DIFFUSE DISEASES OF CONNECTIVE TISSUE

Diffuse connective tissue diseases (DCT) or collagenoses (a term of historical significance) are a group of diseases characterized by systemic immunoinflammatory damage to connective tissue and its derivatives. This is a group, but not a nosological concept, and therefore this term should not denote individual nosological forms.

CTDs 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 on diseases of the cardiovascular system. It has now been proven that with CTD, profound disturbances of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the formation of antibodies or sensitized lymphocytes directed against antigens of one’s own body.

Autoimmune disorders are based on an immunoregulatory imbalance, expressed in the suppression of suppressor and increased helper activity of T-lymphocytes, followed by activation of B-lymphocytes and hyperproduction of various specific autoantibodies.

There are a number of common features that unite DZST:

The common pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixing in tissues with the subsequent development of severe inflammatory reaction(especially in the microvasculature, kidneys, joints, etc.);

Similarities morphological changes(fibrinoid change in the basic substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);

Chronic course with periods of exacerbations and remissions;

Exacerbation under the influence of nonspecific influences ( infectious diseases, insolation, vaccination, etc.);

Multisystem damage (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 characteristics, therefore, in each specific case one should strive for an accurate nosological diagnosis.

This chapter presents the diagnostic search for SLE, SSc and DM.

SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that occurs in young people (mainly women) and develops against the background of a genetically determined imperfection of immunoregulatory processes, which leads to the uncontrolled production of antibodies to one’s own cells and their components and the development of autoimmune and immune complex chronic damage (V.A. Nasonova, 1989). The essence of the disease is immunoinflammatory damage to connective tissue, microvasculature, skin, joints and internal organs, while the leading ones are considered to be visceral lesions that determine the course and prognosis of the disease.

The incidence of SLE ranges from 4 to 25 cases per 100 thousand population. The disease most often develops in women childbearing age. During pregnancy and the 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 affected girls to boys decreases and is 3:1. Mortality in SLE is 3 times higher than in the general population. In men, the disease is as severe as in women.

SLE belongs to genetically determined diseases: studies conducted in the population have shown that the predisposition to the occurrence of SLE is associated with certain histocompatibility class II genes (HLA), genetically determined deficiency of certain complement components, as well as with polymorphism of genes of certain receptors and tumor necrosis factor α (TNF-α).

Etiology

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 allow us to associate SLE with diseases of viral etiology. Currently, importance is attached to RNA viruses (slow or latent viruses). The discovery of family cases of the disease, the frequent existence in families of other rheumatic or allergic diseases and various immune disorders allow us to think about the possible significance of family genetic predisposition.

The manifestation of SLE is facilitated by a number of nonspecific factors - insolation, nonspecific infection, administration of serums, intake of certain medicines(in particular, peripheral vasodilators from the hydralazine group), as well as stress. SLE can begin after childbirth or abortion. All these data allow us to consider SLE as a multifactorial disease.

Pathogenesis

Due to the impact of the virus on the immune system, 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 to approximately forty of the more than two hundred potential antigenic cellular components. Subsequently, the formation of immune complexes occurs and their deposition in various organs and tissues (mainly in the microvasculature). Characterized by various defects of immunoregulation, accompanied by hyperproduction 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, ensuring 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 current;

Activity of the pathological process;

Clinical and morphological characteristics of damage to organs and systems. Nature of the disease

The acute course is characterized by the rapid development of multiorgan 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 damage to the skin and joints. The disease occurs in waves, with periodic exacerbations and the development of multiple organ disorders within 2-3 years from the onset of the first symptoms.

The chronic course is characterized by a long-term predominance of one or more symptoms: recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhof's syndrome or Sjögren's syndrome. Multiple organ lesions occur by the 5th-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 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, mitral valve insufficiency);

Lungs (acute and chronic pneumonitis, pneumosclerosis);

Kidney (lupus nephritis nephrotic or mixed type, urinary syndrome);

Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).

At chronic course 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 (antiphospholipid syndrome will be discussed in more detail below).

There are also three degrees of activity of the pathological process, which characterize the severity of potentially reversible immunoinflammatory damage and determine the characteristics of the treatment of each individual 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 receive information on the basis of which they can formulate an idea:

About the variant of onset of the disease;

The nature of the course of the disease;

The degree of involvement of certain organs and systems in the pathological process;

Previous treatment, its effectiveness and possible complications.

The onset of the disease can be very diverse. Most often it is represented by a combination of various syndromes. Monosymptomatic onset is usually not typical. In this regard, the assumption of SLE disease arises from the moment such a combination is detected in a patient. In this case, it increases diagnostic value certain syndromes.

In the early period of SLE, the most common syndromes are joint, skin and serous membranes, as well as fever. Thus, the most suspicious combinations regarding SLE will be:

Fever, polyarthritis and trophic skin disorders (in particular, hair loss - alopecia);

Polyarthritis, fever and pleural lesions (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. However, this circumstance does not reduce the diagnostic value of the above combinations.

An asymptomatic onset of the disease is not typical, but the debut of SLE is noted with the occurrence of massive edema due to the development from the very beginning of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type.

Involvement in the pathological process various organs manifests itself with symptoms of their inflammatory lesion (arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.).

Information about previous treatment allows us to judge:

About its optimality;

About the severity of the disease and the degree of activity of the process (initial doses of glucocorticoids, duration of their use, maintenance doses, inclusion of cytostatics in the treatment complex for severe immune disorders, high activity of lupus nephritis, etc.);

About complications of glucocorticoid and cytostatic treatment.

At the first stage, it is possible to draw certain conclusions regarding the diagnosis of a long-term 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 damage to organs and the degree of their functional failure.

Damage to the musculoskeletal system manifests itself as polyarthritis, reminiscent of RA with symmetrical damage to the small joints of the hand (proximal interphalangeal, metacarpophalangeal, wrist) and large joints(less often). When deployed clinical picture diseases determine the defiguration of the joints due to periarticular edema. During the course of the disease, deformities of small joints develop. Joint changes can be accompanied by muscle damage in the form of diffuse myalgia, and very rarely - true PM with swelling and muscle weakness. Sometimes the lesion is represented only by arthralgia.

Damage to the skin is noted as often as joints. The most typical are erythematous rashes on the face in the area of ​​the zygomatic arches and the back of the nose (“butterfly”). Inflammatory rashes on the nose and cheeks, repeating the outline of a “butterfly”, are presented in various variants:

Vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse redness of the skin with a cyanotic tint in the middle zone of the face,

aggravated by external factors (insolation, wind, cold) or excitement;

. “butterfly” type of centrifugal erythema (skin changes are localized only in the bridge of the nose).

In addition to the “butterfly”, discoid rashes can be detected - erythematous raised plaques with keratic disorder and subsequent development of atrophy of the skin of the face, limbs and trunk. Finally, some patients experience nonspecific exudative erythema on the skin of the limbs and chest, as well as signs of photodermatosis on exposed parts of the body.

Skin lesions include capillaritis - a pinpoint hemorrhagic rash on the fingertips, nail beds and palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulcerations can be found on the mucous membrane of the mouth or nasopharyngeal area.

Damage to the serous membranes occurs in 90% of patients (classic diagnostic triad - dermatitis, arthritis, polyserositis). Damage to the pleura and pericardium is especially common, and less often to the peritoneum. Symptoms of pleurisy and pericarditis are described in previous sections, so only their features in SLE will be listed below:

Dry pleurisy and pericarditis occur more often;

In effusion forms, the amount of exudate is small;

Damage to the serous membranes is short-lived, and is usually diagnosed retrospectively upon detection of pleuropericardial adhesions or thickening of the costal, interlobar and mediastinal pleura with X-ray examination;

There is a pronounced tendency towards the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities).

SLE is characterized by damage to the cardiovascular system, which occurs at various stages of the disease.

Most often, pericarditis is found, which is prone to recurrence. Much more often than previously thought, endocardial damage is noted in the form of warty endocarditis (lupus endocarditis) on the leaflets of the mitral, aortic or tricuspid valve. If the process lasts for a long time, at the second stage of the search, signs of insufficiency of the corresponding valve can be detected (signs of stenosis of the orifice, as a rule, are absent).

Focal myocarditis is almost never recorded, but diffuse damage, especially in severe cases, is accompanied by certain symptoms (see “Myocarditis”).

Vascular damage can manifest itself as 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. Predominantly, damage occurs to the II-V fingers and toes, less often to other distal areas of the body (nose, ears, chin, etc.).

Lung lesions can be caused by the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) occurs acutely or continues for months and manifests itself with signs of inflammatory infiltration of lung tissue syndrome, similar to those of pneumonia. The peculiarity of the process is the occurrence of an unproductive cough in combination with shortness of breath. Another option for lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), expressed in the development of slowly progressive shortness of breath and changes in the lungs during X-ray examination. There are practically no characteristic physical data, so it is difficult to judge such lung damage at the second stage diagnostic search almost impossible.

Damage to the gastrointestinal tract is usually represented by subjective signs detected at the first stage. A physical examination sometimes reveals vague tenderness in the epigastric region and at the site of the pancreas, as well as signs of stomatitis. In some cases, hepatitis develops: enlargement and tenderness of the liver are noted.

Most often, with SLE, kidney damage occurs (lupus glomerulonephritis or lupus nephritis), the evolution of which depends on further fate sick. Kidney damage in SLE can occur in various ways, so the data from a direct examination of the patient can vary widely. With isolated changes in urinary sediment, no abnormalities are detected during physical examination. With glomerulonephritis occurring with nephrotic syndrome, massive edema and often hypertension are determined. With the formation of chronic nephritis with constant hypertension, an enlargement of the left ventricle and an accent of the second tone in the second intercostal space to the right of the sternum are detected.

Autoimmune thrombocytopenia (Werlhoff syndrome) manifests itself as typical rashes in the form of hemorrhagic spots of varying sizes on the skin inner surface limbs, skin of the chest and abdomen, as well as on 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 as Werlhoff syndrome without other typical clinical symptoms.

Damage to the nervous system is expressed to varying degrees, since almost all of its parts are involved in the pathological process. Patients complain of migraine headaches. Sometimes seizures occur. Possible cerebral circulation disorders, including the development of a stroke. When examining the patient, signs of polyneuritis are detected with impaired sensitivity, pain along the nerve trunks, decreased tendon reflexes and paresthesia. Organic brain syndrome characterized by emotional lability, episodes of depression, memory impairment and dementia.

Damage to the reticuloendothelial system is represented by an early symptom of the generalization of the process - polyadenopathy (an increase in all groups lymph nodes, not reaching a significant extent), as well as, as a rule, a moderate enlargement of the spleen and liver.

Damage to the organ of vision manifests itself as keratoconjunctivitis sicca, which is caused by pathological changes in the lacrimal glands and disruption of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.

With antiphospholipid syndrome, venous (in the deep veins of the lower extremities with repeated pulmonary embolisms) and arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks) thrombosis can be detected. Valve heart defects, intracardiac thrombi simulating cardiac myxoma, and coronary artery thrombosis with the development of MI are recorded. Skin lesions associated with antiphospholipid syndrome are varied, but the most common is livedo reticularis. (livedo reticularis).

Thus, after the second stage of the examination, multiple organ lesions are detected, and their degree is very different: from barely clinically noticeable (subclinical) to pronounced, predominant over the rest, which creates the preconditions for diagnostic errors - interpretation of these changes as signs of independent diseases (for example, glomerulonephritis , myocarditis, arthritis).

The third stage of the diagnostic search in SLE is very important because:

Helps make a final 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, laboratory blood testing becomes most important. There are two groups of indicators.

Indicators that have direct diagnostic significance (indicate pronounced immunological disorders):

LE cells (lupus erythematosus cells) are mature neutrophils that phagocytose nuclear proteins of other blood cells that have disintegrated under the influence of 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 or higher). The absence of ANF in the vast majority of cases argues against the diagnosis of SLE.

ANA - antibodies to native (i.e. to the whole molecule) DNA. An increase in their concentration correlates with disease activity and the development of lupus nephritis. They are found in 50-90% of patients.

Antibodies to 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 “rosette” phenomenon is 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 when determining blood clotting using functional tests (determining increased thromboplastin time) and antibodies to cardiolipin using an enzyme-linked immunosorbent assay. 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 - independent illness, in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis and autoimmune hemolytic anemia occur.

Nonspecific acute phase indicators, which include:

Dysproteinemia with increased contentα 2 - and γ-globulins;

SRB detection;

Increased fibrinogen concentration;

Increase in ESR.

In case of severe articular lesions, RF, an antibody to the Fc fragment of IgG, can be detected in a small titer.

When examining peripheral blood, leukopenia (1-1.2x10 9 /l) can be detected 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 a positive Coombs test. Thrombocytopenia is sometimes recorded in combination with Werlhoff syndrome.

Kidney damage is characterized by changes in the urine, 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 serves as an expression of the nephrotic syndrome accompanying subacute or active lupus nephritis.

Very high proteinuria (as, for example, with amyloidosis) rarely develops. Moderate hematuria is noted. Leukocyturia can be a consequence of both the lupus inflammatory process in the kidneys and the result of the frequent addition of a secondary infectious lesion of the urinary tract.

At needle biopsy kidneys show nonspecific mesangiomembranous changes, often with a fibroplastic component. Considered characteristic:

Detection of freely lying substances in preparations renal tissue altered nuclei (hematoxylin bodies);

The capillary membranes of the glomeruli are in the form of wire loops;

Deposition of fibrin and immune complexes on the basement membrane of glomeruli in the form of electron-dense deposits.

According to the WHO classification, the following morphological types of lupus nephritis are distinguished:

Class I - no changes.

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 subluxations);

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 position of the diaphragm);

Changes in the heart with the development of lupus disease or exudative pericarditis.

An ECG can detect nonspecific changes in the final part of the ventricular complex (wave T and segment ST), similar to those described previously 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)

The end of the table 7-1

Diagnostics

In cases of the classical course of SLE, diagnosis is simple and is based on the detection of “butterfly”, recurrent polyarthritis and polyserositis, which constitute the clinical diagnostic triad, complemented by the presence of LE cells or ANF in diagnostic titers. Of auxiliary importance is the young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation and infectious diseases. 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 help (Table 7-2).

Table 7-2.Diagnostic criteria systemic lupus erythematosus (SLE)

End of table. 7-2

The diagnosis is reliable if four or more criteria are met. If less than four criteria are present, then the diagnosis of SLE is questionable and dynamic monitoring 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) may occur with the same symptoms, in which their use is contraindicated.

Differential diagnosis

SLE should be differentiated from a number of diseases. As large as the list of organs and systems involved in the pathological process in SLE is, the list of diseases that can be misdiagnosed in a patient is equally extensive. SLE can largely mimic various pathological conditions. This especially often happens at the onset of the disease, as well as with dominant damage to 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 DTD group.

Necessity differential diagnosis with rheumatism occurs, as a rule, in adolescents and young men at the onset of the disease - when arthritis and fever occur. Rheumatoid arthritis differs from lupus in the greater severity of symptoms, predominant damage to large joints and transience. You should not attach differential diagnostic significance to a previous infectious lesion (sore throat), since it can serve nonspecific factor, causing the development clinical signs SCV. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic carditis) appear. Subsequent dynamic observation makes it possible to detect an emerging heart defect, whereas in SLE, even if mitral valve insufficiency develops, it is mildly expressed and is not accompanied by clear symptoms.

hemodynamic disorders. Mitral regurgitation is mild. 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: symmetrical damage to the small joints of the hand occurs, new joints are involved in the process, and morning stiffness is characteristic. Differential diagnosis is based on the predominance of the proliferative component in the affected joints in RA, the early development of wasting of the muscles that move the affected joints, and the persistence of articular lesions. Erosion of the articular surfaces is absent in SLE, but is a characteristic sign of RA. A high RF titer is characteristic of RA. In SLE it is rarely found and in low titres. The differential diagnosis of SLE and visceral RA is extremely difficult. Refined diagnosis in both cases does not affect the nature of treatment (prescription of glucocorticoids).

With CAH, systemic disorders may 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 diagnosis, the following should be taken into account:

CAH often develops in middle age;

Patients with CAH have a history of viral hepatitis;

With CAH, pronounced changes in the structure and function of the liver are detected (cytolytic and cholestatic syndrome, signs liver failure, hypersplenism, portal hypertension);

In SLE, liver damage does not always occur and occurs in the form of lung hepatitis course (with moderate signs of cytolytic syndrome);

With CAH, various markers of viral liver damage (antiviral antibodies and viral antigen) are detected.

In primary IE, heart damage quickly occurs (aortic or mitral valve insufficiency), and antibacterial therapy gives a clear effect. LE cells, antibodies to DNA, and ANF are usually absent. With timely bacteriological examination, the growth of pathogenic microflora is detected.

Thrombocytopenic purpura (idiopathic or symptomatic) lacks many of the syndromes seen in SLE, typical laboratory findings (LE cells, ANF, anti-DNA antibodies) and fever.

The most difficult differential diagnosis with other diseases from the CTD group. Conditions such as SSc and MD may share many features with SLE. This circumstance aggravates the possibility of detecting ANF and LE cells in these diseases, although in a smaller titer. The main differential diagnostic features are more frequent and pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin damage in SSc, and a clear myopathic syndrome in DM. In some cases, a correct diagnosis can be made only after a long period of

dynamic observation of the patient. Sometimes this takes many months and even years (especially in chronic SLE with minimal activity).

The formulation of a detailed clinical diagnosis of SLE should take into account all the categories 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 - stage renal failure, with myocarditis - the existence or absence of heart failure, with lung damage - the existence or absence of respiratory failure, etc.);

Indication of treatment (for example, glucocorticoids);

Complications of treatment (if any).

Treatment

Considering the pathogenesis of the disease, complex pathogenetic treatment is recommended for patients with SLE. His tasks:

Suppression of immune inflammation and immune complex disorders (uncontrolled immune response);

Prevention of complications of immunosuppressive therapy;

Treatment of complications arising during immunosuppressive therapy;

Impact on individual, sharply pronounced syndromes;

Removal of CEC and antibodies from the body.

First of all, it is necessary to exclude psycho-emotional stress, insolation, actively treat concomitant infectious diseases, eat low-fat foods high in polyunsaturated fatty acids, calcium and vitamin D. During exacerbation of the disease and during treatment with cytostatic drugs, active contraception is necessary. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.

To suppress immune inflammation and immune complex disorders in the treatment of SLE, the main immunosuppressants are used: short-acting glucocorticoids, cytotoxic drugs and aminoquinoline derivatives. The duration of treatment, choice of drug, as well as maintenance doses are determined:

The degree of disease activity;

The nature of the flow (severity);

The extensive involvement of internal organs in the pathological process;

Tolerability of 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 (prednisolone at a dose of less than 10 mg/day). Patients should be monitored at the dispensary so that when the first signs of exacerbation of the disease occur, the doctor can timely prescribe treatment with glucocorticoids in the optimal dose.

For chronic disease with predominantly skin lesions, 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 involving internal organs occur, it is necessary to immediately switch to more effective immunosuppressive treatment with glucocorticoids: prednisolone is prescribed at a dose of 1 mg/day or more. The duration of high doses 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.

So the main method treatment of SLE- use of glucocorticoids. When using them, you should adhere to the following principles:

Start treatment only if 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;

Treatment with an overwhelming dose should be carried out until a pronounced clinical effect is achieved (improvement in general condition, normalization of body temperature, improvement in 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. To prevent the side effects of glucocorticoids, use:

Potassium preparations (orotic acid, potassium chloride, potassium and magnesium aspartate);

Anabolic agents (methandienone in a dose of 5-10 mg);

Diuretics (saluretics);

Antihypertensive drugs (ACE inhibitors);

Antacids.

During development severe complications prescribe:

Antibiotics (for secondary infection);

Anti-tuberculosis drugs (with the development of tuberculosis, more often in pulmonary localization);

Insulin preparations, dietary food(for diabetes mellitus);

Antifungal agents (for candidiasis);

Antiulcer treatment (in case of steroid ulcer formation).

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 over 30 minutes for three days):

A sharp increase (spike) in process activity ( III degree), despite seemingly optimal treatment;

Resistance to doses that 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 dissociation of larger ones).

Significant suppression of the activity of the process after pulse therapy allows further administration of 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 if complications develop, despite the fact that such therapy is effective in a particular patient;

Intolerance to glucocorticoids;

Resistance to treatment with glucocorticoids (usually detected quite early).

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 prednisolone at a dose of 10-30 mg/day. In the future, you can return to treatment with glucocorticoids, as 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 assessing the effectiveness of the use of cytostatics:

Reduction or disappearance of clinical signs;

Disappearance of steroid resistance;

Persistent decrease in process activity;

Preventing the progression of lupus nephritis. Complications of cytostatic therapy:

Leukopenia;

Anemia and thrombocytopenia;

Dyspeptic phenomena;

Infectious complications.

If the number of leukocytes decreases to less than 3.0x10 9 /l, the dose of the drug should be reduced to 1 mg/kg body weight. With a further increase in leukopenia, the drug is discontinued and the dose of prednisolone is increased by 50%.

Extracorporeal treatment methods - plasmapheresis and hemosorption - have become widespread. They allow you to remove CEC 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.

Typically, 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). For 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, normal doses of NSAIDs can be used.

Forecast

In recent years, due to the use of effective treatments, the prognosis has improved: 10 years after diagnosis, 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 unfavorable.

Prevention

Since the etiology of SLE is unknown, primary prevention is not carried out. Nevertheless, a risk group is identified, which includes, first of all, relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). They should avoid insolation, hypothermia, should not be vaccinated, receive mud therapy and other balneological procedures.

SYSTEMIC SCLERODERMA

SSc is a systemic disease of 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 SSD - fibrous transformation of connective tissue, which serves as a framework for internal organs, constituent element skin and blood vessels. The rampant development of fibrosis is associated with excessive collagen formation due to impaired functioning of fibroblasts.

The prevalence of SSc varies in different geographic areas and ethnic groups, including those living in the same region. Primary incidence ranges from 3.7 to 19.0 cases per 1 million population per year. SSD is more often registered among women (ratio 5:7.1) aged 30-60 years.

Etiology

The cause of the disease is unknown. They attach importance to viruses, since there is indirect evidence of their role in the occurrence of SSc: virus-like inclusions and an increased titer of antiviral antibodies were found in the affected tissues. A family genetic predisposition to SSc has been established, since relatives of patients show changes in protein metabolism in the form of hypergammaglobulinemia, Raynaud's syndrome, and sometimes SSD.

Unfavorable factors contributing to the manifestation of the disease and its exacerbations include environmental factors (prolonged contact with polyvinyl chloride, silica dust), the use of drugs (bleomycin, tryptophan), as well as cooling, trauma, disruption of neuroendocrine functions and exposure to occupational hazards in the form vibrations.

Pathogenesis

The pathogenesis is based on a violation of the interaction process various cells(endothelial, smooth muscle cells vascular wall, fibroblasts, T- and B-lymphocytes, monocytes, mast cells, eosinophils) with each other and components of the connective tissue matrix. The result of all of the above is the selection of a population of fibroblasts that are resistant to apoptosis and function in an autonomous mode of maximum synthetic activity, which activates neofibrillogenesis and promotes changes in the glycoproteins of the main substance of connective tissue. As a result, fibrous-sclerotic changes in the connective tissue develop. At the same time, dysregulation of the body’s immune response to the introduction of the virus occurs, which is expressed in the overproduction of antibodies to its own tissues (autoantibodies). Then immune complexes are formed, settling in the microvasculature and internal organs, which leads to the development of immune inflammation. The severity of immune and autoimmune disorders in SSc 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 SSc 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.

Character of the current:

Rapidly progressive;

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, calcinosis, 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 scleroderma kidney, chronic diffuse glomerulonephritis, focal glomerulonephritis;

Nervous system - polyneuritis, neuropsychiatric disorders, autonomic changes.

The severity of skin thickening is assessed by palpation using a 4-point system:

0 - no seal;

1 - slight compaction;

2 - moderate compaction;

3 - pronounced compaction (impossibility of folding).

In recent years, prescleroderma, diffuse cutaneous scleroderma, 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 SSc).

The chronic course, which is most characteristic of SSD, is characterized by gradually developing vasomotor disturbances such as Raynaud's syndrome and the resulting trophic disorders, which serves as the only sign of the disease for many years. Subsequently, thickening of the skin and periarticular tissues occurs with the development of osteolysis and slowly progressive sclerotic changes in the internal organs (esophagus, heart, lungs).

A rapidly progressing course is characterized by the appearance of severe fibrous peripheral and visceral lesions already 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).

Considering the progressive nature of the disease, to assess the evolution and degree of growth of the pathological process, three stages of the course are distinguished:

Stage I - initial manifestations - mainly articular changes in subacute, and vasospastic - in chronic;

Stage II - generalization of the process - polysyndromic and polysystemic damage to many organs and systems;

Stage III - terminal - the predominance of severe sclerotic, dystrophic or vascular-necrotic processes (often with distinct dysfunctions of one or more organs).

Clinical picture

The clinical picture of the disease is polymorphic and polysyndromic, reflecting its generalized nature. There is practically no organ or system that could not be involved in the pathological process.

On first stage of diagnostic search receive information on the basis of which one can form an idea of ​​the diagnosis and type of onset of the disease, the nature of the process, the involvement of various organs in the pathological process, previous 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), the clinical picture is dominated from the very beginning by damage to internal organs with minimal skin changes, which makes diagnosis difficult. As the disease progresses, you can get an idea of ​​the nature of its course (acute, subacute and chronic).

Complaints from patients when internal organs are involved in the pathological process correspond to subjective symptoms when they are damaged in one way or another (pleurisy, arthritis, Raynaud's syndrome, duodenitis, etc.). At the same time, patients may present complaints that are most characteristic of SSD: difficulty 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 extend to the hands and feet. Patients often 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 oral mucosa and conjunctiva, as well as the inability to cry (no tears). Damage to the facial skin is expressed in a feeling of tightness of the skin and mouth (difficulty opening the mouth). As a rule, 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), a definite conclusion about the diagnosis can be made. It can be extremely difficult to do this at the very beginning, since the symptoms of SSc are in many ways reminiscent of other conditions from the CTD group (SLE, RA, MD), and with mono or oligosyndromicity - other diseases characterized by damage to only one organ (heart, lungs, etc.) .

Ha the second stage of the 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, emphasized vascular pattern and telangiectasia. Damage to the mucous membranes is expressed in increased dryness. Ulcerations and pustular rashes may occur on the skin; hair falls out, nails become deformed. In the final stage of the disease, the skin of the face becomes dense and cannot be folded. The face is amicable, mask-like. The shape of the mouth is characteristic: the lips are thin, gathered in folds that cannot be straightened, and the ability to open the mouth wide is gradually lost (the “pouch” symptom).

Vasospastic changes in Raynaud's syndrome in the form of whitening of the skin surface are found in the face, lips, hands and feet.

Damage to the joints is expressed in their defiguration due to the predominant damage to periarticular tissues, as well as true scleroderma polyarthritis with a predominance of exudative-proliferative or fibrous-indurative changes. The development of a 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. This hand 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, decreased muscle mass and impaired movement. Painful lumps (calcifications) may form in the muscles. Especially often, deposits of calcium salts are found in soft tissues fingers

Gastrointestinal lesions (esophagitis, duodenitis, malabsorption syndrome or persistent constipation) are mainly detected at the first and third stages of the diagnostic search.

Damage to the respiratory system is expressed in the form of pneumonitis, which occurs acutely or chronically, sluggishly. Physical data are extremely scarce; in severe cases, only pulmonary emphysema is detected. Significantly more information is provided by x-ray examination, which provides significant assistance in identifying bilateral basal pneumosclerosis, characteristic of SSc.

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 second 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 caused by hypertrophy of the right ventricle.

Heart damage occupies a major place among visceral symptoms SSD both in frequency and impact on disease outcome. SSc is characterized by so-called primary cardiosclerosis, which is not associated with previous necrotic or inflammatory changes in the myocardium. An enlarged heart (sometimes significant) is noted, as well as cardiac arrhythmias in the form of extrasystole or AF. Damage to the endocardium leads to the development of heart disease, almost always to mitral regurgitation. The combination of the latter with cardiosclerosis in some cases can cause the development of heart failure with all its characteristic signs. Pericarditis in SSc is rarely observed and more often it occurs as dry.

Damage to small vessels - scleroderma angiopathy - manifests itself with vasomotor disturbances (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 pain. In severe cases, Raynaud's syndrome leads to hemorrhages, necrosis of finger tissue and telangiectasia.

Kidney damage in SSc (in 80% of patients) is caused by pathological changes in blood vessels, but not by the development of fibrosis. Most severe symptom- scleroderma renal crisis, usually developing in the first five years of the disease in patients with a diffuse form of SSc and manifesting with 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 convulsions. When kidney damage occurs in the form of isolated changes in urinary sediment, no significant pathological signs are detected during physical examination.

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, a multi-organ lesion is detected with predominant damage to the skin and its derivatives. The degree of changes is very different - from subclinical to significantly pronounced. Possibility of establishing the diagnosis of SSc with predominant skin lesions

higher than with the predominance of visceral disorders. In the latter case, if damage to any one organ (kidneys, heart) comes to the fore, there are prerequisites for making diagnostic errors.

You can:

Determine the degree of activity of the process;

To clarify the severity of damage to internal organs;

Carry out differential diagnosis with other diseases from the group of chronic CTDs.

In determining the degree of disease activity, nonspecific acute-phase indicators are of greatest importance, which include:

Dysproteinemia with increased concentrations of α2 and γ-globulins;

Increasing the content of SRP;

Increased fibrinogen concentration;

Increase in ESR.

The existence and severity of immune disorders can be judged by the definition of RF (detected in 40-50% of cases), antinuclear antibodies (in 95%) and LE cells (in 2-7% of patients). In contrast to SLE, all these indicators in SCD are detected in significantly lower titers and less frequently.

The greatest diagnostic significance is attached to the so-called scleroderma antibodies.

Scl-70 antibodies are more often found in diffuse forms of SSc (40%). Their presence in combination with carriage of HLA-DR3/DRw52 is prognostic unfavorable factor in patients with Raynaud's syndrome, increasing the risk of developing pulmonary fibrosis in SSc by 17 times.

Antibodies to the centromere (chromosomal 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 SSc. They are present predominantly in patients with the diffuse form and are associated with kidney damage and a poor prognosis.

If the kidneys are damaged, proteinuria, expressed to varying degrees, is noted in combination with minimal changes in urinary sediment (microhematuria, cylindruria). With a true scleroderma kidney (the development of necrosis of the renal tissue due to damage to the renal vessels), acute renal failure may develop with an increase in creatinine in the blood.

In SSc, there is a dissociation between the pronounced morphological changes in the renal tissue and blood vessels detected during puncture biopsy and the relatively moderate clinical (including laboratory) signs of kidney damage. If hypertension develops as a result of kidney damage, changes in the fundus of the eye are noted (narrowing of the arteries and dilatation of the veins).

If the heart is damaged, the ECG shows nonspecific changes in the final part of the ventricular complex (decrease in amplitude and wave inversion T), and sometimes - intraventricular conduction disturbances. X-ray visualizes an enlarged heart. X-ray helps

detect calcification of the muscles and soft tissues of the fingers, as well as differentiate changes in the joints in SSc with disorders in RA (in SSD there are no erosions of the articular surfaces). In 60-70% of cases, x-rays show damage to the gastrointestinal tract (especially the esophagus and intestines). Changes in the esophagus are represented by its diffuse expansion combined with narrowing in the lower third, weakening of peristalsis and some rigidity of the walls.

Biopsy of the skin, synovium and muscles reveals fibrous changes characteristic of SSc, as well as vascular damage. Morphological examination data are not decisive in establishing the diagnosis.

Diagnostics

Diagnosis of the disease is based on the detection of major and minor diagnostic criteria.

Major criteria include proximal scleroderma - symmetrical thickening, compaction and induration of the skin of the fingers and the skin located proximal to the metacarpophalangeal and metatarsophalangeal joints. Changes may affect the face, neck and torso (chest and abdomen).

Minor criteria:

Sclerodactyly - the above skin changes, limited to the involvement of the fingers in the pathological process;

Scarring on the fingertips or loss of finger pad substance;

Bilateral basal pulmonary fibrosis.

A patient with SSc must have either a major criterion (major) or at least two minor criteria. Sensitivity - 97%, specificity - 98%.

The most typical combination of SSD is a combination of calcification, Raynaud's syndrome, esophagitis, sclerodactyly and telangiectasia (syndrome CREST- according to the first letters of the English names of the listed symptoms).

Diagnosis of SSc in the early stages is based on the detection of a triad of initial signs (occurring most early): Raynaud's syndrome, articular syndrome (usually polyarthralgia) and dense swelling of the skin. Significantly less often in early stage detect one of the visceral localizations of the process.

Significant difficulties in diagnosing SSc are associated with the absence of a characteristic skin syndrome in patients with severe polysyndromic lesions of internal organs (the so-called SSD without scleroderma). In these cases, X-ray examination provides significant assistance, allowing to detect impaired motility of the esophagus and its expansion, as well as dilatation of the duodenum and colon.

Differential diagnosis

SSc should be differentiated from a number of diseases and, above all, from other DCTs, as well as from diseases whose clinical picture is very similar to that of damage to any organ in SSD (provided it is treated

mining). For example, with scleroderma damage to the heart, differential diagnosis is carried out with atherosclerotic cardiosclerosis, rheumatic carditis and nonspecific myocarditis; at pulmonary lesions- with chronic pneumonia, tuberculosis and occupational lung diseases (pneumoconiosis); if the esophagus is affected, cancer of the esophagus should be excluded.

The basis for differential diagnosis is the detection of signs typical of SSc.

The predominance of peculiar skin lesions in combination with Raynaud's syndrome and slightly expressed laboratory data in SSc, in contrast to skin changes in SLE, combined with higher activity of the pathological process (according to laboratory tests).

Unlike SLE, in SSc, damage to internal organs is not combined with pronounced immune disorders (ANF, RF and antibodies to DNA are detected in lower titers, the frequency of detection and the number of LE cells are also low).

Articular syndrome in SSc, unlike 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 in SSc; damage to the periarticular tissue predominates.

Unlike ischemic heart disease, cardiac damage in SSc is not accompanied by anginal pain. There are no signs of previous MI on the ECG. Unlike rheumatic heart disease, stenosis (mitral, aortic orifice) never develops in SSc; Usually there is moderate isolated mitral regurgitation.

The dominant lesion of any system or organ in SSc is always combined with skin and muscle changes and Raynaud's syndrome. For the clinical picture of other diseases (chronic pneumonia, atherosclerotic cardiosclerosis, intestinal diseases, peptic ulcer), from which it is necessary to differentiate SSD, is characterized by monosyndromy.

In SSc, skin changes and Raynaud's syndrome dominate, while in DM, muscle damage comes to the fore in combination with a peculiar lilac-colored periorbital edema (“spectacles symptom”).

Glucocorticoids in SSc do not have such a dramatic positive effect as in SLE.

In some cases, when SSD manifests itself as 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 categories given in the working classification. The diagnosis should reflect:

The nature of the current;

Stage;

Clinical and morphological characteristics of damage to organs and systems of the body, indicating the stage of functional failure (for example,

measures, for pneumosclerosis - the stage of pulmonary failure, for kidney damage - the stage of renal failure, etc.).

Treatment

Treatment of SSD 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 effect;

Impact on local symptoms of the disease.

Avoid the effects of cold, smoking, local exposure to vibration, stressful situations and taking drugs that cause peripheral vascular spasm (β-blockers without vasodilating effect).

Drug treatment of Raynaud's syndrome involves the prescription of slow calcium channel blockers - amlodipine (5-20 mg/day), long-acting nifedipine (30-90 mg/day), felodipine (5-10 mg/day), as well as long-acting verapamil action (240-480 mg/day) or diltiazem (120-360 mg/day).

A good effect is achieved by taking pentoxifylline orally (400 mg 3 times a day). 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 administered intravenously over 6-24 hours for 2-5 days: alprostadil (0.1-0.4 mcg/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 acute course, rapidly increasing indurative 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 increases significantly. When treating with penicillamine, it is necessary to monitor urine laboratory values, since proteinuria may develop 6-12 months after the start of treatment. When it increases to 0.2 g/day, the drug is discontinued. For severe skin lesions, enzyme therapy is recommended. Prescribe subcutaneous injection of hyaluronidase near the affected areas or electrophoresis with this drug.

Anti-inflammatory and cytotoxic drugs are used in the early (inflammatory) stage of SSc and in rapidly progressing disease.

Glucocorticoids in small doses (15-20 mg/day) are used for progressive diffuse skin lesions and obvious clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory

arthritis and tenosynovitis). Taking large doses is not recommended (risk of developing scleroderma renal crisis).

When prescribed at a dose of 2 mg/kg per day for 12 months, cyclophosphamide reduces skin itching only in patients with the diffuse form of SSc.

Methotrexate is prescribed when SSD is combined with RA or PM.

In case of scleroderma renal crisis, to eliminate vascular spasms and prevent the development of scleroderma kidney, ACE inhibitors (captopril 100-150 mg/day, enalapril 10-40 mg/day) are used under blood pressure control.

In case of damage to the esophagus, in order to prevent dysphagia, frequent small meals and the exclusion of eating later than 18 hours are recommended. Treatment of dysphagia involves the administration of prokinetics (metoclopramide at a dose of 10 mg 3-4 times a day). For reflux esophagitis, omeprazole is prescribed (orally 20 mg/day).

The impact on local symptoms of the disease involves the application of a 25-50% solution of dimethyl sulfoxide. During periods of inactivity of the pathological process, exercise therapy and massage can be recommended.

Forecast

In SSc, the prognosis is determined by the course and stage of development. It is noted that the more time separates the advanced stage from the onset of the first signs of the disease (in particular, Raynaud's syndrome), the more favorable the prognosis. Five-year survival rates range from 34 to 73%, with an average of 68%. The risk of death in SSc is 4.7 times higher than in the population.

Predictors of poor prognosis:

Diffuse form of the disease;

The age of onset of the disease is over 47 years;

Male gender;

Pulmonary fibrosis, pulmonary hypertension, arrhythmias, kidney damage in the first three years of the disease;

Anemia, high ESR, proteinuria at the onset of the disease.

Prevention

The risk group includes persons with a tendency to vasospastic reactions, polyarthralgia, 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 SSc are registered at the dispensary. Systematically carried out treatment (in particular, properly selected maintenance therapy) - the best remedy prevention of exacerbations.

DERMATOMYOSITIS (POLYMYOSITIS)

DM - systemic inflammatory disease skeletal, smooth muscles and skin. Involvement of internal organs in the pathological process is less common. In the absence of skin lesions, the term “polymyositis” is used.

The main symptom of the disease is severe muscle weakness due to progressive severe necrotizing myositis with predominant damage to the muscles of the proximal limbs. As the disease progresses, muscle tissue atrophies and is replaced by fibrous tissue. Similar processes occur in the myocardium. Dystrophic changes develop in 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 (DM) - idiopathic and secondary (tumor). The etiology of idiopathic DM is unclear, but factors contributing to the manifestation and subsequent exacerbation of this disease are known:

Insolation;

Hypothermia;

Infectious lesions (acute respiratory infections, flu, sore throat, etc.);

Hormonal changes (menopause, pregnancy, childbirth);

Emotional stress;

Physical trauma, surgery;

Sensitization medicines(chlorpromazine, insulin preparations, antibiotics, penicillamine);

Vaccination;

Contact with epoxy resins, photosolvents;

Physiotherapeutic procedures.

Hereditary-genetic predisposition is probably important: patients 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 suffering from malignant tumors. Most often, DM occurs with cancer of the lung, intestines, prostate gland, ovary, as well as for hemoblastosis. The occurrence of DM in individuals over the age of 60 years almost always indicates its tumor origin.

Pathogenesis

Under the influence of a virus and genetic predisposition or tumor antigens, a disruption (dysregulation) of the immune response occurs, expressing

resulting from an imbalance of the B- and T-lymphocyte systems: the body produces antibodies to skeletal muscles and develops sensitization of T-lymphocytes to them. The antigen-antibody reaction and the cytotoxic effect of T-lymphocytes sensitized to muscles contribute to 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 the muscles and internal organs. During inflammation, new antigens are released, promoting further formation of immune complexes, which leads to chronicity of the disease and involvement of previously healthy muscles in the pathological process. The main links in the pathogenesis of DM are presented in Fig. 7-2.

Rice. 7-2. Pathogenesis of dermatomyositis

Clinical picture

The clinical picture of the disease is systematic and polysyndromic.

Main syndromes:

Muscular (myositis, muscle atrophy, calcification);

Skin (erythema, skin swelling, dermatitis, pigmentation and depigmentation, telangiectasia, hyperkeratosis, urticaria);

Articular (arthralgia, damage to 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). The following periods of the disease are distinguished:

I period (initial) - lasts from several days to 1 month or more, manifests only with 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 severe functional insufficiency (the development of complications is possible).

There are three forms of the disease:

Acute form, when a generalized lesion quickly increases skeletal muscles, leading to complete immobility of the patient. Muscle damage progresses pharyngeal ring and esophagus (dysphagia, dysarthria). Damage to internal organs (especially the heart) develops rapidly with death within 2-6 months from the onset of the disease;

Subacute form with a slower, gradual increase in symptoms. Heavy defeat muscles and visceritis occur after 1-2 years;

Chronic form with a long cyclical course. The processes of atrophy and sclerosis predominate. Local muscle damage is possible.

On first stage of diagnostic search receive information about the nature of the onset of the disease - acute (increase in body temperature to 38-39 ° C, skin erythema and muscle pain) or gradual (moderate weakness, mild myalgia and arthralgia, worsening after physical activity, insolation or other adverse effects).

The most typical complaints are caused by 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 limbs, back and neck.

When the pharyngeal muscles are affected, patients complain of choking when swallowing, and liquid food pours out through the nose. Nasal tone of voice and hoarseness are caused by damage to the muscles of the larynx.

When the skin is affected, patients note a persistent change in its color in places exposed to the sun (neckline, face, hands), as well as on the outer surfaces of the thighs and legs. The occurrence of purple-colored paraorbital edema (“spectacles symptom”) is characteristic. When the mucous membranes are affected, patients complain of dryness, burning in the eyes and lack 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 being carried out allows us to judge its correct selection, and indirectly, the nature of the course: the use of aminoquinoline drugs indicates a chronic course, the use of prednisolone and cytostatics indicates a more acute course.

On the second stage of the 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 increased in volume and painful on palpation. When the facial muscles are affected, a certain mask-like appearance of the face is noticeable. Subsequently, muscle atrophy occurs, especially pronounced on the side shoulder girdle. The respiratory muscles and diaphragm are also damaged. When palpating the muscles, one can detect local compactions - calcifications, which are also located in the subcutaneous fatty tissue. Calcinosis often develops in young people with widespread muscle damage during the transition from acute to subacute or chronic. A decrease in body weight of 10-20 kg is often noted.

Skin lesions are not a mandatory sign of DM, but when it exists, swelling, erythema (above the joints - supra-articular erythema, in the periungual areas in combination with micronecrosis in the form of dark spots - Gottron's syndrome), capillaritis, petechial rashes and telangiectasia are noted on the exposed parts of the body. Erythema is highly persistent, has a bluish tint, and is accompanied by itching and peeling. A typical “spectacle symptom” is erythema around the eyes. Redness, peeling and cracking of the skin of the palms (“mechanic’s or craftsman’s hand”), brittle nails and increased hair loss are often noted.

Severe Raynaud's syndrome is quite often recorded.

The signs of visceral lesions in DM, as well as in SSc, are not too bright, unlike in SLE. One can note a known dissociation between the severity of pathomorphological changes in organs and their clinical manifestation. Heart damage (myocarditis, cardiosclerosis) is represented by such nonspecific signs as an increase in its size, dullness of tones, tachycardia and rhythm disturbances in the form of extrasystole. Severe changes in the myocardium can lead to symptoms of heart failure.

Damage to the lungs in the form of pneumonitis is accompanied by extremely scanty symptoms. Developing fibrosis is detected by signs of pulmonary emphysema and respiratory failure. Aspiration pneumonia is characterized by all the typical symptoms.

Damage to the gastrointestinal tract is characterized by dysphagia: regurgitation of solid food and pouring of liquid food through the nose. Pathological changes in the vessels of the stomach and intestines can lead to gastrointestinal bleeding. Sometimes a moderate enlargement of the liver is noted, less often - hepatolienal syndrome with enlarged lymph nodes.

Neurological disorders are represented by changes in sensitivity: peripheral or radicular hyperesthesia, hyperalgesia, paresthesia and areflexia.

On third stage of diagnostic search Research methods that allow one to assess the severity of the inflammatory process and the prevalence of muscle damage provide significant assistance.

The severity of the process can be judged by nonspecific acute-phase indicators (increased ESR, increased fibrinogen and CRP levels,

hyper-a 2 -globulinemia) and signs of immune changes (low RF titer, increased content of γ-globulins, antibodies to nucleoprotein and soluble nuclear antigens, antibodies to Mi2, Jol, SRP, and in the case of idiopathic DM - increased concentration of IgG).

In a chronic, sluggish course of the disease, changes in acute phase parameters 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 creatininuria. With significant muscle damage, myoglobinuria may occur. An increase in transaminase activity is not typical for skeletal muscle damage. In some patients with myopathic syndrome, this suggests hepatitis.

Immunological examination reveals myositis-specific antibodies. These include antibodies to transfer RNA aminoacyl synthetases (antisynthetase antibodies) and, primarily, antibodies to histidyl-tRNA synthetase (Jo1). Jo1 antibodies are found in half of patients with DM (DM), while other antisynthetase 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, symmetrical arthritis, interstitial lung disease, Raynaud's phenomenon and mechanic's hand lesions of the hands.

For DM tumor origin in men, the detection of prostate-specific antigen is typical, in women - CA-125 (ovarian tumor antigen). In addition, if the tumor is located at a different location, other tumor-specific antigens can be detected.

Electromyography provides significant assistance in diagnosing muscle damage, making it possible to detect normal electrical activity muscles in a state of voluntary relaxation and low-amplitude - during voluntary contractions.

A biopsy of the skin and muscles reveals a picture of severe myositis with loss of cross-striations 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 significant atrophy.

Other research methods (ECG, X-ray and endoscopic) are necessary for:

Assessment of the condition of affected internal organs;

Search for a tumor if DM of tumor origin is suspected.

Diagnostics

To diagnose DM (DM), the following diagnostic criteria should be used.

Skin damage:

Heliotrope rash (purple-red rash on the eyelids);

Gottron's sign (purple-red scaly atrophic erythema or spots on the extensor surface of the hands over 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 with electromyography (short polyphasic potentials of motor units with spontaneous fibrillation potentials).

Detection of Jo1 antibodies (antibodies to histidyl-tRNA synthetase).

Non-destructive arthritis or arthralgia.

Signs systemic inflammation(increase in body temperature more than 37 ° C, increase in the concentration of CRP or ESR more than 20 mm/h).

Morphological changes consistent with 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 (DM) presents great difficulties, especially at the onset of the disease.

DM (PM) should be differentiated from infectious and neurological diseases, SSc, SLE and RA. The differential diagnosis is based on the following changes:

Persistence of articular syndrome in RA, detection of erosions of the articular surfaces of bones during X-ray examination, absence of skin and muscle changes characteristic of DM.

Unlike SLE, in DM visceral disorders are not so pronounced and occur much less frequently. The clinical picture of DM is dominated by muscle damage, and laboratory parameters (especially immunological) are changed to a much lesser extent.

Unlike SSD, skin changes in DM have a completely different character: there are no typical changes in the hands, and the leading one is considered muscle syndrome(including severe muscle weakness). However, the differential diagnosis of SSc and DM is most difficult. In difficult cases it is necessary to use electrophysiological and morphological methods research.

In the acute course of DM, it is necessary to exclude an infectious lesion (septic condition, erysipelas etc.), which is possible with dynamic monitoring of the patient.

When adynamia dominates and reflexes are impaired, there is a need for differential diagnosis with neurological diseases, which is carried out during joint observation of the patient by a therapist and a neurologist.

The formulation of a detailed clinical diagnosis of DM should reflect:

Flow period;

Flow shape;

Clinical and morphological characteristics of damage to systems and organs, indicating leading syndromes and the existence or absence of functional failure 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. Early initiation of treatment (within the first 3 months of symptom onset) is associated with a more favorable prognosis than later initiation of treatment.

Glucocorticoids have the best effect: for DM, it is preferable to prescribe prednisolone (1-2 mg/kg per day). During the first weeks, the daily dose should be divided into three doses, and then taken all once in the morning, since improvement in the patient’s condition develops more slowly than with SLE or SSc (on average, after 1-3 months). If there is no positive dynamics within 4 weeks, the dose of glucocorticoids should be increased. After achieving the effect (normalization of muscle strength and CK activity), the dose of prednisolone is very slowly reduced to maintenance, 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 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 complications, then cytostatic drugs should be used.

Currently, early administration of methotrexate is recommended, which allows patients to be quickly transferred to maintenance doses of prednisolone. Methotrexate is prescribed orally, subcutaneously or intravenously at a dose of 7.5-25 mg/week. Intravenous administration The drug is recommended if it is insufficiently effective or poorly tolerated when taken orally. It should be remembered that the lack of effect from treatment with prednisolone indicates the possibility of the existence of tumor ANF, therefore, before prescribing cytotoxic drugs, an extensive oncological search should be carried out to exclude a malignant tumor.

Patients with prednisolone-resistant forms of the disease are prescribed oral cyclosporine at 2.5-5.0 mg/kg per day.

Azathioprine is inferior to methotrexate in effectiveness. The maximum effect develops later (on average after 6-9 months). The drug is prescribed to be taken orally at 100-200 mg/day.

Cyclophosphamide is the drug 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 process activity (to control skin lesions);

When reducing the dose of prednisolone or cytostatics to reduce the risk of possible exacerbation.

Plasmapheresis should be prescribed to patients with severe DM (PM) resistant to other treatment methods in combination with glucocorticoids and methotrexate or cytostatic drugs.

In recent years, TNF-α inhibitors have been increasingly used for treatment. Promising direction 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, due to 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 becomes chronic, the patient’s ability to work can be restored.

The prognosis for secondary (tumor) DM depends on the effectiveness of surgery: with a successful operation, all signs of the disease may disappear. Factors that worsen the prognosis of the disease: old age, late diagnosis, incorrect 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%.

Prevention

Prevention of exacerbations (secondary prevention) is achieved by carrying out supportive treatment, sanitizing foci of infection and increasing the body's resistance. The patient's relatives may have primary prevention(exclusion of overloads, insolation, hypothermia).

All diseases from this group have some common features:

• They arise as a result of a dysfunction of the immune system. Immune cells cease to distinguish between “friends” and “foes”, and begin to attack the body’s own connective tissue.
• These diseases are chronic. Following the next exacerbation there comes a period of improvement, and after that there is another exacerbation.
• Exacerbation occurs as a result of the action of certain common factors. Most often it is provoked by infections, exposure to sun rays or in a solarium, administering vaccines.
• Many organs are affected. Most often: skin, heart, lungs, joints, kidneys, pleura and peritoneum (the last two are thin films of connective tissue that cover the internal organs and line the inside of the chest and abdominal cavity, respectively).
• Medicines that suppress the immune system help improve the condition. For example, glucocorticosteroids (drugs of adrenal hormones), cytostatics.

Despite common symptoms, each of more than 200 diseases has own symptoms. True, establishing the correct diagnosis can sometimes be very difficult. Diagnostics and treatment are carried out by a rheumatologist.

Some representatives

A typical representative of the group of systemic connective tissue diseases is rheumatism. After an infection caused by a special type of streptococcus bacteria, the immune system begins to attack its own connective tissue. This can lead to inflammation in the walls of the heart, followed by the formation of heart valve defects, in the joints, nervous system, skin and other organs.

The “calling card” of another disease from this group - systemic lupus erythematosus - is a characteristic rash on the skin of the face in the form of a “butterfly”. Inflammation may also develop in joints, skin, and internal organs.

Dermatomyositis and polymyositis are diseases that, respectively, are accompanied by inflammatory processes in the skin and muscles. Their possible symptoms: muscle weakness, increased fatigue, difficulty breathing and swallowing, fever, weight loss.

With rheumatoid arthritis, the immune system attacks the joints (mainly small ones - the hands and feet), over time they become deformed, mobility in them is impaired, up to the complete loss of movement.

Systemic scleroderma is a disease in which the connective tissue that makes up the skin and internal organs thickens, and blood circulation in small vessels is disrupted.

In Sjögren's syndrome, the immune system attacks the glands, mainly the salivary and lacrimal glands. Patients are concerned about dry eyes and mouth, increased fatigue, and joint pain. The disease can lead to problems with the kidneys, lungs, digestive and nervous systems, blood vessels, and increases the risk of lymphoma.

Nowadays, a common reason for visiting a doctor is joint pain - rheumatism, Reiter's syndrome, arthritis. There are many reasons for the increase in incidence, including environmental disturbances, irrational therapy, and late diagnosis. Systemic connective tissue diseases, or diffuse connective tissue diseases, are a group of diseases characterized by a systemic type of inflammation of various organs and systems, combined with the development of autoimmune and immune complex processes, as well as excessive fibrosis formation.

The group of systemic connective tissue diseases includes:

Modern rheumatology names the following causes of diseases: genetic, hormonal, environmental, viral and bacterial. For successful and effective therapy it is necessary to make a correct diagnosis. To do this, you should contact a rheumatologist, and the sooner the better. Today, doctors are armed with an effective SOIS-ELISA test system, which allows them to carry out high-quality diagnostics. Since very often the cause of joint pain is an infectious process caused by various microorganisms, its timely detection and treatment will not allow the development of an autoimmune process. After diagnosis, it is necessary to receive immunocorrective therapy while preserving and maintaining the functions of internal organs.

It has been proven that with systemic connective tissue diseases, profound disturbances of immune homeostasis occur, expressed in the development of autoimmune processes, that is, reactions of the immune system accompanied by the appearance of antibodies or sensitized lymphocytes directed against the antigens of one’s own body (autoantigens).

Treatment of systemic joint diseases

Among the methods of treating joint diseases are:
- medicinal;
- blockade;
- physiotherapeutic;
- therapeutic exercises;
- method of manual therapy;
- .

Medicines that are prescribed to a patient for arthrosis and arthritis have, for the most part, an effect that is aimed only at relieving the pain symptom and the inflammatory reaction. These are analgesics (including narcotics), non-steroidal anti-inflammatory drugs, corticosteroids, psychotropic drugs, and muscle relaxants. Ointments and rubs are often used for external use.
With the blockade method, the anesthetic device is injected directly into the source of pain - into trigger points in the joints, as well as into the places of the nerve plexuses.

As a result of physiotherapy, warming procedures reduce morning stiffness, ultrasound produces micro-massage of affected tissues, and electrical stimulation improves joint nutrition.
The joints affected by the disease need movement, therefore, under the guidance of a doctor, you need to choose a program of physical therapy exercises and determine their intensity.

In recent years, manual therapy has become popular in the treatment of joint diseases. It allows for a transition from forceful methods to soft, gentle ones, which are ideal for working with pathologically altered periarticular tissues. Manual therapy techniques involve reflex mechanisms, the impact of which improves metabolism in the affected elements of the joint and slows down degenerative processes in them. On the one hand, these techniques relieve pain (reduce unpleasant symptom diseases), on the other hand, promote regeneration and trigger restoration processes in the diseased organ.

Surgical treatment is indicated only in extremely advanced cases. However, before turning to surgery, it is worth thinking: firstly, surgical intervention is always a shock for the body, and secondly, sometimes arthrosis is precisely the consequence of unsuccessful operations.

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They include a wide range of diseases that primarily affect joints and periarticular tissues. A special group among them consists of systemic diseases - collagenosis and vasculitis, characterized by autoimmune genesis, local or diffuse damage to connective tissue. Rheumatic diseases are studied by a specialized branch of internal medicine - rheumatology. The course of rheumatic diseases is often accompanied by multiple organ damage with the development of cardiac, renal, pulmonary, cerebral syndromes, in the treatment of which not only rheumatologists are involved, but also specialized specialists - cardiologists, nephrologists, pulmonologists, neurologists. Rheumatic diseases have a progressive course, disrupt the patient’s functional activity and can lead to disability.

Rheumatic diseases such as gout and arthritis have been known since the time of the ancient Greek healer Hippocrates. In the II century. n. e. The Roman philosopher and surgeon Galen coined the term “rheumatism,” which denoted a variety of diseases of the musculoskeletal system. And only in the XVIII – XIX centuries. Descriptions of individual rheumatic diseases began to appear. Currently, according to the American Society of Rheumatology, there are over 200 types of rheumatic pathology.

Depending on the predominant lesion, the whole variety of rheumatic diseases can be divided into three large groups: joint diseases, systemic vasculitis and diffuse connective tissue diseases. Joint diseases are represented mainly by arthritis (rheumatoid, psoriatic, gouty, reactive, infectious, etc.), as well as osteoarthritis, ankylosing spondylitis, rheumatic diseases of the periarticular soft tissues. To the group systemic vasculitis include hemorrhagic vasculitis, Epstein-Barr viruses, rheumatoid arthritis, and polymyalgia rheumatica are more common in women, but gout, psoriatic arthritis, and ankylosing spondylitis usually affect men.

The clinical manifestations of rheumatic diseases are extremely diverse and changeable, however, certain symptomatic markers can be identified, the presence of which should immediately consult a rheumatologist. The main ones include: prolonged causeless fever, arthralgia, swelling and changes in the configuration of joints, morning stiffness, muscle pain, skin rash, lymphadenitis, tendency to thrombosis or hemorrhage, multiple damage to internal organs. Systemic diseases are often disguised as diseases of the skin, blood, musculoskeletal system, and oncopathology, which require differentiation first of all.

In recent years, significant progress has been made in the diagnosis and treatment of rheumatic diseases, which is associated with the development of genetics, immunology, biochemistry, microbiology, pharmacology, etc. The basis for making a correct diagnosis is immunological studies, which make it possible to identify antibodies corresponding to a specific nosology. Also, radiography, ultrasound, CT, MRI, scintigraphy, arthroscopy, and biopsy are widely used to diagnose rheumatic diseases.

Unfortunately, today a complete cure for rheumatic diseases is impossible. Nevertheless, modern medicine in most cases, it can help alleviate the course of the disease, prolong remission, and avoid disabling outcomes and severe complications. Treatment of rheumatic diseases is a long, sometimes lifelong process and consists of drug therapy, non-drug methods, orthopedic treatment and rehabilitation. The basis of therapy for most rheumatic diseases is basic anti-inflammatory drugs, glucocorticosteroids and biological drugs. A significant role in complex therapy is given to extracorporeal hemocorrection - hemosorption, plasma sorption, etc. Non-drug methods of treating rheumatic diseases, such as physiotherapy, balneotherapy, exercise therapy, acupuncture, kinesiotherapy, can significantly improve the functional status of patients. Orthopedic treatment(orthosis, surgical correction of joint function, endoprosthetics) is indicated mainly in the late period of rheumatic pathology to improve the quality of life of patients.

Prevention of rheumatic diseases is nonspecific. To prevent them, it is important to avoid provoking factors (stress, infections, other stresses on the body), pay sufficient attention to physical activity and taking care of your health, and eliminate bad habits. Rapid development medical technologies allows us to hope for a speedy resolution of unclear issues regarding the occurrence and course of rheumatic diseases.

On the pages of our medical directory, rheumatic and systemic diseases are separated into a separate section. Here you can get acquainted with the main rheumatic diseases, the causes of their occurrence, symptoms, advanced diagnostic methods, modern views for treatment.

DIFFUSE DISEASES OF CONNECTIVE TISSUE (DCTD), or collagenoses (a term of historical significance), is a group of diseases characterized by systemic immunoinflammatory damage to connective tissue and its derivatives. This concept is a group, but not nosological, and therefore this term should not denote individual nosological forms. CTDs combine a fairly large number of diseases. The most common are systemic lupus erythematosus (SLE), systemic scleroderma (SSc), dermatomyositis (DM); This group of diseases also includes rheumatic fever (traditionally described in the section on diseases of the cardiovascular system). It has now been proven that with CTD, profound disturbances of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the appearance of antibodies or sensitized lymphocytes directed against antigens of the body’s own (autoantigens).

The basis of autoimmune pathology is an immunoregulatory imbalance, expressed in the inhibition of suppressor and increase in “helper” activity of T-lymphocytes, followed by activation of B-lymphocytes and hyperproduction of autoantibodies of various specificities.

There are a number of common features that unite DZST:

The commonality of the pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixed in

Tissues with the subsequent development of a severe inflammatory reaction (especially in the microvasculature, kidneys, joints, etc.);

Similarity of morphological changes (fibrinoid change in the basic substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);

Chronic course with periods of exacerbations and remissions;

Exacerbation under the influence of nonspecific influences (infection, insolation, vaccination, etc.);

Multisystem damage (skin, joints, serous membranes, kidneys, heart, lungs);

The therapeutic effect of immunosuppressive drugs (glucocorticosteroids, cytostatics).

All diseases included in this group are distinguished by independent clinical and morphological manifestations, therefore, in each specific case one should strive for an accurate nosological diagnosis.

This chapter discusses the diagnostic search for systemic lupus erythematosus, systemic scleroderma, and dermatomyositis.

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of young people (mainly women), developing against the background of a genetically determined imperfection of immunoregulatory processes, leading to the uncontrolled production of antibodies to one’s own cells and their components, with the development of autoimmune and immune-complex chronic damage [Nasonova V.A., 1989]. The essence of the disease is immunoinflammatory damage to the connective tissue and microvasculature, skin, joints and internal organs (with visceral lesions being the leading ones, determining the course and prognosis of the disease).

SLE, according to various authors, occurs with a frequency of 2.7-4.8 per 100,000 population; in young and middle age, the ratio of sick women to men is 9:1 (in childhood or after menopause the ratio decreases to 2:1). This circumstance confirms the assumption that sex hormones play a certain role in the occurrence and development of SLE. Although the disease develops much less frequently in men, it is as severe as in women.

SLE belongs to genetically determined diseases: population studies have shown that the predisposition to the occurrence of SLE is associated with certain histocompatibility class II genes (HLA), genetically determined deficiency of certain complement components, as well as polymorphism of genes of some receptors and tumor necrosis factor a (TNF-a). A).

Etiology. The specific etiological factor in SLE has not been established, however, a number of clinical manifestations (cytopenic syndrome, erythema and enanthema) and certain patterns of the disease make it possible to bring SLE closer to diseases of viral etiology. Currently, importance is attached to viruses belonging to the RNA group (so-called slow, or latent, viruses). Detection of family cases of the disease, frequent identification in families of other rheumatic or allergic diseases, various immunity disorders allows

You can think about the possible significance of family genetic predisposition.

The detection of SLE is facilitated by a number of nonspecific factors - insolation, nonspecific infection, administration of serums, taking certain medications (in particular, peripheral vasodilators from the group of hydralazines), stress. SLE can begin after childbirth or an abortion. All these data allow us to consider SLE as a multifactorial disease.

Pathogenesis. Due to the impact of the virus (and possibly antiviral antibodies) on the immune system 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, uncontrolled production of antibodies to various tissues, cells, and proteins of the body occurs (including various cellular organelles and DNA). It has been established that in SLE, autoantibodies are produced to only about 40 of more than 200 potential antigenic cellular components. Subsequently, the formation of immune complexes occurs and their deposition in various organs and tissues (mainly in the microvasculature). Various immunoregulatory defects are characteristic, characterized by hyperproduction of cytokines (IL-6, IL-4 and IL-10). Next, processes associated with the elimination of fixed immune complexes play out, 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, in response to which antibodies are formed, new immune complexes are formed, and thus a vicious circle is created that ensures the chronicity of the disease.

Classification. Currently, in our country [Nasonova V.A., 1972-1986] a working classification of clinical variants of the course of SLE has been adopted, taking into account: 1) the nature of the course; 2) activity of the pathological process; 3) clinical and morphological characteristics of damage to organs and systems.

Nature of the disease:

Acute, subacute, chronic (recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhoff's syndrome, Sjögren's syndrome).

Phase and degree of activity of the process.

Active phase: high activity (III), moderate (II), minimal (I).

Inactive phase (remission).

Clinical and morphological characteristics of lesions:

Skin (butterfly symptom, capillaritis, exudative erythema, purpura, discoid lupus, etc.);

Joints (arthralgia, acute, subacute and chronic polyarthritis);

Serous membranes (polyserositis: pleurisy, pericarditis, perespinitis);

Heart (myocarditis, endocarditis, mitral valve insufficiency);

Lungs (acute, chronic pneumonitis, pneumosclerosis);

Kidney (lupus nephritis of nephrotic or mixed type; urinary syndrome);

Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).

There are acute, subacute and chronic course of the disease. Acute course: sudden onset - patients can indicate the day when fever, polyarthritis began, and changes appeared on the skin. In the next 3-6 months, polysyndromic syndrome, glomerulonephritis (lupus nephritis), and central nervous system damage develop. The duration of the disease without treatment is no more than 1-2 years, however, with timely recognition and active treatment with glucocorticosteroids and long-term maintenance therapy, complete remission can be achieved. This variant of the disease is observed mainly in adolescents, children and young people.

Subacute course: occurs most often, begins gradually, with general symptoms, arthralgia, recurrent arthritis, and various nonspecific skin lesions. The undulation of the flow is distinct. A detailed picture of the disease is formed after 2-3, less often - after 3-4 years.

Chronic course: the disease manifests itself for a long time as relapses of various syndromes - polyarthritis, less often polyserositis, discoid lupus syndrome, Raynaud's syndrome. In the 5-10th year of the disease, other organ lesions (kidneys, lungs) appear.

In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, which represents a clinical and laboratory symptom complex (venous and/or arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ damage). A characteristic immunological sign is antibodies that react with phospholipids and phospholipid-binding proteins (antiphospholipid syndrome will be discussed in more detail below).

There are also three degrees of activity of the pathological process, i.e. the severity of potentially reversible immunoinflammatory damage, which determines the nature of therapy in each individual patient. Activity should be distinguished from the “severity” of the disease, which is understood as a set of irreversible changes that are potentially life-threatening for the patient.

Clinical picture. The manifestations of the disease are extremely diverse, which is determined by the multiplicity of damage to organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.

At stage I of the diagnostic search, information is obtained on the basis of which one can form an idea: 1) about the variant of onset of the disease; 2) about the nature of the disease; 3) about the degree of involvement of certain organs and systems in the pathological process; 4) about previous treatment and its effectiveness, as well as possible complications of treatment.

The onset of the disease can be varied. Most often, the disease begins with a combination of various syndromes; monosymptomatic onset is usually uncharacteristic. In this regard, the assumption about the possibility of SLE arises from the moment such a combination is identified in a patient, which is extremely important for the diagnosis of SLE.

In the early stages of SLE, the most common syndromes are damage to the joints, skin, serous membranes, and fever. Thus, the most “suspicious” in relation to SLE will be various combinations: 1) fever, polyarthritis, trophic changes in the skin (in particular, hair loss - alopecia); 2) polyarthritis, fever, damage to the pleura (pleurisy); 3) fever, trophic skin disorders, time

Zkenia pleura. The diagnostic significance of these combinations increases significantly if the skin lesion consists of the development of erythema, however, in the initial period of the disease, erythema occurs only in 25% of cases; nevertheless, this circumstance does not reduce the diagnostic value of the listed combinations.

An asymptomatic onset of the disease is uncharacteristic, however, the debut of SLE with the development of massive edema due to the development from the very beginning of the pathological process of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type has been noted.

Involvement of various organs in the pathological process is manifested by symptoms of their inflammatory damage: arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.

Information about previous treatment allows us to judge: 1) its adequacy; 2) about the severity of the disease and the degree of activity of the process (initial doses of corticosteroids, duration of their use, maintenance doses, inclusion of cytostatics in the treatment complex for severe immune disorders, high activity of lupus nephritis, etc.); 3) about the presence of complications of corticosteroid and cytostatic therapy.

At stage I, certain conclusions can be made regarding the diagnosis during a long course of the disease, however, at the onset of the disease, the diagnosis is established at subsequent stages of the study.

At stage II of the diagnostic search, you can obtain a lot of data indicating damage to organs and the degree of their functional failure.

Damage to the musculoskeletal system is manifested by polyarthritis, reminiscent of rheumatoid arthritis (RA), symmetrical damage to small joints of the hand (proximal interphalangeal, metacarpophalangeal, wrist) and large joints (less often). With a detailed clinical picture of the disease, the defiguration of the joints is determined due to periarticular edema. As the disease progresses, deformities of small joints develop. Joint damage may be accompanied by diffuse myalgia, and very rarely by true polymyositis with swelling and muscle weakness. Sometimes only arthralgia occurs.

The skin is affected as often as the joints. The most typical are erythematous rashes on the face in the area of ​​the zygomatic arches and the back of the nose (“butterfly”). Inflammatory rashes on the nose and cheeks repeating the shape of a “butterfly” are observed in various variants: 1) vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse redness of the skin with a cyanotic tint in the middle zone of the face, intensifying when exposed to external factors (insolation, wind , cold) or excitement; 2) “butterfly” type of centrifugal erythema (skin changes are localized only in the area of ​​the bridge of the nose). In addition to the “butterfly”, discoid rashes can be observed - erythematous raised plaques with keratic disorder and subsequent atrophy of the skin of the face, limbs and trunk. Finally, some patients experience nonspecific exudative erythema on the skin of the extremities, chest, and signs of photodermatosis on exposed parts of the body.

Skin lesions include capillaritis - a pinpoint hemorrhagic rash on the fingertips, nail beds, and palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulcerations may be found on the mucous membrane of the mouth or nasopharyngeal area.

Serous membranes are affected in 90% of patients (classical diagnostic triad: dermatitis, arthritis, polyserositis). Damage to the pleura, pericardium, and, less often, to the peritoneum is especially common. The symptoms of pleurisy and pericarditis are described in previous sections of the Guide; we will only emphasize its features in SLE: 1) dry pleurisy and pericarditis are more common; 2) in effusion forms the amount of exudate is small; 3) damage to the serous membranes lasts for a short time and is usually diagnosed retrospectively during X-ray examination by pleuropericardial adhesions or thickening of the costal, interlobar, mediastinal pleura; 4) there is a pronounced tendency towards the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities).

Damage to the cardiovascular system is very typical for SLE and is observed at various stages of the disease.

The most common occurrence is pericarditis, which tends to recur. Much more often than previously thought, the endocardium is affected in the form of warty endocarditis (lupus endocarditis) on the cusps of the mitral, as well as the aortic or tricuspid valves. If the process lasts for a long time, at stage II it is possible to identify signs of insufficiency of the corresponding valve (as a rule, there are no signs of stenosis of the orifice).

Focal myocarditis is almost never recognized, but diffuse myocarditis, which is severe, gives certain symptoms (see “Myocarditis”).

Vascular damage can manifest itself in the form of Raynaud's syndrome: paroxysmal developing disorders 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, and the fingers are cold. The II-V fingers and toes are predominantly affected, and less commonly other distal areas of the body (nose, ears, chin, etc.).

Lung lesions can be caused by the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) occurs either acutely or lasts for months and manifests itself, as in pneumonia, with signs of inflammatory infiltration syndrome of lung tissue (one should note the peculiarity of the process in the form of an unproductive cough in combination with shortness of breath). Another option for lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), manifested by slowly progressive shortness of breath and changes in the lungs during X-ray examination; physical changes are practically absent, so it is almost impossible to judge such lung damage at the second stage of the diagnostic search.

Damage to the digestive tract is manifested mainly by subjective signs identified at stage I. On physical examination, vague tenderness in the epigastrium and in the area of ​​the pancreas, as well as stomatitis, can sometimes be detected. In some cases, hepatitis develops: during examination, an enlarged liver and its pain are noted.

Most often, SLE affects the kidneys (lupus glomerulonephritis or lupus nephritis), the evolution of which determines the future fate of the patient. Kidney damage in SLE can occur in various ways, so the data from direct examination

The patient's condition may vary widely. With isolated pathology of urinary sediment, no changes are detected during physical examination; with glomerulonephritis occurring with nephrotic syndrome, massive edema and often hypertension are detected. In the case of the formation of chronic nephritis with constant hypertension, an enlargement of the left ventricle is detected, an accent of the second tone in the second intercostal space to the right of the sternum.

Autoimmune thrombocytopenia (Werlhoff syndrome) manifests itself as typical hemorrhagic rashes of varying sizes on the skin inside limbs, chest, abdomen, on mucous membranes. Bleeding is also observed after minor injuries, for example after tooth extraction, nosebleeds, which are rarely profuse in nature and lead to anemia. Skin hemorrhages acquire different colors over time (blue-greenish, brown, yellow). SLE can manifest itself for a long time only as Werlhoff syndrome without other clinical symptoms typical of SLE.

Damage to the nervous system is expressed to varying degrees in many patients in all phases of the disease, since almost all parts of the nervous system are involved in the pathological process. Patients complain of migraine-type headaches and may have seizures. Possible cerebral circulation disorders (up to the development of a stroke). Upon direct examination of the patient, signs of polyneuritis are detected with impaired sensitivity, pain in the nerve trunks, decreased tendon reflexes, and paresthesia. Organic brain syndrome is characterized by emotional lability, episodes of depression, memory impairment, and dementia.

There is an increase in all groups of lymph nodes, spleen, liver (usually moderate) with generalization of the process.

Damage to the organ of vision manifests itself in the form of dry keratoconjunctivitis, which is caused by pathological changes in the lacrimal glands and disruption of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.

With antiphospholipid syndrome, in addition to the indicated clinical picture, thrombosis may be detected - venous (in the deep veins of the lower extremities with repeated pulmonary embolisms), arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks). On the part of the heart, valve defects, intracardiac thrombi (simulating cardiac myxoma), and coronary artery thrombosis with the development of myocardial infarction can be detected. Skin lesions in antiphospholipid syndrome are varied, the most common of which is livedo reticularis.

Thus, after the second stage of the study, multiple organ damage is revealed, and the degree of organ damage is very different: from barely noticeable clinical (even subclinical) to pronounced, significantly prevailing over the rest, which creates the preconditions for diagnostic errors due to the interpretation of these changes as a manifestation of independent diseases (eg, glomerulonephritis, myocarditis, arthritis).

Stage III of the diagnostic search for SLE is very important, since: 1) it helps to make a final diagnosis; 2) demonstrates the severity of immune disorders and the degree of damage to internal organs; 3) reveals the degree of activity of the pathological (lupus) process.

At stage III, laboratory blood tests are of greatest importance. There are two groups of indicators:

1) directly having diagnostic value (detecting pronounced immune disorders):

A) LE cells (lupus erythematosus cells) - mature neutrophils that phagocytose nuclear proteins of other blood cells that have decayed under the influence of antinuclear factor;

B) antinuclear factor (ANF) - a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in a high titer - 1:32 and higher, detected in 95% of patients); the absence of ANF in the vast majority of cases does not confirm the diagnosis of SLE;

C) antibodies to native (i.e., to the whole molecule) DNA; an increase in their concentration correlates with disease activity and the development of lupus nephritis;

D) antibodies to Sm-nuclear antigen, Ro/La ribonucleoprotein; these antibodies are considered to be specific for SLE (they are detected by immunofluorescence in 30% of cases, and by hemagglutination in 20% of cases);

D) the “rosette” phenomenon - lying freely modified nuclei in tissues (hematoxylin bodies), surrounded by leukocytes;

E) diagnosis of antiphospholipid syndrome in SLE is based on the determination of “lupus anticoagulants” - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (increased thromboplastin time) and antibodies to cardiolipin using an enzyme-linked immunosorbent method. The term “lupus anticoagulant” itself is incorrect, since the main clinical manifestation of the presence of these antibodies is thrombus (and not bleeding).

These antibodies are also detected in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis, and autoimmune hemolytic anemia are observed.

2) Nonspecific acute phase indicators, which include:

A) dysproteinemia with an increase in the content of oc2- and γ-globulins in the blood serum;

B) the appearance of C-reactive protein;

B) increase in fibrinogen content;

D) increase in ESR.

With severe articular lesions, a small titer of RF (rheumatoid factor) - an antibody to the Fc fragment of IgG - can be detected. RF is detected using the Waaler-Rose reaction or latex test.

When examining peripheral blood, leukopenia can be detected, often pronounced (1-1.2109/l of blood), with a shift in the leukocyte formula of the blood to metamyelocytes and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Moderate hypochromic anemia is detected, in some cases - hemolytic anemia (with jaundice, reticulocytosis, positive Coombs test). Thrombocytopenia, manifested by hemorrhagic syndrome, is also rarely observed.

Kidney damage is characterized by changes in the urine, which can be classified as follows [Tareeva I.E., 1983]:

1) subclinical proteinuria (protein content in urine 0.5 g/day, often in combination with slight leukocyturia and erythrocyturia);

2) more pronounced proteinuria, which is an expression of nephritic syndrome accompanying subacute or active lupus nephritis. Very high proteinuria (as in amyloidosis) is rare. Moderate hematuria is noted. Leukocyturia can be a consequence of both the lupus inflammatory process in the kidneys and the frequent addition of a secondary urinary tract infection. Very high leukocyturia is a consequence of a secondary urinary infection.

A puncture biopsy of the kidneys reveals nonspecific mesangio-membranous changes, often with a fibroplastic component. Characteristic is: 1) detection in the preparations of altered nuclei (hematoxylin bodies) freely lying in the renal tissue; 2) the capillary membranes of the glomeruli take the form of “wire loops”; 3) deposition of immune complexes in the form of electron-dense deposits on the glomerular basement membrane in “wire loops”, fibrinoid

Sediments.

X-ray examination reveals: 1) changes in the joints with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints; Only with chronic arthritis and deformities is a narrowing of the joint space with subluxations noted; 2) changes in the lungs with the development of pneumonitis; with a long course of the disease - disc-shaped atelectasis, strengthening and deformation of the pulmonary pattern, which is combined with a high position of the diaphragm; 3) development of “lupus” heart disease or exudative pericarditis.

An electrocardiographic study helps to detect nonspecific changes in the final part of the ventricular complex (T wave and segment 57), similar to those previously described for myocarditis and pericarditis.

Computed tomography (CT) of the brain and magnetic resonance imaging (MRI) can detect pathological changes in patients with central nervous system damage.

When conducting a diagnostic search, it is necessary to determine the degree of activity of the lupus process (Table 21).

Diagnostics. In cases of the classic course of SLE, the diagnosis is simple and is based on the detection of “butterfly”, recurrent polyarthritis and polyserositis, which constitute the clinical diagnostic triad, complemented by the presence of LE cells or antinuclear factor in diagnostic titers. Of auxiliary importance are the young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation, and infection. It is much more difficult to establish a diagnosis in other cases, especially if the classic diagnostic signs listed above are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 help (Table 22).

The diagnosis is reliable if four or more criteria are present. If there are fewer than four criteria, then the diagnosis of SLE is questionable and dynamic monitoring of the patient is required. This approach is justified: it clearly warns the doctor against prescribing corticosteroids to patients, since other diseases (including paraneoplastic syndrome) may occur with the same symptoms, for which corticosteroids are contraindicated.

Differential diagnosis. SLE should be differentiated from a number of diseases. As large as the list of organs and systems involved in the pathological process in SLE is, the list of diseases that can be misdiagnosed in SLE is just as extensive.

Table 22. Diagnostic criteria for SLE

To a greater degree, it can imitate various diseases™ ppi ™ ™ Particularly common at the onset of the disease, and about 1-2 organs (systems) are affected. For example, IR nSS? ™* b°L "Knowledge of pleural lesions can be considered

Or HSULZI^^I etiolop™; myocarditis - as a rheumatic butiouet r^rnt^f II^°SOBENNt,° MN0G0 errors occur if SLE de- ™GRU^ IN SIMILAR CASES DIAGNOSIS03 ONLY

FECHTIO^not^6 FREQUENTLY HAVE TO BE DIFFERENTIATED FROM RHEUMATISM, INSHG^SKI^PIA^ TITACHR°NIC hepatitis (CAH), hemorrhagic group (thrombocytopenic purpura), other diseases from

The need to differentiate from rheumatism occurs, as a rule, in adolescents and young men at the onset of the disease in the presence of arthritis and fever. Rheumatoid arthritis differs from lupus in the greater severity of manifestations, predominant damage to large joints, and transience. One should not attach differential diagnostic significance to a previous infection - sore throat, since it may be a nonspecific factor causing clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic carditis) appear; subsequent dynamic observation makes it possible to identify an emerging heart defect, whereas in SLE, if mitral valve insufficiency occurs, it is mildly expressed, without clear hemodynamic disturbances, mitral regurgitation is not pronounced. In contrast to SLE, leukocytosis is observed in the acute stage of rheumatism; LE cells and ANF are not detected.

Differential diagnosis between SLE and rheumatoid arthritis is difficult in the initial stage of the disease due to the similarity of clinical symptoms: symmetrical damage to small joints of the hand, involvement in

Process of other joints, “morning stiffness”. Differentiation is based on the predominance of the proliferative component in the affected joints in RA, the early development of wasting of the muscles that move the affected joints, and the persistence of joint damage. Erosion of the articular surfaces is absent in SLE, but is a characteristic feature of RA. Rheumatoid factor(RF) in high titer is characteristic of RA; in SLE it is rarely detected and in low titer. The differential diagnosis of SLE and visceral RA is extremely difficult. A mitigating factor is that the refined diagnosis in both cases does not affect the nature of treatment (corticosteroid therapy).

With chronic active hepatitis (CAH), systemic manifestations may develop in the form of fever, arthritis, pleurisy, skin rashes, glomerulonephritis; Leukopenia, thrombocytopenia, LE cells, and ANF are detected. When differentiating, one should take into account: 1) CAH develops more often in middle age; 2) patients with CAH have a history of acute viral hepatitis; 3) with CAH, pronounced changes in the structure and function of the liver are detected - cytolytic and cholestatic syndromes, signs of liver failure, hypersplenism, and then portal hypertension; 4) in SLE, liver damage is not too frequent and occurs in the form of mild hepatitis (with moderate signs of cytolytic syndrome); 5) with CAH, various markers of viral liver damage are detected (antiviral antibodies and the viral antigen itself).

In infective endocarditis (primary), heart damage (aortic or mitral valve insufficiency) is quickly detected, a clear effect of antibiotic therapy, LE cells, antibodies to DNA, and ANF are usually not detected. Timely blood culture allows you to detect the growth of pathogenic microflora.

Thrombocytopenic purpura (idiopathic or symptomatic) lacks many of the syndromes seen in SLE and does not have the typical fever laboratory signs(LE cells, ANF, DNA antibodies).

The most difficult thing to differentiate from others is nosological forms from the DZST group. Diseases such as systemic scleroderma and dermatomyositis may share many features with SLE; The difficulty of diagnosis is aggravated by the possibility of detecting ANF and LE cells in these diseases (albeit in a lower titer). The basis of differentiation is the more frequent and more pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin damage in SSc, and a clear myopathic syndrome in DM. However, in some cases, only long-term follow-up of the patient allows a correct diagnosis to be made. Sometimes this takes many months and even years, especially in chronic cases of SLE with minimal activity.

The formulation of a detailed clinical diagnosis of SLE takes into account all the headings given in the working classification of the disease; the diagnosis should reflect: 1) the nature of the disease (acute, subacute, chronic). In case of chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated; 2) process activity; 3) 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 presence or absence of heart failure, with lung damage - the presence or absence of respiratory failure, etc.); 4) indicate

Knowledge of ongoing therapy (eg, corticosteroids); 5) complications of therapy (if any).

Treatment. Taking into account the pathogenesis of the disease, complex pathogenetic therapy is indicated for patients with SLE, the objectives of which are: 1) suppression of immune inflammation and immune complex pathology (uncontrolled immune response); 2) prevention of complications of immunosuppressive therapy; 3) treatment of complications arising during immunosuppressive therapy; 4) impact on individual, pronounced syndromes; 5) removal of circulating immune complexes and antibodies from the body.

First of all, it is necessary to exclude psycho-emotional stress, insolation, actively treat concomitant infections, consume foods low in fat and high in polyunsaturated fatty acids, calcium and vitamin D. During the period of exacerbation of the disease and during treatment with cytostatic drugs, active contraception is necessary. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.

To suppress immune inflammation and immune complex pathology in the treatment of SLE, the main immunosuppressants are used: corticosteroids, cytotoxic drugs, aminoquinoline derivatives. The duration of treatment, magnitude, choice of drug, as well as maintenance doses are determined by: 1) the degree of disease activity; 2) the nature of the flow (severity); 3) the extent of involvement of internal organs in the pathological process; 4) tolerability of corticosteroids or cytostatics and the presence (or absence) of complications of immunosuppressive therapy; 5) the presence of contraindications.

In the initial stages of the disease with signs of minimal activity of the process and the predominance of joint damage in the clinical picture, NSAIDs can be prescribed, however, even with minimal activity of the pathological process, corticosteroids are the drug of choice. Patients should be monitored at the dispensary so that at the first signs of exacerbation of the disease, the doctor can promptly prescribe corticosteroid therapy.

In the chronic course of the disease with predominantly skin lesions, 0.25 g/day of hingamine (Delagil, Resoquin) or hydroxychloroquine (Plaquenil) can be used for many months. If signs of generalization of the process appear (involvement of internal organs in the pathological process), as well as signs of activity, it is necessary to immediately switch to more effective immunosuppressive therapy with GCS.

Thus, the mainstay of treatment for SLE is corticosteroid therapy; when carrying out it, the following principles should be adhered to:

1) start treatment only if there is a definite diagnosis of SLE (if SLE is suspected, corticosteroids should not be prescribed);

2) the dose of GCS should be sufficient to suppress the activity of the pathological process;

3) treatment with a “suppressive” dose should be carried out until a pronounced clinical effect occurs (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes), usually this requires approximately 2 months;

4) after achieving the effect, you should gradually switch to maintenance doses;

5) prevention of complications of corticosteroid therapy is mandatory.

GCS therapy is indicated for II and III degrees of activity of the pathological process, which always happens in subacute and acute SLE. Patients with degree II of activity are prescribed medium doses (
For grade III, large doses are prescribed. The duration of taking large doses is 4-12 weeks. Dose reduction should be carried out slowly, under close clinical and laboratory control, and maintenance doses of drugs (10-15 mg) should be taken for many years.

To prevent side effects of GCS, the following are used: 1) potassium preparations (potassium orotate, potassium chloride, panangin); 2) anabolic drugs (methandrostenolone 5-10 mg); 3) diuretics (saluretics); 4) antihypertensive drugs(ACE inhibitors); 5) antacid drugs.

If severe complications develop, the following are prescribed: 1) antibiotics (for secondary infection); 2) anti-tuberculosis drugs (with the development of tuberculosis, most often of pulmonary localization); 3) insulin preparations, diet (with development diabetes mellitus); 4) antifungal agents (for candidiasis); 5) a course of antiulcer therapy (if a “steroid” ulcer appears).

During corticosteroid therapy, situations arise when it is necessary to administer extra-high doses of prednisolone (1000 mg intravenously drip over 30 minutes for 3 days): 1) a sharp increase (“burst”) in the activity of the process (III degree), despite, it would seem, adequately administered therapy; 2) resistance to doses that previously achieved a positive effect; 3) pronounced organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).

It is believed that such pulse therapy stops the formation of immune complexes by inhibiting the synthesis of antibodies to DNA. The decrease in the level of antibodies to DNA caused by corticosteroids leads to the formation of smaller immune complexes due to the dissociation of larger ones.

Significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of corticosteroids. Pulse therapy is most successful in young patients with a short duration of the disease.

Treatment with GCS is not always successful, which is due to: 1) the need to reduce the dose when complications develop (although such therapy is effective in this patient); 2) drug intolerance; 3) resistance to corticosteroid therapy (usually detected quite early). In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (bolus administration at a dose of 0.5-1 g/m2 intravenously monthly for at least 6 months, and then every 3 months in for 2 years) in combination with 10-30 mg/day of prednisolone. In the future, you can return to GCS therapy, since resistance to them usually disappears.

For the treatment of less severe but GCS-resistant manifestations of the disease, azathioprine or methotrexate (approximately 15 mg/week) and cyclosporine [less than 5 mg/day] are prescribed in combination with low doses of prednisolone (10-30 mg/day).

The criteria for assessing the effectiveness of the use of cytostatics are: 1) reduction or disappearance of clinical signs; 2) disappeared

Low steroid resistance; 3) persistent decrease in process activity; 4) preventing the progression of lupus nephritis.

Complications of cytostatic therapy: 1) leukopenia; 2) anemia and thrombocytopenia; 3) dyspeptic symptoms; 4) infectious complications.

If leukopenia (leukocytes less than 3.0 109/l) appears, the dose of the drug should be reduced to 1 mg/kg, and if leukopenia further increases, the drug is discontinued and the dose of prednisolone is increased by 50%.

In recent years, extracorporeal treatment methods - plasmapheresis, hemosorption - have become widespread. These methods make it possible to remove circulating immune complexes from the body, increase the sensitivity of cellular receptors to GCS, 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 respond to corticosteroid therapy.

Typically, extracorporeal methods are used in combination with pulse therapy or alone if pulse therapy is ineffective. It should be noted that in case of cytopenic syndrome, extracorporeal methods are not used.

In patients with high levels of antiphospholipid antibodies in the blood serum (but without clinical manifestations of antiphospholipid syndrome), small doses of acetylsalicylic acid (75 mg/day) are used. With significant antiphospholipid syndrome (with clinical manifestations) prescribe heparin and low doses of aspirin.

Forecast. In recent years, due to effective treatment methods, the prognosis has improved (approximately 90% of patients achieve remission). However, in 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or with cerebrovasculitis, the prognosis is unfavorable.

Prevention. Timely adequate therapy ensures the prevention of relapse of the disease. For primary prevention, a group of “threatened” persons is identified, which includes primarily relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). These persons should avoid insolation, hypothermia, should not be vaccinated, and they should not undergo mud therapy or other balneological procedures.