This group of diseases is very diverse. You should be aware that in some cases, lesions of the osteoarticular apparatus, muscles, connective tissue are primary, their symptoms occupy a major place in the clinical picture of the disease, and in other cases, damage to bones, muscles, connective tissue are secondary and occur against the background of some other diseases (metabolic, endocrine and others) and their symptoms complement the clinical picture of the underlying disease.
Collagenoses represent a special group of systemic lesions of connective tissue, bones, joints, muscles - a group of diseases with immuno-inflammatory lesions of connective tissue. The following collagenoses are distinguished: systemic lupus erythematosus, systemic scleroderma, periarteritis nodosa, dermatomyositis and rheumatism and rheumatoid arthritis, which are very close to them in their mechanism of development.
Among the pathology of the osteoarticular apparatus, muscle tissue, inflammatory diseases of various etiologies (arthritis, myositis), metabolic-dystrophic (arthrosis, myopathies), tumors, and congenital developmental anomalies are distinguished.
Causes of diseases of the musculoskeletal system.
Until the end, the causes of these diseases have not been clarified. It is believed that the main factor causing the development of these diseases is genetic (the presence of these diseases in close relatives) and autoimmune disorders (the immune system produces antibodies to the cells and tissues of its body). Other factors that provoke diseases of the musculoskeletal system are endocrine disorders, disorders of normal metabolic processes, chronic microtrauma of the joints, hypersensitivity to some food products and drugs, the infectious factor (transferred viral, bacterial, especially streptococcal, infections) and the presence of chronic foci of infection (caries, tonsillitis, sinusitis), hypothermia are also important.
Symptoms of diseases of the musculoskeletal system.
Patients with diseases of the musculoskeletal system and systemic lesions of the connective tissue can present a variety of complaints.
Most often these are complaints of pain in the joints, spine or muscles, morning stiffness in movements, sometimes muscle weakness, fever. Symmetrical defeat small joints hands and feet with their soreness during movement is characteristic of rheumatoid arthritis, large joints (wrist, knee, elbow, hip) are affected much less often. It also increases pain at night, with damp weather, cold.
Defeat large joints characteristic of rheumatism and deforming arthrosis, with deforming arthrosis, pain often occurs during physical exertion and intensifies in the evening. If pains are localized in the spine and sacroiliac joints and appear during prolonged immobility, more often at night, then we can assume the presence of ankylosing spondylitis.
If various large joints hurt alternately, then we can assume the presence of rheumatic arthritis. If the pain is mainly localized in the metatarsophalangeal joints and occurs more often at night, then these may be manifestations of gout.
Thus, if a patient complains of pain, difficulty in movement in the joints, it is necessary to thoroughly find out the features of pain (localization, intensity, duration, influence of load and other factors that can provoke pain).
Fever, various skin rashes can also be a manifestation of collagenosis.
Muscle weakness is observed with prolonged immobility of the patient in bed (for some kind of disease), with some neurological diseases: myasthenia gravis, myatonia, progressive muscular dystrophy and others.
Sometimes patients complain of cold spells and blanching of the fingers of the upper extremity, arising under the influence of external cold, sometimes trauma, mental experiences, this sensation is accompanied by pain, decreased skin pain and temperature sensitivity. Such attacks are characteristic of Raynaud's syndrome, which occurs in various vascular diseases and nervous system... However, these attacks are not uncommon with such serious illness connective tissue like systemic scleroderma.
It is also important for diagnosis how the disease began and proceeded. Many chronic diseases of the musculoskeletal system occur imperceptibly and progress slowly. Acute and violent onset of the disease is observed in rheumatism, some forms of rheumatoid arthritis, infectious arthritis: brucellosis, dysentery, gonorrheal and others. Acute muscle damage is observed in myositis, acute paralysis, including those not associated with injuries.
On examination, it is possible to reveal the peculiarities of the patient's posture, in particular, pronounced thoracic kyphosis (curvature of the spine) in combination with a smoothed lumbar lordosis and limited mobility of the spine make it possible to diagnose ankylosing spondylitis. Lesions of the spine, joints, acute muscle diseases of inflammatory origin (myositis) restrict and restrict movement up to the complete immobility of patients. Deformation distal phalanges fingers with sclerotic changes in the adjacent skin, the presence of peculiar folds of the skin tightening it in the mouth area (a pouch symptom), especially if these changes were found in women predominantly of young age, make it possible to diagnose systemic scleroderma.
Sometimes the examination reveals a spastic shortening of the muscles, more often the flexors (muscle contracture).
Palpation of the joints can reveal a local increase in temperature and swelling of the skin around them (with acute diseases), their soreness, deformation. During palpation, passive mobility of various joints is also examined: its limitation may be the result of joint pain (with arthritis, arthrosis), as well as ankylosis (i.e., immobility of the joints). It should be remembered that restriction of movement in the joints can also be the result of cicatricial changes in muscles and their tendons as a result of myositis, inflammation of the tendons and their sheaths, and injuries. Palpation of the joint can reveal fluctuation, which appears in acute inflammation with a large inflammatory effusion into the joint, the presence of purulent effusion.
Laboratory and instrumental research methods.
Laboratory diagnostics of systemic lesions of the connective tissue is aimed mainly at determining the activity of inflammatory and destructive processes in it. The activity of the pathological process in these systemic diseases leads to changes in the content and qualitative composition of serum proteins.
Determination of glycoproteins... Glycoproteins (glycoproteins) are biopolymers consisting of protein and carbohydrate components. Glycoproteins are part of the cell membrane, circulate in the blood as transport molecules (transferrin, ceruloplasmin), glycoproteins include some hormones, enzymes, and immunoglobulins.
Indicative (although far from specific) for the active phase of the rheumatic process is the definition seromucoid protein content in the blood, which includes several mucoproteins. The total content of seromucoid is determined by the protein component (biuret method), in healthy people it is 0.75 g / l.
The detection of a copper-containing blood glycoprotein in the blood of patients with rheumatic diseases has a certain diagnostic value - ceruloplasmin... Ceruloplasmin is a transport protein that binds copper in the blood and belongs to α2-globulins. Determine ceruloplasmin in deproteinized serum using paraphenyldiamine. Normally, its content is 0.2-0.05 g / l, in the active phase of the inflammatory process, its level in the blood serum increases.
Determination of the content of hexoses... The most accurate is the method in which a color reaction with orcin or resorcinol is used, followed by colorimetry of the color solution and calculation using a calibration curve. The concentration of hexoses increases especially sharply with the maximum activity of the inflammatory process.
Determination of fructose content... For this, a reaction is used in which cysteine hydrochloride is added to the product of the interaction of the glycoprotein with sulfuric acid (Dische's method). The normal fructose content is 0.09 g / l.
Determination of sialic acid content... During the period of maximum activity of the inflammatory process in patients with rheumatic diseases, the content of sialic acids in the blood increases, which are most often determined by the method (reaction) of Hess. The normal content of sialic acids is 0.6 g / l. Determination of fibrinogen content.
With the maximum activity of the inflammatory process in patients with rheumatic diseases, the the content of fibrinogen in the blood which has healthy people usually does not exceed 4.0 g / l.
Determination of C-reactive protein... In rheumatic diseases, C-reactive protein appears in the blood serum of patients, which is absent in the blood of healthy people.
Also use determination of rheumatoid factor.
In the analysis of blood in patients with systemic diseases of the connective tissue, it is found increased ESR, sometimes neutrophilic leukocytosis.
X-ray examination allows you to detect calcifications in soft tissues, appearing, in particular, in systemic scleroderma, but it gives the most valuable data for the diagnosis of lesions of the osteoarticular apparatus. X-rays of bones and joints are usually taken.
Biopsy It has great importance in the diagnosis of rheumatological diseases. A biopsy is indicated if there is a suspicion of a tumor nature of the disease, with systemic myopathies, to determine the nature of muscle damage, especially in collagen diseases.
Prevention of diseases of the musculoskeletal system.
It is to timely prevent the impact of factors that can become the causes of these diseases. This is the timely treatment of diseases of an infectious and non-infectious nature, prevention of exposure to low and high temperatures, and exclude traumatizing factors.
If symptoms of bone or muscle diseases occur, since most of them have serious consequences and complications, it is necessary to consult a doctor in order for the correct treatment to be prescribed.
Diseases of the musculoskeletal system and connective tissue in this section:
Infectious arthropathies
Inflammatory polyarthropathies
Arthrosis
Other joint lesions
Systemic lesions of connective tissue
Deforming dorsopathies
Spondylopathy
Other dorsopathies
Muscle diseases
Lesions of the synovial membranes and tendons
Other soft tissue diseases
Disorders of bone density and structure
Other osteopathies
Chondropathy
Other disorders of the musculoskeletal system and connective tissue
Injuries are discussed in the "Emergency" section
DIFFUSE DISEASES OF THE CONNECTING TISSUE (DZST), or collagenoses (a term of historical significance), is a group of diseases characterized by systemic immunoinflammatory lesions of connective tissue and its derivatives. This concept is a group, but not nosological, in connection with which this term should not denote individual nosological forms. DZST unite a fairly large number of diseases. The most common are systemic lupus erythematosus (SLE), systemic scleroderma (SJS), dermatomyositis (DM); this group of diseases also includes rheumatic fever(traditionally described in the section on diseases of the cardiovascular system). Currently, it has been proven that with DZST, profound disorders of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the appearance of antibodies or sensitized lymphocytes directed against antigens of its own body (autoantigens).
The basis of autoimmune pathology is an immunoregulatory imbalance, which is expressed in suppressive suppression and an increase in the "helper" activity of T-lymphocytes, followed by activation of B-lymphocytes and overproduction of autoantibodies of very different specificity.
There are a number of common features that unite DZST:
The commonality of pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of immune antigen-antibody complexes circulating in the blood and fixing in
Tissues with the subsequent development of a severe inflammatory reaction (especially in the microvasculature, kidneys, joints, etc.);
The similarity of morphological changes (fibrinoid changes in the basic substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbation and remission;
Aggravation under the influence of nonspecific influences (infection, insolation, vaccination, etc.);
Multiple lesions (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, dermatomyositis.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of young people (mainly women), which develops against a background of genetically determined imperfection of immunoregulatory processes, leading to uncontrolled production of antibodies to its own cells and their components, with the development of autoimmune and immuno-complex chronic lesions [Nasonova VA, 1989]. The essence of the disease consists in immuno-inflammatory lesions of the connective tissue and microvasculature, skin, joints and internal organs (while visceral lesions are the leading ones, determining the course and prognosis of the disease).
SLE, according to different authors, occurs with a frequency of 2.7-4.8 per 100,000 population, in young and middle age the ratio of sick women and 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 onset and development of SLE. Although the disease develops in men much less frequently, it is as severe as in women.
SLE belongs to genetically determined diseases: population studies have shown that the predisposition to the onset of SLE is associated with certain genes of class II histocompatibility (HLA), genetically determined deficiency of certain complement components, as well as gene polymorphism of some receptors and tumor necrosis factor a (TNF- 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 viral etiology... Currently, importance is attached to viruses belonging to the RNA group (the 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
Yut think about the possible significance of familial genetic predisposition.
The detection of SLE is facilitated by a number of nonspecific factors - insolation, nonspecific infection, administration of sera, taking certain drugs (in particular, peripheral vasodilators from the hydralazine group), 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 effect on the immune system of the virus (and possibly antiviral antibodies) against the background of a hereditary predisposition, dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, uncontrolled production of antibodies to various fabrics, cells, body proteins (including various cell organelles and DNA). It has been established that in SLE, autoantibodies are produced only to about 40 out of more than 200 potential antigenic cellular components. Subsequently, the formation of immune complexes and their deposition in various organs and tissues (mainly in the microvasculature) occurs. Various defects in immunoregulation are characteristic, characterized by overproduction of cytokines (IL-6, IL-4 and IL-10). Further, the processes associated with the elimination of fixed immune complexes are played 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, vicious circle ensuring the chronicity of the disease.
Classification. Currently in our country [Nasonova VA, 1972-1986] adopted a working classification of clinical variants of the course of SLE, taking into account: 1) the nature of the course; 2) the activity of the pathological process; 3) clinical and morphological characteristics of damage to organs and systems.
The nature of the course of the disease:
Acute, subacute, chronic (recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Verlhof's syndrome, Sjogren's syndrome).
Phase and degree of activity of the process.
Active phase: high activity (III), moderate (II), minimal (I).
The phase is inactive (remission).
Clinical and morphological characteristics of the lesions:
Skin (butterfly symptom, capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis: pleurisy, pericarditis, peresplenit);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute, chronic pneumonitis, pneumosclerosis);
Kidney (lupus nephritis nephrotic or mixed type; urinary syndrome);
Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).
Allocate acute, subacute and chronic course of the disease. Acute course: sudden onset - patients can indicate the day when the fever began, polyarthritis, changes in the skin appeared. In the next 3-6 months, polysyndromism, glomerulonephritis (lupus nephritis), and CNS 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 as if gradually, with general symptoms, arthralgia, recurrent arthritis, various nonspecific skin lesions. The undulation of the current is distinct. A detailed picture of the disease is formed after 2-3, less often - after 3-4 years.
Chronic course: the disease is manifested for a long time by 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) join.
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, which is 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 (more details on antiphospholipid syndrome will be discussed later).
There are also three degrees of activity of the pathological process, i.e. the severity of potentially reversible immune-inflammatory damage, which determines the nature of therapy in each particular patient. Activity should be distinguished from the "severity" of the disease, which is understood as a set of irreversible changes that are potentially dangerous to the patient's life.
The 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 the first stage of the diagnostic search, information is obtained, on the basis of which it is possible to form an idea: 1) about the variant of the onset of the disease; 2) the nature of the course of the disease; 3) the degree of involvement in the pathological process of certain organs and systems; 4) about previous treatment and its effectiveness, as well as possible complications of treatment.
The options for 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 a patient has such a combination, which is extremely important for the diagnosis of SLE.
In the early period of SLE, the most common syndromes are lesions of the joints, skin, serous membranes, as well as 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, pleural damage (pleurisy); 3) fever, trophic skin disorders, pores
Zkenia of the pleura. The diagnostic significance of these combinations increases significantly if the skin lesion consists in the development of erythema, however, in the initial period of the disease, erythema occurs only in 25% of cases; nevertheless, this circumstance does not diminish the diagnostic value of the listed combinations.
The malosymptomatic onset of the disease is uncharacteristic, however, the debut of SLE with the development of massive edema due to the development of diffuse glomerulonephritis (lupus nephritis) of the nephrotic or mixed type from the very beginning of the pathological process was noted.
Involvement of various organs in the pathological process is manifested by the symptoms of their inflammatory lesion: arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.
Information about the treatment carried out earlier allows one to judge: 1) about its adequacy; 2) about the severity of the course of the disease and the degree of activity of the process (initial doses of corticosteroids, duration of their use, maintenance doses, inclusion in medical complex cytostatics for severe immune disorders, high activity of lupus nephritis, etc.); 3) the presence of complications of corticosteroid and cytostatic therapy.
At the first stage, certain conclusions can be made regarding the diagnosis with a long course of the disease, however, at the onset of the disease, the diagnosis is established at subsequent stages of the study.
At the II stage of the diagnostic search, it is possible to obtain a lot of data indicating organ damage and the degree of their functional failure.
Damage to the musculoskeletal system is manifested by polyarthritis resembling rheumatoid arthritis (RA), symmetric damage to small joints of the hand (proximal interphalangeal, metacarpophalangeal, wrist) and large joints (less often). With an expanded clinical picture of the disease, defiguration of the joints is determined, due to periarticular edema. With the course of the disease, deformities of small joints develop. The defeat of the joints can be accompanied by diffuse myalgias, very rarely - true polymyositis with edema and muscle weakness. Sometimes only arthralgia occurs.
The skin is affected as often as the joints. The most typical erythematous rash on the face in the area of the zygomatic arches and the nasal bridge ("butterfly"). Inflammatory rashes on the nose and cheeks repeating the outlines of the "butterfly" are observed in various variants: 1) vascular (vasculitic) "butterfly" - unstable, pulsating, diffuse reddening of the skin with a cyanotic shade in the middle zone of the face, intensifying under the influence of external factors (insolation, wind , cold) or excitement; 2) "butterfly" type of centrifugal erythema (skin changes are localized only in the nose bridge). In addition to the "butterfly", discoid eruptions can be observed - erythematous ascending plaques with keratic disorders and subsequent atrophy of the skin of the face, limbs and trunk. Finally, in some patients, nonspecific exudative erythema is observed on the skin of the extremities, chest, signs of photodermatosis on open parts of the body.
Skin lesions include capillaritis - this is a small-point hemorrhagic rash on the pads of the fingers, nail beds, palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulceration may be found on the mucous membrane of the mouth or nasopharyngeal region.
Serous membranes are affected in 90% of patients (classic diagnostic triad: dermatitis, arthritis, polyserositis). Especially often, lesions of the pleura, pericardium, and less often the peritoneum are detected. Symptoms of pleurisy and pericarditis are described in the previous sections of the "Guide", we only emphasize its features in SLE: 1) dry pleurisy and pericarditis are more common; 2) with effusion forms, the amount of exudate is small; 3) the defeat of the serous membranes lasts for a short time and is usually diagnosed retrospectively by X-ray examination for pleuropericardial adhesions or thickening of the costal, interlobar, mediastinal pleura; 4) there is a pronounced tendency to the development of adhesive processes (all kinds of adhesion and obliteration of serous cavities).
Damage to the cardiovascular system is very characteristic of SLE and is observed at various stages of the disease.
Most often, pericarditis occurs, with a tendency to relapse. Much more often than it seemed before, the endocardium is affected in the form of warty endocarditis (lupus endocarditis) on the cusps of the mitral, as well as aortic or tricuspid valves. With a long course of the process at stage II, signs of insufficiency of the corresponding valve can be detected (signs of stenosis of the hole, as a rule, are not noted).
Focal myocarditis is almost never recognized, but diffuse myocarditis, which is difficult, gives certain symptoms (see "Myocarditis").
Vascular damage can manifest itself in the form of Raynaud's syndrome: paroxysmal arterial blood supply disturbances to the hands and / or feet, arising under the influence of cold or excitement. During an attack, paresthesias are noted, the skin of the fingers becomes pale and / or cyanotic, the fingers are cold. Mostly the II-V fingers of the hands and feet are affected, less often other distal parts of the body (nose, ears, chin, etc.).
Lung involvement may be due to an underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) proceeds either acutely or lasts for months and manifests itself, as in pneumonia, with signs of inflammatory infiltration syndrome lung tissue(it should be noted that there is a peculiarity of the process in the form of an unproductive cough in combination with shortness of breath). Another variant of lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), manifested by slowly progressive dyspnea and changes in the lungs on X-ray examination; there are practically no physical changes, so it is almost impossible to judge about a similar lesion of the lungs at the II stage of the diagnostic search.
The defeat of the digestive tract is manifested mainly by subjective signs, detected at stage I. On physical examination, it is sometimes possible to find vague pain in the epi-gastria and in the projection of the pancreas, as well as stomatitis. In a number of cases, hepatitis develops: during examination, an enlargement of the liver and its soreness are noted.
SLE most often affects the kidneys (lupus glomerulonephritis or lupus nephritis), on the evolution of which depends further destiny sick. Kidney damage in SLE can occur in the form of various options, therefore, the data of direct examination
The patient can vary widely. In isolated pathology of urinary sediment, no changes are detected during physical examination; with glomerulonephritis, proceeding with nephrotic syndrome, massive edema is determined, often AH. In the case of the formation of chronic nephritis with constant hypertension, an increase in the left ventricle is revealed, an accent of the II tone in the second intercostal space to the right of the sternum.
Autoimmune thrombocytopenia (Werlhof syndrome) manifests itself as typical hemorrhagic rashes of various sizes on the skin inside limbs, chest, abdomen, mucous membranes. Bleeding is also observed after minor injuries, for example, after tooth extraction, nosebleeds, occasionally profuse and leading to anemization. Over time, skin hemorrhages acquire different colors (blue-greenish, brown, yellow). SLE can be manifested for a long time only by Werlhof's syndrome without other clinical symptoms typical for SLE.
The defeat of 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 there may be seizures. Possible cerebral circulation disorders (up to the development of a stroke). Direct examination of the patient reveals signs of polyneuritis with impaired sensitivity, soreness of the nerve trunks, decreased tendon reflexes, paresthesias. 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 a violation of their function. Dry eyes lead to the development of conjunctivitis, corneal erosion, or keratitis with visual impairment.
With antiphospholipid syndrome, in addition to the indicated clinical picture, thrombosis - venous (in deep veins lower limbs with repeated pulmonary embolism), arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks). From the side of the heart, valvular defects, intracardiac thrombi (imitating myxoma of the heart), thrombosis of the coronary arteries 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 stage II of the study, multiple organ lesions are 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 (for example, glomerulonephritis, myocarditis, arthritis).
Stage III of the diagnostic search for SLE is very important because: 1) it helps to make the 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 the greatest importance. There are two groups of indicators:
1) directly having diagnostic value (revealing pronounced immune disorders):
A) LE-cells (lupus erythematosus cells) - mature neutrophils, phago-citing nuclear proteins of other blood cells, 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, it is detected in 95% of patients); the absence of ANF in the overwhelming 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 the activity of the disease and the development of lupus nephritis;
D) antibodies to the Sm-nuclear antigen, Ro / La ribonucleoprotein; these antibodies are considered specific for SLE (they are detected by immunofluorescence in 30%, and by hemagglutination in 20% of cases);
E) the phenomenon of "rosette" - lying freely changed nuclei in tissues (hematoxylin bodies), surrounded by leukocytes;
E) the diagnosis of antiphospholipid syndrome in SLE is based on the definition 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 the enzyme immunoassay. The very term "lupus anticoagulant" is incorrect, since the main clinical manifestation of the presence of these antibodies is thrombosis (and not bleeding).
These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, reticular livedo, and autoimmune hemolytic anemia are observed.
2) Nonspecific acute phase indicators, which include:
A) dysproteinemia with an increase in the content of oc2- and y-globulins in the blood serum;
B) the appearance of C-reactive protein;
C) an increase in the content of fibrinogen;
D) increased ESR.
With pronounced articular lesions, it can be detected in a small titer of RF (rheumatoid factor) - an antibody to the Fc-fragment of IgG. RF is detected using the Vaaler-Rose test or latex test.
When researching peripheral blood leukopenia can be detected, often expressed (1-1.2109 / l of blood), with a shift in the leukocyte blood count to metamyelocytes and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Moderate hypochromic anemia is found, in some cases - hemolytic anemia (with jaundice, reticulocytosis, positive Coombs' test). Thrombocytopenia, manifested by hemorrhagic syndrome, is also rarely observed.
For kidney damage, changes in urine are characteristic, 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 the 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 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.
Puncture biopsy of the kidneys reveals nonspecific mesangio-membranous changes, often with a fibroplastic component. Characteristic is: 1) detection of altered nuclei (hematoxylin bodies) freely lying in the renal tissue in preparations; 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 basement membrane of the glomeruli in "wire loops", fibrinoid
Deposits.
X-ray examination reveals: 1) changes in the joints in the articular syndrome - epiphyseal osteoporosis in the joints of the hands and the wrist joints; only in the chronic course of arthritis and deformities is a narrowing of the joint space with subluxation noted; 2) changes in the lungs with the development of pneumonitis; with a long course of the disease - disco-like atelectasis, strengthening and deformation of the pulmonary pattern, which is combined with a high standing of the diaphragm; 3) the development of "lupus" heart disease or exudative pericarditis.
An electrocardiographic study helps to detect nonspecific changes in the terminal part of the ventricular complex (T wave and segment 57), similar to those described earlier in myocarditis and pericarditis.
Computed tomography (CT) of the brain and magnetic resonance imaging (MRI) can detect pathological changes in patients with CNS 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 make up the clinical diagnostic triad, supplemented by the presence of LE-cells or antinuclear factor in diagnostic titers. The young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation, and infection are of secondary importance. It is much more difficult to establish a diagnosis in other cases, especially if the classical diagnostic signs listed above are absent. In this situation, help the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 (Table 22).
The diagnosis is reliable if four or more criteria are met. If there are less than four criteria, then the diagnosis of SLE is doubtful 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) can occur with the same symptoms, in which corticosteroids are contraindicated.
Differential diagnosis. SLE must be differentiated from a variety of diseases. The list of organs and systems involved in the pathological process in SLE is as large as the list of diseases that can be misdiagnosed in
Table 22. Diagnostic criteria for SLE
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The need to differentiate with rheumatism arises, as a rule, in adolescents and young men at the onset of the disease in the presence of arthritis and fever. Rheumatic arthritis differs from lupus in greater severity of manifestations, predominant damage to large joints, transience. You should not attach the differential diagnostic value of the previous infection - angina, since it can be a nonspecific factor that causes the clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic heart disease) appear; the subsequent dynamic observation allows to identify the emerging heart defect, whereas in SLE, if there is a mitral valve insufficiency, then it is expressed insignificantly, without distinct hemodynamic disturbances, mitral regurgitation is not clearly expressed. Unlike SLE, leukocytosis is noted in the acute stage of rheumatism; LE cells, ANF are not detected.
Differential diagnosis between SLE and rheumatoid arthritis is difficult in the initial stage of the disease due to the similarities clinical symptoms: symmetric lesion of small joints of the hand, involvement in the
Cessation of other joints, morning stiffness. Differentiation is based on the prevalence of a proliferative component in the affected joints in RA in the affected joints, early development of muscle wasting, setting the affected joints in motion, and the persistence of joint damage. Erosion of the articular surfaces is absent in SLE, but is characteristic feature RA. Rheumatoid factor (RF) in a high titer is characteristic of RA, in SLE it is rarely found and in a low titer. Exceptionally difficult differential diagnosis SLE and visceral RA. A facilitating circumstance is that the refined diagnosis in both cases does not affect the nature of the treatment (corticosteroid therapy).
In chronic active hepatitis (CAH), systemic manifestations can develop in the form of fever, arthritis, pleurisy, skin rashes, glomerulonephritis; leukopenia, thrombocytopenia, LE-cells, ANF are found. Differentiation should take into account: 1) CAH develops more often in middle age; 2) a history of CAH patients has acute viral hepatitis; 3) with CAH, pronounced changes in the structure and function of the liver are revealed - cytolytic and cholestatic syndromes, signs of liver failure, hypersplenism, and then portal hypertension; 4) with SLE, liver damage is not too frequent and proceeds in the form of mild hepatitis (with moderate signs of cytolytic syndrome); 5) in CAH, various markers of viral liver damage (antiviral antibodies and the viral antigen itself) are detected.
With infective endocarditis (primary), heart damage (aortic or mitral valve insufficiency) is quickly detected, a clear effect of antibiotic therapy, LE cells, antibodies to DNA, ANF, as a rule, are not detected. Timely blood culture can detect the growth of pathogenic microflora.
With thrombocytopenic purpura (idiopathic or symptomatic), many of the syndromes observed in SLE are absent, there is no fever, typical laboratory signs (LE cells, ANF, antibodies to DNA).
Differentiation with other nosological forms from the DZST group is the most difficult. Diseases such as systemic scleroderma and dermatomyositis can have many similarities with SLE; the complexity 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 more frequent and more pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin lesions in SJS, a clear myopathic syndrome in DM. However, in some cases, only long-term dynamic observation of the patient allows the correct diagnosis to be made. Sometimes it takes many months or even years, especially in the chronic course of SLE with minimal activity.
The formulation of a detailed clinical diagnosis of SLE takes into account all the headings given in the working classification of the disease; the diagnosis should reflect: 1) the nature of the course of the disease (acute, subacute, chronic). In a chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated; 2) the activity of the process; 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. Given the pathogenesis of the disease, patients with SLE are shown a complex pathogenetic therapy, whose tasks are: 1) suppression of immune inflammation and immunocomplex pathology (uncontrolled immune response); 2) prevention of complications of immunosuppressive therapy; 3) treatment of complications arising in the course of 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 psychoemotional stress, insolation, actively treat concomitant infections, consume food with a low fat content and high content polyunsaturated fatty acids, calcium and vitamin D. During an exacerbation of the disease and during treatment with cytostatic drugs, active contraception is required. Contraceptives with a high estrogen content should not be taken as they exacerbate the disease.
To suppress immune inflammation and immunocomplex pathology in the treatment of SLE, the main immunosuppressants are used: corticosteroids, cytostatic drugs, aminoquinoline derivatives. The duration of treatment, the magnitude, the choice of the drug, as well as the maintenance doses are determined by: 1) the degree of disease activity; 2) the nature of the flow (sharpness); 3) the extensive involvement of internal organs in the pathological process; 4) tolerance 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 a predominance of joint damage in the clinical picture, NSAIDs can be prescribed, however, even with minimal activity of the pathological process, GCS are the means of choice. Patients should be registered with a dispensary so that at the first signs of an exacerbation of the disease, the doctor can promptly prescribe corticosteroid therapy.
In the chronic course of the disease with a predominant skin lesion, 0.25 g / day of hingamine (delagil, rezohin) or hydroxychloroquine (plaquenil) can be used for many months. When 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 main treatment for SLE is corticosteroid therapy; during its implementation, the following principles should be adhered to:
1) start treatment only with a reliable 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 an "overwhelming" dose should be carried out before the onset of a pronounced clinical effect (improvement general condition, normalization of body temperature, improvement of laboratory parameters, positive dynamics of organ changes), usually this requires about 2 months;
4) after achieving the effect, you should gradually switch to maintenance doses;
5) prophylaxis of complications of corticosteroid therapy is mandatory.
GCS therapy is indicated for the II and III degree of activity of the pathological process, which always happens with the subacute and acute course of SLE. Patients with II degree of activity are prescribed medium doses (
In 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, use: 1) potassium preparations (potassium orotate, potassium chloride, panangin); 2) anabolic drugs (methandrostenolone 5-10 mg); 3) diuretics (saluretics); 4) antihypertensive drugs (ACE inhibitors); 5) antacids.
With the development of severe complications, the following are prescribed: 1) antibiotics (with a secondary infection); 2) anti-tuberculosis drugs (with the development of tuberculosis, most often pulmonary localization); 3) insulin preparations, diet (with the development of diabetes mellitus); 4) antifungal agents (for candidiasis); 5) a course of antiulcer therapy (with the appearance of a "steroid" ulcer).
During corticosteroid therapy, situations arise when it is necessary to administer extra-high doses of prednisolone (1000 mg intravenously infusion over 30 minutes for 3 days): 1) a sharp increase ("surge") in the activity of the process (III degree), despite the seemingly 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. Corticosteroid-induced lowering of the level of antibodies to DNA leads to the formation of immune complexes of smaller sizes due to the dissociation of larger ones.
A significant suppression of the activity of the process after the pulse therapy allows in the future to prescribe small maintenance doses of corticosteroids. Pulse therapy is most successful in young patients with a short duration of the disease.
Treatment of corticosteroids is not always successful, which is due to: 1) the need to reduce the dose with the development of complications (although such therapy is effective in this patient); 2) drug intolerance; 3) resistance to corticosteroid therapy (usually detected early enough). 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 for within 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 Dkgsut)] 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) decrease or disappearance of clinical signs; 2) disappeared
Nie steroid resistance; 3) a persistent decrease in the activity of the process; 4) preventing the progression of lupus nephritis.
Complications of cytostatic therapy: 1) leukopenia; 2) anemia and thrombocytopenia; 3) dyspeptic symptoms; 4) infectious complications.
When leukopenia appears (leukocytes less than 3.0 109 / l), the dose of the drug should be reduced to 1 mg / kg, and with a further increase in leukopenia, the drug is canceled and the dose of prednisolone is increased by 50%.
In recent years, extracorporeal methods of treatment - plasmapheresis, hemosorption - have become widespread. These methods allow you 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.
Usually, extracorporeal methods are used in combination with pulse therapy or independently if pulse therapy is ineffective. It should be noted that extracorporeal methods are not used in cytopenic syndrome.
In patients with a high level of antiphospholipid antibodies in the blood serum (but without clinical manifestations of antiphospholipid syndrome), small doses are used acetylsalicylic acid(75 mg / day). With a significant antiphospholipid syndrome (with clinical manifestations), heparin and small doses of aspirin are prescribed.
Forecast. In recent years, due to effective treatment methods, the prognosis has improved (approximately 90% of patients manage to achieve remission). However, in 10% of patients, especially with kidney damage (death occurs due to the progression of chronic renal failure) or with cerebrovasculitis, the prognosis is poor.
Prevention. Timely adequate therapy ensures the prevention of recurrence of the disease. For primary prevention, a group of “threatened” persons is identified, which include primarily the relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). These persons should avoid sun exposure, hypothermia, should not be vaccinated, they should not be shown mud therapy and other balneological procedures.
Systemic connective tissue diseases or, as they are also called, diffuse connective tissue diseases are a group of diseases that stimulate systemic disorders and inflammation of many systems of the body and its organs, combining this process with autoimmune and immunocomplex processes. In this case, excessive fibrous formation may be present. They all have pronounced symptoms.
List of systemic diseases
This includes:
- dermatomyositis is idiopathic;
- recurrent polychondritis
- systemic scleroderma;
- systemic lupus erythematosus;
- recurrent panniculitis;
- polymyalgia rheumatica;
- Sjogren's disease;
- diffuse fasciitis;
- mixed connective tissue disease;
- Behcet's disease;
- systemic vasculitis.
There is a lot in common between all these diseases. Each connective tissue disease has a very similar pathogenesis, general symptoms... Quite often in the photo you can not even distinguish patients with one disease from patients with another diagnosis from the same group.
Connective tissue. What is it?
To understand the severity of disease, let's first look at what connective tissue is.
Connective tissue is all the tissues of the body that are not specifically responsible for the functions of any organ or system of the body. Moreover, its auxiliary role can hardly be overestimated. It protects the body from damage and keeps it in the right position, since this is the frame of the whole body. All integuments of each organ, as well as the bone skeleton and all body fluids, are composed of connective tissue. These tissues occupy from 60% to 90% of the weight of organs, therefore, connective tissue disease most often covers most organism, although sometimes they act locally, covering only one organ.
Factors affecting the development of systemic connective tissue diseases
Depending on how the connective tissue disease spreads, the classification divides them into undifferentiated disease or systemic. On the development of both types of disease, the most important factor of influence can be safely called a genetic predisposition. Therefore, they are called autoimmune diseases connective tissue. But for the development of any of these diseases, one factor is not enough.
The state of the organism exposed to them is also influenced by:
- various infections that disrupt the normal immune process;
- hormonal disorders that can occur during menopause or pregnancy;
- the effect on the body of various radiation and toxic substances;
- intolerance to certain medications;
- increased insolation;
- irradiation with photo rays;
- temperature regime and much more.
It is known that during the development of each of the diseases of this group, a serious violation of some immune processes occurs, as a result of which all changes in the body occur.
Common signs
In addition to the fact that systemic connective tissue diseases have a similar development, they still have many common features:
- each of them has a genetic predisposition, often caused by the characteristics of the sixth chromosome;
- changes in connective tissues have similar features;
- some of the symptoms of the disease are common;
- the diagnosis of this series of diseases is carried out according to a similar scheme;
- most often, the symptoms of the development of the disease at the first stage of development are not taken seriously, since everything happens in a weakly manifested form;
- all these disorders cover several body systems at the same time;
- with appropriate laboratory research some indicators of the activity of the inflammatory process will be very similar;
- the principle by which the treatment of each disease is carried out is close to the principles of treatment of the others.
If specialists could accurately establish the real reasons that trigger this hereditary connective tissue disease in the body, then the diagnosis would become much easier. At the same time, they would be able to accurately establish the necessary methods that require treatment and prevention of the disease. That is why research in this area does not stop. All that scientists can say about environmental factors, including viruses, is that they can only exacerbate the disease, which had previously proceeded in a latent form, and also be its catalysts in an organism that has all the genetic prerequisites.
Treatment
The classification of the disease according to the form of its course occurs in the same way as in many other cases:
- easy form;
- severe form;
- period of prevention.
Systemic connective tissue disease almost always prompts active treatment with daily doses of corticosteroids large sizes... If the disease passes in a more relaxed course, then there is no need for a large dosage. In such cases, treatment with small doses of corticosteroids may be supplemented with anti-inflammatory drugs.
If treatment with corticosteroids is ineffective, it is carried out in parallel with the use of cytostatics. In such a combination, the inhibition of the development of cells most often occurs, which carry out erroneous reactions of protection from the cells of their own body.
Treatment of diseases in severe form occurs in a slightly different way. It requires getting rid of immunocomplexes that have begun to work incorrectly, for which the plasmapheresis technique is used. To prevent the production of new groups of abnormal immunoactive cells, a number of procedures are performed to irradiate the lymph nodes.
For the treatment to be successful, the doctor's efforts alone are not enough. Many experts say that in order to get rid of any ailment, 2 more obligatory things are needed. First, there must be a positive attitude of the patient and his desire to recover. It was noticed more than once that faith in oneself helped people to get out of incredibly terrible situations. Secondly, support is needed in the family circle and among friends. It is extremely important to understand loved ones, it gives a person strength. And then in the photo, despite the illness, he looks happy, and receiving the support of his loved ones, he feels the fullness of life in all its manifestations.
Timely diagnosis of the disease at its initial stage allows for the treatment and prevention of procedures with the greatest efficiency. It requires special attention to all patients, since mild symptoms can be a warning of an impending danger. Diagnostics should be especially detailed when working with people who have symptoms of special sensitivity to some food and drugs, allergies, bronchial asthma. The risk group also includes patients whose relatives have already asked for help and are undergoing treatment, recognizing the symptoms of diffuse diseases. If there are violations that are noticeable at the level of a general blood test, this person also falls into a group that should be closely monitored. And do not forget about persons whose symptoms indicate the presence of focal diseases of the connective tissue.
Systemic connective tissue diseases
Systemic lupus erythematosus, systemic scleroderma, dermatomyositis-polymyositis refer to systemic connective tissue diseases (SCDT) - a group of nosologically independent diseases that have a certain similarity in etiology, pathogenesis, and clinical manifestations. They are treated with similar drugs.
A common point in the etiology of all CTDs is latent infection with various viruses. Taking into account the tissue tropism of viruses, the patient's genetic predisposition, expressed in the carriage of well-defined histocompatibility antigens HLA, may develop various diseases from the group in question.
Triggering or "triggering" mechanisms for the inclusion of pathogenetic processes of SZST are nonspecific. Most often it is hypothermia, physical influences (vibration), vaccination, intercurrent viral infection.
The burst of immunoreactivity arising under the influence of the triggering factor in the body of a predisposed patient is not able to fade away on its own. As a result of antigenic mimicry of cells affected by the virus, a vicious circle of a self-sustaining inflammatory process is formed, leading to the degradation of the entire system of specialized tissue structures in the patient's body to the level of collagen-rich fibrous connective tissue. Hence the old name of this group of diseases - collagenoses.
For all CFTs, damage to epithelial structures is characteristic - skin, mucous membranes, epithelial glands of external secretion. Therefore, one of the typical clinical manifestations of this group of diseases is Sjogren's dry syndrome.
Muscles, serous and synovial membranes are necessarily involved in one way or another, which is manifested by myalgia, arthralgia, polyserositis.
Systemic damage to organs and tissues in SSTD is facilitated by the mandatory formation in all diseases of this group of secondary immune complex vasculitis of medium and small vessels, including microscopic ones involved in microcirculation.
A typical manifestation of immune complex vasculitis is Raynaud's angiospastic syndrome, an essential component of the clinical picture of all diseases from the group under consideration.
Clinical cases with convincing signs of several diseases from this group at once, for example, systemic lupus erythematosus, systemic scleroderma, dermatomyositis-polymyositis, point to the closest connection between all STDs. In such cases, we can talk about a mixed diffuse connective tissue disease - Sharp's syndrome.
... Systemic lupus erythematosus
connective disease lupus polymyositis
Definition
Systemic lupus erythematosus (SLE) is a diffuse disease of the connective tissue with the formation of autoantibodies to structural elements tissues, components of cell nuclei, circulation in the blood of immune complexes conjugated with active complement, capable of causing direct immune and immune complex damage to cellular structures, blood vessels, dysfunction of internal organs.
Etiology
The disease is more common in individuals with HLA DR2 and DR3, in families with inherited deficiency of certain complement components. Infection with RNA-containing retroviruses from the "slow" group may play an etiological role. The pathogenetic mechanism of SLE can be triggered by intense solar insolation, medicinal, toxic, nonspecific infectious effects, and pregnancy. Women aged 15-35 are prone to the disease.
Pathogenesis
A genetic defect and / or modification by "slow" retroviruses of the genetic base of the immune system causes dysregulation of the immune response to some external influences... Cross-immunoreactivity occurs with the movement of normal tissue and intracellular structures into the category of antigens.
A wide range of autoantibodies is formed that are aggressive to their own tissues. Including autoantibodies against native DNA, short nuclear RNA polypeptides (anti-Sm), ribonucleoprotein polypeptides (anti-RNP), RNA polymerase (anti-Ro), protein in RNA (anti-La), cardiolipin (antiphospholipid antibodies) , histones, neurons, blood cells - lymphocytes, erythrocytes, platelets, etc.
Immune complexes appear in the blood that can combine with complement and activate it. First of all, these are complexes of IgM with native DNA. Conjugates of immune complexes with active complement are fixed on the vascular wall, in the tissues of internal organs. The microphage system consists mainly of neutrophils, which, in the process of destruction of immune complexes, are released from their cytoplasm. a large number of proteases, release atomic oxygen. Together with the proteases of the active complement, these substances damage tissues and blood vessels. At the same time, the processes of fibrinogenesis, followed by collagen synthesis, are activated through the C3 component of the complement.
An immune attack on lymphocytes by autoantibodies that react with the DNA-histone complex and active complement ends with the destruction of lymphocytes, and their nuclei is phagocytosed by neutrophils. Neutrophils containing in the cytoplasm the absorbed nuclear material of lymphocytes, possibly other cells, are called LE cells. It is a classic marker of systemic lupus erythematosus.
Clinical picture
The clinical course of SLE can be acute, subacute, chronic.
In an acute course, characteristic of the youngest patients, the temperature suddenly rises to 38 0From and above, there are joint pains, changes in the skin, serous membranes, and vasculitis characteristic of SLE appear. Combined lesions of internal organs - lungs, kidneys, nervous system, etc. are quickly formed. Without treatment, after 1-2 years these changes become incompatible with life. In the case of a subacute variant, which is most typical for SLE, the disease begins with a gradual deterioration in general well-being, a decrease in working capacity. Joint pains appear. Skin changes and other typical manifestations of SLE occur. The disease proceeds in waves with periods of exacerbation and remission. Multiple organ disorders, incompatible with life, appear no earlier than 2-4 years later. In a chronic course, the onset of SLE is difficult to establish. The disease remains unrecognized for a long time, as it manifests itself as symptoms of one of the many syndromes characteristic of this disease. Clinical masks of chronic SLE may be local discoid lupus, benign polyarthritis unclear etiology, polyserositis of unknown etiology, angiospastic Raynaud's syndrome, thrombocytopenic Verlhof's syndrome, dry Sjogren's syndrome, etc. In this variant of the disease, the clinical picture typical of SLE appears no earlier than 5-10 years later. The expanded phase of SLE is characterized by multiple symptoms lesions of various tissue structures, blood vessels, internal organs. The minimum typical deviations are characterized by a triad: dermatitis, polyserositis, arthritis. There are at least 28 variants of skin lesions in SLE. Below are a number of the most common pathological changes in the skin and its appendages, mucous membranes. · Erythematous dermatitis of the face. On the cheeks and bridge of the nose, persistent erythema is formed, resembling a butterfly in its shape. · Discoid lesion. Raised rounded foci, similar to coins, with hyperemic edges, depigmentation and atrophic changes in the center. · Nodular (nodular) skin lesions. · Photosensitization - pathological skin hypersensitivity to solar insolation. · Alopecia is a generalized or patchy baldness. · Vasculitis of skin vessels in the form of urticaria, capillaritis (small-point hemorrhagic rash on the pads of the fingers, palms, nail beds), ulceration at the sites of skin microinfarctions. A vascular "butterfly" may appear on the face - a pulsating reddening of the nose and cheeks with a cyanotic hue. · Erosion on the mucous membranes, cheilitis (persistent thickening of the lips with the formation of small granulomas in their thickness). Lupus polyserositis includes lesions of the pleura, pericardium, and sometimes the peritoneum. The defeat of the joints in SLE is limited to arthralgias, symmetric non-erosive arthritis without deformation, ankylosis. Lupus arthritis is characterized by symmetrical lesions of the small joints of the hand, knee joints, severe morning stiffness. Jaccoux syndrome can form - arthropathy with persistent deformities of the joints due to damage to tendons, ligaments, but without erosive arthritis. In connection with vasculitis, aseptic necrosis of the heads of the femur, humerus, and other bones often develops Concomitant SLE myositis is manifested by myalgias, muscle weakness. The lungs and pleura are often affected. The defeat of the pleura is usually bilateral. Possible adhesive (adhesive), dry, exudative pleurisy. Adhesive pleurisy may not be accompanied by objective symptoms. Dry pleurisy is manifested by pain in the chest, pleural friction noise. Dullness of percussion sound, limitation of the mobility of the diaphragm indicate the accumulation of fluid in the pleural cavities, usually in a small volume. Aseptic pneumonitis, characteristic of SLE, is manifested by an unproductive cough, shortness of breath. Its objective symptomatology does not differ from pneumonia. Vasculitis of the pulmonary arteries can cause hemoptysis, pulmonary insufficiency, increased pressure in the small circle with overload of the right heart. Possible thrombosis of the branches of the pulmonary artery with the formation of pulmonary infarction. Clinical manifestations of cardiac pathology are caused by pancarditis characteristic of SLE: pericarditis, myocarditis, endocarditis, vasculitis of the coronary arteries. Pericarditis with SLE is usually adhesive (sticky) or dry, and may be manifested by pericardial rubbing noise. Less commonly, pericardial effusion occurs with a small accumulation of fluid in the pericardial cavity. Lupus myocarditis is the main cause of rhythm disturbances, conduction, heart failure. Libman-Sachs warty endocarditis can be accompanied by multiple thromboembolisms in the vessels of internal organs with subsequent heart attacks, and cause the formation of heart defects. Typically, there are valve insufficiency of the aortic mouth, mitral valve insufficiency. Valvular stenosis is rare. Lupus vasculitis of the coronary arteries causes ischemic damage heart muscle up to myocardial infarction. The range of possible changes in the kidneys is very wide. Focal nephritis can be asymptomatic or with minimal changes in urinary sediment (microhematuria, proteinuria, cylindruria). Diffuse forms of lupus nephritis can cause nephrotic syndrome with edema, hypoproteinemia, proteinuria, hypercholesterolemia. Often, kidney damage occurs with a malignant arterial hypertension... In most cases of diffuse lupus nephritis, renal failure occurs and rapidly decompensates. Lupus hepatitis is benign, manifested by moderate hepatomegaly, moderate impairment liver function. It never leads to liver failure, liver cirrhosis. Abdominal pain, sometimes very intense, muscle tension of the anterior abdominal wall (lupus abdominal crisis) is usually associated with mesenteric vasculitis. Most patients develop focal and diffuse changes in the central nervous system caused by vasculitis, cerebral vascular thrombosis, and direct immune damage to nerve cells. Typical are headaches, depression, psychoses, epileptiform seizures, polyneuropathy, and motor dysfunctions are possible. With SLE, peripheral lymph nodes increase, splenomegaly appears, which is not associated with impaired portal hemodynamics. SLE patients are anemic. Often there is hypochromic anemia belonging to the group of iron redistribution. In immunocomplex diseases, which include SLE, macrophages react intensively with hemosiderin bodies, which are an iron depot, removing (redistributing) them from bone marrow... There is a deficiency of iron for hematopoiesis while maintaining the total content of this element in the body within normal limits. Hemolytic anemia in SLE patients occurs when erythrocytes are destroyed during the elimination of immune complexes fixed on their membrane, as well as as a result of hyperreactivity of macrophages of an enlarged spleen (hypersplenism). SLE is characterized by clinical Raynaud's, Sjogren's, Verlhof's, antiphospholipid syndromes. Raynaud's syndrome is caused by immune complex vasculitis. In patients after exposure to cold or emotional stress there is an acute spastic ischemia of certain parts of the body. Suddenly, fingers turn pale and icy except thumb, less often - toes, chin, nose, ears. After a short period of time, pallor is replaced by a purple-cyanotic color, swelling of the skin as a result of postischemic vascular paresis. Sjogren's syndrome is an autoimmune lesion of the salivary, lacrimal and other exocrine glands with the development of dry stomatitis, keratoconjunctivitis, pancreatitis, secretory insufficiency of the gastric mucosa. In patients, the shape of the face may change due to compensatory hypertrophy of the parotid salivary glands... Sjogren's syndrome often occurs with Raynaud's syndrome. Werlhof's syndrome (symptomatic thrombocytopenic purpura) in SLE is caused by autoimmune suppression of platelet formation, high consumption of platelets in the process of autoimmune reactions. It is characterized by intradermal petechial hemorrhages - purple. In patients with chronic variant the clinical course of SLE, Verlhof's syndrome can be the only manifestation of this disease for a long time. With lupus, often even a deep drop in the level of platelets in the blood is not accompanied by hemorrhages. In the practice of the author of this book, there were cases when in patients in the initial period of SLE the number of platelets in the peripheral blood did not rise above 8-12 per 1000 leukocytes in the absence of bleeding, while the level below which thrombocytopenic purpura usually begins - 50 per 1000. Antiphospholipid syndrome is formed in connection with the emergence of autoantibodies to phospholipids, cardiolipin. Antiphospholipid antibodies are called lupus anticoagulants. They negatively affect some stages of blood clotting, increasing the thromboplastin time. Paradoxically, the presence of a lupus anticoagulant in the blood is characterized by a tendency to thrombosis and not to bleeding. The syndrome in question is usually manifested by deep vein thrombosis of the lower extremities. Mesh livedo is a treelike vascular pattern on the skin of the lower extremities; it can also form as a result of thrombosis of the small veins of the legs. In SLE patients, antiphospholipid syndrome is one of the main causes of cerebral, pulmonary and hepatic vein thrombosis. Often combined with Raynaud's syndrome. Diagnostics Complete blood count: a decrease in the number of erythrocytes, hemoglobin, in some cases simultaneously with a decrease in the values of the color index (CP). In some cases, reticulocytosis is detected - evidence of hemolytic anemia. Leukopenia, often pronounced. Thrombocytopenia, often deep. Increased ESR. General urine analysis: hematuria, proteinuria, cylindruria. Biochemical blood test: an increase in the content of fibrinogen, alpha-2- and gamma-globulins, total and indirect bilirubin (with hemolytic anemia). With kidney damage, hypoproteinemia, hypercholesterolemia, an increase in the content of urea, creatinine. Immunological research allows you to get positive results a number of reactions that are quite specific for SLE. · LE-cells are neutrophils containing the nucleus of a phagocytosed lymphocyte in the cytoplasm. Detection of more than five LE-cells per thousand leukocytes is of diagnostic value. · Increased levels of circulating immune complexes (CICs). · Antibodies to Sm antigen - short nuclear RNA polypeptides. · Antinuclear factor is a complex of antinuclear autoantibodies specific to various components of the cell nucleus. · Antibodies to native DNA. · The rosette phenomenon is the identification of groups of leukocytes surrounding free-lying cell nuclei. · Antiphospholipid autoantibodies. · Positive Coombs' test in hemolytic anemia. · Rheumatoid factor appears in moderate diagnostic titers only with pronounced articular manifestations of SLE. ECG - signs of left ventricular myocardial hypertrophy with formed defects (mitral insufficiency and / or aortic valves), arterial hypertension of renal origin, various rhythm and conduction disturbances, ischemic disturbances. Radiography of the lungs - pleural effusion, focal infiltration (pneumonitis), interstitial changes (pulmonary vasculitis), triangular shadows of heart attacks with embolism of the branches of the pulmonary artery. Radiography of the affected joints - moderate osteoporosis without usuration, ankylosis. Ultrasound: pleural effusion, sometimes a small amount of free fluid in the abdomen. Determined by moderate hepatomegaly, splenomegaly without disturbance of portal hemodynamics. In some cases, signs of hepatic vein thrombosis are determined - Bad Chiari syndrome. Echocardiography - effusion in the pericardial cavity, often significant (up to cardiac tamponade), dilatation of the heart chambers, a decrease in the ejection fraction of the left ventricle, areas of hypokinesia of the wall of the left ventricle of ischemic origin, defects of the mitral and aortic valves. Ultrasound examination of the kidneys: a diffuse, symmetrical increase in the echogenicity of the parenchyma of both organs, sometimes signs of nephrosclerosis. Puncture biopsy of the kidneys - one of the morphological variants of lupus nephritis is excluded or confirmed. The degree of SLE activity is determined based on the following criteria. · I Art. - minimal activity. Body temperature is normal. A little weight loss. Discoid lesions on the skin. Arthralgia. Adhesive pericarditis. Myocardial dystrophy. Adhesive pleurisy. Polyneuritis. Hemoglobin more than 120 g / l. ESR 16-20 mm / hour. Fibrinogen less than 5 g / l. Gamma globulins 20-23%. LE cells are absent or single. Antinuclear factor less than 1:32. The titer of antibodies to DNA is low. The CEC level is low. · II Art. - moderate activity... Fever up to 38 0C. Moderate weight loss. Nonspecific erythema on the skin. Subacute polyarthritis. Dry pericarditis. Moderate myocarditis. Dry pleurisy. Diffuse glomerulonephritis of mixed type with arterial hypertension, hematuria, proteinuria. Encephaloneuritis. Hemoglobin 100-110 g / l. ESR 30-40 mm / hour. Fibrinogen 5-6 g / l. Gamma globulins 24-25%. LE cells 1-4 per 1000 leukocytes. Antinuclear factor 1:64. The titer of antibodies to DNA is average. The CEC level is average. · III Art. - maximum activity. Fever over 38 0C. Expressed weight loss. Skin lesions in the form of erythema lupus, "butterfly" on the face, capillaritis. Acute or subacute polyarthritis. Pericardial effusion. Expressed myocarditis. Lupus endocarditis. Exudative pleurisy. Diffuse glomerulonephritis with nephrotic syndrome. Acute encephaloradiculoneuritis. Hemoglobin less than 100 g / l. ESR more than 45 mm / hour. Fibrinogen is more than 6 g / l. Gamma globulins 30-35%. LE cells are more than 5 per 1000 leukocytes. Antinuclear factor is higher than 1: 128. The titer of antibodies to DNA is high. The CEC level is high. Revised American Rheumatologic Association SLE Diagnostic Criteria:
The diagnosis is considered reliable if 4 or more of the criteria listed below are met. If there are fewer criteria, the diagnosis is considered presumptive (not excluded). 1.
Lupoid "butterfly»: Flat or raised, fixed erythema on the cheekbones, with a tendency to spread to the nasolabial area. 2.
Discoid rash:raised erythematous plaques with adjacent scales, follicular plugs, atrophic scars on old foci. 3.
Photodermatitis:rashes on the skin that appear as a result of exposure to sunlight. 4.
Erosion and ulceration in oral cavity:
painful ulceration of the oral mucosa or nasopharynx. 5.
Arthritis:non-erosive arthritis of two or more peripheral joints, manifested by soreness, edema, exudation. 6.
Serositis:pleurisy, manifested by pleural pain, pleural rubbing, or signs of pleural effusion; pericarditis, manifested by pericardial rubbing, intrapericardial effusion detected by echocardiography. 7.
Kidney damage:persistent proteinuria 0.5 g / day or more or hematuria, the presence of cylinders in the urine (erythrocytic, tubular, granular, mixed). 8.
Damage to the central nervous system:convulsions - in the absence of drug or drug intoxication, metabolic disorders (ketoacidosis, uremia, electrolyte disturbances); psychosis - in the absence of taking psychotropic drugs, electrolyte disturbances. 9.
Hematological changes:leukopenia 4 10 9/ l and less, registered two or more times; lymphopenia 1.5 10 9/ l and less, registered at least twice; thrombocytopenia less than 100 10 9/ l not due to medication. 10.
Immunological disorders:antibodies against native DNA in an increased titer; antibodies to smooth muscles (anti-Sm); antiphospholipid antibodies (an increased level of IgG or IgM - antibodies to cardiolipin, the presence of lupus coagulant in the blood; false positive Wasserman reaction in the absence of evidence of syphilitic infection (according to the results of RIT - the reaction of immobilization of treponema or RIF - the reaction of immunofluorescent identification of treponemal antibodies). 11.
Antinuclear antibodies:identifying them in an increased titer in the absence of taking medications that can cause lupus-like syndrome. Differential diagnosis It is carried out primarily with lupoid hepatitis (chronic autoimmune hepatitis with extra-infantile manifestations), rheumatoid arthritis, as well as with mixed systemic connective tissue disease (Sharp's syndrome), chronic glomerulonephritis, systemic vasculitis. Chronic autoimmune hepatitis with extrahepatic manifestations is also called lupoid, as it is accompanied by multiple lesions of internal organs, arthralgias, polyserositis, vasculitis, etc., resembling SLE. However, unlike lupoid hepatitis, in SLE, liver damage is benign. There are no massive necrosis of hepatocytes. Lupus hepatitis does not progress to cirrhosis of the liver. In contrast, with lupoid hepatitis, according to puncture biopsy, there are pronounced and severe necrotic damage to the liver parenchyma, followed by a transition to cirrhosis. During the formation of remission of lupoid hepatitis, the symptoms of extrahepatic lesions first fade away, but at least minimal signs of the inflammatory process in the liver remain. In systemic lupus erythematosus, the opposite is true. Signs of liver damage are the first to fade. At the initial stages of the disease, SLE and rheumatoid arthritis have almost the same clinical manifestations: fever, morning stiffness, arthralgia, symmetric arthritis of the small joints of the hands. However, in rheumatoid arthritis, joint damage is more severe. Erosion of the articular surfaces, proliferative processes followed by ankylosis of the affected joint are typical. For SLE, erosive ankylosing arthritis is not typical. Differential diagnosis of SLE and rheumatoid arthritis with systemic manifestations presents significant difficulties, especially at the initial stages of the disease. A common manifestation of SLE is severe glomerulonephritis, leading to renal failure. Glomerulonephritis is rare in rheumatoid arthritis. In cases where it is not possible to distinguish between SLE and rheumatoid arthritis, one should think of Sharpe's syndrome - a mixed systemic disease of connective tissue that combines signs of SLE, rheumatoid arthritis, systemic sclerosis, polymyositis, etc. Survey plan · Complete blood count with platelet count. · General urine analysis. · Test according to Zimnitsky. · Biochemical blood test: fibrinogen, total protein and fractions, bilirubin, cholesterol, urea, creatinine. · Immunological analysis: LE cells, CEC, rheumatoid factor, antibodies to Sm antigen, antinuclear factor, antibodies to native DNA, antiphospholipid antibodies, Wasserman reaction, direct and indirect Coombs' tests. · Radiography of the lungs. · X-ray of the affected joints. · ECG. · Ultrasound of the pleural, abdominal, liver, spleen, kidneys. · Echocardiography. · Biopsy of the musculocutaneous flap (according to indications - if necessary, differential diagnosis with other systemic connective tissue diseases, evidence of mixed connective tissue disease - Sharp's syndrome). · Kidney biopsy (according to indications - if necessary, differential diagnosis with other systemic kidney disease, chronic glomerulonephritis). Treatment SLE treatment tactics include: · Suppression of hyperreactivity of immune mechanisms, immune inflammation, immune complex lesions. · Treatment of selected clinically significant syndromes. In order to reduce the hyperreactivity of the immune system, inflammatory processes, glucocorticosteroids, immunodepressants (cytostatics), aminoquinoline drugs, efferent methods (plasmapheresis, hemosorption) are used. The basis for prescribing glucocorticoid drugs is convincing evidence of the diagnosis of SLE. At the initial stages of the disease with minimal signs of activity, glucocorticosteroid drugs are necessarily used, but not non-steroidal anti-inflammatory drugs. Depending on the course of SLE, the activity of immune-inflammatory processes, various schemes of monotherapy with glucocorticoids, combined with their use with other drugs, are used. Treatment is started with an "overwhelming" dose of glucocorticoids with a gradual transition to a supportive dose when the activity of the immune-inflammatory process dies down. Most often, oral prednisolone and parenteral methylprednisolone are used to treat SLE. · In the chronic course of SLE with minimal activity of immune inflammation, oral prednisolone is prescribed in minimal maintenance doses of 5-7.5 mg / day. · In acute and subacute clinical course with II and III st. SLE activity, prednisolone is prescribed at a dose of 1 mg / kg / day. If after 1-2 days the patient's condition does not improve, the dose is increased to 1.2-1.3 mg / kg / day. This treatment is continued for 3-6 weeks. With a decrease in the activity of the immune-inflammatory process, the dose is first reduced by 5 mg per week. Upon reaching the level of 20-50 mg / day, the rate of decline is reduced to 2.5 mg per week until the minimum maintenance dose of 5-7.5 mg / day is reached. · With highly active SLE with severe vasculitis, lupus nephritis, severe anemia, leukopenia, thrombocytopenia, lupus encephaloradiculneuritis with acute mental, movement disorders against the background of systematic treatment with prednisolone, pulse therapy with methylprednisolone is performed. For three consecutive days, 1000 mg of methylprednisolone is injected intravenously over 30 minutes. This procedure can be repeated monthly for 3-6 months. In the following days after pulse therapy, the patient should continue the systematic oral administration of prednisolone in order to avoid renal failure due to a decrease in glomerular filtration. Immunosuppressants (cytostatics) are prescribed for SLE only together with glucocorticosteroid drugs or against the background of their systematic use. Immunosuppressants can enhance the anti-inflammatory effect and, at the same time, reduce the required dose of glucocorticoids, thereby reducing the side effects of their long-term use. Cyclophosphamide, azathioprine are used, less often other cytostatics. · With high SLE activity, systemic vasculitis with widespread ulcerative necrotic skin lesions, severe pathological changes in the lungs, central nervous system, active lupus nephritis, if it is impossible to further increase the dose of glucocorticoids, the following is additionally prescribed: o Cyclophosphamide 1-4 mg / kg / day orally, or: o Azathioprine 2.5 mg / kg / day by mouth. · With active lupus jade: o Azathioprine 0.1 once a day by mouth and cyclophosphamide 1000 mg intravenously 1 time in 3 months. · To increase the effectiveness of three-day pulse therapy with methylprednisolone, 1000 mg of cyclophosphamide is additionally administered intravenously on the second day. Aminoquinoline preparations are of secondary importance. They are intended for long-term use with low activity of the inflammatory process, chronic course of SLE with predominantly skin lesions. · · To eliminate excess autoantibodies, immune complexes, and inflammatory mediators from the blood, the following are used: · Plasmapheresis - 3-5 procedures with a single removal of up to 1000 ml of plasma. · Hemosorption on activated carbons and fiber sorbents - 3-5 procedures. For the treatment of thrombocytopenic syndrome are used: · immunoglobulin preparations at 0.4 g / kg / day for 5 days; · dinazole at 10-15 mg / kg / day. When a tendency to thrombosis appears, low molecular weight heparin is prescribed, 5 thousand units under the skin of the abdomen 4 times a day, antiplatelet agents - 150 mg of chimes a day. If necessary, use broad-spectrum antibiotics, anabolic hormones, diuretics, ACE inhibitors, peripheral vasodilators. Forecast. Adverse. Especially in cases of highly active lupus nephritis, cerebral vasculitis. Relatively favorable prognosis in patients with chronic, inactive course of SLE. In such cases, adequate treatment provides patients with a life expectancy of over 10 years. ... Systemic scleroderma
Definition Systemic scleroderma (SS) or systemic sclerosis is a diffuse disease of connective tissue with fibrosclerotic changes in the skin and internal organs, vasculitis of small vessels in the form of obliterating endarteritis. ICD 10:M 34 - Systemic sclerosis. M34.0 - Progressive systemic sclerosis. M34.1 - CR (E) ST syndrome. Etiology. The disease is preceded by an infection with an unknown RNA-containing virus, prolonged professional contact with polyvinyl chloride, and work in conditions of intense vibration. Persons with HLA type B35 and Cw4 histocompatibility antigens are predisposed to the disease. The overwhelming majority of patients with SS have chromosomal aberrations - chromatid ruptures, ring chromosomes, etc. Pathogenesis As a result of exposure to endothelial cells of the etiological factor, an immunopathological reaction occurs. T-lymphocytes sensitized to the antigens of damaged endothelial cells produce lymphokines that stimulate the macrophage system. In turn, monokines from stimulated macrophages even more damage the endothelium and, at the same time, stimulate the function of fibroblasts. A vicious immune-inflammatory circle ensues. Damaged walls of small muscle-type vessels become hypersensitive to vasoconstrictor influences. Pathogenetic mechanisms of vasospastic ischemic Raynaud's syndrome are formed. Active fibrogenesis in the vascular wall leads to a decrease in the lumen and obliteration of the affected vessels. As a result of similar immune-inflammatory reactions, circulatory disorders in small vessels, interstitial tissue edema occurs, stimulation of tissue fibroblasts, followed by irreversible sclerosis of the skin and internal organs. Depending on the nature of immune shifts, various variants of the disease are formed. The appearance of antibodies to Scl-70 (Scleroderma-70) in the blood is associated with a diffuse form of CC. Antibodies to centromeres are typical of CREST syndrome. Nuclear antibodies - for scleroderma kidney damage and overlap syndrome with dermatomyositis-polymyositis. Limited and diffuse forms of SS are pathogenetically significantly different: · The limited (limited) form of CC is known as CREST-syndrome. Its signs are calcification ( Calcinosis), Raynaud's syndrome ( Reynaud), esophageal motility disorders ( Esophageal motility disorders), sclerodactyly ( Sclerodactilya), telangiectasia ( Teleangiectasia). Pathological changes are characteristic mainly of the skin of the face and fingers of the hands distal to the metacarpophalangeal joint. This is a relatively benign variant of the disease. Injuries to internal organs are rare and appear only with a prolonged course of the disease, and if they occur, they proceed more easily than with the diffuse form of SS. · The diffuse form of SS (progressive systemic sclerosis) is characterized by sclerotic skin changes upper limbs proximal to the metacarpophalangeal joints, other parts of the body, up to its entire surface. Lesions of internal organs occur much earlier than with a limited form. More organs and tissue structures are involved in the pathological process. The kidneys and lungs are especially often and severely affected. Clinical picture The disease can occur in acute, subacute, chronic forms. The acute form of diffuse SS is characterized by the rapid development of all stages of skin lesions within less than one year. At the same time, lesions of internal organs, primarily kidneys and lungs, appear and reach their culminating development. During the entire period of the disease, the maximum deviations of the indicators of general, biochemical blood tests are revealed, demonstrating the high activity of the pathological process. With a subacute course, the disease develops at a relatively slow pace, but with the presence of all skin lesions, vasomotor disorders, and internal organ lesions typical of diffuse CVS. Deviations of laboratory and biochemical parameters are noted, reflecting the moderate activity of the pathological process. The chronic course of SS is characterized by a gradual onset, slow progression over a long time. Most often, a limited form of the disease is formed - CREST syndrome. Clinically significant lesions of internal organs, deviations of laboratory and biochemical parameters are usually not observed. Over time, patients may develop symptoms of pulmonary hypertension caused by obliterating endarteritis of the pulmonary artery and its branches, signs of pulmonary fibrosis. In typical cases, SS begins with pathological changes in the skin. Patients notice the appearance of a painful thickening of the skin of the fingers of both hands (edematous phase). Then the skin thickens (inductive phase). The subsequent sclerosis causes its thinning (atrophic phase). Sclerosed skin becomes smooth, shiny, tight, very dry. It cannot be folded, since it is fused with the underlying fascia, periosteum, periarticular structures. The vellus hair disappears. The nails are deformed. On the thinned skin of the hands, traumatic injuries, spontaneous ulcerations, and abscesses easily arise and slowly heal. Telangiectasias appear. The facial skin lesion, which is very characteristic of SS, cannot be confused with anything. The face becomes amimic, mask-like, unnaturally shiny, unevenly pigmented, often with purple foci of telangiectasias. The nose is pointed in the shape of a bird's beak. A "surprised" look appears, as the sclerotic contraction of the skin of the forehead and cheeks widens the eye slits and makes it difficult to blink. The mouth gap narrows. The skin around the mouth shrinks to form non-expanding radial folds, resembling the shape of a "pouch". In the limited form of CC, the lesions are limited to the skin of the fingers and face. With a diffuse form, edematous, indurative-sclerotic changes gradually spread to the chest, back, legs, and the whole body. The defeat of the skin of the chest and back creates in the patient the sensation of a corset that interferes with the respiratory movements of the chest. Total sclerosis of all skin forms a picture of the patient's pseudo-mummification - the phenomenon of "living relics". Along with the skin, mucous membranes may be affected. Patients often point to dryness, lack of saliva in the mouth, pain in the eyes, and the inability to cry. Often these complaints indicate the formation of a "dry" Sjogren's syndrome in a patient with SS. Together with edematous-indurative changes in the skin, and in some cases up to skin lesions, Raynaud's angiospastic syndrome can form. Patients begin to be bothered by attacks of sudden pallor, numbness of the fingers, less often of the legs, the tips of the nose, ears after exposure to cold, against the background of emotions, and even for no apparent reason. Pallor soon turns into bright hyperemia, moderate swelling with the appearance of pain at first, and then sensations of pulsating heat. The absence of Raynaud's syndrome is usually associated with the formation of severe scleroderma kidney damage in the patient. Articular syndrome also refers to early manifestations SS. It can be limited to polyarthralgia without affecting the joints and periarticular structures. In some cases, it is symmetrical fibrosing scleroderma polyarthritis of small joints of the hands with complaints of stiffness and pain. It is characterized by first exudative and then proliferative changes as in rheumatoid arthritis. Pseudoarthritis scleroderma can also form, characterized by limited joint mobility caused not by damage to the articular surfaces, but by adhesions of the joint capsule and muscle tendons with inductively altered or sclerosed skin. Often, articular syndrome is combined with osteolysis, shortening of the terminal phalanges of the fingers - sclerodactyly. Carpal tunnel syndrome with parasthesias of the middle and index fingers of the hand, pain extending up the forearm to the elbow, flexion contractures of the hand can form. Muscle weakness is characteristic of the diffuse form of CC. Its causes are diffuse muscle atrophy, non-inflammatory muscle fibrosis. In some cases, this is a manifestation of inflammatory myopathy, which is identical to that in patients with dermatomyositis-polymyositis (cross syndrome). Subcutaneous calcifications are found mainly in limited CV (CREST syndrome), and only in a small number of patients with a diffuse form of the disease. Calcifications are more often located in places of natural trauma - the tips of the fingers of the hands, the outer surface of the elbows, knees - Tibierge-Weissenbach syndrome. Swallowing disorders in SS are caused by disturbances in the structure of the wall and motor function esophagus. In patients with SS, the smooth muscles of the lower third of the esophagus are replaced by collagen. The striated muscles of the upper third of the esophagus are usually unaffected. There is a stenosis of the lower esophagus and compensatory expansion of the upper. The structure of the esophageal mucosa changes - Beretta metaplasia. As a result of gastroesophageal reflux, erosive reflux esophagitis often occurs, ulcers of the esophagus, post-ulcerative strictures of the esophageal-gastric junction develop. Possible atony and dilatation of the stomach, duodenum... When diffuse gastric fibrosis occurs, iron absorption may be impaired with the formation of sideropenic syndrome. Atony, dilatation of the small intestine often develops. Fibrosis of the wall of the small intestine is manifested by malabsorption syndrome. The defeat of the colon leads to diverticulosis, manifested by constipation. In patients with a limited form of the disease in the form of CREST-syndrome, sometimes primary biliary cirrhosis of the liver can form, the first symptom of which may be "causeless" itching of the skin. In patients with diffuse CV, lung damage in the form of basal and then diffuse pulmonary fibrosis is manifested by progressive pulmonary insufficiency. Patients complain of constant shortness of breath, aggravated by physical activity. Dry pleurisy may occur with chest pain, pleural friction noise. In patients with limited CV, during the formation of obliterating endarteritis of the pulmonary artery and its branches, pulmonary hypertension occurs with overload of the right heart. The diffuse form of CC is sometimes complicated by heart damage. Myocarditis, myocardial fibrosis, myocardial ischemia caused by obliterating vasculitis of the coronary arteries, fibrosis of the mitral valve leaflets with the formation of its insufficiency can cause hemodynamic decompensation. Kidney damage is characteristic of the diffuse form of CC. Kidney pathology is a kind of alternative to Raynaud's syndrome. The sclerodermic kidney is characterized by damage to blood vessels, glomeruli, tubules, interstitial tissues. By clinical manifestations sclerodermic kidney does not differ from glomerulonephritis, occurring with arterial hypertension, urinary syndrome in the form of proteinuria, hematuria. A progressive decrease in glomerular filtration leads to chronic renal failure. As a result of obliterating fibrosis of interlobular arteries in combination with any vasoconstrictor effect (hypothermia, blood loss, etc.), cortical necrosis of the kidney can occur with a clinical picture of acute renal failure - sclerodermic renal crisis. The defeat of the nervous system is due to obliterating vasculitis of the cerebral arteries. Spastic seizures involving intracranial arteries, as one of the manifestations of Raynaud's syndrome, can cause seizures, psychosis, and transient hemiparesis. The diffuse form of SS is characterized by damage to the thyroid gland in the form of autoimmune thyroiditis, fibrous atrophy of the organ. Diagnostics · Complete blood count: May be normal. Sometimes signs of mild hypochromic anemia, mild leukocytosis, or leukopenia. There is an increased ESR. · General urine analysis: proteinuria, cylindruria, microhematuria, leukocyturia, with chronic renal failure - a decrease in the specific gravity of urine. Increased excretion of oskiproline is a sign of impaired collagen metabolism. · Biochemical blood test: may be normal. The active process is accompanied by an increase in the content of fibrinogen, alpha-2- and gamma-globulins, seromucoid, haptoglobins, oxyproline. · Immunological analysis: specific autoantibodies to Scl-70 in diffuse form of CC, autoantibodies to centromeres in a limited form of the disease, nuclear antibodies in renal damage, cross syndrome of CC-dermatomyositis-polymyositis. In most patients, rheumatoid factor is detected, in some cases, single LE-cells. · Biopsy of the musculocutaneous flap: obliterating vasculitis of small vessels, fibrosclerotic changes. · Puncture biopsy of the thyroid gland: identification of morphological signs of autoimmune thyroiditis, vasculitis of small vessels, fibrous arthrophy of the organ. · X-ray examination: calcifications in the tissues of the terminal phalanges of the fingers, elbow, knee joints; osteolysis of the distal phalanges of the fingers; osteoporosis, narrowing of the joint space, sometimes ankylosis of the affected joints. Chest - interpleural adhesions, basal, diffuse, often cystic (cellular lung) pulmonary fibrosis. · ECG: signs of myocardial dystrophy, ischemia, large-focal cardiosclerosis with impaired conduction, excitability, hypertrophy of the left ventricular and atrial myocardium with formed mitral valve insufficiency. · Echocardiography: verification of mitral defect, abnormalities contractile function myocardium, dilatation of the heart chambers, signs of pericarditis may be detected. · Ultrasound examination: identification of structural signs of bilateral diffuse kidney damage, characteristic of nephritis, evidence of autoimmune thyroiditis, fibrous atrophy of the thyroid gland, in some cases, signs of biliary cirrhosis. American Rheumatological Association clinical criteria for the recognition of systemic scleroderma: · "Big" criteria: o Proximal scleroderma - bilateral, symmetrical thickening, induration, induration, sclerosis of the dermis of the fingers, skin of the extremities proximally from the metacarpophalangeal and metatarsophalangeal joints, involvement of the skin of the face, neck, chest, abdomen in the pathological process. · "Small" criteria: o Sclerodactyly - induration, sclerosis, osteolysis of the terminal phalanges, deformation of the fingers; o Scars, tissue defects on the pads of the fingers of the hands; o Basal pulmonary fibrosis on both sides. To be diagnosed with CC, a patient must have either a “major” or at least two “minor” criteria. Clinical and laboratory signs of the activity of the indurative-sclerotic process in patients with SS: · 0 tbsp. - lack of activity. · I Art. - minimal activity. Moderate trophic disorders, arthralgias, vasospastic Raynaud's syndrome, ESR up to 20 mm / h. · II Art. - moderate activity. Arthralgia and / or arthritis, adhesive pleurisy, symptoms of cardiosclerosis, ESR - 20-35 mm / hour. · III Art. - high activity. Fever, polyarthritis with erosive lesions, large focal or diffuse cardiosclerosis, mitral valve insufficiency, scleroderma kidney. ESR exceeds 35 mm / hour. Differential diagnosis It is carried out primarily with focal scleroderma, other diffuse connective tissue diseases - rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis-polymyositis. Distinguish between plaque, teardrop, annular, linear forms of focal (local) scleroderma. In contrast to the limited and diffuse forms of SS, with focal scleroderma, the skin of the fingers and face is not involved in the pathological process. Systemic manifestations occur rarely and only with a prolonged course of the disease. It is easier to distinguish between rheumatoid arthritis and SS when articular syndrome forms in patients with SS in the form of pseudoarthritis with indurative-sclerotic lesions of the periarticular skin. Radiographically, in these cases, there are no serious lesions of the joint itself. However, in both SS and rheumatoid arthritis, symmetric polyarthritis of the small joints of the hands can occur, with a characteristic stiffness, a tendency to ankylosis. Under such circumstances, the differentiation of diseases in favor of SS helps to identify the symptoms of indurative and then sclerotic lesions of the skin of the fingers, face, and in the diffuse form of SS, the skin of other parts of the body. For SS, lung damage (pneumofibrosis) is characteristic, which does not happen in patients with rheumatoid arthritis. Differential diagnosis with systemic lupus erythematosus is based on the identification of skin lesions specific to CC. In lupus, unlike SS, polyarthritis is benign, never leads to deformities, ankylosis of the joints. Lupus pseudoarthritis - Jaccoux syndrome - arthropathy with persistent deformities of the joints due to damage to tendons and ligaments. It proceeds without erosive arthritis. It differs from pseudoarthritis scleroderma in the absence of fusion of the joint capsule with induratively altered or sclerosed skin over the affected joint. The diffuse form of the disease can be distinguished from systemic lupus erythematosus by the presence in the blood of SS-specific autoantibodies to the Scl-70 antigen. For SS, in contrast to dermatomyositis-polymyositis, indurative and sclerotic skin lesions, secondary moderately expressed myopathy are characteristic. With dermatomyositis-polymyositis, high levels of creatine phosphokinase activity are detected in the blood, which is not the case with classical SS variants. If there is a combination of SS symptoms with signs of dermatomyositis-polymyositis, then the likelihood of the diagnosis of overlap syndrome of systemic connective tissue damage should be considered. Survey plan · General blood analysis. · General urine analysis. · The content of hydroxyproline in the urine. · Immunological analysis: autoantibodies to Scl-70, autoantibodies to centromeres, antinuclear antibodies, rheumatoid factor, LE cells, CEC. · Biopsy of the musculocutaneous flap. · Fine needle biopsy of the thyroid gland. · X-ray examination of the hands, affected elbow, knee joints. · Chest X-ray. · ECG. · Echocardiography. · Ultrasound examination of the abdominal organs, kidneys, thyroid gland. Treatment The tactics of treatment involves the implementation of the following effects on the patient's body: · Inhibition of the activity of obliterating endarteritis of small vessels, skin hardening, fibrosis of internal organs. · Symptomatic treatment pain (arthralgia, myalgia) and other syndromes, impaired functions of internal organs. To suppress excess collagen formation in patients with active inflammatory process, the subacute course of the SS is assigned: · D-penicylamine (cuprenil) orally at 0.125-0.25 per day every other day. If ineffective, the dosage is increased to 0.3-0.6 per day. If the intake of D-penicylamine is accompanied by the appearance of skin rashes, its dose is reduced and prednisolone is added to the treatment - 10-15 mg / day by mouth. The appearance of increasing proteinuria against the background of such treatment is the basis for the complete abolition of D-penicylamine. To reduce the activity of collagen synthesis mechanisms, especially in case of ineffectiveness or the occurrence of contraindications for D-penicylamine, you can apply: · colchicine - 0.5 mg / day (3.5 mg per week) with a gradual increase in the dose to 1-1.5 mg / day (about 10 mg per week). The drug can be taken for one and a half to four years in a row. In the case of diffuse CC with severe and severe systemic manifestations, it is advisable to use immunosuppressive doses of glucocorticoids and cytostatics. · oral prednisolone at 20-30 mg / day until a clinical effect is achieved. Then the dosage of the drug is slowly reduced to a maintenance dosage of 5-7.5 mg / day, which is recommended to be taken within 1 year. In the absence of effect, the occurrence adverse reactions for taking large doses of glucocorticoids, cytostatics are used: · Oral azathioprine 150-200 mg / day in combination with oral administration of 15-20 mg / day prednisolone for 2-3 months. In the chronic course of SS with predominantly cutaneous manifestations, minimal activity of the fibrosing process, aminoquinoline preparations should be prescribed: · Hydroxychloroquine (Plaquenil) 0.2 - 1-2 tablets per day for 6-12 months. · Chloroquine (delagil) 0.25 - 1-2 tablets per day for 6-12 months. Symptomatic agents are intended primarily to compensate for vasospastic reactivity, treatment of Raynaud's syndrome, and other vascular disorders. For this purpose, calcium channel blockers, ACE inhibitors, antiplatelet agents are used: · Nifedipine - up to 100 mg / day. · Verapapil - up to 200-240 mg / day. · Captopril - up to 100-150 mg / day. · Lisinopril - up to 10-20 mg / day. · Curantil - 200-300 mg / day. With articular syndrome, drugs from the group of non-steroidal anti-inflammatory drugs are shown: · Diclofenac sodium (ortofen) 0.025-0.05 - 3 times a day by mouth. · Ibuprofen 0.8 - 3-4 times a day by mouth. · Naproxen 0.5-0.75 - 2 times a day by mouth. · Indomethacin 0.025-0.05 - 3 times a day by mouth. · Nimesulide 0.1 - 2 times a day by mouth. This drug selectively acts on COX-2 and therefore can be used in patients with erosive and ulcerative lesions of the esophagus, stomach and duodenum, for whom non-selective non-steroidal anti-inflammatory drugs are contraindicated. For local treatment you can use 25-50% Dimexide solution in the form of applications on the affected skin for 20-30 minutes daily - up to 30 applications per course of treatment. Shown are sulfated glycosaminoglycans in ointments. You can apply lidase by intradermal injection, electrophoresis, phonophoresis in inductively changed areas of the skin. Forecast Determined by the pathomorphological variant of the disease. In the limited form, the forecast is quite favorable. In the diffuse form, it depends on the development and decompensation of damage to the kidneys, lungs, heart. Timely and adequate treatment significantly prolongs the life of patients with CC. 4. Dermatomyositis-polymyositis
Definition Dermatomyositis (DM) or dermatopolymyositis is a systemic inflammatory disease with the replacement of affected tissues with fibrous structures with the predominant involvement of skeletal and smooth muscles, skin, and small vessels in the pathological process. In the absence of skin lesions, the term "polymyositis" (PM) is used. ICD 10:M33 - Dermatopolymyositis. M33.2 - Polymyositis. Etiology The etiological factor of DM-PM may be latent infection with picarnoviruses, some viruses from the Coxsackie group with the introduction of the pathogen into the genome of muscle cells. The association of DM-PM with a number of tumor processes may either testify in favor of the viral etiology of these tumors, or be a demonstration of antigenic mimicry of tumor structures and muscle tissue. Persons with HLA type B8 or DR3 histocompatibility antigens are predisposed to the disease. Pathogenesis The launch of the pathogenetic mechanisms of the disease in infected and genetically predisposed persons can carry out nonspecific effects: hypothermia, excessive solar insolation, vaccinations, acute intoxication, etc. the defeat of antigenically related cell populations. The inclusion of microphage mechanisms for the elimination of immune complexes from the body causes the activation of fibrogenesis processes, concomitant systemic inflammation of small vessels. Due to the hyperreactivity of the immune system, aimed at the destruction of intranuclear positions of the virion, antibodies Mi2, Jo1, SRP, autoantibodies to nucleoproteins and soluble nuclear antigens appear in the blood. Clinical picture The disease can occur in acute, subacute and chronic forms. The acute form is characterized by the sudden onset of fever with a body temperature of up to 39-40 0C. Immediately pain, muscle weakness, arthralgia, arthritis, cutaneous erythema occur. Generalized lesion of all skeletal muscles is rapidly developing. Myopathy progresses rapidly. In a short period of time, the patient becomes almost completely immobilized. There are severe disorders of swallowing and breathing. Defeats of internal organs, primarily the heart, appear and rapidly decompensate. Life expectancy in the acute form of the disease does not exceed 2-6 months. The subacute course is characterized by the absence of a memory onset of the disease in the patient. There are myalgias, arthralgias, gradually increasing muscle weakness. After solar insolation, characteristic erythema forms on the face, open surfaces of the chest. There are signs of damage to internal organs. The full development of the clinical picture of the disease and death occur in 1-2 years. The chronic form is benign, cyclical with long periods of remission. This variant of the disease rarely leads to a rapid death, limited to moderate, often local atrophic and sclerotic changes in muscles, skin, mild myopathy, compensated by changes in internal organs. Muscle pathology is the most striking feature of DM-PM. Patients note the appearance of progressive weakness, which is usually accompanied by myalgias of varying intensity. On objective examination, the affected muscles are doughy due to edema, with reduced tone, painful. Over time, the volume of the muscles involved in the pathological process decreases as a result of atrophy and fibrosis. First of all, the proximal skeletal muscle groups change. The distal muscle groups of the arms and legs are later involved. Inflammation and fibrosis of the muscles of the chest, diaphragm disrupts ventilation of the lungs, leading to hypoxemia, increased pressure in the pulmonary artery. The defeat of the striated muscles of the pharynx and the proximal segment of the esophagus disrupt the swallowing processes. Patients choke easily. Liquid food may be poured out through the nose. The defeat of the muscles of the larynx changes the voice, which becomes unrecognizably hoarse, with a nasal timbre tint. The oculomotor, chewing, and other muscles of the face are usually not affected. Pathological changes in the skin are characteristic of DM and are not necessary for PM. The following types of skin lesions are possible: ·