Connective tissue is a rather rare pathology. The clinical picture of this disease is characterized by a combination of signs of various collagenous diseases. This pathology is otherwise called Sharpe's syndrome. Most often, such a symptom complex is observed in puberty and in middle-aged patients. In advanced form, pathology can lead to severe and life-threatening consequences. In this article, we will take a closer look at the symptoms and treatment of mixed disease. connective tissue.
What it is
In the past, this pathology was very difficult to diagnose. After all, the signs of Sharpe's syndrome resemble the manifestations of various rheumatic ailments. Only relatively recently has this disease been described as a distinct autoimmune disorder.
With mixed connective tissue disease (MCTD), the patient has individual signs of various rheumatic pathologies:
- dermatomyositis;
- scleroderma;
- rheumatoid arthritis;
- polymyositis.
The patient does not necessarily have a complete clinical picture of all of the above diseases. Usually there are several symptoms characteristic of different autoimmune pathologies.
ICD code
According to ICD-10, mixed connective tissue disease is distinguished in separate group pathologies under the code M35 ("Other diseases of the connective tissue"). The full code for the NWST is M35.1. This group includes cross rheumatic syndromes. The word "cross" means that with this pathology there are signs of various diseases of the connective tissue (collagenosis).
Causes
The exact causes of Sharp's syndrome have not yet been clarified. Mixed connective tissue disease is an autoimmune disorder. This means that a person's immunity, for unknown reasons, begins to attack their own healthy cells.
What can provoke such a failure in the work of the body's defenses? Doctors suggest that long-term use of certain medications can affect the functioning of the immune system. Hormonal disorders and age-related changes play a large role in the occurrence of autoimmune reactions. endocrine system. For this reason, CTD is often observed in adolescents and in women during menopause.
A negative emotional background can also affect the functioning of the immune system. Psychosomatics of mixed connective tissue disease is associated with severe stress. This pathology is more often observed in people prone to depression, as well as in patients with neurosis and psychosis.
It is usually noted in people who have a hereditary predisposition to rheumatic diseases. The impact of adverse factors is only a trigger for the occurrence of autoimmune lesions.
Symptoms
Mixed connective tissue disease occurs in a chronic form and gradually progresses without treatment. This pathology is systemic, it affects not only the skin and joints, but the entire body.
Very often, the initial symptom of the disease is a violation of blood circulation in the fingers and toes. It resembles manifestations of Raynaud's syndrome. Due to vasospasm, a person turns pale and becomes cold fingers and toes. Then the skin on the hands and feet acquires a bluish tint. Cold extremities are accompanied by severe pain syndrome. Such vasospasms can occur several years before the development of other signs of the disease.
Most patients experience joint pain. The fingers are very swollen, movements become painful. Muscle weakness is noted. Due to pain and swelling, it becomes difficult for the patient to bend his fingers and hold various objects in his hands. This is similar to the initial manifestations of rheumatoid arthritis or However, very rarely, bone deformity occurs. In the future, other articular joints are also involved in the pathological process, most often the knees and elbows.
In the future, a person develops red and white spots on the skin, especially in the area of \u200b\u200bthe hands and face. Compacted areas of the muscles are palpated, as with the skin thickens, in rare cases, ulcers appear on the epidermis.
The patient's condition gradually worsens. Joint pain and skin rashes are accompanied by the following symptoms:
- general weakness;
- feeling of stiffness in the joints after a night's sleep;
- hypersensitivity to ultraviolet;
- drying of the oral mucosa and difficulty swallowing;
- hair loss;
- causeless weight loss with normal nutrition;
- rise in temperature;
- enlargement of the lymph nodes.
In advanced cases, the pathological process extends to the kidneys and lungs. Glomerulonephritis occurs, the protein content in the urine increases. Patients complain of chest pain and difficulty breathing.
Possible Complications
Mixed connective tissue disease is a rather dangerous pathology. If the pathological process affects the internal organs, then with poor-quality treatment, the following complications may occur:
- kidney failure;
- stroke;
- inflammation of the esophageal mucosa;
- perforation of the intestinal wall;
- myocardial infarction.
Such complications are noted in the unfavorable course of the disease and in the absence of proper therapy.
Diagnostics
A rheumatologist deals with the treatment of CTD. Symptoms of mixed connective tissue disease are extremely diverse and resemble the manifestations of many other pathologies. Because of this, it is often difficult to make a diagnosis.
Patients are prescribed a serological blood test for antibodies to nuclear ribonucleoprotein. If the indicators of this study exceed the permissible value and at the same time arthralgia and Raynaud's syndrome are noted in patients, then the diagnosis is considered confirmed.
Additionally, the following studies are prescribed:
- clinical and biochemical blood and urine tests;
- study of urine according to Nechiporenko;
- analysis for rheumatoid factor and specific immunoglobulins.
If necessary, an ultrasound of the kidneys is prescribed, as well as an x-ray of the lungs and an echocardiogram.
Treatment Methods
The treatment of mixed connective tissue disease is primarily aimed at suppressing the autoimmune reaction. Patients are prescribed the following medications:
- Corticosteroid hormones: Dexamethasone, Metipred, Prednisolone. These drugs reduce the autoimmune response and inflammation in the joints.
- Cytostatics: "Azathioprine", "Imuran", "Plaquenil". Takei drugs also suppress the immune system.
- Non-steroidal anti-inflammatory drugs: Diclofenac, Voltaren. They are prescribed for severe pain and swelling of the joints.
- Calcium antagonists: Verapamil, Diltiazem, Nifedipine. These drugs are prescribed to prevent damage to the cardiovascular system.
- Proton pump inhibitors: Omeprazole. Patients with Sharpe's syndrome have to take medication for a long time, and sometimes for life. This can adversely affect the digestive tract. The drug "Omeprazole" helps protect the gastric mucosa from the aggressive effects of drugs.
Such complex treatment prevents exacerbation of the disease and allows achieving stable remission.
It is important to remember that drugs for the treatment of CTD significantly reduce immunity. Therefore, patients need to protect themselves from contact with infectious patients and hypothermia.
Forecast
Does Sharp's syndrome affect life expectancy? The prognosis of this disease is considered conditionally favorable. Dangerous defeats internal organs in CTD develop less frequently than in other autoimmune pathologies. Lethal outcome is noted only when running forms diseases and the presence of complications from the heart and kidneys.
However, it should be remembered that this disease is chronic and cannot be completely cured. Often, patients are shown lifelong medication. If the patient adheres to the recommended treatment regimen, then the prognosis of the disease is favorable. Timely therapy helps to maintain a normal quality of life for the patient.
Prevention
Specific prophylaxis this disease has not been developed, since the exact causes of autoimmune pathologies have not been established. Rheumatologists advise to adhere to the following recommendations:
- Uncontrolled medication should be avoided. A long course of treatment with drugs can be carried out only under the supervision of a physician.
- With a hereditary predisposition to autoimmune pathologies, excessive exposure to sunlight should be avoided and regular preventive examinations by a rheumatologist should be carried out.
- It is important to avoid stress as much as possible. Emotionally labile people need to take sedatives and visit a psychotherapist.
- If you experience pain in the joints of the limbs and spasms of peripheral vessels, you should consult a doctor and undergo an examination.
These measures will help reduce the likelihood of autoimmune rheumatic pathologies.
DIFFUSE DISEASES OF THE CONNECTIVE TISSUE
Diffuse connective tissue diseases (DCTD) or collagenoses (a term that has historical meaning) - a group of diseases characterized by systemic immunoinflammatory lesions of the connective tissue and its derivatives. This is a group, but not a nosological concept, and therefore this term should not denote individual nosological forms.
DZST combine a fairly large number of diseases. The most common are SLE, SJS and DM. This group of diseases also includes ARF, traditionally described in the section on diseases of the cardiovascular system. At present, it has been proven that with DZT, profound disorders of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the formation of antibodies or sensitized lymphocytes directed against the antigens of one's own body.
The basis of autoimmune disorders is an immunoregulatory imbalance, expressed in the suppression of the suppressor and enhancement of the helper activity of T-lymphocytes, followed by the activation of B-lymphocytes and the hyperproduction of various specific autoantibodies.
There are a number of common features that unite the DZST:
The generality of pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixed in tissues, followed by the development of severe inflammatory response(especially in the microcirculatory bed, kidneys, joints, etc.);
The similarity of morphological changes (fibrinoid changes in the basic substance of the connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbations and remissions;
Exacerbation under the influence of non-specific influences ( infectious diseases, insolation, vaccination, etc.);
Multisystem lesions (skin, joints, serous membranes, kidneys, heart, lungs);
The therapeutic effect of immunosuppressive agents (glucocorticoids, cytostatic drugs).
All diseases included in this group differ in clinical and morphological features, therefore, in each case, one should strive for an accurate nosological diagnosis.
This chapter presents a diagnostic search for SLE, SJS and DM.
systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that occurs in individuals young age(mainly in women) and developing against the background of a genetically determined imperfection of immunoregulatory processes, which leads to uncontrolled production of antibodies to one's own cells and their components and the development of autoimmune and immunocomplex chronic lesions (V.A. Nasonova, 1989). The essence of the disease is immuno-inflammatory lesions of the connective tissue, microvasculature, skin, joints and internal organs, while the leading ones are visceral lesions that determine the course and prognosis of the disease.
The incidence of SLE ranges from 4 to 25 cases per 100,000 population. The disease most often develops in women of childbearing age. During pregnancy and in postpartum period significantly increases the risk of exacerbation. Women suffer from SLE 8-10 times more often than men. The peak incidence occurs at the age of 15-25 years. In children, the ratio of sick girls and boys is reduced and is 3:1. Mortality in SLE is 3 times higher than in the general population. In men, the disease is just as severe as in women.
SLE belongs to a genetically determined disease: studies conducted in the population have shown that predisposition to the occurrence of SLE is associated with certain class II histocompatibility (HLA) genes, genetically determined deficiency of certain complement components, as well as with gene polymorphisms of some receptors and tumor necrosis factor α (TNF-α).
Etiology
Specific etiological factor in SLE has not been established, but a number of clinical symptoms (cytopenic syndrome, erythema and enanthema) and certain patterns of disease development allow us to associate SLE with diseases of viral etiology. Currently, RNA viruses (slow or latent viruses) are of importance. Detection of family cases of the disease, frequent existence in families of other rheumatic or allergic diseases and various violations immunity allow us to think about the possible significance of family genetic predisposition.
The manifestation of SLE is facilitated by a number of non-specific factors - insolation, non-specific infection, administration of sera, intake of certain drugs (in particular, peripheral vasodilators from the hydralazine group), as well as stress. SLE can start after childbirth or an abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis
Due to the impact on immune system virus, and possibly antiviral antibodies, against the background of hereditary predisposition, a dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, uncontrolled production of antibodies to its various tissues, cells and proteins (including various cell organelles and DNA) occurs. It has been established that autoantibodies are produced in SLE to about forty out of more than two hundred potential antigenic cellular components. Subsequently, the formation of immune complexes and their deposition in various organs and tissues (mainly in the microvasculature) occur. Various defects in immunoregulation are characteristic, accompanied by hyperproduction of cytokines (IL-6, IL-4 and IL-10). Then, processes associated with the elimination of fixed immune complexes develop, which leads to the release of lysosomal enzymes, damage to organs and tissues, and the development of immune inflammation. In the process of inflammation and destruction of the connective tissue, new antigens are released, causing the formation of antibodies and the formation of new immune complexes. Thus, there is vicious circle providing a chronic course of the disease.
Classification
At present, a working classification of clinical variants of the course of SLE has been adopted in our country, taking into account:
The nature of the flow;
The activity of the pathological process;
Clinical and morphological characteristics of damage to organs and systems. The nature of the course of the disease
The acute course is characterized by the rapid development of multiorgan changes (including damage to the kidneys and central nervous system) and high immunological activity.
Subacute course: in the debut of the disease, the main symptoms occur, nonspecific damage to the skin and joints. The disease proceeds in waves, with periodic exacerbations and the development of multiple organ disorders within 2-3 years from the onset of the first symptoms.
The chronic course is characterized by a long-term predominance of one or more signs: recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhof's syndrome or Sjögren's syndrome. Multiple organ lesions occur by the 5-10th year of the disease.
Phase and degree of activity of the process:
Active (high activity - III, moderate - II, minimal - I);
Inactive (remission).
Clinical and morphological characteristics of lesions:
Skin (symptom of "butterfly", capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis - pleurisy, pericarditis and splenitis);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute and chronic pneumonitis, pneumosclerosis);
Kidneys (lupus nephritis nephrotic or mixed type, urinary syndrome);
Nervous system (meningoencephalopyradiculoneuritis, polyneuritis).
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, represented by a clinical and laboratory symptom complex, including venous and (or) arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ lesions. A characteristic immunological sign is the formation of antibodies that react with phospholipids and phospholipid-binding proteins (more on the antiphospholipid syndrome will be discussed later).
There are also three degrees of activity of the pathological process, which characterizes the severity of potentially reversible immune-inflammatory damage and determines the characteristics of the treatment of each individual patient. Activity should be distinguished from the severity of the disease, which refers to the totality of irreversible changes that are potentially dangerous for the patient.
Clinical picture
The clinical picture of the disease is extremely diverse, which is associated with the multiplicity of lesions of organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
They receive information on the basis of which it is possible to draw up an idea:
About the onset of the disease;
The nature of the course of the disease;
The degree of involvement in the pathological process of certain organs and systems;
Previous treatment, its effectiveness and possible complications.
Variants of the onset of the disease can be very diverse. Most often it is represented by a combination of various syndromes. Monosymptomatic onset is usually not typical. In this regard, the assumption of SLE disease arises from the moment such a combination is discovered in a patient. In this case, the diagnostic value of certain syndromes increases.
AT early period SLE is considered the most common syndromes of damage to the joints, skin and serous membranes, as well as fever. Thus, the combinations that are most suspicious in relation to SLE will be:
Fever, polyarthritis and trophic skin disorders (in particular, hair loss - alopecia);
Polyarthritis, fever and lesions of the pleura (pleurisy);
Fever, trophic skin disorders and pleural lesions.
The diagnostic significance of these combinations increases significantly if the skin lesion is represented by erythema, but in the initial period of the disease it is recorded only in 25% of cases. Nevertheless, this circumstance does not reduce the diagnostic value of the above combinations.
The oligosymptomatic onset of the disease is not typical, but the onset of SLE was noted with the onset of massive edema due to the development from the very beginning of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type.
Involvement in the pathological process various bodies manifests with symptoms inflammatory lesion(arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.).
Information about previous treatment allows you to judge:
About its optimality;
About the severity of the course of the disease and the degree of activity of the process (initial doses of glucocorticoids, duration of their use, maintenance doses, inclusion in medical complex cytostatics with severe immune disorders, high activity of lupus nephritis, etc.);
On the complications of glucocorticoid and cytostatic treatment.
At the first stage, certain conclusions can be drawn regarding the diagnosis with a long course of the disease, but in its debut, the diagnosis is established at further stages of the study.
On you can get a lot of data indicating damage to organs and the degree of their functional insufficiency.
The defeat of the musculoskeletal system manifests as polyarthritis, resembling RA with a symmetrical lesion of the small joints of the hand (proximal interphalangeal, metacarpophalangeal, radiocarpal) and large joints(less often). With a detailed clinical picture of the disease, the defiguration of the joints due to periarticular edema is determined. During the course of the disease, deformities of small joints develop. Articular changes may be accompanied by muscle damage in the form of diffuse myalgias, and very rarely, true PM with edema and muscle weakness. Sometimes the lesion is represented only by arthralgia.
Damage to the skin is noted as often as the joints. The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose ("butterfly"). Inflammatory rashes on the nose and cheeks, repeating the outlines of the "butterfly", are represented by various options:
Vascular (vasculitic) "butterfly" - unstable, pulsating, diffuse reddening of the skin with a cyanotic tinge in middle zone face,
intensified under the influence external factors(insolation, wind, cold) or unrest;
. "butterfly" type of centrifugal erythema (skin changes are localized only in the region of the nose).
In addition to the “butterfly”, discoid rashes can be detected - erythematous ascending plaques with keratic disturbance and subsequent development of atrophy of the skin of the face, limbs and trunk. Finally, in some patients, nonspecific exudative erythema is noted on the skin of the extremities and chest, as well as signs of photodermatosis on open parts of the body.
Skin lesions include capillaritis - a small-dotted hemorrhagic rash on the fingertips, nail beds and palms. Skin lesions may be associated with enanthema on the hard palate. Painless ulcerations can be found on the mucous membrane of the mouth or nasopharyngeal region.
The defeat of the serous membranes occurs in 90% of patients (the classic diagnostic triad - dermatitis, arthritis, polyserositis). Especially often, lesions of the pleura and pericardium are found, less often - the peritoneum. Symptoms of pleurisy and pericarditis are described in the previous sections, so only their features in SLE will be listed below:
More often there is dry pleurisy and pericarditis;
With effusion forms, the amount of exudate is small;
The lesion of the serous membranes is short-lived, and is usually diagnosed retrospectively when pleuropericardial adhesions or thickening of the costal, interlobar, and mediastinal pleura are detected. x-ray examination;
A pronounced tendency to the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities) is noted.
SLE is characterized by damage to the cardiovascular system that occurs at various stages of the course of the disease.
Most often, pericarditis is found that is prone to recurrence. Significantly more often than previously thought, endocardial damage is noted in the form of warty endocarditis (lupus endocarditis) on the leaflets of the mitral, aortic, or tricuspid valves. With a long course of the process, at the second stage of the search, signs of insufficiency of the corresponding valve can be detected (as a rule, there are no signs of stenosis of the hole).
Focal myocarditis is almost never recorded, but diffuse lesions, especially in severe cases, are accompanied by certain symptoms (see "Myocarditis").
Vascular damage can manifest Raynaud's syndrome, which is characterized by paroxysmal developing disorders of the arterial blood supply to the hands and (or) feet that occur 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. Predominantly there is a lesion of the II-V fingers of the hands and feet, less often - other distal parts of the body (nose, ears, chin, etc.).
Lung lesions can be due to the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) is acute or lasts for months and manifests with signs of the syndrome of inflammatory infiltration of the lung tissue, similar to those in pneumonia. The peculiarity of the process is the occurrence of an unproductive cough in combination with shortness of breath. Another variant of lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), expressed in the development of slowly progressive dyspnea and lung changes during x-ray examination. There are practically no characteristic physical data, so it is almost impossible to judge such a lesion of the lungs at the second stage of the diagnostic search.
The defeat of the gastrointestinal tract, as a rule, is represented by subjective signs detected at the first stage. Physical examination sometimes reveals vague pain in the epigastric region and at the site of the projection of the pancreas, as well as signs of stomatitis. In some cases, hepatitis develops: an increase and soreness of the liver are noted.
Most often, with SLE, kidney damage occurs (lupus glomerulonephritis or lupus nephritis), the evolution of which depends on the further fate of the patient. Kidney damage in SLE can occur in the form of various options, so the data of the direct examination of the patient can vary widely. With isolated changes in the urinary sediment, no disturbances are found during physical examination. With glomerulonephritis occurring with nephrotic syndrome, massive edema and often AH are determined. When forming chronic nephritis with constant hypertension, an increase in the left ventricle and an accent of the II tone in the second intercostal space to the right of the sternum are found.
Autoimmune thrombocytopenia (Werlhof's syndrome) manifests itself with typical rashes in the form of hemorrhagic spots of various sizes on the skin inner surface limbs, the skin of the chest and abdomen, as well as on the mucous membranes. After minor injuries (for example, after tooth extraction), bleeding occurs. Nosebleeds sometimes become profuse and lead to anemia. Skin hemorrhages can have a different color: blue-greenish, brown or yellow. Often, SLE manifests for a long time only with Werlhof's syndrome without other typical clinical symptoms.
Damage to the nervous system is expressed to varying degrees, since almost all its departments are involved in the pathological process. Patients complain of migraine headaches. Sometimes seizures occur. Possible violations of cerebral circulation up to the development of a stroke. When examining a patient, signs of polyneuritis are found with a violation of sensitivity, pain along the nerve trunks, a decrease in tendon reflexes and paresthesias. Organic brain syndrome characterized by emotional lability, episodes of depression, memory impairment and dementia.
The defeat of the reticuloendothelial system is represented by an early symptom of the generalization of the process - polyadenopathy (enlargement of all groups of lymph nodes, not reaching a significant degree), as well as, as a rule, a moderate enlargement of the spleen and liver.
Damage to the organ of vision manifests dry keratoconjunctivitis, which is due to pathological changes in the lacrimal glands and a violation of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.
With antiphospholipid syndrome, venous (in the deep veins of the lower extremities with repeated pulmonary embolism) and arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks) thromboses can be detected. Valvular heart disease, intracardiac thrombi mimicking myxoma of the heart, and thrombosis of the coronary arteries with the development of MI are recorded. Skin lesions in antiphospholipid syndrome are diverse, but the most common of them is livedo reticularis. (livedo reticularis).
Thus, after the second stage of the examination, multiple organ lesions are detected, and their degree is very different: from barely clinically noticeable (subclinical) to pronounced, prevailing over the rest, which creates the prerequisites for diagnostic errors- interpretation of these changes as signs of independent diseases (for example, glomerulonephritis, myocarditis, arthritis).
The third stage of diagnostic search with SLE is very important, because:
Helps to make a definitive diagnosis;
Demonstrates the severity of immune disorders and the degree of damage to internal organs;
Allows you to determine the degree of activity of the pathological (lupus) process.
At the third stage highest value acquires a laboratory blood test. There are two groups of indicators.
Indicators that have a direct diagnostic value (indicate severe immunological disorders):
LE cells (lupus erythematosus cells) are mature neutrophils that phagocytize the nuclear proteins of other blood cells degraded by ANF.
ANF is a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in 95% of patients it is found in a titer of 1:32 and above). The absence of ANF in the vast majority of cases is evidence against the diagnosis of SLE.
ANA - antibodies to native (i.e. to the whole molecule) DNA. An increase in their concentration correlates with the activity of the disease and the development of lupus nephritis. They are found in 50-90% of patients.
Antibodies to the Sm-nuclear antigen (anti-Sm) are highly specific for SLE. Antibodies to Ro/La ribonucleoprotein are considered specific for SLE (they are detected by immunofluorescence in 30% of cases, by hemagglutination in 20% of patients).
The “rosette” phenomenon is the altered nuclei (hematoxylin bodies) freely lying in the tissues, surrounded by leukocytes.
Diagnosis of antiphospholipid syndrome in SLE is based on the determination of lupus anticoagulants - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (determination of increased thromboplastin time) and antibodies to cardiolipin using enzyme immunoassay. The term "lupus anticoagulant" is not correct, since the main clinical sign of the presence of the above antibodies is thrombosis, not bleeding. These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis and autoimmune hemolytic anemia occur.
Nonspecific acute phase indicators, which include:
Dysproteinemia with a high content of α 2 - and γ-globulins;
CRP detection;
Increasing the concentration of fibrinogen;
ESR increase.
With severe articular lesions in a small titer, RF can be detected - an antibody to the Fc fragment of IgG.
In the study of peripheral blood, leukopenia (1-1.2x10 9 / l) can be detected with a shift in the leukocyte formula to young forms and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Possible moderate hypochromic anemia, in some cases - hemolytic anemia, accompanied by jaundice, reticulocytosis and a positive Coombs test. Sometimes thrombocytopenia is recorded in combination with Werlhof's syndrome.
Kidney damage is characterized by changes in the urine, which can be classified as follows (I.E. Tareeva, 1983):
Subclinical proteinuria (protein content in the urine 0.5 g / day, often in combination with a small leukocyturia and erythrocyturia);
More pronounced proteinuria, serving as an expression of the nephrotic syndrome that accompanies subacute or active lupus nephritis.
Very high proteinuria (as, for example, with amyloidosis) rarely develops. Note moderate hematuria. Leukocyturia can be a consequence of both a lupus inflammatory process in the kidneys, and the result of the frequent addition of a secondary infectious lesion of the urinary tract.
Puncture biopsy of the kidneys reveals nonspecific mesangiomembranous changes, often with a fibroplastic component. Considered characteristic:
Detection in preparations of altered nuclei freely lying in the renal tissue (hematoxylin bodies);
Capillary glomerular membranes in the form of wire loops;
Deposition on the basement membrane of the glomeruli of fibrin and immune complexes in the form of electron-dense deposits.
According to the WHO classification, the following morphological types of lupus nephritis are distinguished:
Class I - no change.
Class II - mesangial type;
Class III - focal proliferative type;
Class IV - diffuse proliferative type;
Class V - membranous type;
Class VI - chronic glomerulosclerosis.
X-ray examination reveals:
Changes in the joints (with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints, with chronic arthritis and deformities - narrowing of the joint space with subluxations);
Changes in the lungs during the development of pneumonitis (with a long course of the disease - discoid atelectasis, strengthening and deformation of the pulmonary pattern in combination with a high standing diaphragm);
Changes in the heart with the development of lupus disease or exudative pericarditis.
ECG allows you to detect non-specific changes in the final part of the ventricular complex (wave T and segment ST), similar to those previously described for myocarditis and pericarditis.
CT and MRI of the brain reveal pathological changes with CNS damage.
When conducting a diagnostic search, it is also necessary to determine the degree of activity of the lupus process (Table 7-1).
Table 7-1. Criteria for the activity of the pathological process in systemic lupus erythematosus (Nasonova V.A., 1989)
Ending the table. 7-1
Diagnostics
In cases of the classical course of SLE, the diagnosis is simple and based on the detection of a "butterfly", recurrent polyarthritis and polyserositis, which make up the clinical diagnostic triad, supplemented by the presence of LE cells or ANF in diagnostic titers. Of secondary importance is the young age of patients, the relationship with childbirth, abortion, the onset of menstrual function, insolation and infectious diseases. It is much more difficult to establish a diagnosis in other cases, especially if the above classic diagnostic features are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 (Table 7-2) help.
Table 7-2.Diagnostic criteria systemic lupus erythematosus (ARA)
The end of the table. 7-2
The diagnosis is certain when four or more criteria are met. If less than four criteria are present, then the diagnosis of SLE is doubtful, and dynamic monitoring of the patient is required. This approach has a clear justification: it warns against prescribing glucocorticoids to such patients, since other diseases (including paraneoplastic syndrome) can occur with the same symptoms, in which their use is contraindicated.
Differential Diagnosis
SLE should be differentiated from a number of diseases. How large is the list of organs and systems involved in the pathological process in SLE, just as extensive is the list of diseases that can be misdiagnosed in a patient. SLE can mimic various pathological conditions to a greater extent. This especially often happens at the onset of the disease, as well as with a dominant lesion of one or two organs (systems). For example, the detection of pleural lesions at the beginning of the disease can be regarded as pleurisy of tuberculous etiology; myocarditis can be interpreted as rheumatic or nonspecific. Especially many mistakes are made if SLE debuts with glomerulonephritis. In such cases, only glomerulonephritis is diagnosed.
SLE most often has to be differentiated from ARF (rheumatism), IE, chronic active hepatitis (CAH), hemorrhagic diathesis (thrombocytopenic purpura), and other diseases from the CTD group.
The need for differential diagnosis with rheumatism occurs, as a rule, in adolescents and young men in the debut of the disease - when arthritis and fever occur. Rheumatic arthritis differs from lupus in greater severity of symptoms, predominant damage to large joints and transience. It should not be given differential diagnostic value to a previous infectious lesion (tonsillitis), since it can serve as a nonspecific factor causing the development clinical signs SLE. The diagnosis of rheumatism becomes reliable from the moment of occurrence of signs of heart damage (rheumatic heart disease). Subsequent dynamic observation allows to detect the emerging heart disease, while in SLE, if mitral valve insufficiency is formed, it is expressed slightly and is not accompanied by distinct
hemodynamic disturbances. Mitral regurgitation is mild. Unlike SLE, leukocytosis is noted in the acute stage of rheumatism. ANF is not detected.
Differential diagnosis between SLE and RA is difficult in the initial stage of the disease, which is associated with the similarity of the clinical picture: a symmetrical lesion of the small joints of the hand occurs, new joints are involved in the process, and morning stiffness is typical. Differential diagnosis is based on the predominance of the proliferative component in RA in the affected joints, the early development of hypotrophy of the muscles that move the affected joints, and the stability of the articular lesions. Erosions of the articular surfaces in SLE are absent, but are a characteristic sign of RA. A high RF titer is characteristic of RA. With SLE, it is rarely found and in a low titer. The differential diagnosis of SLE and the visceral form of RA is extremely difficult. A refined diagnosis in both cases does not affect the nature of the treatment (prescription of glucocorticoids).
With CAH, systemic disorders can occur in the form of fever, arthritis, pleurisy, skin rashes, and glomerulonephritis. Leukopenia, thrombocytopenia, LE cells, and ANF can be detected. When conducting a differential diagnosis, the following should be considered:
CAH often develops in middle age;
In the anamnesis, patients with CAH have indications of past viral hepatitis;
With CAH, pronounced changes in the structure and function of the liver are detected (cytolytic and cholestatic syndrome, signs of liver failure, hypersplenism, portal hypertension);
With SLE, liver damage does not always occur and proceeds in the form of mild hepatitis (with moderate signs of a cytolytic syndrome);
With CAH, various markers of viral liver damage (antiviral antibodies and viral antigen) are detected.
In primary IE, heart damage (inadequacy of the aortic or mitral valve) quickly occurs, and antibiotic therapy has a clear effect. LE cells, anti-DNA antibodies, and ANF are usually absent. With timely bacteriological examination, the growth of pathogenic microflora is detected.
Thrombocytopenic purpura (either idiopathic or symptomatic) lacks many of the syndromes seen in SLE, typical laboratory findings (LE cells, ANF, anti-DNA antibodies), and fever.
The most difficult differential diagnosis with other diseases from the CTD group. Conditions such as SJS and DM may share many features with SLE. This circumstance exacerbates the possibility of detecting ANF and LE cells in these diseases, albeit in a lower titer. The main differential diagnostic signs are more frequent and pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin lesions in SJS, and a clear myopathic syndrome in DM. In some cases, a correct diagnosis can only be made for a long time.
dynamic observation of the patient. Sometimes it takes many months and even years (especially in chronic SLE with a minimal degree of activity).
The formulation of a detailed clinical diagnosis of SLE should take into account all the headings given in the working classification of the disease. The diagnosis should reflect:
The nature of the course of the disease (acute, subacute, chronic), and in the case of a chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated;
Process activity;
Clinical and morphological characteristics of damage to organs and systems indicating the stage of functional insufficiency (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the presence or absence of heart failure, with lung damage - the existence or absence respiratory failure and etc.);
Indication of ongoing treatment (eg, glucocorticoids);
Complications of treatment (if any).
Treatment
Given the pathogenesis of the disease, complex pathogenetic treatment is recommended for SLE patients. His tasks:
Suppression of immune inflammation and immunocomplex disorders (uncontrolled immune response);
Prevention of complications of immunosuppressive therapy;
Treatment of complications arising in the course of immunosuppressive therapy;
Impact on individual, pronounced syndromes;
Removal of CEC and antibodies from the body.
First of all, it is necessary to exclude psycho-emotional stresses, insolation, actively treat concomitant infectious diseases, eat low-fat foods high in polyunsaturated fatty acids, calcium and vitamin D. Active contraception is necessary during an exacerbation of the disease and against the background of treatment with cytostatic drugs. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.
To suppress immune inflammation and immunocomplex disorders in the treatment of SLE, the main immunosuppressors are used: glucocorticoids short action, cytotoxic drugs and aminoquinoline derivatives. The duration of treatment, the choice of drug, as well as maintenance doses are determined by:
The degree of disease activity;
The nature of the flow (sharpness);
Extensive involvement of internal organs in the pathological process;
Tolerability of glucocorticoids or cytostatics, as well as the existence or absence of complications of immunosuppressive therapy;
The existence of contraindications.
In the initial stages of the disease, with minimal activity of the process and the prevalence of joint damage in the clinical picture, glucocorticoids should be prescribed in small doses (prednisolone at a dose of less than 10 mg / day). Patients should be registered at the dispensary so that when the first signs of an exacerbation of the disease occur, the doctor can timely prescribe treatment with glucocorticoids in the optimal dose.
In the chronic course of the disease with a predominant skin lesion for many months, chloroquine (at a dose of 0.25 g / day) or hydroxychloroquine can be used.
If there are signs of high activity and generalization of the process with the involvement of internal organs, it is necessary to immediately switch to a more effective immunosuppressive treatment with glucocorticoids: prednisolone is prescribed at a dose of 1 mg / day or more. The duration of high doses ranges from 4 to 12 weeks. Dose reduction should be carried out gradually, under careful clinical and laboratory control. Maintenance doses (5-10 mg/day) should be taken by patients for many years.
Thus, the main treatment for SLE is the use of glucocorticoids. When using them, the following principles should be observed:
Start treatment only when the diagnosis of SLE is confirmed (if suspected, these drugs should not be used);
The dose of glucocorticoids should be sufficient to suppress the activity of the pathological process;
Treatment with an overwhelming dose should be carried out until a pronounced clinical effect is achieved (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes);
After achieving the effect, you should gradually switch to maintenance doses;
Mandatory prevention of complications of treatment with glucocorticoids. To prevent the side effects of glucocorticoids, use:
Potassium preparations (orotic acid, potassium chloride, potassium and magnesium aspartate);
Anabolic agents (methandienone at a dose of 5-10 mg);
Diuretics (saluretics);
Antihypertensive drugs ( ACE inhibitors);
Antacids.
With the development of severe complications appoint:
Antibiotics (for secondary infection);
Anti-tuberculosis drugs (with the development of tuberculosis, more often - pulmonary localization);
Insulin preparations, diet food (for diabetes mellitus);
Antifungal agents (for candidiasis);
Antiulcer treatment (with the formation of a steroid ulcer).
During treatment with glucocorticoids, there are situations when it is necessary to administer extra-high doses of prednisolone (intravenous drip at a dose of 1000 mg over 30 minutes for three days):
A sharp increase (splash) in the activity of the process (III degree), despite the seemingly optimal treatment;
Resistance to doses that have previously achieved positive effect;
Severe organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).
Such pulse therapy stops the formation of immune complexes due to inhibition of the synthesis of antibodies to DNA. A decrease in the concentration of the latter, caused by glucocorticoids, leads to the formation of smaller immune complexes (as a result of dissociation of larger ones).
A significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of glucocorticoids. Pulse therapy is most effective in young patients with a short duration of the disease.
Treatment with glucocorticoids is not always successful, due to:
The need to reduce the dose with the development of complications, despite the fact that such therapy is effective in a particular patient;
Intolerance to glucocorticoids;
Resistance to treatment with glucocorticoids (usually detected early enough).
In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (monthly intravenous bolus administration at a dose of 0.5-1 g / m 2 for at least 6 months, and then every 3 months for 2 years) in combination with prednisolone at a dose of 10-30 mg / day. In the future, you can return to treatment with glucocorticoids, since resistance to them usually disappears.
For the treatment of less severe, but resistant to glucocorticoid symptoms of the disease, azathioprine (1-4 mg / kg per day) or methotrexate (15 mg / week) and cyclosporine (at a dose of less than 5 mg / kg per day) are prescribed in combination with low doses of prednisolone (10-30 mg / day).
Criteria for evaluating the effectiveness of the use of cytostatics:
Reduction or disappearance of clinical signs;
The disappearance of steroid resistance;
Persistent decrease in process activity;
Prevention of the progression of lupus nephritis. Complications of cytostatic therapy:
Leukopenia;
Anemia and thrombocytopenia;
Dyspeptic phenomena;
infectious complications.
With a decrease in the number of leukocytes less than 3.0x10 9 /l, the dose of the drug should be reduced to 1 mg / kg of body weight. With a further increase in leukopenia, the drug is canceled and the dose of prednisolone is increased by 50%.
Extracorporeal methods of treatment - plasmapheresis and hemosorption are widely used. They allow you to remove the CEC from the body, increase the sensitivity of cell receptors to glucocorticoids and reduce intoxication. They are used for generalized vasculitis, severe organ damage (lupus nephritis, pneumonitis, cerebrovasculitis), as well as for severe immune disorders that are difficult to treat with glucocorticoids.
Usually, extracorporeal methods are used in combination with pulse therapy or, if it is ineffective, on its own. It should be noted that extracorporeal methods are not used in cytopenic syndrome.
Patients with a high titer of antiphospholipid antibodies in the blood, but without clinical signs of antiphospholipid syndrome, are prescribed small doses. acetylsalicylic acid(75 mg / day). With confirmed antiphospholipid syndrome, accompanied by clinical signs, sodium heparin and small doses of acetylsalicylic acid are used.
For the treatment of musculoskeletal disorders (arthritis, arthralgia, myalgia) and moderate serositis, the usual doses of NSAIDs can be used.
Forecast
AT last years due to the use of effective methods of treatment, the prognosis has improved: 10 years after the diagnosis, the survival rate is 80%, and after 20 years - 60%. In 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or cerebrovasculitis, the prognosis remains unfavorable.
Prevention
Since the etiology of SLE is unknown, primary prevention is not carried out. Nevertheless, a risk group is distinguished, which includes, first of all, relatives of patients, as well as persons suffering from an isolated skin lesion (discoid lupus). They should avoid insolation, hypothermia, should not be vaccinated, receive mud therapy and other balneological procedures.
systemic scleroderma
SJS is a systemic disease of the connective tissue and small vessels, characterized by inflammation and widespread fibro-sclerotic changes in the skin and internal organs. This definition of the disease reflects the essence of SJS - a fibrous transformation of the connective tissue that serves as the frame of the internal organs, an integral element of the skin and blood vessels. The uncontrolled development of fibrosis is associated with excessive collagen formation due to impaired functioning of fibroblasts.
The prevalence of SSc varies by geographic area and ethnic groups including those living in the same region. The primary incidence ranges from 3.7 to 19.0 cases per 1 million population per year. SJS is more often registered among women (ratio 5:7.1) aged 30-60 years.
Etiology
The cause of the development of the disease is unknown. They attach importance to viruses, since there is indirect evidence of their role in the occurrence of SJS: virus-like inclusions and an increased titer of antiviral antibodies were found in the affected tissues. A family genetic predisposition to SJS has been established, since changes in protein metabolism in the form of hypergammaglobulinemia, Raynaud's syndrome, and sometimes SJS are found in relatives of patients.
Unfavorable factors contributing to the manifestation of the disease and its exacerbations include environmental factors (prolonged contact with polyvinyl chloride, silicon dust), the use of drugs (bleomycin, tryptophan), as well as cooling, trauma, impaired neuroendocrine functions and exposure to occupational hazards in the form vibrations.
Pathogenesis
The basis of pathogenesis is a violation of the process of interaction various cells(endothelial, smooth muscle cells of the vascular wall, fibroblasts, T- and B-lymphocytes, monocytes, mast cells, eosinophils) with each other and the components of the connective tissue matrix. The result of all of the above is the selection of a population of fibroblasts that are resistant to apoptosis and function in an autonomous mode of maximum synthetic activity, which activates neofibrillogenesis and contributes to a change in glycoproteins of the main substance of the connective tissue. As a result, fibro-sclerotic changes in the connective tissue develop. At the same time, there is a dysregulation of the body's immune response to the introduction of the virus, which is expressed in the overproduction of antibodies to its own tissues (autoantibodies). Then immune complexes are formed that settle in the microvasculature and internal organs, which leads to the development of immune inflammation. The severity of immune and autoimmune disorders in SJS is not as great as in SLE.
Fibrosclerotic changes in the connective tissue, damage to blood vessels and internal organs as a result of immune inflammation cause a variety of clinical signs of the disease (Fig. 7-1).
Classification
In our country, a working classification of SJS has been adopted, taking into account the nature of the course, the stage of development of the disease, and the clinical and morphological characteristics of damage to organs and systems.
The nature of the flow:
Rapidly progressing;
Chronic.
Stage:
Initial;
Generalized;
Terminal.
Rice. 7-1. The pathogenesis of systemic scleroderma
Clinical and morphological characteristics of the lesion:
Skin and peripheral vessels - dense edema, induration, hyperpigmentation, telangiectasia, Raynaud's syndrome;
Musculoskeletal system - arthralgia, polyarthritis, pseudoarthritis, PM, calcification, osteolysis;
Hearts - myocardial dystrophy, cardiosclerosis, heart disease (most often - valve insufficiency);
Lungs - interstitial pneumonia, sclerosis, adhesive pleurisy;
Digestive system - esophagitis, duodenitis, sprue-like syndrome;
Kidney - true scleroderma kidney, chronic diffuse glomerulonephritis, focal glomerulonephritis;
Nervous system - polyneuritis, neuropsychiatric disorders, vegetative shifts.
The severity of skin compaction is assessed by palpation according to a 4-point system:
0 - no seal;
1 - slight compaction;
2 - moderate compaction;
3 - pronounced compaction (impossibility to fold).
In recent years, prescleroderma, diffuse cutaneous scleroderma, limited (limited) scleroderma, including the syndrome CREST(this syndrome will be discussed below), and scleroderma without scleroderma (this variant is very rare and accounts for no more than 5% of all patients with SJS).
The chronic course, which is most characteristic of SJS, is characterized by gradually developing vasomotor disorders of the type of Raynaud's syndrome and the trophic disorders caused by them, which is the only sign of the disease for many years. In the future, thickening of the skin and periarticular tissues joins with the development of osteolysis and slowly progressive sclerotic changes in internal organs (esophagus, heart, lungs).
The rapidly progressive course is characterized by the occurrence of severe fibrous peripheral and visceral lesions already in the first year of the disease and frequent kidney damage according to the type of true scleroderma kidney (most common cause death of patients).
Given the progressive nature of the disease, three stages of the course are distinguished to assess the evolution and degree of growth of the pathological process:
Stage I - initial manifestations - mainly articular changes in subacute, and vasospastic - in chronic course;
Stage II - generalization of the process - polysyndromic and polysystemic lesions of many organs and systems;
Stage III - terminal - the predominance of severe sclerotic, dystrophic or vascular-necrotic processes (often with distinct dysfunctions of one or more organs).
Clinical picture
The clinical picture of the disease is polymorphic and polysyndromic, reflecting its generalized nature. There is practically no organ or system that could not be involved in the pathological process.
On the first stage of diagnostic search receive information on the basis of which it is possible to form an idea about the diagnosis and the onset of the disease, the nature of the course of the process, the involvement of various organs in the pathological process, previous treatment and its effectiveness, as well as complications.
More often, the disease begins with a skin lesion, and then organ damage gradually joins (typical form). In other cases (atypical form), the clinical picture from the very beginning is dominated by damage to internal organs with minimal skin changes, which makes diagnosis difficult. As the disease progresses, one can get an idea of the nature of its course (acute, subacute and chronic).
Complaints of patients with involvement in the pathological process of internal organs correspond to subjective symptoms in one or another of their lesions (pleurisy, arthritis, Raynaud's syndrome, duodenitis, etc.). At the same time, patients may present complaints that are most characteristic of SJS: difficulty in swallowing and choking when swallowing as a result of damage to the upper
parts of the esophagus. Vasospastic disorders in Raynaud's syndrome are not limited to the fingers, but extend to the hands and feet. Often, patients experience a feeling of numbness in the lips, any part of the face and the tip of the tongue. They complain of dryness of the mucous membrane of the mouth and conjunctiva, as well as the inability to cry (no tears). The defeat of the skin of the face is expressed in a feeling of tightness of the skin and mouth (it is difficult to open the mouth). As a rule, body temperature is not increased. Weight loss (sometimes significant) is usually noted with the progression and generalization of the disease.
After the first stage (with a long course of the disease), a definite conclusion about the diagnosis can be made. It can be extremely difficult to do this at the very beginning, since the symptoms of SJS in many ways resemble other conditions from the CTD group (SLE, RA, DM), and with mono- or oligosyndrome, other diseases characterized by damage to only one organ (heart, lungs, etc.) .
Ha second stage of diagnostic search receive data indicating damage to organs and systems and their functional insufficiency. With a detailed clinical picture of the disease, skin lesions are noted in the vast majority of patients. It is expressed in the sequential development of edema, induration, and then atrophy with predominant localization on the face and hands. Trophic changes in the skin are also possible in the form of depigmentation, accentuated vascular pattern and telangiectasias. The defeat of the mucous membranes is expressed in increased dryness. Ulceration and pustular rash may occur on the skin; hair falls out, nails are deformed. In the final stage of the disease, the skin of the face becomes dense, it is impossible to take it into a fold. The face is mimic, mask-like. The shape of the mouth is characteristic: the lips are thin, collected in non-expanding folds, the ability to open the mouth wide is gradually lost (symptom "pouch bag").
Vasospastic changes in Raynaud's syndrome in the form of whitening of the skin surface are found in the face, lips, hands and feet.
Joint damage is expressed in their defiguration due to the predominant damage to periarticular tissues, as well as true scleroderma polyarthritis with a predominance of exudative-proliferative or fibrous-indurative changes. The development of a scleroderma hand is characteristic: shortening of the fingers due to osteolysis of the nail phalanges, thinning of their tips, deformation of the nails and slight flexion contractures. Such a brush is compared with a bird's paw (sclerodactyly).
Muscle damage, morphologically representing fibrous interstitial myositis or myositis with dystrophic and necrotic changes, is expressed in myasthenic syndrome, atrophy, reduction muscle mass and movement disorders. Perhaps the formation of painful seals (calcifications) in the muscles. Especially often deposits of calcium salts are found in the soft tissues of the fingers.
The defeat of the gastrointestinal tract (esophagitis, duodenitis, malabsorption syndrome or persistent constipation) is mainly detected at the first and third stages of the diagnostic search.
The defeat of the respiratory system is expressed in the form of pneumonitis, occurring acutely or chronically, sluggishly. Physical data are extremely scarce, in severe cases only emphysema is detected. Significantly more information is provided by X-ray examination, which provides significant assistance in the detection of bilateral basal pneumosclerosis, characteristic of SJS.
With severe pneumosclerosis and its long-term existence develops pulmonary hypertension, leading first to right ventricular hypertrophy, and then to its insufficiency. Pulmonary hypertension manifests itself with cyanosis, an accent of the II tone in the second intercostal space to the left of the sternum, shortness of breath, a sharp decrease in exercise tolerance and a pronounced increase in pulsation in the epigastric region due to right ventricular hypertrophy.
Heart disease occupies a major place among the visceral symptoms of SJS, both in terms of frequency and impact on the outcome of the disease. SJS is characterized by the so-called primary cardiosclerosis, not associated with previous necrotic or inflammatory changes in the myocardium. An increase in the heart is noted (sometimes significant), as well as cardiac arrhythmias in the form of extrasystole or MA. The defeat of the endocardium leads to the development of heart disease, almost always - to mitral insufficiency. The combination of the latter with cardiosclerosis in some cases can lead to the development of heart failure with all its characteristic features. Pericarditis in SJS is rare and more often it proceeds as dry.
The defeat of small vessels - scleroderma angiopathy - manifests vasomotor disorders (Raynaud's syndrome) and is characterized by paroxysmal vasospasm with a characteristic sequence of changes in the color of the skin of the fingers (whitening, cyanosis, redness), a feeling of tension and soreness. In severe cases, Raynaud's syndrome leads to hemorrhages, necrosis of the tissues of the fingers and telangiectasias.
Kidney damage in SJS (in 80% of patients) is due to pathological changes in blood vessels, but not the development of fibrosis. Most severe symptom- scleroderma renal crisis, usually developing in the first five years of the disease in patients with a diffuse form of SJS and manifesting malignant hypertension (BP over 170/130 mm Hg), rapidly progressive renal failure, hyperreninemia (in 90% of cases) and nonspecific signs . The latter are represented by shortness of breath, headache and convulsions. With kidney damage in the form of isolated changes in the urinary sediment during a physical examination, no significant pathological signs are detected.
The damage to the nervous system is based on vascular, dystrophic and fibrotic changes, represented by symptoms of polyneuritis with impaired reflexes and sensitivity.
Thus, after the second stage, a multiple organ lesion is detected with a predominant lesion of the skin and its derivatives. The degree of changes is very different - from subclinical to significantly pronounced. The possibility of establishing the diagnosis of SJS with a predominant skin lesion
higher than with the predominance of visceral disorders. In the latter case, if the defeat of any one organ (kidney, heart) comes to the fore, there are prerequisites for making diagnostic errors.
You can:
Determine the degree of activity of the process;
Specify the severity of damage to internal organs;
Conduct a differential diagnosis with other diseases from the group of chronic CTD.
In determining the degree of disease activity, nonspecific acute phase indicators are of the greatest importance, which include:
Dysproteinemia with an increase in the concentration of a 2 - and γ-globulins;
Increasing the content of CRP;
Increasing the concentration of fibrinogen;
ESR increase.
The existence and severity of immune disorders can be judged by the definition of RF (found in 40-50% of cases), antinuclear antibodies (in 95%) and LE cells (in 2-7% of patients). In contrast to SLE, all these indicators in SKD are found in a much lower titer and less frequently.
The greatest diagnostic value is attached to the so-called scleroderma antibodies.
Scl-70 antibodies are more often found in diffuse forms of SJS (40%). Their presence in combination with carriage of HLA-DR3/DRw52 is an unfavorable prognostic factor in patients with Raynaud's syndrome, increasing the risk of developing pulmonary fibrosis in SJS by 17 times.
Antibodies to the centromere (an element of the chromosome) are found in 20-30% of patients (most of them have signs of CREST syndrome).
Antibodies to RNA polymerase I and III are highly specific for SJS. They are present predominantly in patients with a diffuse form and are associated with kidney damage and a poor prognosis.
With kidney damage, proteinuria expressed to varying degrees is noted in combination with minimal changes in urinary sediment (microhematuria, cylindruria). With a true scleroderma kidney (development of necrosis of the renal tissue due to damage to the renal vessels), acute renal failure may develop with an increase in the content of creatinine in the blood.
With SJS, dissociation is noted between the pronounced morphological changes in the renal tissue and blood vessels detected by puncture biopsy and relatively mild clinical (including laboratory) signs of kidney damage. If hypertension develops due to kidney damage, then changes in the fundus of the eye (narrowing of the arteries and dilation of the veins) are noted.
When the heart is damaged, the ECG determines nonspecific changes in the final part of the ventricular complex (decrease in amplitude and inversion of the wave T), and sometimes - violations of intraventricular conduction. Radiologically visualize an increase in the heart. X-ray helps
detect calcification of the muscles and soft tissues of the fingers, as well as differentiate joint changes in SJS with disorders in RA (there are no erosions of the articular surfaces in SJS). In 60-70% of cases, a lesion of the gastrointestinal tract (especially the esophagus and intestines) is noted on the radiograph. Changes in the esophagus are represented by its diffuse expansion in combination with narrowing in the lower third, weakening of peristalsis and some rigidity of the walls.
Biopsy of the skin, synovium, and muscles reveals fibrotic changes characteristic of SJS, as well as vascular damage. Morphological examination data are not decisive in establishing the diagnosis.
Diagnostics
Diagnosis of the disease is based on the detection of major and minor diagnostic criteria.
The big criteria include proximal scleroderma - symmetrical thickening, thickening and induration of the skin of the fingers and skin located proximal to the metacarpophalangeal and metatarsophalangeal joints. Changes may affect the face, neck, and torso (chest and abdomen).
Small Criteria:
Sclerodactyly - the above skin changes, limited to the involvement of the fingers in the pathological process;
Scarring of the fingertips or loss of pad material;
Bilateral basal pulmonary fibrosis.
A patient with SJS must meet either the major criterion (major) or at least two minor criteria. Sensitivity - 97%, specificity - 98%.
Most typical for SJS is a combination of calcification, Raynaud's syndrome, esophagitis, sclerodactyly and telangiectasias (syndrome CREST- by the first letters of the English names of the listed symptoms).
Diagnosis of SJS in the early stages is based on the detection of a triad of initial signs (arising the earliest): Raynaud's syndrome, articular syndrome (more often - polyarthralgia) and dense swelling of the skin. Significantly less often, one of the visceral localizations of the process is detected at an early stage.
Significant difficulties in the diagnosis of SJS are associated with the absence of a characteristic skin syndrome in patients with severe polysyndromic lesions of internal organs (the so-called SJS without scleroderma). In these cases, an X-ray examination is of great help, which allows detecting esophageal motility and its expansion, as well as dilatation of the duodenum and colon.
Differential Diagnosis
SJS should be differentiated from a number of diseases and, first of all, from other CTDs, as well as from diseases, the clinical picture of which is very similar to that of an organ lesion in SJS (provided it is additionally
mining). For example, with scleroderma heart disease, differential diagnosis is carried out with atherosclerotic cardiosclerosis, rheumatic heart disease and nonspecific myocarditis; with pulmonary lesions - with chronic pneumonia, tuberculosis and occupational lung diseases (pneumoconiosis); if the esophagus is affected, its cancer should be excluded.
The basis for differential diagnosis is the detection of signs typical of SJS.
The predominance of peculiar skin lesions in combination with Raynaud's syndrome and slightly pronounced laboratory data in SJS, in contrast to skin changes in SLE, combined with a higher activity of the pathological process (according to laboratory studies).
In contrast to SLE, in SJS, damage to internal organs is not combined with severe immune disorders (ANF, RF, and anti-DNA antibodies are found in a lower titer, the frequency of detection and the number of LE cells are also small).
The articular syndrome in SJS, in contrast to RA, is combined with muscle contractures, calcium deposition in soft tissues and muscles, fibrous ankylosis, and osteolysis of the terminal phalanges. Destructive changes in bone tissue in SJS are absent, damage to periarticular tissues predominates.
Unlike coronary artery disease, heart failure in SJS is not accompanied by anginal pain. There are no signs of a prior MI on the ECG. Unlike rheumatic lesion hearts, with SJS, stenosis never develops (mitral, aortic orifices); usually there is moderately expressed isolated mitral insufficiency.
The dominant lesion of any system or organ in SJS is always combined with skin and muscle changes and Raynaud's syndrome. For the clinical picture of other diseases (chronic pneumonia, atherosclerotic cardiosclerosis, intestinal diseases, peptic ulcer), from which it is necessary to differentiate SJS, monosyndromicity is characteristic.
In SJS, skin changes and Raynaud's syndrome dominate, while in DM, muscle damage in combination with a kind of purple paraorbital edema (“spectacle symptom”) comes to the fore.
Glucocorticoids in SJS do not give such a striking positive effect as in SLE.
In a number of cases, when SJS manifests itself as an articular, skin and asthenovegetative syndrome, only a long-term dynamic observation allows a correct diagnosis to be made.
The formulation of a detailed clinical diagnosis should take into account the headings given in the working classification. The diagnosis should reflect:
The nature of the flow;
stage;
Clinical and morphological characteristics of damage to organs and systems of the body, indicating the stage of functional insufficiency (for example,
measures, with pneumosclerosis - the stage of pulmonary insufficiency, with kidney damage - the stage of renal failure, etc.).
Treatment
Treatment of SJS should be comprehensive and take into account the following aspects:
Impact on vascular complications and, first of all, on Raynaud's syndrome;
Impact on the development of fibrotic changes;
Immunosuppression and anti-inflammatory action;
Impact on local symptoms of the disease.
Avoid exposure to cold, smoking, local vibration, stressful situations and taking drugs that cause peripheral vascular spasm (beta-blockers without vasodilating action).
Drug treatment of Raynaud's syndrome involves the appointment of slow calcium channel blockers - amlodipine (5-20 mg / day), long-acting nifedipine (30-90 mg / day), felodipine (5-10 mg / day), as well as prolonged verapamil action (240-480 mg/day) or diltiazem (120-360 mg/day).
A good effect is the ingestion of pentoxifylline (400 mg 3 times a day). Antiplatelet agents are also prescribed - dipyridamole (300-400 mg / day) or ticlopidine (500 mg / day).
In critical situations (pulmonary hypertension, gangrene, renal crisis) for 6-24 hours for 2-5 days, synthetic prostaglandins are administered intravenously: alprostadil (0.1-0.4 mcg / kg per minute) or iloprost (0 .5-2 ng/kg per minute).
The drug that destroys the internal bonds in the collagen molecule and inhibits excessive collagen formation is penicillamine. It is prescribed for subacute course, rapidly increasing indurative skin changes and symptoms of progressive generalized fibrosis on an empty stomach every other day at a dose of 250-500 mg / day. Previously recommended high doses (750-1000 mg / day) do not increase the effectiveness of treatment, but the incidence of side effects increases significantly. When treating with penicillamine, it is necessary to monitor laboratory parameters of urine, since proteinuria may develop at 6-12 months from the start of treatment. With its increase to 0.2 g / day, the drug is canceled. For severe skin lesions, enzyme therapy is recommended. Assign subcutaneous injection of hyaluronidase near the affected areas or electrophoresis with this drug.
Anti-inflammatory and cytotoxic drugs are used in the early (inflammatory) stage of SJS and in the rapidly progressive course of the disease.
Glucocorticoids in small doses (15-20 mg / day) are used for progressive diffuse skin lesions and obvious clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory
arthritis and tendosynovitis). Taking large doses is not recommended (risk of developing scleroderma renal crisis).
When administered at a dose of 2 mg / kg per day for 12 months, cyclophosphamide reduces pruritus only in patients with diffuse SSc.
Methotrexate is prescribed when SJS is combined with RA or PM.
In scleroderma renal crisis, to eliminate vascular spasms and prevent the development of scleroderma kidney, ACE inhibitors (captopril 100-150 mg / day, enalapril 10-40 mg / day) are used under the control of blood pressure.
In case of damage to the esophagus, in order to prevent dysphagia, frequent fractional meals and the exclusion of food intake later than 18 hours are recommended. Treatment of dysphagia involves the appointment of prokinetics (metoclopramide at a dose of 10 mg 3-4 times a day). With reflux esophagitis, omeprazole is prescribed (by mouth, 20 mg / day).
The impact on local symptoms of the disease involves the application of a 25-50% solution of dimethyl sulfoxide. During periods of inactivity of the pathological process, exercise therapy and massage can be recommended.
Forecast
With SJS, the prognosis is determined by the variant of the course and the stage of development. It is noted that the more time separates the advanced stage from the onset of the first signs of the disease (in particular, Raynaud's syndrome), the more favorable the prognosis. Five-year survival ranges from 34 to 73%, averaging 68%. The risk of death in SJS is 4.7 times higher than in the general population.
Poor prognosis predictors:
Diffuse form of the disease;
The age of onset of the disease is over 47 years;
Male;
Fibrosis of the lungs, pulmonary hypertension, arrhythmias, kidney damage in the first three years of the disease;
Anemia, high ESR, proteinuria at the onset of the disease.
Prevention
The risk group includes persons with a tendency to vasospastic reactions, polyarthralgia, as well as relatives of patients suffering from various diffuse connective tissue diseases. They should not be exposed to provoking factors (cooling, vibration, injury, chemical substances, infectious agents, etc.). Patients with SJS are placed on dispensary records. Systematically conducted treatment (in particular, properly selected supportive therapy) - the best remedy exacerbation prevention.
DERMATOMYOSITIS (POLYMYOSITIS)
DM is a systemic inflammatory disease of the skeletal, smooth muscles and skin. Less often, involvement of internal organs in the pathological process is noted. In the absence of skin lesions, the term "polymyositis" PM is used.
The main symptom of the disease is severe muscle weakness due to progressive severe necrotizing myositis with a predominant lesion of the muscles of the proximal extremities. As the disease progresses, muscle tissue atrophies and is replaced by fibrous tissue. Similar processes occur in the myocardium. In parenchymal organs, dystrophic changes develop. Vessels of muscles, internal organs and skin are also involved in the pathological process.
DM (PM) is a rare disease. The frequency of its occurrence in the population ranges from 2 to 10 cases per 1 million population per year. The disease affects people of mature age (40-60 years), more often men than women (ratio 2:1).
Etiology
There are two forms of DM (PM) - idiopathic and secondary (tumor). The etiology of idiopathic DM is unclear, but there are known factors that contribute to the manifestation, and further exacerbation of this disease:
Insolation;
hypothermia;
Infectious lesions (ARI, influenza, tonsillitis, etc.);
Hormonal changes (menopause, pregnancy, childbirth);
emotional stress;
Physical trauma, surgery;
Drug sensitization (chlorpromazine, insulin preparations, antibiotics, penicillamine);
Vaccination;
Contact with epoxy resins, photosolvents;
Physiotherapy procedures.
Probably, hereditary-genetic predisposition matters: in patients, antigens B-8 / DR3, B14 and B40 of the HLA system are found. This is closely related not to the disease itself, but to certain immune disorders and, first of all, to the overproduction of myosin-specific autoantibodies.
Tumor (secondary) DM accounts for 25% of all cases of the disease and develops in patients suffering from malignant tumors. Most often, DM occurs with cancer of the lung, intestines, prostate, ovary, and also with hemoblastoses. The occurrence of DM in persons over the age of 60 almost always indicates its tumor origin.
Pathogenesis
Under the influence of a virus and a genetic predisposition or tumor antigens, a violation (dysregulation) of the immune response occurs, expressing
occurring in the imbalance of the B- and T-systems of lymphocytes: antibodies to skeletal muscles are produced in the body and sensitization of T-lymphocytes to them develops. The "antigen-antibody" reaction and the cytotoxic effect of muscle-sensitized T-lymphocytes contribute to the formation and deposition of immune complexes in the muscles and microcirculatory bed of various organs. Their elimination leads to the release of lysosomal enzymes and the development of immune inflammation in muscles and internal organs. During inflammation, new antigens are released that contribute to the further formation of immune complexes, which leads to chronicity of the disease and involvement in the pathological process earlier. healthy muscles. The main links in the pathogenesis of DM are shown in fig. 7-2.
Rice. 7-2. Pathogenesis of dermatomyositis
Clinical picture
The clinical picture of the disease is systemic and polysyndromic.
Main Syndromes:
Muscular (myositis, muscle atrophy, calcification);
Skin (erythema, skin edema, dermatitis, pigmentation and depigmentation, telangiectasia, hyperkeratosis, urticaria);
Articular (arthralgia, damage to periarticular tissues, rarely - true arthritis);
Visceral (myocarditis, cardiosclerosis, pneumonitis, aspiration pneumonia, pneumofibrosis, gastrointestinal bleeding, myoglo-
bulinuric kidney with the development of acute renal failure, polyneuropathy). Allocate next periods course of the disease:
I period (initial) - lasts from several days to 1 month or more, manifests only muscle and (or) skin changes;
II period (manifest) - a detailed picture of the disease;
III period (terminal) - presented dystrophic changes internal organs and signs of their pronounced functional insufficiency (possible development of complications).
There are three forms of the course of the disease:
An acute form, when a generalized lesion of the skeletal muscles rapidly increases, leading to complete immobility of the patient. Progressive muscle damage pharyngeal ring and esophagus (dysphagia, dysarthria). Damage to internal organs (especially the heart) develops rapidly with a fatal outcome in 2-6 months from the onset of the disease;
Subacute form with a slower, gradual increase in symptoms. Severe muscle damage and visceritis occur after 1-2 years;
Chronic form with a long cyclic course. The processes of atrophy and sclerosis predominate. Possible local muscle damage.
On the first stage of diagnostic search receive information about the nature of the onset of the disease - acute (fever up to 38-39 ° C, skin erythema and muscle pain) or gradual (moderate weakness, mild myalgia and arthralgia, aggravated after exercise, insolation or other adverse effects).
The most characteristic complaints are caused by muscle damage: patients note weakness, cannot sit or stand on their own, it is extremely difficult for them to climb stairs, and muscle pain is not uncommon. Muscle weakness and soreness are localized symmetrically in the proximal limbs, back and neck.
With damage to the pharyngeal muscles, patients complain of choking when swallowing, liquid food is poured out through the nose. Nasal tone of voice and hoarseness are due to damage to the muscles of the larynx.
With skin lesions, patients note a persistent change in its color in places exposed to the sun (décolleté, face, hands), as well as on the outer surfaces of the thighs and legs. Characterized by the occurrence of lilac paraorbital edema (“spectacle symptom”). With the defeat of the mucous membranes, patients complain of dryness, burning in the eyes and the absence of tears ("dry" syndrome).
Involvement in the pathological process of various organs is expressed by symptoms characteristic of myocarditis, cardiosclerosis, pneumonitis, glomerulonephritis, polyneuritis, arthritis, etc.
Information about the ongoing treatment allows us to judge its correct selection, and indirectly - about the nature of the course: the use of aminoquinoline drugs indicates a chronic course, the use of prednisolone and cytostatics - more acute.
On the second stage of diagnostic search with a detailed clinical picture of the disease, first of all, a symmetrical muscle lesion is noted: dense, doughy to the touch, they are enlarged and painful on palpation. With the defeat of the mimic muscles, some maskiness of the face is noticeable. In the future, muscle atrophy occurs, especially pronounced from the side of the shoulder girdle. The respiratory muscles and diaphragm are also affected. On palpation of the muscles, local seals can be detected - calcifications, which are also located in the subcutaneous fatty tissue. Calcification often develops in young people with widespread muscle damage during the transition of an acute course to subacute or chronic. Often there is a decrease in body weight by 10-20 kg.
Skin lesions are not a mandatory sign of DM, but when it exists, edema, erythema are noted on open parts of the body (above the joints - supraarticular erythema, in the periungual zones in combination with micronecrosis in the form of dark dots - Gottron's syndrome), capillaries, petechial rashes and telangiectasias. Erythema is characterized by great persistence, bluish tint, accompanied by itching and flaking. A typical "glass symptom" is erythema around the eyes. Often, redness, peeling and cracking of the skin of the palms (“mechanic or craftsman’s hand”), brittle nails and increased hair loss are noted.
Quite often, a pronounced Raynaud's syndrome is recorded.
Signs of visceral lesions in DM, as well as in SJS, are not too bright, in contrast to SLE. It can be noted that there is a known dissociation between the severity of pathomorphological changes in organs and their clinical manifestation. Damage to the heart (myocarditis, cardiosclerosis) is represented by such non-specific signs as an increase in its size, deafness of tones, tachycardia and rhythm disturbance in the form of extrasystole. Pronounced changes in the myocardium can lead to symptoms of heart failure.
The defeat of the lungs in the form of pneumonitis is accompanied by extremely poor symptoms. Developing fibrosis is detected by signs of emphysema and respiratory failure. Aspiration pneumonia is characterized by all the typical symptoms.
For the defeat of the gastrointestinal tract is characterized by dysphagia: there is a regurgitation of solid and pouring liquid food through the nose. Pathological changes in the vessels of the stomach and intestines can lead to gastrointestinal bleeding. Sometimes a moderate enlargement of the liver is noted, less often - hepatolienal syndrome with an increase in lymph nodes.
Neurological disorders are represented by changes in sensitivity: peripheral or radicular hyperesthesia, hyperalgesia, paresthesia and areflexia.
On the third stage of diagnostic search significant assistance is provided by research methods that allow assessing the severity of the inflammatory process and the prevalence of muscle damage.
The severity of the process can be judged by non-specific acute-phase indicators (an increase in ESR, an increase in the content of fibrinogen and CRP,
hyper-a 2 -globulinemia) and signs of immune changes (low RF titer, an increase in the content of γ-globulins, antibodies to the nucleoprotein and soluble nuclear antigens, antibodies to Mi2, Jol, SRP, and in the case of idiopathic DM - an increase in the concentration of IgG).
In a chronic, sluggish course of the disease, changes in acute phase indicators may be absent (ESR is often normal).
The prevalence of muscle damage is characterized by a number of biochemical changes. The creatine / creatinine index increases, which is associated with the presence of creatine in the urine with a decrease in creatininuria. With significant muscle damage, myoglobinuria may occur. An increase in transaminase activity is not typical for skeletal muscle damage. In some patients with myopathic syndrome, this suggests hepatitis.
Immunological examination reveals myositis-specific antibodies. These include antibodies to aminoacyl synthetases of transfer RNA (antisynthetase antibodies) and, first of all, antibodies to histidyl-tRNA synthetase (Jo1). Jo1 antibodies are found in half of patients with DM (PM), while other antisynthetase antibodies are extremely rare (5%). The production of anti-synthetase antibodies is associated with the development of the so-called anti-synthetase syndrome, characterized by acute onset, fever, symmetrical arthritis, interstitial lung disease, Raynaud's syndrome, and mechanic's hands.
For DM of tumor origin in men, the detection of a prostate-specific antigen is characteristic, in women - CA-125 (ovarian tumor antigen). In addition, with a different localization of the tumor, other tumor-specific antigens can be detected.
Significant assistance in the diagnosis of muscle damage is provided by electromyography, which makes it possible to detect normal electrical activity of muscles in a state of their voluntary relaxation and low-amplitude - with voluntary contractions.
When biopsy of the skin and muscles, a picture of severe myositis is noted with loss of transverse striation of muscle fibers, fragmentation, granular and waxy degeneration, as well as foci of necrosis, lymphoid-plasmocellular infiltration and fibrosis phenomena. Muscle biopsy is performed to confirm the diagnosis of DM even in the presence of characteristic clinical, laboratory and instrumental signs of the disease. The most informative biopsy of the muscle involved in the pathological process, but without severe atrophy.
Other research methods (ECG, X-ray and endoscopic) are necessary for:
Assessment of the state of the affected internal organs;
Search for a tumor in case of suspected DM of tumor origin.
Diagnostics
For the diagnosis of DM (PM), the following diagnostic criteria should be used.
Skin lesion:
Heliotrope rash (purple-red rashes on the eyelids);
Gottron's sign (purple-red, scaly, atrophic erythema or patches on the extensor surface of the hands over the joints);
Erythema on the extensor surface of the limbs over the elbow and knee joints.
Proximal muscle weakness (upper and lower limbs and trunk).
Increased activity of CPK or aldolase in the blood.
Muscle pain on palpation or myalgia.
Myogenic changes in electromyography (short polyphasic potentials of motor units with spontaneous fibrillation potentials).
Detection of Jo1 antibodies (antibodies to histidyl-tRNA synthetase).
Non-destructive arthritis or arthralgia.
Signs of systemic inflammation (fever more than 37 ° C, an increase in the concentration of CRP or ESR more than 20 mm / h).
Morphological changes consistent with inflammatory myositis (inflammatory infiltrates in skeletal muscle with degeneration or necrosis of muscle fibers, active phagocytosis or signs of active regeneration).
If at least one type of skin lesion and at least four other signs are detected, the diagnosis of DM is reliable (sensitivity - 94.1%, specificity - 90.3%).
The presence of at least four features is consistent with the diagnosis of PM (sensitivity 98.9%, specificity 95.2%).
Differential Diagnosis
Despite the high sensitivity and specificity of the criteria, the diagnosis of DM (PM) presents great difficulties, especially in the onset of the disease.
DM (PM) should be differentiated from infectious and neurological diseases, SJS, SLE, and RA. The basis of differential diagnosis is the following changes:
The persistence of the articular syndrome in RA, the detection of erosions of the articular surfaces of the bones during X-ray examination, the absence of changes in the skin and muscles characteristic of DM.
In contrast to SLE, in DM, visceral disorders are not so pronounced and occur much less frequently. In the clinical picture of DM, muscle damage predominates, and laboratory parameters (especially immunological ones) are changed to a much lesser extent.
Unlike SJS, skin changes in DM have a completely different character: there are no typical changes in the hands, and a muscular syndrome (including severe muscle weakness) is considered the leading one. Nevertheless, the differential diagnosis of SJS and DM is the most difficult. In difficult cases, it is necessary to use electrophysiological and morphological research methods.
In the acute course of DM, it is necessary to exclude an infectious lesion (septic condition, erysipelas, etc.), which is possible with dynamic monitoring of the patient.
With the dominance of adynamia and impaired reflexes, it becomes necessary to conduct a differential diagnosis with neurological diseases, which is carried out with the joint observation of the patient by a therapist and a neuropathologist.
The formulation of a detailed clinical diagnosis of DM should reflect:
flow period;
flow shape;
Clinical and morphological characteristics of damage to systems and organs, indicating the leading syndromes and the existence or absence of functional insufficiency of organs (systems).
Treatment
The main task is to suppress the activity of immune reactions and the inflammatory process, as well as to normalize the function of individual, most affected organs and systems. early start treatment (within the first 3 months of symptom onset) is associated with a better prognosis than later.
Glucocorticoids have the best effect: in DM, it is most preferable to prescribe prednisolone (1-2 mg/kg per day). During the first weeks, the daily dose should be divided into three doses, and then taken all of it once in the morning, since the improvement in the patient's condition develops more slowly than with SLE or SJS (on average, after 1-3 months). In the absence of positive dynamics within 4 weeks, the dose of glucocorticoids should be increased. After achieving the effect (normalization of muscle strength and CPK activity), the dose of prednisolone is very slowly reduced to maintenance, every month - by 1/4 of the total. Dose reduction should be carried out under strict clinical and laboratory control.
Pulse therapy is rarely effective. It is prescribed for the rapid progression of dysphagia (risk of aspiration pneumonia) and the development of systemic lesions (myocarditis, alveolitis).
If treatment with prednisolone is not effective or cannot be prescribed due to intolerance and the development of complications, then cytotoxic drugs should be used.
Currently, early administration of methotrexate is recommended, which allows faster transfer of patients to maintenance doses of prednisolone. Methotrexate is administered orally, subcutaneously or intravenously at a dose of 7.5-25 mg/week. Intravenous administration the drug is recommended for lack of efficacy or poor tolerability when taken orally. It should be remembered that the lack of effect of prednisolone treatment indicates the possibility of the existence of a tumor ANF, therefore, before prescribing cytostatic drugs, an extended oncological search should be carried out to exclude a malignant tumor.
Patients with prednisolone-resistant forms of the disease are prescribed oral cyclosporine at a dose of 2.5-5.0 mg/kg per day.
Azathioprine is less effective than methotrexate. The maximum effect develops later (on average, after 6-9 months). Assign the drug inside at 100-200 mg / day.
Cyclophosphamide is the drug of choice for interstitial pulmonary fibrosis (2 mg/kg per day).
Aminoquinoline drugs (chloroquine, hydroxychloroquine) are used in the following situations:
In the chronic course of the disease without signs of process activity (to control skin lesions);
With a decrease in the dose of prednisolone or cytostatics to reduce the risk of a possible exacerbation.
Plasmapheresis should be considered in patients with severe, resistant to other therapies, DM (PM) in combination with glucocorticoids and methotrexate or cytotoxic drugs.
In recent years, TNF-α inhibitors have been increasingly used for treatment. A promising direction of treatment is associated with the use of rituximab. The maximum effect develops 12 weeks after the first injection, which is associated with a decrease in the content of CD20+ B-lymphocytes in the peripheral blood.
Forecast
Currently, in connection with the use of prednisolone and cytostatics in acute and subacute forms, the prognosis has improved significantly: a five-year survival rate is 90%. In the case of acquiring a chronic course of the disease, the patient's ability to work can be restored.
The prognosis for secondary (tumor) DM depends on the effectiveness of the surgical intervention: with a successful operation, all signs of the disease may disappear. Factors that worsen the prognosis of the disease: advanced age, late diagnosis, improper treatment at the onset of the disease, severe myositis (fever, dysphagia, damage to the lungs, heart and gastrointestinal tract), antisynthetase syndrome. With tumor DM, the five-year survival rate is only 50%.
Prevention
Exacerbation warnings ( secondary prevention) are achieved through supportive treatment, sanitation of foci of infection and an increase in the body's resistance. Relatives of the patient may carry out primary prevention (exclusion of overload, insolation, hypothermia).
Systemic connective tissue diseases are a group serious illnesses, which are united by one common mechanism of occurrence - autoimmune. The human body, which is very complex, is able to independently fight various infectious pathogens. But sometimes, by mistake, he begins to fight against his own cells and tissues, producing autoantibodies. The mechanism of occurrence of systemic diseases is such that these autoantibodies destroy connective tissue cells that are in the human body. Thus, these diseases are chronic and gradually progressive, and, unfortunately, today medicine is not able to completely rid the patient of this serious illness.
Classification of systemic diseases
The most common systemic connective tissue diseases are:
- rheumatoid arthritis ,
- systemic lupus erythematosus,
- systemic scleroderma,
- dermatomyositis,
- rheumatoid polymyalgia,
- Sjögren's disease, etc.
What do all systemic diseases have in common?
Systemic connective tissue diseases are quite diverse, and each disease has its own individual characteristics. But they all have common features, according to which the doctor begins to suspect that the patient has a disease from this group.
- Polyorganism of the lesion. Systemic diseases affect various organs, systems and tissues of the body: joints, skin, muscles, kidneys, heart and blood vessels, etc.
- Nonspecific complaints. Patients at the onset of the disease may consult a doctor with complaints of severe weakness, muscle and joint pain, prolonged fever, and widespread skin rash. That is, without a special examination for these complaints, it is difficult to suspect any one specific disease.
- Similar laboratory picture. The general and biochemical analysis of blood in patients with systemic connective tissue diseases does not differ in variety. AT general analysis blood levels are usually high ESR level and the number of leukocytes. In the biochemical analysis, there is an increase in the level of C reactive protein, fibrinogen, circulating immune complexes, a positive rheumatoid factor, etc.
- Similar medical tactics. Many diseases from the group of systemic diseases are treated with the same groups of drugs, such as glucocorticosteroids, cytostatics, etc.
How are systemic diseases treated?
The treatment of systemic connective tissue diseases is handled by a rheumatologist. At the onset of the disease, the patient is placed for examination in a hospital, where certain drugs are selected for him, which he will need to take constantly. Unfortunately, it is currently impossible to completely recover from a systemic disease. However, constant and regular monitoring by a doctor and careful intake of all medications will help the patient lead a normal life, which is no different from healthy people.
Mixed connective tissue disease is a rare disease characterized by the simultaneous presence of manifestations of systemic lupus erythematosus, systemic scleroderma, polymyositis or dermatomyositis and rheumatoid arthritis with very high titers of circulating antinuclear autoantibodies to ribonucleoproteins (RNP). The development of edema of the hands, Raynaud's phenomenon, polyarthralgia, inflammatory myopathy, hypotension of the esophagus and impaired lung function is characteristic. Diagnosis is based on the analysis of the clinical picture of the disease and the detection of antibodies to RNP in the absence of antibodies characteristic of other autoimmune diseases. Treatment is similar to that for systemic lupus erythematosus and involves the use of glucocorticoids for moderate to severe disease.
Mixed connective tissue disease (MCTD) occurs worldwide, in all races. The maximum incidence occurs in adolescence and the second decade of life.
Clinical manifestations of mixed connective tissue disease
Raynaud's phenomenon may precede other manifestations of the disease by several years. Often, the first manifestations of mixed connective tissue disease may resemble the onset of systemic lupus erythematosus, scleroderma, rheumatoid arthritis, polymyositis, or dermatomyositis. However, regardless of the nature of the initial manifestations of the disease, the disease is prone to progression and spread with a change in the nature of clinical manifestations.
The most common swelling of the hands, especially the fingers, as a result of which they resemble sausages. Skin changes resemble those of lupus or dermatomyositis. Skin lesions similar to those seen in dermatomyositis, as well as ischemic necrosis and fingertip ulceration, are less common.
Almost all patients complain of polyarthralgia, 75% have clear signs of arthritis. Usually, arthritis does not lead to anatomical changes, but erosions and deformities can occur, as in rheumatoid arthritis. Weakness of the proximal muscles is often observed, both with and without soreness.
Kidney damage occurs in approximately 10% of patients and is often unexpressed, but in some cases it can lead to complications and death. In mixed connective tissue disease, more often than in other connective tissue diseases, sensory trigeminal neuropathy develops.
Diagnosis of mixed connective tissue disease
Mixed connective tissue disease should be suspected in all patients with SLE, scleroderma, polymyositis, or RA who develop additional clinical features. First of all, it is necessary to conduct a study on the presence of antinuclear antibodies (ARA), antibodies to the extractable nuclear antigen and RNP. If the results obtained correspond to a possible CTD (for example, a very high titer of antibodies to RNA is detected), studies of the concentration of gamma globulins, complement, rheumatoid factor, antibodies to Jo-1 antigen (histidyl-t-RNA) should be performed to rule out other diseases. -synthetase), antibodies to the ribonuclease-resistant component of the extractable nuclear antigen (Sm) and the DNA double helix. The plan for further research depends on the symptoms of damage to organs and systems: myositis, damage to the kidneys and lungs require the implementation of appropriate diagnostic methods (in particular, MRI, electromyography, muscle biopsy).
Nearly all patients have high titers (often >1:1000) of antinuclear antibodies detected by fluorescence. Antibodies to extractable nuclear antigen are usually present in very high titer (>1:100,000). The presence of antibodies to RNP is characteristic, while antibodies to the Sm component of the extracted nuclear antigen are absent.
In sufficiently high titers, rheumatoid factor can be detected. ESR is often elevated.
Prognosis and treatment of mixed connective tissue disease
Ten-year survival corresponds to 80%, but the prognosis depends on the severity of symptoms. The main causes of death are pulmonary hypertension, renal failure, myocardial infarction, colon perforation, disseminated infections, and cerebral hemorrhage. In some patients, it is possible to maintain a long-term remission without any treatment.
The initial and maintenance treatment of mixed connective tissue disease is similar to that of systemic lupus erythematosus. Most patients with moderate to severe disease respond to glucocorticoid treatment, especially if started early enough. Mild disease is successfully controlled by salicylates, other NSAIDs, antimalarial drugs, in some cases - low doses of glucocorticoids. Severe damage to organs and systems requires the appointment of high doses of glucocorticoids (for example, prednisolone at a dose of 1 mg/kg 1 time per day, orally) or immunosuppressants. With the development of systemic sclerosis, appropriate treatment is carried out.
DIFFUSED CONNECTIVE TISSUE DISEASES (DCTD), or collagenoses (a term of historical significance), is a group of diseases characterized by systemic immuno-inflammatory lesions of the connective tissue and its derivatives. This concept is group, but not nosological, and therefore this term should not denote individual nosological forms. DZST combine a fairly large number of diseases. The most common are systemic lupus erythematosus (SLE), systemic scleroderma (SSD), dermatomyositis (DM); This group of diseases also includes rheumatic fever(traditionally described in the section on diseases of the cardiovascular system). At present, it has been proven that with DZT, 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 one's own body (self-antigens).
The basis of autoimmune pathology is an immunoregulatory imbalance, expressed in suppression of the suppressor and increase in the "helper" activity of T-lymphocytes, followed by activation of B-lymphocytes and hyperproduction of autoantibodies of very different specificity.
There are a number of common features that unite the DZST:
Common pathogenesis - violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixed in
Tissues with the subsequent development of a severe inflammatory reaction (especially in the microvasculature, kidneys, joints, etc.);
Similarity of morphological changes (fibrinoid change in the basic substance of the connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbations and remissions;
Exacerbation under the influence of non-specific effects (infection, insolation, vaccination, etc.);
Multisystem lesions (skin, joints, serous membranes, kidneys, heart, lungs);
The therapeutic effect of immunosuppressive agents (glucocorticosteroids, cytostatics).
All diseases included in this group are distinguished by independent clinical and morphological manifestations, therefore, in each 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 the background of a genetically determined imperfection of immunoregulatory processes, leading to uncontrolled production of antibodies to one's own cells and their components, with the development of autoimmune and immunocomplex chronic lesions [Nasonova V.A., 1989]. The essence of the disease is immuno-inflammatory lesions of the connective tissue and microvasculature, skin, joints and internal organs (with visceral lesions being the leading ones, determining the course and prognosis of the disease).
SLE, according to 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 occurrence and development of SLE. Although the disease in men develops much less frequently, it is as severe as in women.
SLE is a genetically determined disease: population studies have shown that predisposition to SLE is associated with certain histocompatibility class II (HLA) genes, genetically determined deficiency of individual complement components, as well as polymorphisms in the genes of some receptors and tumor necrosis factor a (TNF-α). a).
Etiology. A specific etiological factor in SLE has not been established, however, a number of clinical manifestations (cytopenic syndrome, erythema and enanthema) and certain patterns of the disease make it possible to bring SLE closer to diseases of viral etiology. Currently, importance is attached to viruses belonging to the RNA group (the so-called slow, or latent, viruses). Detection of family cases of the disease, frequent detection in families of other rheumatic or allergic diseases, various disorders of immunity allow
Hut think about the possible significance of family genetic predisposition.
The detection of SLE is facilitated by a number of non-specific factors - insolation, non-specific infection, administration of sera, intake of certain drugs (in particular, peripheral vasodilators from the hydralazine group), and stress. SLE can begin after childbirth, an abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis. Due to the impact on the immune system of the virus (and possibly antiviral antibodies), against the background of hereditary predisposition, a dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, uncontrolled production of antibodies to various tissues, cells, proteins of the body (including various cell organelles and DNA) occurs. It has been found that SLE produces autoantibodies to only about 40 of the 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 hyperproduction 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 the connective tissue, new antigens are released, in response to which antibodies are formed, new immune complexes are formed, and thus a vicious circle is created that ensures the chronicity of the disease.
Classification. At present, in our country [Nasonova V.A., 1972-1986], a working classification of clinical variants of the course of SLE has been adopted, taking into account: 1) the nature of the course; 2) activity of the pathological process; 3) clinical and morphological characteristics of damage to organs and systems.
The nature of the course of the disease:
Acute, subacute, chronic (recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhof's syndrome, Sjögren'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 lesions:
Skin (symptom of "butterfly", capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis: pleurisy, pericarditis, resplenitis);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute, chronic pneumonitis, pneumosclerosis);
Kidneys (lupus nephritis nephrotic or mixed type; urinary syndrome);
Nervous system (meningoencephalopyradiculoneuritis, polyneuritis).
Allocate acute, subacute and chronic course of the disease. Acute course: sudden onset - patients can indicate the day when fever, polyarthritis began, skin changes appeared. In the next 3-6 months, polysyndromicity, 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 many years of 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 non-specific skin lesions. The undulation of the flow is distinct. A detailed picture of the disease is formed after 2-3, less often - after 3-4 years.
Chronic course: the disease is manifested for a long time by relapses of various syndromes - polyarthritis, less often polyserositis, discoid lupus syndrome, Raynaud's syndrome. At 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 lesions). A characteristic immunological sign is antibodies that react with phospholipids and phospholipid-binding proteins (more on the 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 individual patient. Activity should be distinguished from the "severity" of the disease, which is understood as a set of irreversible changes that are potentially life-threatening for the patient.
clinical picture. The manifestations of the disease are extremely diverse, which is determined by the multiplicity of lesions of organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
At stage I of the diagnostic search, information is obtained, on the basis of which it is possible to form an idea: 1) about the variant of the onset of the disease; 2) about the nature of the course of the disease; 3) about the degree of involvement in the pathological process of certain organs and systems; 4) about the previous treatment and its effectiveness, as well as possible complications of treatment.
Variants of the onset of the disease can be varied. Most often, the disease begins with a combination of various syndromes; monosymptomatic onset is usually uncharacteristic. In this regard, the assumption about the possibility of SLE arises from the moment such a combination is revealed in a patient, 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, and fever. Thus, the most "suspicious" in relation to SLE will be a variety of combinations: 1) fever, polyarthritis, trophic changes in the skin (in particular, hair loss - alopecia); 2) polyarthritis, fever, damage to the pleura (pleurisy); 3) fever, trophic skin disorders,
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 reduce the diagnostic value of the listed combinations.
The oligosymptomatic onset of the disease is uncharacteristic, however, the onset of SLE was noted with the development of massive edema due to the development from the very beginning of the pathological process of diffuse glomerulonephritis (lupus nephritis) of a nephrotic or mixed type.
Involvement in the pathological process of various organs is manifested by symptoms of their inflammatory lesions: arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.
Information about previous treatment allows us to judge: 1) its adequacy; 2) about the severity of the course of the disease and the degree of activity of the process (initial doses of corticosteroids, the duration of their use, maintenance doses, the inclusion of cytostatics in the treatment complex for severe immune disorders, high activity of lupus nephritis, etc.); 3) about the presence of complications of corticosteroid and cytostatic therapy.
At stage I, certain conclusions can be drawn regarding the diagnosis in the case of a long-term course of the disease, however, at the onset of the disease, the diagnosis is established at subsequent stages of the study.
At stage II of the diagnostic search, a lot of data can be obtained indicating damage to organs and the degree of their functional insufficiency.
The defeat of the musculoskeletal system is manifested by polyarthritis resembling rheumatoid arthritis (RA), symmetrical lesions of the small joints of the hand (proximal interphalangeal, metacarpophalangeal, radiocarpal) and large joints (less often). With a detailed clinical picture of the disease, defiguration of the joints is determined due to periarticular edema. As the disease progresses, small joint deformities develop. Joint damage may be accompanied by diffuse myalgia, very rarely - true polymyositis with swelling and muscle weakness. Sometimes only arthralgia occurs.
The skin is affected as often as the joints. The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose ("butterfly"). Inflammatory rashes on the nose and cheeks repeating the outlines of a “butterfly” are observed in various variants: 1) vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse reddening of the skin with a cyanotic tinge in the middle zone of the face, aggravated by external factors (insolation, wind , cold) or excitement; 2) "butterfly" type of centrifugal erythema (skin changes are localized only in the region of the nose). In addition to the "butterfly", discoid rashes can be observed - erythematous raised plaques with keratic disturbance 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.
The lesions of the skin include capillaritis - a small-dotted hemorrhagic rash on the fingertips, nail beds, palms. Skin lesions may be associated with enanthema on the hard palate. Painless ulcerations may be found on the mucous membrane of the mouth or nasopharyngeal region.
Serous membranes are affected in 90% of patients (the classic diagnostic triad: dermatitis, arthritis, polyserositis). Especially often, lesions of the pleura, pericardium, less often - the peritoneum are detected. The symptomatology of pleurisy and pericarditis is described in the previous sections of the Guide, we will 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 of 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 adhesions and obliteration of serous cavities).
The defeat of the cardiovascular system is very characteristic of SLE and is observed at various stages of the disease.
The most common pericarditis occurs, with a tendency to relapse. Much more frequently than previously thought, the endocardium is affected in the form of verrucous endocarditis (lupus endocarditis) on the mitral and aortic or tricuspid valves. With a long course of the process at stage II, it is possible to identify signs of insufficiency of the corresponding valve (as a rule, there are no signs of stenosis of the orifice).
Focal myocarditis is almost never recognized, but diffuse myocarditis, which is severe, gives some symptoms (see "Myocarditis").
Vascular damage can manifest itself in the form of Raynaud's syndrome: paroxysmal developing disorders of the arterial blood supply to the hands and / or feet that occur under the influence of cold or unrest. During an attack, paresthesias are noted, the skin of the fingers becomes pale and / or cyanotic, the fingers are cold. The II-V fingers of the hands and feet are mainly affected, less often other distal parts of the body (nose, ears, chin, etc.).
Lung lesions can be due to the 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 the syndrome of inflammatory infiltration of the lung tissue (it should be noted the 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 shortness of breath and changes in the lungs during x-ray examination; there are practically no physical changes, so it is almost impossible to judge such a lesion of the lungs at the second stage of the diagnostic search.
The lesion of the digestive tract is manifested mainly by subjective signs detected at stage I. Physical examination can sometimes reveal vague pain in the epigastrium and in the area of the projection of the pancreas, as well as stomatitis. In some cases, hepatitis develops: during the examination, an increase in the liver, its soreness is noted.
Most often, SLE affects the kidneys (lupus glomerulonephritis or lupus nephritis), the evolution of which determines the further fate of the patient. Kidney damage in SLE can occur in the form of various options, so the data of direct examination
The patient's condition can vary widely. With an isolated pathology of the urinary sediment, no changes are found during the physical examination; with glomerulonephritis occurring 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 detected, the accent of the II tone is in the second intercostal space to the right of the sternum.
Autoimmune thrombocytopenia (Werlhof's syndrome) is manifested by 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 having a profuse character and leading to anemia. Skin hemorrhages acquire over time a different color (blue-greenish, brown, yellow). SLE can be manifested for a long time only by Werlhof's syndrome without other clinical symptoms typical of SLE.
Damage to the nervous system is expressed to varying degrees in many patients in all phases of the disease, since almost all parts of the nervous system are involved in the pathological process. Patients complain of headaches such as migraine, there may be convulsive seizures. Possible violations of cerebral circulation (up to the development of a stroke). Upon direct examination of the patient, signs of polyneuritis are found with impaired sensitivity, soreness of the nerve trunks, decreased tendon reflexes, and paresthesias. Organic brain syndrome is characterized by emotional lability, episodes of depression, memory impairment, dementia.
There is an increase in all groups of lymph nodes, spleen, liver (usually moderate) with a generalization of the process.
Damage to the organ of vision manifests itself in the form of dry keratoconjunctivitis, which is due to pathological changes in the lacrimal glands and a violation of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.
With antiphospholipid syndrome, in addition to the indicated clinical picture, thrombosis can be detected - venous (in the deep veins of the lower extremities 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 (mimicking myxoma of the heart), thrombosis of the coronary arteries with the development of myocardial infarction can be detected. Skin lesions in antiphospholipid syndrome are diverse, the most common of them is livedo reticularis.
Thus, after stage II of the study, a polyorganism of the lesion is revealed, and the degree of organ damage is very different: from barely noticeable clinical (even subclinical) to pronounced, significantly prevailing over the rest, which creates the prerequisites for diagnostic errors due to the interpretation of these changes as a manifestation of independent diseases (eg, glomerulonephritis, myocarditis, arthritis).
Stage III of the diagnostic search for SLE is of great importance, since: 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, the most important are laboratory research blood. There are two groups of indicators:
1) directly of diagnostic value (detecting pronounced immune disorders):
A) LE cells (lupus erythematosus cells) - mature neutrophils that phagocytize the nuclear proteins of other blood cells that have decomposed under the influence of an 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 high titer - 1:32 and above, detected in 95% of patients); the absence of ANF in the vast majority of cases does not confirm the diagnosis of SLE;
C) antibodies to native (i.e. to the whole molecule) DNA; an increase in their concentration correlates with the activity of the disease and the development of lupus nephritis;
D) antibodies to 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 “rosette” phenomenon - lying freely altered nuclei in tissues (hematoxylin bodies), surrounded by leukocytes;
E) the diagnosis of antiphospholipid syndrome in SLE is based on the determination of "lupus anticoagulants" - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (increased thromboplastin time) and antibodies to cardiolipin using enzyme immunoassay. The term "lupus anticoagulant" itself is incorrect, since the main clinical manifestation of the presence of these antibodies is thrombosis (rather than bleeding).
These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis, autoimmune hemolytic anemia are observed.
2) Non-specific acute phase indicators, which include:
A) dysproteinemia with an increase in the content of oc2- and γ-globulins in the blood serum;
B) the appearance of C-reactive protein;
C) an increase in the content of fibrinogen;
D) increase in ESR.
With severe 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 Waaler-Rose reaction or the latex test.
In the study of peripheral blood, leukopenia can be detected, often pronounced (1-1.2109 / l of blood), with a shift in the leukocyte blood formula 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.
Kidney damage is characterized by changes in the urine, which can be classified as follows [Tareeva I.E., 1983]:
1) subclinical proteinuria (protein content in the urine 0.5 g / day, often in combination with a small 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. There is moderate hematuria. Leukocyturia can be the result of both a lupus inflammatory process in the kidneys and the frequent addition of a secondary infection. urinary tract. 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 in preparations of altered nuclei freely lying in the renal tissue (hematoxylin bodies); 2) 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
Sediments.
X-ray examination reveals: 1) changes in the joints in articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints; only in the chronic course of arthritis and deformities is there a narrowing of the joint space with subluxations; 2) changes in the lungs during the development of pneumonitis; with a long course of the disease - disc-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 lesions.
When conducting a diagnostic search, it is necessary to determine the degree of activity of the lupus process (Table 21).
Diagnostics. In cases of classical SLE, the diagnosis is simple and based on the detection of a butterfly, recurrent polyarthritis, and polyserositis, which constitute the clinical diagnostic triad, supplemented by the presence of LE cells or antinuclear factor in diagnostic titers. Of secondary importance are the young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation, and infection. It is much more difficult to establish a diagnosis in other cases, especially if the classic diagnostic features listed above are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 help (Table 22).
The diagnosis is certain if four or more criteria are present. 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 number of diseases. How large is the list of organs and systems involved in the pathological process in SLE, just as extensive is the list of diseases that can be erroneously diagnosed in
Table 22. Diagnostic criteria for SLE
rrSfinJb0lshe" degree can imitate various diseases ™ ppi ™ ™ especially often found in the onset of the disease, but ok ™e * „YAIRTM n ° Damage to 1-2 organs (systems). For example, ir nSS? ™ * b ° L "ZNI p ° Lesions of the pleura can be regarded
Or HSULZI^^I etiolop™; myocarditis - as a rheumatic butiouet
Fekgthio^not^6 FREQUENTLY HAVE TO DIFFERENTIATE from rheumatism, in- shg^ski^piya^ TITakChr°NiChr° NICh ^-active hepatitis (CAH), hemorrhagic-g^uppy will give (thrombocytopenic purpura), other diseases from
The need for differentiation with rheumatism occurs, 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. It should not be given the differential diagnostic value of a previous infection - angina, since it can be a non-specific factor that causes clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic heart disease) appear; subsequent dynamic observation allows to identify the emerging heart disease, while in SLE, if mitral valve insufficiency occurs, it is expressed slightly, without distinct hemodynamic disturbances, mitral regurgitation is not pronounced. In contrast to 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 similarity of clinical symptoms: symmetrical lesions of the small joints of the hand, involvement in pro-
Cessus of other joints, "morning stiffness." Differentiation is based on the predominance of the proliferative component in the affected joints in RA, the early development of hypotrophy of the muscles that move the affected joints, and the resistance of joint lesions. Erosions of the articular surfaces are absent in SLE, but are a characteristic feature of RA. Rheumatoid factor (RF) in a high titer is characteristic of RA; in SLE it is found rarely and in a low titer. Exceptionally difficult differential diagnosis SLE and visceral form of RA. An easing circumstance is that the specified diagnosis in both cases does not affect the nature of the treatment (corticosteroid therapy).
In chronic active hepatitis (CAH), systemic manifestations may develop in the form of fever, arthritis, pleurisy, skin rashes, glomerulonephritis; leukopenia, thrombocytopenia, LE-cells, ANF are found. When differentiating, one should take into account: 1) CAH develops more often in middle age; 2) in the anamnesis of CAH patients there is acute viral hepatitis; 3) with CAH, pronounced changes in the structure and function of the liver are detected - cytolytic and cholestatic syndromes, signs of liver failure, hypersplenism, and then portal hypertension; 4) with SLE, liver damage is not too frequent and occurs in the form of mild hepatitis (with moderate signs of cytolytic syndrome); 5) with CAH, various markers of viral liver damage (antiviral antibodies and the viral antigen itself) are detected.
In infective endocarditis (primary), heart damage (insufficiency of the aortic or mitral valve) is quickly detected, a clear effect of antibiotic therapy, LE cells, antibodies to DNA, and ANF, as a rule, are not detected. Timely blood cultures 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).
The most difficult differentiation with other nosological forms from the DZST group. Diseases such as systemic scleroderma and dermatomyositis may share many features with SLE; The complexity of diagnostics is exacerbated 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, and a clear myopathic syndrome in DM. However, in some cases, only long-term follow-up of the patient makes it possible to make the correct diagnosis. Sometimes it takes many months and even years, especially in chronic SLE with a minimal degree of 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) process activity; 3) clinical and morphological characteristics of damage to organs and systems indicating the stage of functional failure (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the presence or absence of heart failure, with lung damage - the presence or absence of respiratory failure, etc.); 4) point-
Knowledge of ongoing therapy (eg, corticosteroids); 5) complications of therapy (if any).
Treatment. Given the pathogenesis of the disease, patients with SLE are shown complex pathogenetic therapy, the objectives of which 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 psycho-emotional stress, insolation, actively treat concomitant infections, consume food with low content fat and a high content of polyunsaturated fatty acids, calcium and vitamin D. Active contraception is necessary during an exacerbation of the disease and against the background of treatment with cytostatic drugs. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.
To suppress immune inflammation and immunocomplex pathology in the treatment of SLE, the main immunosuppressive agents are used: corticosteroids, cytostatic drugs, aminoquinoline derivatives. Duration of treatment, magnitude, choice of drug, as well as maintenance doses are determined by: 1) the degree of disease activity; 2) the nature of the flow (acuteness); 3) extensive involvement of internal organs in the pathological process; 4) tolerance to 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 process activity and a predominance of joint damage in the clinical picture, NSAIDs can be prescribed, however, even with minimal activity of the pathological process, corticosteroids are the means of choice. Patients should be registered at the dispensary so that at the first signs of an exacerbation of the disease, the doctor can prescribe corticosteroid therapy in a timely manner.
In the chronic course of the disease with a predominant skin lesion, 0.25 g / day of hingamin (delagil, rezoquin) or hydroxychloroquine (plaquenil) can be used for many months. If signs of a 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 a more effective immunosuppressive therapy with corticosteroids.
Thus, the main treatment for SLE is corticosteroid therapy; it should adhere to the following principles:
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 a "suppressive" dose should be carried out until a pronounced clinical effect occurs (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes), usually this takes approximately 2 months;
4) after achieving the effect, one should gradually switch to maintenance doses;
5) prevention of complications of corticosteroid therapy is mandatory.
GCS therapy is indicated for II and III degrees of activity of the pathological process, which always happens in subacute and acute SLE. Patients with 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 careful clinical and laboratory control, and maintenance doses of drugs (10-15 mg) should be taken for many years.
To prevent side effects of corticosteroids, apply: 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); 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 drip over 30 minutes for 3 days): 1) a sharp increase (“splash”) in the activity of the process (III degree), despite, it would seem adequate therapy; 2) resistance to doses that previously achieved a positive effect; 3) pronounced organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).
It is believed that such pulse therapy stops the formation of immune complexes by inhibiting the synthesis of antibodies to DNA. The corticosteroid-induced decrease in the level of antibodies to DNA leads to the formation of smaller immune complexes due to the dissociation of larger ones.
A significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of corticosteroids. Pulse therapy is most successful in young patients with a short duration of the disease.
Treatment 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 quite early). In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (bolus administration at a dose of 0.5-1 g / m2 intravenously monthly for at least 6 months, and then every 3 months for for 2 years) in combination with 10-30 mg/day of prednisolone. In the future, you can return to GCS therapy, since resistance to them usually disappears.
For the treatment of less severe, but resistant to GCS manifestations of the disease, azathioprine or methotrexate (about 15 mg / week) and cyclosporine [less than 5 mg Dkg / day)] are prescribed in combination with low doses of prednisolone (10-30 mg / day).
The criteria for evaluating the effectiveness of the use of cytostatics are. 1) reduction or disappearance of clinical signs; 2) disappear
Nier steroid resistance; 3) a persistent decrease in the activity of the process; 4) prevention of progression of lupus nephritis.
Complications of cytostatic therapy: 1) leukopenia; 2) anemia and thrombocytopenia; 3) dyspeptic phenomena; 4) infectious complications.
With the appearance of leukopenia (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 make it possible to remove circulating immune complexes from the body, increase the sensitivity of cell 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 alone 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 the antiphospholipid syndrome), small doses of acetylsalicylic acid (75 mg / day) are used. With significant antiphospholipid syndrome (with clinical manifestations) prescribe heparin and small doses of aspirin.
Forecast. In recent years, due to effective methods treatment, the prognosis improved (approximately 90% of patients achieve remission). However, in 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or with cerebrovasculitis, the prognosis is unfavorable.
Prevention. timely adequate therapy ensures the prevention of recurrence of the disease. For primary prevention, a group of “threatened” persons is selected, which primarily include relatives of patients, as well as persons suffering from an isolated skin lesion (discoid lupus). These persons should avoid insolation, hypothermia, should not be vaccinated, they are not shown mud therapy and other balneological procedures.
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