connective tissue diseases - rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis. Distinguish between plaque, teardrop, annular, linear forms of focal (local) scleroderma. In contrast to the limited and diffuse forms of SS, with focal scleroderma, the skin of the fingers and face is not involved in the pathological process. Systemic manifestations occur rarely and only with a prolonged course of the disease. Rheumatoid arthritis and SS are easier to distinguish when articular syndrome in the form of pseudoarthritis with indurative-sclerotic lesions of the periarticular skin forms in patients with SS. Radiographically, in these cases, there are no serious lesions of the joint itself. However, in both SS and rheumatoid arthritis, symmetric polyarthritis of the small joints of the hands can occur, with a characteristic stiffness, a tendency to ankylosis. Under such circumstances, the differentiation of diseases in favor of SS helps to identify the symptoms of indurative and then sclerotic lesions of the skin of the fingers, face, and in the diffuse form of SS, the skin of other parts of the body. For SS, lung damage (pneumofibrosis) is characteristic, which does not happen in patients with rheumatoid arthritis. Differential diagnosis with systemic lupus erythematosus is based on the identification of skin lesions specific to CC. In lupus, unlike SS, polyarthritis is benign, never leads to deformities, ankylosis of the joints. Lupus pseudoarthritis - Jaccoux syndrome - arthropathy with persistent deformities of the joints due to damage to tendons and ligaments. It proceeds without erosive arthritis. It differs from pseudoarthritis scleroderma in the absence of adhesion of the joint capsule with induratively altered or sclerosed skin over the affected joint. The diffuse form of the disease can be distinguished from systemic lupus erythematosus by the presence in the blood of SS-specific autoantibodies to the Scl-70 antigen. In contrast to dermatomyositis-polymyositis, SS is characterized by indurative and sclerotic skin lesions, secondary moderate myopathy. With dermatomyositis-polymyositis, high levels of creatine phosphokinase activity are detected in the blood, which is not the case with classical SS variants. If there is a combination of SS symptoms with signs of dermatomyositis-polymyositis, then the likelihood of a diagnosis of overlap syndrome of systemic connective tissue damage should be considered. Survey plan · General blood analysis. · General urine analysis. · The content of hydroxyproline in the urine. · Immunological analysis: autoantibodies to Scl-70, autoantibodies to centromeres, antinuclear antibodies, rheumatoid factor, LE cells, CEC. · Biopsy of the musculocutaneous flap. · Fine needle biopsy of the thyroid gland. · X-ray examination of the hands, affected elbow, knee joints. · Chest X-ray. · ECG. · Echocardiography. · Ultrasound examination of the abdominal organs, kidneys, thyroid gland. Treatment The tactics of treatment involves the implementation of the following effects on the patient's body: · Inhibition of the activity of obliterating endarteritis of small vessels, skin hardening, fibrosis of internal organs. · Symptomatic treatment of pain (arthralgia, myalgia) and other syndromes, impaired functions of internal organs. To suppress excess collagen formation in patients with an active inflammatory process, a subacute course of SS, the following is prescribed: · D-penicylamine (cuprenil) orally at 0.125-0.25 per day, every other day. If ineffective, the dosage is increased to 0.3-0.6 per day. If the intake of D-penicylamine is accompanied by the appearance of skin rashes, its dose is reduced and prednisolone is added to the treatment - 10-15 mg / day by mouth. The appearance of increasing proteinuria against the background of such treatment is the basis for the complete abolition of D-penicylamine. To reduce the activity of collagen synthesis mechanisms, especially in case of ineffectiveness or the occurrence of contraindications for D-penicylamine, you can apply: · colchicine - 0.5 mg / day (3.5 mg per week) with a gradual increase in the dose to 1-1.5 mg / day (about 10 mg per week). The drug can be taken for one and a half to four years in a row. In the case of diffuse CC with severe and severe systemic manifestations, it is advisable to use immunosuppressive doses of glucocorticoids and cytostatics. · oral prednisolone at 20-30 mg / day until a clinical effect is achieved. Then the dosage of the drug is slowly reduced to a maintenance dosage of 5-7.5 mg / day, which is recommended to be taken within 1 year. In the absence of an effect, the occurrence of adverse reactions to taking large doses of glucocorticoids, cytostatics are used: · Oral azathioprine 150-200 mg / day in combination with oral administration 15-20 mg / day of prednisolone for 2-3 months. In the chronic course of SS with predominantly cutaneous manifestations, minimal activity of the fibrosing process, aminoquinoline preparations should be prescribed: · Hydroxychloroquine (Plaquenil) 0.2 - 1-2 tablets per day for 6-12 months. · Chloroquine (delagil) 0.25 - 1-2 tablets per day for 6-12 months. Symptomatic remedies are intended primarily for compensation of vasospastic reactivity, treatment of Raynaud's syndrome, and other vascular disorders. For this purpose, calcium channel blockers, ACE inhibitors, antiplatelet agents are used: · Nifedipine - up to 100 mg / day. · Verapapil - up to 200-240 mg / day. · Captopril - up to 100-150 mg / day. · Lisinopril - up to 10-20 mg / day. · Curantil - 200-300 mg / day. With articular syndrome, drugs from the group of non-steroidal anti-inflammatory drugs are shown: · Diclofenac sodium (ortofen) 0.025-0.05 - 3 times a day by mouth. · Ibuprofen 0.8 - 3-4 times a day by mouth. · Naproxen 0.5-0.75 - 2 times a day by mouth. · Indomethacin 0.025-0.05 - 3 times a day by mouth. · Nimesulide 0.1 - 2 times a day by mouth. This drug selectively acts on COX-2 and therefore can be used in patients with erosive and ulcerative lesions of the esophagus, stomach and duodenum, for whom non-selective non-steroidal anti-inflammatory drugs are contraindicated. For local treatment, you can use a 25-50% solution of Dimexide in the form of applications on the affected skin for 20-30 minutes daily - up to 30 applications per course of treatment. Shown are sulfated glycosaminoglycans in ointments. You can apply lidase by intradermal injection, electrophoresis, phonophoresis in inductively changed areas of the skin. Forecast Determined by the pathomorphological variant of the disease. In the limited form, the forecast is quite favorable. In the diffuse form, it depends on the development and decompensation of damage to the kidneys, lungs, and heart. Timely and adequate treatment significantly prolongs the life of patients with CC. 4. Dermatomyositis-polymyositis
Definition Dermatomyositis (DM) or dermatopolymyositis is a systemic inflammatory disease with the replacement of affected tissues with fibrous structures with the predominant involvement of skeletal and smooth muscles, skin, and small vessels in the pathological process. In the absence of skin lesions, the term "polymyositis" (PM) is used. ICD 10:M33 - Dermatopolymyositis. M33.2 - Polymyositis. Etiology The etiological factor of DM-PM may be latent infection with picarnoviruses, some viruses from the Coxsackie group with the introduction of the pathogen into the genome of muscle cells. Association DM-PM with a number tumor processes, may indicate either in favor of the viral etiology of these tumors, or be a demonstration of antigenic mimicry of tumor structures and muscle tissue. Persons with HLA type B8 or DR3 histocompatibility antigens are predisposed to the disease. Pathogenesis The launch of the pathogenetic mechanisms of the disease in infected and genetically predisposed individuals can carry out nonspecific effects: hypothermia, excessive solar insolation, vaccinations, acute intoxication, etc. the defeat of antigenically related cell populations. The inclusion of microphage mechanisms for the elimination of immune complexes from the body causes the activation of fibrogenesis processes, concomitant systemic inflammation of small vessels. Due to the hyperreactivity of the immune system, aimed at the destruction of intranuclear positions of the virion, antibodies Mi2, Jo1, SRP, autoantibodies to nucleoproteins and soluble nuclear antigens appear in the blood. Clinical picture The disease can occur in acute, subacute and chronic forms. The acute form is characterized by the sudden onset of fever with a body temperature of up to 39-40 0C. Pains, muscle weakness, arthralgia, arthritis, cutaneous erythema immediately appear. Generalized lesion of all skeletal muscles is rapidly developing. Myopathy progresses rapidly. In a short period of time, the patient becomes almost completely immobilized. There are severe disorders of swallowing and breathing. Damage to internal organs, primarily the heart, appears and rapidly decompensates. Life expectancy in the acute form of the disease does not exceed 2-6 months. The subacute course is characterized by the absence of a memory onset of the disease in the patient. There are myalgias, arthralgias, gradually increasing muscle weakness. After solar insolation, characteristic erythema is formed on the face, open surfaces of the chest. Signs of damage to internal organs appear. The full development of the clinical picture of the disease and death occur in 1-2 years. The chronic form is benign, cyclical with long periods of remission. This variant of the disease rarely leads to a rapid death, limited to moderate, often local atrophic and sclerotic changes in muscles, skin, mild myopathy, compensated by changes in internal organs. Muscle pathology is the most striking feature of DM-PM. Patients note the appearance of progressive weakness, which is usually accompanied by myalgias of varying intensity. On objective examination, the affected muscles are doughy due to edema, with decreased tone, painful. Over time, the volume of the muscles involved in the pathological process decreases as a result of atrophy and fibrosis. First of all, the proximal skeletal muscle groups are changed. The distal muscle groups of the arms and legs are later involved. Inflammation and fibrosis of the muscles of the chest, diaphragm disrupts ventilation of the lungs, leading to hypoxemia, increased pressure in the pulmonary artery. The defeat of the striated muscles of the pharynx and the proximal segment of the esophagus disrupt the swallowing processes. Patients choke easily. Liquid food may be poured out through the nose. The defeat of the muscles of the larynx changes the voice, which becomes unrecognizably hoarse, with a nasal timbre tint. The oculomotor, chewing, and other muscles of the face are usually not affected. Pathological changes in the skin are characteristic of DM and are not necessary for PM. The following skin lesions are possible: ·