Connective tissue is a fairly rare pathology. The clinical picture of this disease is characterized by a combination of signs of various collagen diseases. This pathology is otherwise called Sharpe's syndrome. Most often, this symptom complex is observed in puberty and in middle-aged patients. In its advanced form, the pathology can lead to serious and life-threatening consequences. In this article we will look in detail 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 manifestations of various rheumatic ailments. Only relatively recently has this disease been described as a distinct autoimmune disorder.
In mixed connective tissue disease (MCTD), the patient exhibits 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. Typically, several symptoms characteristic of various autoimmune pathologies are observed.
ICD code
According to ICD-10, mixed connective tissue disease is classified as separate group pathologies coded M35 (“Other connective tissue diseases”). The full code of the NWTA is M35.1. This group includes cross rheumatic syndromes. The word “cross” means that with this pathology there are signs of various connective tissue diseases (collagenoses).
Causes
At present, the exact causes of Sharp's syndrome are not clear. Mixed connective tissue disease is autoimmune in nature. This means that a person’s immune system, for unknown reasons, begins to attack its own healthy cells.
What can provoke such a malfunction in 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 major role in the occurrence of autoimmune reactions. endocrine system. For this reason, CTD is often observed in adolescents and women during menopause.
A negative emotional background can also affect the functioning of the immune system. The psychosomatics of mixed connective tissue disease is associated with serious stress. This pathology is more often observed in people prone to depression, as well as in patients with neuroses and psychoses.
Usually observed in people with a hereditary predisposition to rheumatic diseases. Exposure to unfavorable 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 sign of the disease is impaired blood circulation in the fingers and toes. This resembles the manifestations of Raynaud's syndrome. Due to vascular spasm, a person’s fingers and toes become pale and cold. Then the skin on the hands and feet takes on a bluish tint. Coldness of the extremities is accompanied by severe pain. Such vascular spasms may occur several years before other signs of the disease develop.
Most patients experience joint pain. The fingers swell greatly and 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, bone deformation very rarely occurs. Subsequently, other articular joints are also involved in the pathological process, most often the knees and elbows.
Later, the person develops red and white spots on the skin, especially in the area of the hands and face. Condensed areas of muscles can be felt, as if the skin thickens, and in rare cases, ulcers appear on the epidermis.
The patient's health gradually worsens. Joint pain and skin rashes are accompanied by the following symptoms:
- general weakness;
- a feeling of stiffness in the joints after a night's sleep;
- increased sensitivity to ultraviolet radiation;
- drying of the oral mucosa and difficulty swallowing;
- hair loss;
- causeless weight loss with normal nutrition;
- increased temperature;
- enlarged lymph nodes.
In advanced cases, the pathological process spreads to the kidneys and lungs. Glomerulonephritis occurs and 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 internal organs, then the following complications may occur with poor treatment:
- renal failure;
- stroke;
- inflammation of the esophageal mucosa;
- perforation of the intestinal wall;
- myocardial infarction.
Such complications occur when the course of the disease is unfavorable and in the absence of proper therapy.
Diagnostics
CTD is treated by a rheumatologist. Symptoms of mixed connective tissue disease are extremely varied and resemble the manifestations of many other pathologies. Because of this, difficulties often arise in making a diagnosis.
Patients are prescribed a serological blood test for antibodies to nuclear ribonucleoprotein. If the indicators of this study exceed the permissible level and the patients have arthralgia and Raynaud's syndrome, then the diagnosis is considered confirmed.
Additionally, the following studies are prescribed:
- clinical and biochemical blood and urine tests;
- urine test according to Nechiporenko;
- analysis for rheumatoid factor and specific immunoglobulins.
If necessary, an ultrasound of the kidneys is prescribed, as well as a chest x-ray and an echocardiogram.
Treatment methods
Treatment of mixed connective tissue disease is aimed primarily at suppressing the autoimmune reaction. Patients are prescribed the following medications:
- Corticosteroid hormones: Dexamethasone, Metipred, Prednisolone. These drugs reduce autoimmune reactions and inflammation in the joints.
- Cytostatics: "Azathioprine", "Imuran", "Plaquenil". Takei medications 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 syndrome have to take medications for a long time, and sometimes for life. This can negatively affect the gastrointestinal tract. The drug "Omeprazole" helps protect the gastric mucosa from the aggressive effects of drugs.
This comprehensive treatment prevents exacerbations of the disease and allows for 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 Sharpe syndrome affect life expectancy? The prognosis of this disease is considered conditionally favorable. Dangerous defeats internal organs develop less frequently in CTD than in other autoimmune pathologies. Lethal outcome is observed only when running forms illness 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. Patients are often prescribed lifelong medication. If the patient adheres to the recommended treatment regimen, the prognosis of the disease is favorable. Timely therapy helps maintain a normal quality of life for the patient.
Prevention
Specific prevention This disease has not been developed, since the exact causes of autoimmune pathologies have not been established. Rheumatologists advise adhering to the following recommendations:
- Uncontrolled use of medications should be avoided. Long-term treatment with medications can only be carried out under the supervision of a physician.
- If you have a hereditary predisposition to autoimmune pathologies, you should avoid excessive exposure to sunlight and regularly undergo preventive examinations by a rheumatologist.
- It is very 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 CONNECTIVE TISSUE
Diffuse connective tissue diseases (DCT) or collagenosis (a term that has historical meaning) - a group of diseases characterized by systemic immunoinflammatory damage to connective tissue and its derivatives. This is a group, but not a nosological concept, and therefore this term should not denote individual nosological forms.
CTDs combine a fairly large number of diseases. The most common are SLE, SSD and DM. This group of diseases also includes ARF, traditionally described in the section on diseases of the cardiovascular system. It has now been proven that with CTD, profound disturbances of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the formation of antibodies or sensitized lymphocytes directed against antigens of one’s own body.
Autoimmune disorders are based on an immunoregulatory imbalance, expressed in the inhibition of suppressor and increased helper activity of T-lymphocytes, followed by activation of B-lymphocytes and hyperproduction of various specific autoantibodies.
There are a number of common features that unite DZST:
The common pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixed in tissues with the subsequent development of severe inflammatory reaction(especially in the microvasculature, kidneys, joints, etc.);
Similarity of morphological changes (fibrinoid change in the main substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbations and remissions;
Exacerbation under the influence of nonspecific influences ( infectious diseases, insolation, vaccination, etc.);
Multisystem damage (skin, joints, serous membranes, kidneys, heart, lungs);
The therapeutic effect of immunosuppressive drugs (glucocorticoids, cytostatic drugs).
All diseases included in this group differ in clinical and morphological characteristics, therefore, in each specific case one should strive for an accurate nosological diagnosis.
This chapter presents the diagnostic search for SLE, SSc and DM.
SYSTEMIC LUPUS ERYTHEMATOSUS
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that occurs in individuals young(mainly in women) and developing against the background of a genetically determined imperfection of immunoregulatory processes, which leads to the uncontrolled production of antibodies to one’s own cells and their components and the development of autoimmune and immunocomplex chronic damage (V.A. Nasonova, 1989). The essence of the disease is immunoinflammatory damage to connective tissue, microvasculature, skin, joints and internal organs, with visceral lesions considered the leading ones, which determine the course and prognosis of the disease.
The incidence of SLE ranges from 4 to 25 cases per 100 thousand population. The disease most often develops in women of childbearing age. During pregnancy and postpartum period the risk of exacerbation increases significantly. Women suffer from SLE 8-10 times more often than men. The peak incidence occurs at the age of 15-25 years. In children, the ratio of sick girls to boys decreases and is 3:1. Mortality in SLE is 3 times higher than in the general population. In men, the disease is as severe as in women.
SLE belongs to genetically determined diseases: studies conducted in the population have shown that the predisposition to the occurrence of SLE is associated with certain histocompatibility class II genes (HLA), genetically determined deficiency of certain complement components, as well as with polymorphism of genes of certain receptors and tumor necrosis factor α (TNF-α).
Etiology
Specific etiological factor in SLE has not been established, but a number of clinical symptoms (cytopenic syndrome, erythema and enanthema) and certain patterns of disease development allow us to associate SLE with diseases of viral etiology. Currently, importance is attached to RNA viruses (slow or latent viruses). Detection of familial 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 nonspecific factors - insolation, nonspecific infection, administration of serums, taking certain medications (in particular, peripheral vasodilators from the hydralazine group), as well as stress. SLE can begin after childbirth or abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis
Due to the impact on immune system virus, and possibly antiviral antibodies, against the background of a hereditary predisposition, dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, there is an uncontrolled production of antibodies to its various tissues, cells and proteins (including various cellular organelles and DNA). It has been established that in SLE, autoantibodies are produced to approximately forty of the more than two hundred potential antigenic cellular components. Subsequently, the formation of immune complexes occurs and their deposition in various organs and tissues (mainly in the microvasculature). Characterized by various defects of immunoregulation, accompanied by hyperproduction of cytokines (IL-6, IL-4 and IL-10). Then processes associated with the elimination of fixed immune complexes develop, which leads to the release of lysosomal enzymes, damage to organs and tissues and the development of immune inflammation. In the process of inflammation and destruction of connective tissue, new antigens are released, causing the formation of antibodies and the formation of new immune complexes. Thus, there arises vicious circle, ensuring the chronic course of the disease.
Classification
Currently, our country has adopted a working classification of clinical variants of the course of SLE, taking into account:
The nature of the current;
Activity of the pathological process;
Clinical and morphological characteristics of damage to organs and systems. Nature of the disease
The acute course is characterized by the rapid development of multiorgan changes (including kidney and central nervous system damage) and high immunological activity.
Subacute course: at the onset of the disease, the main symptoms appear, nonspecific damage to the skin and joints. The disease occurs in waves, with periodic exacerbations and the development of multiple organ disorders within 2-3 years from the onset of the first symptoms.
The chronic course is characterized by a long-term predominance of one or more symptoms: recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhof's syndrome or Sjögren's syndrome. Multiple organ lesions occur by the 5th-10th year of the disease.
Phase and degree of activity of the process:
Active (high activity - III, moderate - II, minimal - I);
Inactive (remission).
Clinical and morphological characteristics of lesions:
Skin (butterfly symptom, capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis - pleurisy, pericarditis and peresplenitis);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute and chronic pneumonitis, pneumosclerosis);
Kidney (lupus nephritis of nephrotic or mixed type, urinary syndrome);
Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, represented by a clinical and laboratory symptom complex, including venous and (or) arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ damage. A characteristic immunological sign is the formation of antibodies that react with phospholipids and phospholipid-binding proteins (antiphospholipid syndrome will be discussed in more detail below).
There are also three degrees of activity of the pathological process, which characterize the severity of potentially reversible immunoinflammatory damage and determine the characteristics of the treatment of each individual patient. Activity should be distinguished from the severity of the disease, which is understood as a set of irreversible changes that are potentially dangerous for the patient.
Clinical picture
The clinical picture of the disease is extremely diverse, which is associated with the multiplicity of damage to organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
They receive information on the basis of which they can formulate an idea:
About the variant of onset of the disease;
The nature of the disease;
The degree of involvement of certain organs and systems in the pathological process;
Previous treatment, its effectiveness and possible complications.
The onset of the disease can be very diverse. Most often it is represented by a combination of various syndromes. Monosymptomatic onset is usually not typical. In this regard, the assumption of SLE disease arises from the moment such a combination is detected in a patient. In this case, the diagnostic value of certain syndromes increases.
IN early period SLE is considered the most common syndromes of damage to the joints, skin and serous membranes, as well as fever. Thus, the most suspicious combinations regarding SLE will be:
Fever, polyarthritis and trophic skin disorders (in particular, hair loss - alopecia);
Polyarthritis, fever and pleural lesions (pleurisy);
Fever, trophic skin disorders and pleural lesions.
The diagnostic significance of these combinations increases significantly if the skin lesion is represented by erythema, but in the initial period of the disease it is recorded only in 25% of cases. However, this circumstance does not reduce the diagnostic value of the above combinations.
An asymptomatic onset of the disease is not typical, but the debut of SLE is noted with the occurrence of massive edema due to the development from the very beginning of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type.
Involvement in the pathological process various organs manifests symptoms inflammatory lesion(arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.).
Information about previous treatment allows us to judge:
About its optimality;
About the severity of the disease and the degree of activity of the process (initial doses of glucocorticoids, duration of their use, maintenance doses, inclusion in medical complex cytostatics for severe immune disorders, high activity of lupus nephritis, etc.);
About complications of glucocorticoid and cytostatic treatment.
At the first stage, it is possible to draw certain conclusions regarding the diagnosis of a long-term course of the disease, but in its debut, the diagnosis is established at further stages of the study.
You can get a lot of data indicating damage to organs and the degree of their functional failure.
Damage to the musculoskeletal system manifests itself as polyarthritis, reminiscent of RA with symmetrical damage to the small joints of the hand (proximal interphalangeal, metacarpophalangeal, wrist) and large joints(less often). 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. Joint changes can be accompanied by muscle damage in the form of diffuse myalgia, and very rarely - true PM with swelling and muscle weakness. Sometimes the lesion is represented only by arthralgia.
Damage to the skin is noted as often as joints. The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose (“butterfly”). Inflammatory rashes on the nose and cheeks, repeating the outline of a “butterfly”, are presented in various variants:
Vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse redness of the skin with a cyanotic tint in middle zone faces,
increasing under the influence external factors(insulation, wind, cold) or disturbances;
. “butterfly” type of centrifugal erythema (skin changes are localized only in the bridge of the nose).
In addition to the “butterfly”, discoid rashes can be detected - erythematous raised plaques with keratic disorder and subsequent development of atrophy of the skin of the face, limbs and trunk. Finally, some patients experience nonspecific exudative erythema on the skin of the extremities and chest, as well as signs of photodermatosis on exposed parts of the body.
Skin lesions include capillaritis - a pinpoint hemorrhagic rash on the fingertips, nail beds and palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulcerations can be found on the mucous membrane of the mouth or nasopharyngeal area.
Damage to the serous membranes occurs in 90% of patients (classic diagnostic triad - dermatitis, arthritis, polyserositis). Damage to the pleura and pericardium is especially common, and less often to the peritoneum. Symptoms of pleurisy and pericarditis are described in previous sections, so only their features in SLE will be listed below:
Dry pleurisy and pericarditis occur more often;
In effusion forms, the amount of exudate is small;
Damage to the serous membranes is short-lived, and is usually diagnosed retrospectively upon detection of pleuropericardial adhesions or thickening of the costal, interlobar and mediastinal pleura with x-ray examination;
There is a pronounced tendency towards the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities).
SLE is characterized by damage to the cardiovascular system, which occurs at various stages of the disease.
Most often, pericarditis is found, which is prone to recurrence. Much more often than previously thought, endocardial damage is noted in the form of warty endocarditis (lupus endocarditis) on the leaflets of the mitral, aortic or tricuspid valve. If the process lasts for a long time, at the second stage of the search, signs of insufficiency of the corresponding valve can be detected (signs of stenosis of the orifice, as a rule, are absent).
Focal myocarditis is almost never recorded, but diffuse damage, especially in severe cases, is accompanied by certain symptoms (see “Myocarditis”).
Vascular damage can manifest itself as Raynaud's syndrome, which is characterized by paroxysmal developing disorders of the arterial blood supply to the hands and (or) feet, arising under the influence of cold or excitement. During an attack, paresthesia is noted; the skin of the fingers becomes pale and (or) cyanotic, the fingers are cold. Predominantly, damage occurs to the II-V fingers and toes, less often to other distal areas of the body (nose, ears, chin, etc.).
Lung lesions can be caused by the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) occurs acutely or continues for months and manifests itself with signs of inflammatory infiltration of lung tissue syndrome, similar to those of pneumonia. The peculiarity of the process is the occurrence of an unproductive cough in combination with shortness of breath. Another option for lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), expressed in the development of slowly progressive shortness of breath and changes in the lungs during X-ray examination. There are practically no characteristic physical data, so it is almost impossible to judge such lung damage at the second stage of the diagnostic search.
Damage to the gastrointestinal tract is usually represented by subjective signs detected at the first stage. A physical examination sometimes reveals vague tenderness in the epigastric region and at the site of the pancreas, as well as signs of stomatitis. In some cases, hepatitis develops: enlargement and tenderness of the liver are noted.
Most often, with SLE, kidney damage occurs (lupus glomerulonephritis or lupus nephritis), the evolution of which determines the future fate of the patient. Kidney damage in SLE can occur in various ways, so the data from a direct examination of the patient can vary widely. With isolated changes in urinary sediment, no abnormalities are detected during physical examination. With glomerulonephritis occurring with nephrotic syndrome, massive edema and often hypertension are determined. When forming chronic nephritis with constant hypertension, an enlargement of the left ventricle and an accent of the second tone in the second intercostal space to the right of the sternum are detected.
Autoimmune thrombocytopenia (Werlhoff syndrome) manifests itself as typical rashes in the form of hemorrhagic spots of varying sizes on the skin inner surface limbs, skin of the chest and abdomen, as well as on mucous membranes. After minor injuries (for example, after tooth extraction), bleeding occurs. Nosebleeds sometimes become profuse and lead to anemia. Skin hemorrhages can have different colors: blue-greenish, brown or yellow. Often, SLE manifests itself for a long time only as Werlhoff syndrome without other typical clinical symptoms.
Damage to the nervous system is expressed to varying degrees, since almost all of its parts are involved in the pathological process. Patients complain of migraine headaches. Sometimes seizures occur. Possible cerebral circulation disorders, including the development of a stroke. When examining the patient, signs of polyneuritis are detected with impaired sensitivity, pain along the nerve trunks, decreased tendon reflexes and paresthesia. Organic brain syndrome characterized by emotional lability, episodes of depression, memory impairment and dementia.
Damage to the reticuloendothelial system is represented by an early symptom of the generalization of the process - polyadenopathy (enlargement of all groups of lymph nodes, not reaching a significant degree), as well as, as a rule, moderate enlargement of the spleen and liver.
Damage to the organ of vision manifests itself as keratoconjunctivitis sicca, which is caused by pathological changes in the lacrimal glands and disruption of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.
With antiphospholipid syndrome, venous (in the deep veins of the lower extremities with repeated pulmonary embolisms) and arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks) thrombosis can be detected. Valve heart defects, intracardiac thrombi simulating cardiac myxoma, and coronary artery thrombosis with the development of MI are recorded. Skin lesions associated with antiphospholipid syndrome are varied, but the most common is livedo reticularis. (livedo reticularis).
Thus, after the second stage of the examination, multiple organ lesions are discovered, and their degree is very different: from barely clinically noticeable (subclinical) to pronounced, predominant over the rest, which creates the preconditions for diagnostic errors- interpretation of these changes as signs of independent diseases (for example, glomerulonephritis, myocarditis, arthritis).
The third stage of the diagnostic search in SLE is very important because:
Helps make a final diagnosis;
Demonstrates the severity of immune disorders and the degree of damage to internal organs;
Allows you to determine the degree of activity of the pathological (lupus) process.
At the third stage highest value purchases laboratory blood tests. There are two groups of indicators.
Indicators that have direct diagnostic significance (indicate pronounced immunological disorders):
LE cells (lupus erythematosus cells) are mature neutrophils that phagocytose nuclear proteins of other blood cells that have decayed under the influence of ANF.
ANF is a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in 95% of patients they are found in a titer of 1:32 or higher). The absence of ANF in the vast majority of cases argues against the diagnosis of SLE.
ANA - antibodies to native (i.e., to the whole molecule) DNA. An increase in their concentration correlates with disease activity and the development of lupus nephritis. They are found in 50-90% of patients.
Antibodies to Sm nuclear antigen (anti-Sm) are highly specific for SLE. Antibodies to Ro/La ribonucleoprotein are considered specific for SLE (they are detected by immunofluorescence in 30% of cases, by hemagglutination in 20% of patients).
The “rosette” phenomenon is altered nuclei (hematoxylin bodies) freely lying in the tissues, surrounded by leukocytes.
Diagnosis of antiphospholipid syndrome in SLE is based on the determination of lupus anticoagulants - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (determining increased thromboplastin time) and antibodies to cardiolipin using an enzyme-linked immunosorbent assay. The term “lupus anticoagulant” is not correct, since the main clinical sign of the presence of the above antibodies is thrombosis, not bleeding. These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis and autoimmune hemolytic anemia occur.
Nonspecific acute phase indicators, which include:
Dysproteinemia with increased content of α 2 - and γ-globulins;
SRB detection;
Increased fibrinogen concentration;
Increase in ESR.
In case of severe articular lesions, RF, an antibody to the Fc fragment of IgG, can be detected in a small titer.
When examining peripheral blood, leukopenia (1-1.2x10 9 /l) can be detected with a shift in the leukocyte formula to young forms and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Possible moderate hypochromic anemia, in some cases - hemolytic anemia, accompanied by jaundice, reticulocytosis and a positive Coombs test. Thrombocytopenia is sometimes recorded in combination with Werlhoff syndrome.
Kidney damage is characterized by changes in the urine, which can be classified as follows (I.E. Tareeva, 1983):
Subclinical proteinuria (protein content in urine 0.5 g/day, often in combination with slight leukocyturia and erythrocyturia);
More pronounced proteinuria, which serves as an expression of nephrotic syndrome accompanying subacute or active lupus nephritis.
Very high proteinuria (as, for example, with amyloidosis) rarely develops. Moderate hematuria is noted. Leukocyturia can be a consequence of both the lupus inflammatory process in the kidneys and the result of the frequent addition of a secondary infectious lesion of the urinary tract.
A puncture biopsy of the kidneys reveals nonspecific mesangiomembranous changes, often with a fibroplastic component. Considered characteristic:
Detection of altered nuclei (hematoxylin bodies) freely lying in the renal tissue in preparations;
The capillary membranes of the glomeruli are in the form of wire loops;
Deposition of fibrin and immune complexes on the basement membrane of glomeruli in the form of electron-dense deposits.
According to the WHO classification, the following morphological types of lupus nephritis are distinguished:
Class I - no changes.
Class II - mesangial type;
Class III - focal proliferative type;
Class IV - diffuse proliferative type;
Class V - membranous type;
Class VI - chronic glomerulosclerosis.
X-ray examination reveals:
Changes in the joints (with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints, with chronic arthritis and deformities - narrowing of the joint space with subluxations);
Changes in the lungs with the development of pneumonitis (with a long course of the disease - disc-shaped atelectasis, strengthening and deformation of the pulmonary pattern in combination with a high position of the diaphragm);
Changes in the heart with the development of lupus disease or exudative pericarditis.
An ECG can detect nonspecific changes in the final part of the ventricular complex (wave T and segment ST), similar to those described previously for myocarditis and pericarditis.
CT and MRI of the brain reveal pathological changes with damage to the central nervous system.
When conducting a diagnostic search, it is also necessary to determine the degree of activity of the lupus process (Table 7-1).
Table 7-1. Criteria for the activity of the pathological process in systemic lupus erythematosus (Nasonova V.A., 1989)
The end of the table 7-1
Diagnostics
In cases of the classic course of SLE, diagnosis is simple and is based on the detection of “butterfly”, recurrent polyarthritis and polyserositis, which constitute the clinical diagnostic triad, complemented by the presence of LE cells or ANF in diagnostic titers. Of additional importance is the young age of patients, the connection with childbirth, abortion, the onset of menstruation, insolation and infectious diseases. It is much more difficult to establish a diagnosis in other cases, especially if the above classical diagnostic signs are absent. Diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 help in this situation (Table 7-2).
Table 7-2.Diagnostic criteria systemic lupus erythematosus (SLE)
End of table. 7-2
The diagnosis is reliable if four or more criteria are met. If fewer than four criteria are present, the diagnosis of SLE is questionable and dynamic monitoring of the patient is required. This approach has a clear rationale: it warns against prescribing glucocorticoids to such patients, since other diseases (including paraneoplastic syndrome) may occur with the same symptoms, in which their use is contraindicated.
Differential diagnosis
SLE should be differentiated from a number of diseases. As large as the list of organs and systems involved in the pathological process in SLE is, the list of diseases that can be misdiagnosed in a patient is just as extensive. SLE can largely mimic various pathological conditions. This especially often happens at the onset of the disease, as well as with dominant damage to one or two organs (systems). For example, detection of pleural lesions at the onset of the disease can be regarded as pleurisy of tuberculous etiology; myocarditis can be interpreted as rheumatic or nonspecific. Especially many mistakes are made if SLE debuts with glomerulonephritis. In such cases, only glomerulonephritis is diagnosed.
SLE most often has to be differentiated from ARF (rheumatism), IE, chronic active hepatitis (CAH), hemorrhagic diathesis (thrombocytopenic purpura) and other diseases from the DTD group.
The need for differential diagnosis with rheumatism usually arises in adolescents and young men at the onset of the disease - when arthritis and fever occur. Rheumatoid arthritis differs from lupus in the greater severity of symptoms, predominant damage to large joints and transience. One should not attach differential diagnostic significance to a previous infectious lesion (sore throat), since it can serve as a nonspecific factor causing the development of clinical signs SCV. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic carditis) appear. Subsequent dynamic observation makes it possible to detect an emerging heart defect, whereas in SLE, even if mitral valve insufficiency develops, it is mildly expressed and is not accompanied by clear symptoms.
hemodynamic disorders. Mitral regurgitation is mild. Unlike SLE, leukocytosis is noted in the acute stage of rheumatism. ANF is not detected.
Differential diagnosis between SLE and RA is difficult in the initial stage of the disease, which is due to the similarity of the clinical picture: symmetrical damage to the small joints of the hand occurs, new joints are involved in the process, and morning stiffness is characteristic. Differential diagnosis is based on the predominance of the proliferative component in the affected joints in RA, the early development of wasting of the muscles that move the affected joints, and the persistence of articular lesions. Erosion of the articular surfaces is absent in SLE, but is a characteristic sign of RA. A high RF titer is characteristic of RA. In SLE it is rarely found and in low titres. The differential diagnosis of SLE and visceral RA is extremely difficult. Refined diagnosis in both cases does not affect the nature of treatment (prescription of glucocorticoids).
With CAH, systemic disorders may occur in the form of fever, arthritis, pleurisy, skin rashes and glomerulonephritis. Leukopenia, thrombocytopenia, LE cells and ANF can be detected. When carrying out differential diagnosis, the following should be taken into account:
CAH often develops in middle age;
Patients with CAH have a history of viral hepatitis;
With CAH, pronounced changes in the structure and function of the liver are detected (cytolytic and cholestatic syndrome, signs of liver failure, hypersplenism, portal hypertension);
In SLE, liver damage does not always occur and occurs in the form of mild hepatitis (with moderate signs of cytolytic syndrome);
With CAH, various markers of viral liver damage (antiviral antibodies and viral antigen) are detected.
With primary IE, heart damage quickly occurs (aortic or mitral valve insufficiency), and antibacterial therapy has a clear effect. LE cells, antibodies to DNA, and ANF are usually absent. With timely bacteriological examination, the growth of pathogenic microflora is detected.
Thrombocytopenic purpura (idiopathic or symptomatic) lacks many of the syndromes seen in SLE, typical laboratory findings (LE cells, ANF, anti-DNA antibodies) and fever.
The most difficult differential diagnosis with other diseases from the CTD group. Conditions such as SSc and MD may share many features with SLE. This circumstance aggravates the possibility of detecting ANF and LE cells in these diseases, although in a smaller titer. The main differential diagnostic features are more frequent and pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin damage in SSc, and a clear myopathic syndrome in DM. In some cases, a correct diagnosis can be made only after a long period of
dynamic observation of the patient. Sometimes this takes many months and even years (especially in chronic SLE with minimal activity).
The formulation of a detailed clinical diagnosis of SLE should take into account all the headings given in the working classification of the disease. The diagnosis should reflect:
The nature of the course of the disease (acute, subacute, chronic), and in the case of a chronic course (usually mono or oligosyndromic), the leading clinical syndrome should be indicated;
Process activity;
Clinical and morphological characteristics of damage to organs and systems, indicating the stage of functional failure (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the existence or absence of heart failure, with lung damage - the existence or absence respiratory failure and etc.);
Indication of treatment (for example, glucocorticoids);
Complications of treatment (if any).
Treatment
Considering the pathogenesis of the disease, complex pathogenetic treatment is recommended for patients with SLE. His tasks:
Suppression of immune inflammation and immune complex disorders (uncontrolled immune response);
Prevention of complications of immunosuppressive therapy;
Treatment of complications arising during immunosuppressive therapy;
Impact on individual, pronounced syndromes;
Removal of CEC and antibodies from the body.
First of all, it is necessary to exclude psycho-emotional stress, insolation, actively treat concomitant infectious diseases, eat low-fat foods high in polyunsaturated fatty acids, calcium and vitamin D. During the period of exacerbation of the disease and during treatment with cytostatic drugs, active contraception is necessary. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.
To suppress immune inflammation and immune complex disorders in the treatment of SLE, the main immunosuppressants are used: glucocorticoids short acting, cytotoxic drugs and aminoquinoline derivatives. The duration of treatment, choice of drug, as well as maintenance doses are determined:
The degree of disease activity;
The nature of the flow (severity);
The extensive involvement of internal organs in the pathological process;
Tolerability of glucocorticoids or cytostatics, as well as the existence or absence of complications of immunosuppressive therapy;
The existence of contraindications.
In the initial stages of the disease, with minimal activity of the process and the predominance of joint damage in the clinical picture, glucocorticoids should be prescribed in small doses (prednisolone at a dose of less than 10 mg/day). Patients should be registered with a dispensary so that when the first signs of exacerbation of the disease occur, the doctor can timely prescribe treatment with glucocorticoids in the optimal dose.
In case of a chronic course of the disease with predominantly skin lesions, chloroquine (at a dose of 0.25 g/day) or hydroxychloroquine can be used for many months.
If signs of high activity and generalization of the process involving internal organs occur, it is necessary to immediately switch to more effective immunosuppressive treatment with glucocorticoids: prednisolone is prescribed at a dose of 1 mg/day or more. The duration of high doses ranges from 4 to 12 weeks. The dose reduction should be carried out gradually, under close clinical and laboratory control. Patients should take maintenance doses (5-10 mg/day) for many years.
Thus, the main treatment method for SLE is the use of glucocorticoids. When using them, you should adhere to the following principles:
Start treatment only if the diagnosis of SLE is confirmed (if suspected, these drugs should not be used);
The dose of glucocorticoids should be sufficient to suppress the activity of the pathological process;
Treatment with an overwhelming dose should be carried out until a pronounced clinical effect is achieved (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes);
After achieving the effect, you should gradually switch to maintenance doses;
Prevention of complications of glucocorticoid treatment is mandatory. To prevent the side effects of glucocorticoids, use:
Potassium preparations (orotic acid, potassium chloride, potassium and magnesium aspartate);
Anabolic agents (methandienone in a dose of 5-10 mg);
Diuretics (saluretics);
Antihypertensive drugs ( ACE inhibitors);
Antacids.
If severe complications develop, the following is prescribed:
Antibiotics (for secondary infection);
Anti-tuberculosis drugs (with the development of tuberculosis, more often in pulmonary localization);
Insulin preparations, diet food (for diabetes mellitus);
Antifungal agents (for candidiasis);
Antiulcer treatment (in case of steroid ulcer formation).
During treatment with glucocorticoids, situations arise when it is necessary to administer extra-high doses of prednisolone (intravenous drip at a dose of 1000 mg over 30 minutes for three days):
A sharp increase (surge) in the activity of the process (III degree), despite seemingly optimal treatment;
Resistance to doses 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 immune complexes of smaller sizes (as a result of dissociation of larger ones).
Significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of glucocorticoids. Pulse therapy is most effective in young patients with a short duration of the disease.
Treatment with glucocorticoids is not always successful, due to:
The need to reduce the dose if complications develop, despite the fact that such therapy is effective in a particular patient;
Intolerance to glucocorticoids;
Resistance to treatment with glucocorticoids (usually detected quite early).
In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (monthly intravenous bolus administration at a dose of 0.5-1 g/m2 for at least 6 months, and then every 3 months for 2 years) in combination with prednisolone at a dose of 10-30 mg/day. In the future, you can return to treatment with glucocorticoids, as resistance to them usually disappears.
For the treatment of less severe but glucocorticoid-resistant symptoms of the disease, azathioprine (1-4 mg/kg per day) or methotrexate (15 mg/week) and cyclosporine (at a dose of less than 5 mg/kg per day) are prescribed in combination with low doses of prednisolone (10-30 mg/day).
Criteria for assessing the effectiveness of the use of cytostatics:
Reduction or disappearance of clinical signs;
Disappearance of steroid resistance;
Persistent decrease in process activity;
Preventing the progression of lupus nephritis. Complications of cytostatic therapy:
Leukopenia;
Anemia and thrombocytopenia;
Dyspeptic phenomena;
Infectious complications.
If the number of leukocytes decreases to less than 3.0x10 9 /l, the dose of the drug should be reduced to 1 mg/kg body weight. With further increase in leukopenia, the drug is discontinued and the dose of prednisolone is increased by 50%.
Extracorporeal treatment methods - plasmapheresis and hemosorption - have become widespread. They allow you to remove CEC from the body, increase the sensitivity of cellular receptors to glucocorticoids and reduce intoxication. They are used for generalized vasculitis, severe organ damage (lupus nephritis, pneumonitis, cerebrovasculitis), as well as for severe immune disorders that are difficult to treat with glucocorticoids.
Typically, extracorporeal methods are used in combination with pulsartherapy or, if it is ineffective, independently. It should be noted that in case of cytopenic syndrome, extracorporeal methods are not used.
Patients with a high titer of antiphospholipid antibodies in the blood, but without clinical signs of antiphospholipid syndrome, are prescribed small doses acetylsalicylic acid(75 mg/day). For confirmed antiphospholipid syndrome, accompanied by clinical signs, sodium heparin and small doses of acetylsalicylic acid are used.
For the treatment of musculoskeletal disorders (arthritis, arthralgia, myalgia) and moderate serositis, normal doses of NSAIDs can be used.
Forecast
IN last years Due to the use of effective treatment methods, the prognosis has improved: 10 years after diagnosis, survival rate is 80%, and after 20 years - 60%. In 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or cerebrovasculitis, the prognosis remains unfavorable.
Prevention
Since the etiology of SLE is unknown, primary prevention is not carried out. Nevertheless, a risk group is identified, which includes, first of all, relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). They should avoid insolation, hypothermia, should not be vaccinated, receive mud therapy and other balneological procedures.
SYSTEMIC SCLERODERMA
SSc is a systemic disease of connective tissue and small vessels, characterized by inflammation and widespread fibrosclerotic changes in the skin and internal organs. This definition of the disease reflects the essence of SSD - a fibrous transformation of connective tissue that serves as a framework for internal organs, a constituent element of the skin and blood vessels. The rampant development of fibrosis is associated with excessive collagen formation due to impaired functioning of fibroblasts.
The prevalence of SSc varies in different geographical areas and ethnic groups, including those living in the same region. Primary incidence ranges from 3.7 to 19.0 cases per 1 million population per year. SSD is more often registered among women (ratio 5:7.1) aged 30-60 years.
Etiology
The cause of the disease is unknown. They attach importance to viruses, since there is indirect evidence of their role in the occurrence of SSc: virus-like inclusions and an increased titer of antiviral antibodies were found in the affected tissues. A family genetic predisposition to SSc has been established, since relatives of patients show changes in protein metabolism in the form of hypergammaglobulinemia, Raynaud's syndrome, and sometimes SSD.
Unfavorable factors contributing to the manifestation of the disease and its exacerbations include environmental factors (prolonged contact with polyvinyl chloride, silica dust), the use of drugs (bleomycin, tryptophan), as well as cooling, trauma, disruption of neuroendocrine functions and exposure to occupational hazards in the form vibrations.
Pathogenesis
Pathogenesis is based on disruption of the interaction process various cells(endothelial, smooth muscle cells of the vascular wall, fibroblasts, T- and B-lymphocytes, monocytes, mast cells, eosinophils) with each other and components of the connective tissue matrix. The result of all of the above is the selection of a population of fibroblasts that are resistant to apoptosis and function in an autonomous mode of maximum synthetic activity, which activates neofibrillogenesis and promotes changes in the glycoproteins of the main substance of connective tissue. As a result, fibrous-sclerotic changes in the connective tissue develop. At the same time, dysregulation of the body’s immune response to the introduction of the virus occurs, which is expressed in the hyperproduction of antibodies to its own tissues (autoantibodies). Then immune complexes are formed, settling in the microvasculature and internal organs, which leads to the development of immune inflammation. The severity of immune and autoimmune disorders in SSc is not as great as in SLE.
Fibrosclerotic changes in connective tissue, damage to blood vessels and internal organs as a result of immune inflammation cause a variety of clinical signs of the disease (Fig. 7-1).
Classification
In our country, a working classification of SSc has been adopted, taking into account the nature of the course, the stage of development of the disease and the clinical and morphological characteristics of damage to organs and systems.
Character of the current:
Rapidly progressive;
Chronic.
Stage:
Initial;
Generalized;
Terminal.
Rice. 7-1. Pathogenesis of systemic scleroderma
Clinical and morphological characteristics of the lesion:
Skin and peripheral vessels - dense edema, induration, hyperpigmentation, telangiectasia, Raynaud's syndrome;
Musculoskeletal system - arthralgia, polyarthritis, pseudoarthritis, PM, calcinosis, osteolysis;
Heart - myocardial dystrophy, cardiosclerosis, heart disease (most often - valve insufficiency);
Lungs - interstitial pneumonia, sclerosis, adhesive pleurisy;
Digestive system - esophagitis, duodenitis, spruce-like syndrome;
Kidney - true scleroderma kidney, chronic diffuse glomerulonephritis, focal glomerulonephritis;
Nervous system - polyneuritis, neuropsychiatric disorders, autonomic changes.
The severity of skin thickening is assessed by palpation using a 4-point system:
0 - no seal;
1 - slight compaction;
2 - moderate compaction;
3 - pronounced compaction (impossibility of folding).
In recent years, prescleroderma, diffuse cutaneous scleroderma, limited scleroderma, including the syndrome CREST(this syndrome will be discussed below), and scleroderma without scleroderma (this option is very rare and accounts for no more than 5% of all patients with SSc).
The chronic course, which is most characteristic of SSD, is characterized by gradually developing vasomotor disorders of the Raynaud's syndrome type and the resulting trophic disorders, which serves as the only sign of the disease for many years. Subsequently, thickening of the skin and periarticular tissues occurs with the development of osteolysis and slowly progressive sclerotic changes in the internal organs (esophagus, heart, lungs).
A rapidly progressing course is characterized by the appearance of severe fibrous peripheral and visceral lesions already in the first year of the disease and frequent kidney damage of the type of true scleroderma kidney (most common reason death of patients).
Considering the progressive nature of the disease, to assess the evolution and degree of growth of the pathological process, three stages of the course are distinguished:
Stage I - initial manifestations - mainly articular changes in subacute, and vasospastic - in chronic;
Stage II - generalization of the process - polysyndromic and polysystemic damage to many organs and systems;
Stage III - terminal - the predominance of severe sclerotic, dystrophic or vascular-necrotic processes (often with distinct dysfunctions of one or more organs).
Clinical picture
The clinical picture of the disease is polymorphic and polysyndromic, reflecting its generalized nature. There is practically no organ or system that could not be involved in the pathological process.
On first stage of diagnostic search receive information on the basis of which one can form an idea of the diagnosis and type of onset of the disease, the nature of the process, the involvement of various organs in the pathological process, previous treatment and its effectiveness, as well as complications.
More often, the disease begins with skin lesions, and then organ damage gradually joins (typical form). In other cases (atypical form), the clinical picture is dominated from the very beginning by damage to internal organs with minimal skin changes, which makes diagnosis difficult. As the disease progresses, you can get an idea of the nature of its course (acute, subacute and chronic).
Complaints from patients when internal organs are involved in the pathological process correspond to subjective symptoms when they are damaged in one way or another (pleurisy, arthritis, Raynaud's syndrome, duodenitis, etc.). At the same time, patients may present complaints that are most characteristic of SSD: difficulty swallowing and choking when swallowing as a result of damage to the upper
parts of the esophagus. Vasospastic disorders in Raynaud's syndrome are not limited to the fingers, but extend to the hands and feet. Patients often experience a feeling of numbness in the lips, any part of the face and the tip of the tongue. They complain of dryness of the oral mucosa and conjunctiva, as well as the inability to cry (no tears). Damage to the skin of the face is expressed in a feeling of tightness of the skin and mouth (difficulty opening the mouth). As a rule, body temperature is not elevated. Weight loss (sometimes significant) is usually noted with the progression and generalization of the disease.
After the first stage (with a long course of the disease), a definite conclusion about the diagnosis can be made. It can be extremely difficult to do this at the very beginning, since the symptoms of SSc are in many ways reminiscent of other conditions from the DTD group (SLE, RA, MD), and with mono or oligosyndromicity - other diseases characterized by damage to only one organ (heart, lungs, etc.) .
Ha the second stage of the diagnostic search receive data indicating damage to organs and systems and their functional failure. With a detailed clinical picture of the disease, skin lesions are noted in the vast majority of patients. It is expressed in the sequential development of edema, induration, and then atrophy with predominant localization on the face and hands. Trophic changes in the skin are also possible in the form of depigmentation, emphasized vascular pattern and telangiectasia. Damage to the mucous membranes is expressed in increased dryness. Ulcerations and pustular rashes may occur on the skin; hair falls out, nails become deformed. In the final stage of the disease, the skin of the face becomes dense and cannot be folded. The face is amicable, mask-like. The shape of the mouth is characteristic: the lips are thin, gathered in folds that cannot be straightened, and the ability to open the mouth wide is gradually lost (the “pouch” symptom).
Vasospastic changes in Raynaud's syndrome in the form of whitening of the skin surface are found in the face, lips, hands and feet.
Damage to the joints is expressed in their defiguration due to the predominant damage to periarticular tissues, as well as true scleroderma polyarthritis with a predominance of exudative-proliferative or fibrous-indurative changes. The development of a scleroderma hand is characteristic: shortening of the fingers due to osteolysis of the nail phalanges, thinning of their tips, deformation of the nails and mild flexion contractures. This hand is compared to a bird's paw (sclerodactyly).
Muscle damage, morphologically representing fibrous interstitial myositis or myositis with dystrophic and necrotic changes, is expressed in myasthenic syndrome, atrophy, reduction muscle mass and movement disorders. Painful lumps (calcifications) may form in the muscles. Especially often, deposits of calcium salts are found in the soft tissues of the fingers.
Gastrointestinal lesions (esophagitis, duodenitis, malabsorption syndrome or persistent constipation) are mainly detected at the first and third stages of the diagnostic search.
Damage to the respiratory system is expressed in the form of pneumonitis, which occurs acutely or chronically, sluggishly. Physical data are extremely scarce; in severe cases, only pulmonary emphysema is detected. Significantly more information is provided by x-ray examination, which provides significant assistance in identifying bilateral basal pneumosclerosis, characteristic of SSc.
With severe pneumosclerosis and its long-term existence, it develops pulmonary hypertension, leading first to hypertrophy of the right ventricle, and then to its failure. Pulmonary hypertension manifests itself with cyanosis, an accent of the second tone in the second intercostal space to the left of the sternum, shortness of breath, a sharp decrease in exercise tolerance and a pronounced increase in pulsation in the epigastric region caused by hypertrophy of the right ventricle.
Heart damage occupies the main place among the visceral symptoms of SSc both in frequency and in its impact on the outcome of the disease. SSc is characterized by so-called primary cardiosclerosis, which is not associated with previous necrotic or inflammatory changes in the myocardium. An enlarged heart (sometimes significant) is noted, as well as cardiac arrhythmias in the form of extrasystole or AF. Damage to the endocardium leads to the development of heart disease, almost always to mitral regurgitation. The combination of the latter with cardiosclerosis in some cases can cause the development of heart failure with all its characteristic signs. Pericarditis in SSc is rarely observed and more often it occurs as dry.
Damage to small vessels - scleroderma angiopathy - manifests itself with vasomotor disturbances (Raynaud's syndrome) and is characterized by paroxysmal vasospasm with a characteristic sequence of changes in the color of the skin of the fingers (whitening, cyanosis, redness), a feeling of tension and pain. In severe cases, Raynaud's syndrome leads to hemorrhages, necrosis of finger tissue and telangiectasia.
Kidney damage in SSc (in 80% of patients) is caused by pathological changes in blood vessels, but not by the development of fibrosis. Most severe symptom- scleroderma renal crisis, usually developing in the first five years of the disease in patients with a diffuse form of SSc and manifesting with malignant hypertension (BP more than 170/130 mm Hg), rapidly progressing renal failure, hyperreninemia (in 90% of cases) and nonspecific signs . The latter are represented by shortness of breath, headache and convulsions. When kidney damage occurs in the form of isolated changes in urinary sediment, no significant pathological signs are detected during physical examination.
Damage to the nervous system is based on vascular, dystrophic and fibrotic changes, represented by symptoms of polyneuritis with impaired reflexes and sensitivity.
Thus, after the second stage, a multi-organ lesion is detected with predominant damage to the skin and its derivatives. The degree of changes is very different - from subclinical to significantly pronounced. Possibility of establishing the diagnosis of SSc with predominant skin lesions
higher than with the predominance of visceral disorders. In the latter case, if damage to any one organ (kidneys, heart) comes to the fore, there are prerequisites for making diagnostic errors.
You can:
Determine the degree of activity of the process;
To clarify the severity of damage to internal organs;
Carry out differential diagnosis with other diseases from the group of chronic chronic diseases.
In determining the degree of disease activity, nonspecific acute-phase indicators are of greatest importance, which include:
Dysproteinemia with increased concentrations of α2 and γ-globulins;
Increasing the content of SRP;
Increased fibrinogen concentration;
Increase in ESR.
The existence and severity of immune disorders can be judged by the definition of RF (detected in 40-50% of cases), antinuclear antibodies (in 95%) and LE cells (in 2-7% of patients). In contrast to SLE, all these indicators in SCD are detected in significantly lower titers and less frequently.
The greatest diagnostic significance is attached to the so-called scleroderma antibodies.
Scl-70 antibodies are more often found in diffuse forms of SSc (40%). Their presence in combination with carriage of HLA-DR3/DRw52 is an unfavorable prognostic factor in patients with Raynaud's syndrome, increasing the risk of developing pulmonary fibrosis in SSc by 17 times.
Antibodies to the centromere (chromosome element) are found in 20-30% of patients (most of them have signs of CREST syndrome).
Antibodies to RNA polymerase I and III are highly specific for SSc. They are present predominantly in patients with the diffuse form and are associated with kidney damage and a poor prognosis.
If the kidneys are damaged, proteinuria, expressed to varying degrees, is noted in combination with minimal changes in urinary sediment (microhematuria, cylindruria). With a true scleroderma kidney (the development of necrosis of the renal tissue due to damage to the renal vessels), acute renal failure may develop with an increase in creatinine in the blood.
In SSc, there is a dissociation between the pronounced morphological changes in the renal tissue and blood vessels detected during puncture biopsy and the relatively moderate clinical (including laboratory) signs of kidney damage. If hypertension develops as a result of kidney damage, changes in the fundus of the eye are noted (narrowing of the arteries and dilatation of the veins).
If the heart is damaged, the ECG shows nonspecific changes in the final part of the ventricular complex (decreased amplitude and wave inversion T), and sometimes - intraventricular conduction disturbances. X-ray visualizes an enlarged heart. X-ray helps
detect calcification of the muscles and soft tissues of the fingers, as well as differentiate changes in the joints in SSc with disorders in RA (in SSD there are no erosions of the articular surfaces). In 60-70% of cases, x-rays show damage to the gastrointestinal tract (especially the esophagus and intestines). Changes in the esophagus are represented by its diffuse expansion combined with narrowing in the lower third, weakening of peristalsis and some rigidity of the walls.
Biopsy of the skin, synovium and muscles reveals fibrous changes characteristic of SSc, as well as vascular damage. Morphological examination data are not decisive in establishing the diagnosis.
Diagnostics
Diagnosis of the disease is based on the detection of major and minor diagnostic criteria.
Major criteria include proximal scleroderma - symmetrical thickening, compaction and induration of the skin of the fingers and the skin located proximal to the metacarpophalangeal and metatarsophalangeal joints. Changes may affect the face, neck and torso (chest and abdomen).
Minor criteria:
Sclerodactyly - the above skin changes, limited to the involvement of the fingers in the pathological process;
Scarring on the fingertips or loss of finger pad substance;
Bilateral basal pulmonary fibrosis.
A patient with SSc must have either a major criterion (major) or at least two minor criteria. Sensitivity - 97%, specificity - 98%.
The most typical combination of SSc is calcification, Raynaud's syndrome, esophagitis, sclerodactyly and telangiectasia (syndrome CREST- according to the first letters of the English names of the listed symptoms).
Diagnosis of SSc in the early stages is based on the detection of a triad of initial signs (occurring most early): Raynaud's syndrome, articular syndrome (usually polyarthralgia) and dense swelling of the skin. Much less often, one of the visceral localizations of the process is detected at an early stage.
Significant difficulties in diagnosing SSc are associated with the absence of a characteristic skin syndrome in patients with severe polysyndromic lesions of internal organs (the so-called SSD without scleroderma). In these cases, X-ray examination provides significant assistance, allowing to detect impaired motility of the esophagus and its expansion, as well as dilatation of the duodenum and colon.
Differential diagnosis
SSc should be differentiated from a number of diseases and, above all, from other DCTs, as well as from diseases whose clinical picture is very similar to that of damage to any organ in SSD (provided it is treated
mining). For example, with scleroderma damage to the heart, differential diagnosis is carried out with atherosclerotic cardiosclerosis, rheumatic carditis and nonspecific myocarditis; in case of pulmonary damage - with chronic pneumonia, tuberculosis and occupational lung diseases (pneumoconiosis); if the esophagus is affected, cancer of the esophagus should be excluded.
The basis for differential diagnosis is the detection of signs typical of SSc.
The predominance of peculiar skin lesions in combination with Raynaud's syndrome and slightly expressed laboratory data in SSc, in contrast to skin changes in SLE, combined with higher activity of the pathological process (according to laboratory tests).
Unlike SLE, in SSc, damage to internal organs is not combined with pronounced immune disorders (ANF, RF and antibodies to DNA are detected in lower titers, the frequency of detection and the number of LE cells are also low).
Articular syndrome in SSc, unlike RA, is combined with muscle contractures, calcium deposition in soft tissues and muscles, fibrous ankylosis and osteolysis of the terminal phalanges. There are no destructive changes in bone tissue in SSc; damage to periarticular tissue predominates.
Unlike ischemic heart disease, cardiac damage in SSc is not accompanied by anginal pain. There are no signs of previous MI on the ECG. Unlike rheumatic lesions hearts, with SSD stenoses never develop (mitral, aortic orifice); Usually there is moderate isolated mitral regurgitation.
The dominant lesion of any system or organ in SSc is always combined with skin and muscle changes and Raynaud's syndrome. For the clinical picture of other diseases (chronic pneumonia, atherosclerotic cardiosclerosis, intestinal diseases, peptic ulcer), from which it is necessary to differentiate SSD, is characterized by monosyndromy.
In SSc, skin changes and Raynaud's syndrome dominate, while in DM, muscle damage comes to the fore in combination with a peculiar lilac-colored periorbital edema (“spectacles symptom”).
Glucocorticoids in SSc do not have such a dramatic positive effect as in SLE.
In some cases, when SSD manifests itself as articular, skin and asthenovegetative syndrome, only long-term follow-up allows a correct diagnosis to be made.
The formulation of a detailed clinical diagnosis should take into account the categories given in the working classification. The diagnosis should reflect:
The nature of the current;
Stage;
Clinical and morphological characteristics of damage to organs and systems of the body, indicating the stage of functional failure (for example,
measures, for pneumosclerosis - the stage of pulmonary failure, for kidney damage - the stage of renal failure, etc.).
Treatment
Treatment of SSD should be comprehensive and take into account the following aspects:
Impact on vascular complications and, first of all, on Raynaud's syndrome;
Impact on the development of fibrotic changes;
Immunosuppression and anti-inflammatory effect;
Impact on local symptoms of the disease.
Avoid exposure to cold, smoking, local vibration, stressful situations and taking drugs that cause peripheral vascular spasm (β-blockers without vasodilating effect).
Drug treatment of Raynaud's syndrome involves the prescription of slow calcium channel blockers - amlodipine (5-20 mg/day), long-acting nifedipine (30-90 mg/day), felodipine (5-10 mg/day), as well as long-acting verapamil action (240-480 mg/day) or diltiazem (120-360 mg/day).
A good effect is achieved by taking pentoxifylline orally (400 mg 3 times a day). Antiplatelet agents are also prescribed - dipyridamole (300-400 mg/day) or ticlopidine (500 mg/day).
In critical situations (pulmonary hypertension, gangrene, renal crisis), synthetic prostaglandins are administered intravenously over 6-24 hours for 2-5 days: alprostadil (0.1-0.4 mcg/kg per minute) or iloprost (0. .5-2 ng/kg per minute).
A drug that destroys internal bonds in the collagen molecule and inhibits excess collagen formation is penicillamine. It is prescribed for subacute cases, rapidly increasing indurative skin changes and symptoms of progressive generalized fibrosis on an empty stomach every other day at a dose of 250-500 mg/day. Previously recommended high doses (750-1000 mg/day) do not increase the effectiveness of treatment, but the incidence of side effects increases significantly. When treating with penicillamine, it is necessary to monitor urine laboratory values, since proteinuria may develop 6-12 months after the start of treatment. When it increases to 0.2 g/day, the drug is discontinued. For severe skin lesions, enzyme therapy is recommended. Prescribe subcutaneous injection of hyaluronidase near the affected areas or electrophoresis with this drug.
Anti-inflammatory and cytotoxic drugs are used in the early (inflammatory) stage of SSc and in rapidly progressing disease.
Glucocorticoids in small doses (15-20 mg/day) are used for progressive diffuse skin lesions and obvious clinical signs of inflammatory activity (myositis, alveolitis, serositis, refractory
arthritis and tenosynovitis). Taking large doses is not recommended (risk of developing scleroderma renal crisis).
When prescribed at a dose of 2 mg/kg per day for 12 months, cyclophosphamide reduces skin itching only in patients with the diffuse form of SSc.
Methotrexate is prescribed when SSD is combined with RA or PM.
In scleroderma renal crisis, to eliminate vascular spasms and prevent the development of scleroderma kidney, ACE inhibitors (captopril 100-150 mg/day, enalapril 10-40 mg/day) are used under blood pressure control.
In case of damage to the esophagus, in order to prevent dysphagia, frequent small meals and the exclusion of eating later than 18 hours are recommended. Treatment of dysphagia involves the administration of prokinetics (metoclopramide at a dose of 10 mg 3-4 times a day). For reflux esophagitis, omeprazole is prescribed (orally 20 mg/day).
The impact on local symptoms of the disease involves the application of a 25-50% solution of dimethyl sulfoxide. During periods of inactivity of the pathological process, exercise therapy and massage can be recommended.
Forecast
In SSc, the prognosis is determined by the course and stage of development. It is noted that the more time separates the advanced stage from the onset of the first signs of the disease (in particular, Raynaud's syndrome), the more favorable the prognosis. Five-year survival rates range from 34 to 73%, with an average of 68%. The risk of death in SSc is 4.7 times higher than in the population.
Predictors of poor prognosis:
Diffuse form of the disease;
Age of onset of disease over 47 years;
Male gender;
Pulmonary fibrosis, pulmonary hypertension, arrhythmias, kidney damage in the first three years of the disease;
Anemia, high ESR, proteinuria at the onset of the disease.
Prevention
The risk group includes persons with a tendency to vasospastic reactions, polyarthralgia, as well as relatives of patients suffering from various diffuse connective tissue diseases. They should not be exposed to provoking factors (cooling, vibration, injury, exposure to chemical substances, infectious agents, etc.). Patients with SSc are registered at the dispensary. Systematically carried out treatment (in particular, properly selected supportive therapy) - the best remedy prevention of exacerbations.
DERMATOMYOSITIS (POLYMYOSITIS)
DM is a systemic inflammatory disease of skeletal, smooth muscle and skin. Involvement of internal organs in the pathological process is less common. In the absence of skin lesions, the term “polymyositis” is used.
The main symptom of the disease is severe muscle weakness due to progressive severe necrotizing myositis with predominant damage to the muscles of the proximal limbs. As the disease progresses, muscle tissue atrophies and is replaced by fibrous tissue. Similar processes occur in the myocardium. Dystrophic changes develop in parenchymal organs. The pathological process also involves the vessels of muscles, internal organs and skin.
DM (PM) is a rare disease. The frequency of its occurrence in the population ranges from 2 to 10 cases per 1 million population per year. The disease affects people of mature age (40-60 years), more often men than women (ratio 2:1).
Etiology
There are two forms of DM (DM) - idiopathic and secondary (tumor). The etiology of idiopathic DM is unclear, but factors contributing to the manifestation and subsequent exacerbation of this disease are known:
Insolation;
Hypothermia;
Infectious lesions (acute respiratory infections, flu, sore throat, etc.);
Hormonal changes (menopause, pregnancy, childbirth);
Emotional stress;
Physical trauma, surgery;
Sensitization by drugs (chlorpromazine, insulin preparations, antibiotics, penicillamine);
Vaccination;
Contact with epoxy resins, photosolvents;
Physiotherapeutic procedures.
Probably, hereditary genetic predisposition is important: patients have antigens B-8/DR3, B14 and B40 of the HLA system. This is closely related not to the disease itself, but to certain immune disorders and, first of all, to the overproduction of myosin-specific autoantibodies.
Tumor (secondary) DM accounts for 25% of all cases of the disease and develops in patients suffering from malignant tumors. Most often, DM occurs with cancer of the lung, intestine, prostate, ovary, and also with hematological malignancies. The occurrence of DM in individuals over the age of 60 years almost always indicates its tumor origin.
Pathogenesis
Under the influence of a virus and genetic predisposition or tumor antigens, a disruption (dysregulation) of the immune response occurs, expressing
resulting from an imbalance of the B- and T-lymphocyte systems: the body produces antibodies to skeletal muscles and develops sensitization of T-lymphocytes to them. The antigen-antibody reaction and the cytotoxic effect of T-lymphocytes sensitized to muscles contribute to the formation and deposition of immune complexes in the muscles and microvasculature of various organs. Their elimination leads to the release of lysosomal enzymes and the development of immune inflammation in the muscles and internal organs. During inflammation, new antigens are released, promoting further formation of immune complexes, which leads to chronicity of the disease and involvement in the pathological process earlier. healthy muscles. The main links in the pathogenesis of DM are presented in Fig. 7-2.
Rice. 7-2. Pathogenesis of dermatomyositis
Clinical picture
The clinical picture of the disease is systematic and polysyndromic.
Main syndromes:
Muscular (myositis, muscle atrophy, calcification);
Skin (erythema, skin swelling, dermatitis, pigmentation and depigmentation, telangiectasia, hyperkeratosis, urticaria);
Articular (arthralgia, damage to periarticular tissues, rarely true arthritis);
Visceral (myocarditis, cardiosclerosis, pneumonitis, aspiration pneumonia, pulmonary fibrosis, gastrointestinal bleeding, myoglo-
bulinuric kidney with the development of acute renal failure, polyneuropathy). Highlight following periods course of the disease:
I period (initial) - lasts from several days to 1 month or more, manifests only with muscle and (or) skin changes;
II period (manifest) - a detailed picture of the disease;
III period (terminal) - presented dystrophic changes internal organs and signs of their severe functional insufficiency (complications may develop).
There are three forms of the disease:
Acute form, when generalized damage to skeletal muscles quickly increases, leading to complete immobility of the patient. Muscle damage progresses pharyngeal ring and esophagus (dysphagia, dysarthria). Damage to internal organs (especially the heart) develops rapidly with death within 2-6 months from the onset of the disease;
Subacute form with a slower, gradual increase in symptoms. Severe muscle damage and visceritis occur after 1-2 years;
Chronic form with a long cyclical course. The processes of atrophy and sclerosis predominate. Local muscle damage is possible.
On first stage of diagnostic search receive information about the nature of the onset of the disease - acute (increase in body temperature to 38-39 ° C, skin erythema and muscle pain) or gradual (moderate weakness, mild myalgia and arthralgia, worsening after physical activity, insolation or other adverse effects).
The most typical complaints are caused by muscle damage: patients note weakness, cannot sit or stand on their own, it is extremely difficult for them to climb stairs, and muscle pain is not uncommon. Muscle weakness and soreness are localized symmetrically in the proximal limbs, back and neck.
When the pharyngeal muscles are affected, patients complain of choking when swallowing, and liquid food pours out through the nose. Nasal tone of voice and hoarseness are caused by damage to the muscles of the larynx.
When the skin is affected, patients note a persistent change in its color in places exposed to the sun (neckline, face, hands), as well as on the outer surfaces of the thighs and legs. The occurrence of purple-colored paraorbital edema (“spectacles symptom”) is characteristic. When the mucous membranes are affected, patients complain of dryness, burning in the eyes and lack of tears (“dry” syndrome).
Involvement of various organs in the pathological process is expressed by symptoms characteristic of myocarditis, cardiosclerosis, pneumonitis, glomerulonephritis, polyneuritis, arthritis, etc.
Information about the treatment being carried out allows us to judge its correct selection, and indirectly, the nature of the course: the use of aminoquinoline drugs indicates a chronic course, the use of prednisolone and cytostatics indicates a more acute course.
On the second stage of the diagnostic search with a detailed clinical picture of the disease, first of all, symmetrical muscle damage is noted: dense, doughy to the touch, they are increased in volume and painful on palpation. When the facial muscles are affected, a certain mask-like appearance of the face is noticeable. Subsequently, muscle atrophy occurs, especially pronounced on the side of the shoulder girdle. The respiratory muscles and diaphragm are also damaged. When palpating the muscles, one can detect local compactions - calcifications, which are also located in the subcutaneous fatty tissue. Calcinosis often develops in young people with widespread muscle damage during the transition from acute to subacute or chronic. A decrease in body weight of 10-20 kg is often noted.
Skin lesions are not a mandatory sign of DM, but when it exists, swelling, erythema (above the joints - supra-articular erythema, in the periungual areas in combination with micronecrosis in the form of dark spots - Gottron's syndrome), capillaritis, petechial rashes and telangiectasia are noted on the exposed parts of the body. Erythema is highly persistent, has a bluish tint, and is accompanied by itching and peeling. A typical “spectacle symptom” is erythema around the eyes. Redness, peeling and cracking of the skin of the palms (“mechanic’s or artisan’s hand”), brittle nails and increased hair loss are often noted.
Severe Raynaud's syndrome is quite often recorded.
The signs of visceral lesions in DM, as well as in SSc, are not too bright, unlike in SLE. One can note a known dissociation between the severity of pathomorphological changes in organs and their clinical manifestation. Heart damage (myocarditis, cardiosclerosis) is represented by such nonspecific signs as an increase in its size, dullness of tones, tachycardia and rhythm disturbances in the form of extrasystole. Severe changes in the myocardium can lead to symptoms of heart failure.
Damage to the lungs in the form of pneumonitis is accompanied by extremely scanty symptoms. Developing fibrosis is detected by signs of pulmonary emphysema and respiratory failure. Aspiration pneumonia is characterized by all the typical symptoms.
Damage to the gastrointestinal tract is characterized by dysphagia: regurgitation of solid food and pouring of liquid food through the nose. Pathological changes in the vessels of the stomach and intestines can lead to gastrointestinal bleeding. Sometimes a moderate enlargement of the liver is noted, less often - hepatolienal syndrome with enlarged lymph nodes.
Neurological disorders are represented by changes in sensitivity: peripheral or radicular hyperesthesia, hyperalgesia, paresthesia and areflexia.
On third stage of diagnostic search Research methods that allow one to assess the severity of the inflammatory process and the prevalence of muscle damage provide significant assistance.
The severity of the process can be judged by nonspecific acute-phase indicators (increased ESR, increased fibrinogen and CRP levels,
hyper-a 2 -globulinemia) and signs of immune changes (low RF titer, increased content of γ-globulins, antibodies to nucleoprotein and soluble nuclear antigens, antibodies to Mi2, Jol, SRP, and in the case of idiopathic DM - increased concentration of IgG).
In a chronic, sluggish course of the disease, changes in acute phase parameters may be absent (ESR is often normal).
The prevalence of muscle damage is characterized by a number of biochemical changes. The creatine/creatinine index increases, which is associated with the presence of creatine in the urine with a decrease in creatininuria. With significant muscle damage, myoglobinuria may occur. An increase in transaminase activity is not typical for skeletal muscle damage. In some patients with myopathic syndrome, this suggests hepatitis.
Immunological examination reveals myositis-specific antibodies. These include antibodies to transfer RNA aminoacyl synthetases (antisynthetase antibodies) and, primarily, antibodies to histidyl-tRNA synthetase (Jo1). Jo1 antibodies are found in half of patients with DM (DM), while other antisynthetase antibodies are extremely rare (5%). The production of antisynthetase antibodies is associated with the development of the so-called antisynthetase syndrome, characterized by acute onset, fever, symmetrical arthritis, interstitial lung disease, Raynaud's phenomenon and mechanic's hand lesions.
DM of tumor origin in men is characterized by the detection of prostate-specific antigen, in women - CA-125 (ovarian tumor antigen). In addition, if the tumor is located at a different location, other tumor-specific antigens can be detected.
Electromyography provides significant assistance in diagnosing muscle damage, allowing one to detect normal electrical activity of muscles in a state of voluntary relaxation and low-amplitude activity during voluntary contractions.
A biopsy of the skin and muscles reveals a picture of severe myositis with loss of cross-striations of muscle fibers, fragmentation, granular and waxy degeneration, as well as foci of necrosis, lymphoid-plasma cell infiltration and fibrosis. Muscle biopsy is performed to confirm the diagnosis of DM even in the presence of characteristic clinical, laboratory and instrumental signs of the disease. The most informative is a biopsy of a muscle involved in the pathological process, but without significant atrophy.
Other research methods (ECG, X-ray and endoscopic) are necessary for:
Assessment of the condition of affected internal organs;
Search for a tumor if DM of tumor origin is suspected.
Diagnostics
To diagnose DM (DM), the following diagnostic criteria should be used.
Skin damage:
Heliotrope rash (purple-red rash on the eyelids);
Gottron's sign (purple-red scaly atrophic erythema or spots on the extensor surface of the hands over the joints);
Erythema on the extensor surface of the limbs above the elbow and knee joints.
Proximal muscle weakness (upper and lower limbs and trunk).
Increased activity of CPK or aldolase in the blood.
Muscle pain on palpation or myalgia.
Myogenic changes with electromyography (short polyphasic potentials of motor units with spontaneous fibrillation potentials).
Detection of Jo1 antibodies (antibodies to histidyl-tRNA synthetase).
Non-destructive arthritis or arthralgia.
Signs of systemic inflammation (increased body temperature more than 37 ° C, increased concentration of CRP or ESR more than 20 mm/h).
Morphological changes consistent with inflammatory myositis (inflammatory infiltrates in skeletal muscles with degeneration or necrosis of muscle fibers, active phagocytosis or signs of active regeneration).
If at least one type of skin lesion and at least four other signs are detected, the diagnosis of DM is reliable (sensitivity - 94.1%, specificity - 90.3%).
The presence of at least four signs corresponds to the diagnosis of PM (sensitivity - 98.9%, specificity - 95.2%).
Differential diagnosis
Despite the high sensitivity and specificity of the criteria, the diagnosis of DM (DM) presents great difficulties, especially at the onset of the disease.
DM (PM) should be differentiated from infectious and neurological diseases, SSc, SLE and RA. The differential diagnosis is based on the following changes:
Persistence of articular syndrome in RA, detection of erosions of the articular surfaces of bones during X-ray examination, absence of skin and muscle changes characteristic of DM.
Unlike SLE, in DM visceral disorders are not so pronounced and occur much less frequently. The clinical picture of DM is dominated by muscle damage, and laboratory parameters (especially immunological) are changed to a much lesser extent.
Unlike SSD, skin changes in DM are of a completely different nature: there are no typical changes in the hands, and muscle syndrome (including severe muscle weakness) is considered to be the leading one. However, the differential diagnosis of SSc and DM is 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.
When adynamia dominates and reflexes are impaired, there is a need for differential diagnosis with neurological diseases, which is carried out with joint observation of the patient by a therapist and a neurologist.
The formulation of a detailed clinical diagnosis of DM should reflect:
Flow period;
Flow shape;
Clinical and morphological characteristics of damage to systems and organs, indicating leading syndromes and the existence or absence of functional failure of organs (systems).
Treatment
The main task is to suppress the activity of immune reactions and the inflammatory process, as well as normalize the function of individual, most affected organs and systems. Early start treatment (within the first 3 months from the onset of symptoms) is associated with a more favorable prognosis than later.
Glucocorticoids have the best effect: for DM, it is preferable to prescribe prednisolone (1-2 mg/kg per day). During the first weeks, the daily dose should be divided into three doses, and then taken all once in the morning, since improvement in the patient’s condition develops more slowly than with SLE or SSc (on average, after 1-3 months). If there is no positive dynamics within 4 weeks, the dose of glucocorticoids should be increased. After achieving the effect (normalization of muscle strength and CPK activity), the dose of prednisolone is very slowly reduced to maintenance, every month - by 1/4 of the total. Dose reduction must be carried out under strict clinical and laboratory supervision.
Pulse therapy is rarely effective. It is prescribed for rapid progression of dysphagia (risk of aspiration pneumonia) and the development of systemic lesions (myocarditis, alveolitis).
If treatment with prednisolone is not effective or cannot be prescribed due to intolerance and complications, then cytostatic drugs should be used.
Currently, early administration of methotrexate is recommended, which allows patients to be quickly transferred to maintenance doses of prednisolone. Methotrexate is prescribed orally, subcutaneously or intravenously at a dose of 7.5-25 mg/week. Intravenous administration The drug is recommended if it is insufficiently effective or poorly tolerated when taken orally. It should be remembered that the lack of effect from treatment with prednisolone indicates the possibility of the existence of tumor ANF, therefore, before prescribing cytotoxic drugs, an extensive oncological search should be carried out to exclude a malignant tumor.
Patients with prednisolone-resistant forms of the disease are prescribed oral cyclosporine at 2.5-5.0 mg/kg per day.
Azathioprine is inferior to methotrexate in effectiveness. The maximum effect develops later (on average after 6-9 months). The drug is prescribed to be taken orally at 100-200 mg/day.
Cyclophosphamide is the drug of choice for interstitial pulmonary fibrosis (2 mg/kg per day).
Aminoquinoline drugs (chloroquine, hydroxychloroquine) are used in the following situations:
In the chronic course of the disease without signs of process activity (to control skin lesions);
When reducing the dose of prednisolone or cytostatics to reduce the risk of possible exacerbation.
Plasmapheresis should be prescribed to patients with severe DM (PM) resistant to other treatment methods in combination with glucocorticoids and methotrexate or cytostatic drugs.
In recent years, TNF-α inhibitors have been increasingly used for treatment. A promising treatment option involves the use of rituximab. The maximum effect develops 12 weeks after the first injection, which is associated with a decrease in the content of CD20+ B-lymphocytes in the peripheral blood.
Forecast
Currently, due to the use of prednisolone and cytostatics in acute and subacute forms, the prognosis has improved significantly: the five-year survival rate is 90%. If the disease becomes chronic, the patient’s ability to work can be restored.
The prognosis for secondary (tumor) DM depends on the effectiveness of surgery: with a successful operation, all signs of the disease may disappear. Factors that worsen the prognosis of the disease: old age, late diagnosis, 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
Warnings of exacerbations ( secondary prevention) is achieved by carrying out supportive treatment, sanitizing foci of infection and increasing the body's resistance. The patient's relatives can carry out primary prevention (excluding overload, insolation, hypothermia).
Mixed connective tissue disease is a rare disorder characterized by the coexistence of systemic lupus erythematosus, systemic scleroderma, polymyositis or dermatomyositis, and rheumatoid arthritis with very high titers of circulating antinuclear ribonucleoprotein (RNP) autoantibodies. The development of hand edema, Raynaud's phenomenon, polyarthralgia, inflammatory myopathy, esophageal hypotension and pulmonary dysfunction is characteristic. Diagnosis is based on analysis of the clinical picture of the disease and detection of antibodies to RNP in the absence of antibodies characteristic of other autoimmune diseases. Treatment is similar to that for systemic lupus erythematosus and involves the use of glucocorticoids for moderate to severe disease.
Mixed connective tissue disease (MCTD) occurs throughout the world in all races. The maximum incidence occurs in adolescence and the second decade of life.
Clinical manifestations of mixed connective tissue disease
Raynaud's phenomenon can 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 changes in the nature of clinical manifestations.
The most common condition is swelling of the hands, especially the fingers, causing them to resemble sausages. Skin changes resemble those seen in lupus or dermatomyositis. Skin lesions similar to those seen in dermatomyositis, as well as ischemic necrosis and ulceration of the fingertips, are less common.
Almost all patients complain of polyarthralgia, 75% have obvious signs of arthritis. Arthritis usually does not lead to anatomical changes, but erosions and deformities may occur, as with rheumatoid arthritis. Proximal muscle weakness, with or without tenderness, is common.
Kidney damage occurs in approximately 10% of patients and is often mild, but in some cases it can lead to complications and death. In mixed connective tissue disease, sensory neuropathy of the trigeminal nerve develops more often than in other connective tissue diseases.
Diagnosis of mixed connective tissue disease
Mixed connective tissue disease should be suspected in all patients suffering from SLE, scleroderma, polymyositis or RA if additional clinical manifestations develop. First of all, it is necessary to conduct a study for the presence of antinuclear antibodies (ARA), antibodies to the extractable nuclear antigen and RNP. If the results obtained are consistent with 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-tRNA) should be performed to exclude 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 existing symptoms of damage to organs and systems: myositis, damage to the kidneys and lungs require appropriate diagnostic methods (in particular, MRI, electromyography, muscle biopsy).
Almost all patients have high titers (often >1:1000) of antinuclear antibodies detected by fluorescence. Antibodies to the extractable nuclear antigen are usually present in very high titers (>1:100,000). The presence of antibodies to RNP is characteristic, while antibodies to the Sm component of the extracted nuclear antigen are absent.
In sufficiently high titers, rheumatoid factor can be detected. ESR is often elevated.
Prognosis and treatment of mixed connective tissue disease
Ten-year survival rate is 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. Some patients may be able to maintain long-term remission without any treatment.
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 it is started early enough. Mild disease is successfully controlled with salicylates, other NSAIDs, antimalarial drugs, in some cases - low doses of glucocorticoids. Severe damage to organs and systems requires the administration of glucocorticoids in high doses (for example, prednisolone at a dose of 1 mg/kg 1 time per day, orally) or immunosuppressants. If systemic sclerosis develops, appropriate treatment is carried out.
DIFFUSE DISEASES OF CONNECTIVE TISSUE (DCTD), or collagenoses (a term of historical significance), is a group of diseases characterized by systemic immunoinflammatory damage to connective tissue and its derivatives. This concept is a group one, but not a nosological one, and therefore this term should not denote individual nosological forms. CTDs combine a fairly large number of diseases. The most common are systemic lupus erythematosus (SLE), systemic scleroderma (SSc), dermatomyositis (DM); This group of diseases also includes rheumatic fever(traditionally described in the section on diseases of the cardiovascular system). It has now been proven that with CTD, profound disturbances of immune homeostasis occur, expressed in the development of autoimmune processes, i.e. reactions of the immune system, accompanied by the appearance of antibodies or sensitized lymphocytes directed against antigens of the body’s own (autoantigens).
The basis of autoimmune pathology is an immunoregulatory imbalance, expressed in the inhibition of suppressor and increase in “helper” activity of T-lymphocytes, followed by activation of B-lymphocytes and hyperproduction of autoantibodies of various specificities.
There are a number of common features that unite DZST:
The common pathogenesis is a violation of immune homeostasis in the form of uncontrolled production of autoantibodies and the formation of antigen-antibody immune complexes circulating in the blood and fixed in
Tissues with the subsequent development of a severe inflammatory reaction (especially in the microvasculature, kidneys, joints, etc.);
Similarity of morphological changes (fibrinoid change in the basic substance of connective tissue, vasculitis, lymphoid and plasma cell infiltrates, etc.);
Chronic course with periods of exacerbations and remissions;
Exacerbation under the influence of nonspecific influences (infection, insolation, vaccination, etc.);
Multisystem damage (skin, joints, serous membranes, kidneys, heart, lungs);
The therapeutic effect of immunosuppressive drugs (glucocorticosteroids, cytostatics).
All diseases included in this group are distinguished by independent clinical and morphological manifestations, therefore, in each specific case one should strive for an accurate nosological diagnosis.
This chapter discusses the diagnostic search for systemic lupus erythematosus, systemic scleroderma, and dermatomyositis.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of young people (mainly women), developing against the background of a genetically determined imperfection of immunoregulatory processes, leading to the uncontrolled production of antibodies to one’s own cells and their components, with the development of autoimmune and immune-complex chronic damage [Nasonova V.A., 1989]. The essence of the disease is immunoinflammatory damage to the connective tissue and microvasculature, skin, joints and internal organs (with visceral lesions being the leading ones, determining the course and prognosis of the disease).
SLE, according to various authors, occurs with a frequency of 2.7-4.8 per 100,000 population; in young and middle age, the ratio of affected women to men is 9:1 (in childhood or after menopause, the ratio decreases to 2:1). This circumstance confirms the assumption that sex hormones play a certain role in the occurrence and development of SLE. Although the disease develops much less frequently in men, it is as severe as in women.
SLE belongs to genetically determined diseases: population studies have shown that the predisposition to the occurrence of SLE is associated with certain histocompatibility class II genes (HLA), genetically determined deficiency of certain complement components, as well as polymorphism of genes of some receptors and tumor necrosis factor a (TNF-a). A).
Etiology. The specific etiological factor in SLE has not been established, however, a number of clinical manifestations (cytopenic syndrome, erythema and enanthema) and certain patterns of the disease make it possible to bring SLE closer to diseases of viral etiology. Currently, importance is attached to viruses belonging to the RNA group (so-called slow, or latent, viruses). Detection of family cases of the disease, frequent identification in families of other rheumatic or allergic diseases, various immunity disorders allows
You can think about the possible significance of family genetic predisposition.
The detection of SLE is facilitated by a number of nonspecific factors - insolation, nonspecific infection, administration of serums, taking certain medications (in particular, peripheral vasodilators from the group of hydralazines), stress. SLE can begin after childbirth or an abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis. Due to the impact of the virus (and possibly antiviral antibodies) on the immune system against the background of a hereditary predisposition, dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, uncontrolled production of antibodies to various tissues, cells, and proteins of the body occurs (including various cellular organelles and DNA). It has been established that in SLE, autoantibodies are produced to only about 40 of more than 200 potential antigenic cellular components. Subsequently, the formation of immune complexes occurs and their deposition in various organs and tissues (mainly in the microvasculature). Various immunoregulatory defects are characteristic, characterized by hyperproduction of cytokines (IL-6, IL-4 and IL-10). Next, processes associated with the elimination of fixed immune complexes play out, which leads to the release of lysosomal enzymes, damage to organs and tissues and the development of immune inflammation. In the process of inflammation and destruction of connective tissue, new antigens are released, in response to which antibodies are formed, new immune complexes are formed, and thus a vicious circle is created that ensures the chronicity of the disease.
Classification. Currently, in our country [Nasonova V.A., 1972-1986] a working classification of clinical variants of the course of SLE has been adopted, taking into account: 1) the nature of the course; 2) activity of the pathological process; 3) clinical and morphological characteristics of damage to organs and systems.
Nature of the disease:
Acute, subacute, chronic (recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhoff's syndrome, Sjögren's syndrome).
Phase and degree of activity of the process.
Active phase: high activity (III), moderate (II), minimal (I).
Inactive phase (remission).
Clinical and morphological characteristics of lesions:
Skin (butterfly symptom, capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis: pleurisy, pericarditis, perespinitis);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute, chronic pneumonitis, pneumosclerosis);
Kidney (lupus nephritis of nephrotic or mixed type; urinary syndrome);
Nervous system (meningoencephalopolyradiculoneuritis, polyneuritis).
There are acute, subacute and chronic course of the disease. Acute course: sudden onset - patients can indicate the day when fever, polyarthritis, and changes in the skin began. In the next 3-6 months, polysyndromic syndrome, glomerulonephritis (lupus nephritis), and central nervous system damage develop. The duration of the disease without treatment is no more than 1-2 years, however, with timely recognition and active treatment with glucocorticosteroids and long-term maintenance therapy, complete remission can be achieved. This variant of the disease is observed mainly in adolescents, children and young people.
Subacute course: occurs most often, begins gradually, with general symptoms, arthralgia, recurrent arthritis, and various nonspecific skin lesions. The undulation of the flow is distinct. A detailed picture of the disease is formed after 2-3, less often - after 3-4 years.
Chronic course: the disease manifests itself for a long time as relapses of various syndromes - polyarthritis, less often polyserositis, discoid lupus syndrome, Raynaud's syndrome. In the 5-10th year of the disease, other organ lesions (kidneys, lungs) appear.
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, which represents a clinical and laboratory symptom complex (venous and/or arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ damage). A characteristic immunological sign is antibodies that react with phospholipids and phospholipid-binding proteins (antiphospholipid syndrome will be discussed in more detail below).
There are also three degrees of activity of the pathological process, i.e. the severity of potentially reversible immunoinflammatory damage, which determines the nature of therapy in each individual patient. Activity should be distinguished from the “severity” of the disease, which is understood as a set of irreversible changes that are potentially life-threatening for the patient.
Clinical picture. The manifestations of the disease are extremely diverse, which is determined by the multiplicity of damage to organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
At stage I of the diagnostic search, information is obtained on the basis of which one can form an idea: 1) about the variant of onset of the disease; 2) about the nature of the disease; 3) about the degree of involvement of certain organs and systems in the pathological process; 4) about previous treatment and its effectiveness, as well as possible complications of treatment.
The onset of the disease can be varied. Most often, the disease begins with a combination of various syndromes; monosymptomatic onset is usually uncharacteristic. In this regard, the assumption about the possibility of SLE arises from the moment such a combination is identified in a patient, which is extremely important for the diagnosis of SLE.
In the early stages of SLE, the most common syndromes are damage to the joints, skin, serous membranes, and fever. Thus, the most “suspicious” in relation to SLE will be various combinations: 1) fever, polyarthritis, trophic changes in the skin (in particular, hair loss - alopecia); 2) polyarthritis, fever, damage to the pleura (pleurisy); 3) fever, trophic skin disorders, time
Zkenia pleura. The diagnostic significance of these combinations increases significantly if the skin lesion consists of the development of erythema, however, in the initial period of the disease, erythema occurs only in 25% of cases; nevertheless, this circumstance does not reduce the diagnostic value of the listed combinations.
An asymptomatic onset of the disease is uncharacteristic, however, the debut of SLE with the development of massive edema due to the development from the very beginning of the pathological process of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type has been noted.
Involvement of various organs in the pathological process is manifested by symptoms of their inflammatory damage: arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.
Information about previous treatment allows us to judge: 1) its adequacy; 2) about the severity of the disease and the degree of activity of the process (initial doses of corticosteroids, duration of their use, maintenance doses, inclusion of cytostatics in the treatment complex for severe immune disorders, high activity of lupus nephritis, etc.); 3) about the presence of complications of corticosteroid and cytostatic therapy.
At stage I, certain conclusions can be made regarding the diagnosis during a long course of the disease, however, at the onset of the disease, the diagnosis is established at subsequent stages of the study.
At stage II of the diagnostic search, you can obtain a lot of data indicating damage to organs and the degree of their functional failure.
Damage to the musculoskeletal system is manifested by polyarthritis, reminiscent of rheumatoid arthritis (RA), symmetrical damage to small joints of the hand (proximal interphalangeal, metacarpophalangeal, wrist) and large joints (less often). With a detailed clinical picture of the disease, the defiguration of the joints is determined due to periarticular edema. As the disease progresses, deformities of small joints develop. Joint damage may be accompanied by diffuse myalgia, and very rarely by true polymyositis with swelling and muscle weakness. Sometimes only arthralgia occurs.
The skin is affected as often as the joints. The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose (“butterfly”). Inflammatory rashes on the nose and cheeks repeating the shape of a “butterfly” are observed in various variants: 1) vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse redness of the skin with a cyanotic tint in the middle zone of the face, intensifying when exposed to external factors (insolation, wind , cold) or excitement; 2) “butterfly” type of centrifugal erythema (skin changes are localized only in the area of the bridge of the nose). In addition to the “butterfly”, discoid rashes can be observed - erythematous raised plaques with keratic disorder and subsequent atrophy of the skin of the face, limbs and trunk. Finally, some patients experience nonspecific exudative erythema on the skin of the extremities, chest, and signs of photodermatosis on exposed parts of the body.
Skin lesions include capillaritis - a pinpoint hemorrhagic rash on the fingertips, nail beds, and palms. Skin lesions can be combined with enanthema on the hard palate. Painless ulcerations may be found on the mucous membrane of the mouth or nasopharyngeal area.
Serous membranes are affected in 90% of patients (classical diagnostic triad: dermatitis, arthritis, polyserositis). Damage to the pleura, pericardium, and, less often, to the peritoneum is especially common. The symptoms of pleurisy and pericarditis are described in previous sections of the Guide; we will only emphasize its features in SLE: 1) dry pleurisy and pericarditis are more common; 2) in effusion forms the amount of exudate is small; 3) damage to the serous membranes lasts for a short time and is usually diagnosed retrospectively by X-ray examination by pleuropericardial adhesions or thickening of the costal, interlobar, mediastinal pleura; 4) there is a pronounced tendency towards the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities).
Damage to the cardiovascular system is very typical for SLE and is observed at various stages of the disease.
The most common occurrence is pericarditis, which tends to recur. Much more often than previously thought, the endocardium is affected in the form of warty endocarditis (lupus endocarditis) on the leaflets of the mitral, as well as the aortic or tricuspid valves. If the process lasts for a long time, at stage II it is possible to identify signs of insufficiency of the corresponding valve (as a rule, there are no signs of stenosis of the orifice).
Focal myocarditis is almost never recognized, but diffuse myocarditis, which is severe, gives certain symptoms (see “Myocarditis”).
Vascular damage can manifest itself in the form of Raynaud's syndrome: paroxysmal disturbances in the arterial blood supply to the hands and/or feet, occurring under the influence of cold or excitement. During an attack, paresthesia is noted, the skin of the fingers becomes pale and/or cyanotic, and the fingers are cold. Mostly the II-V fingers and toes are affected, and less commonly other distal areas of the body (nose, ears, chin, etc.).
Lung lesions can be caused by the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) occurs either acutely or lasts for months and manifests itself, as in pneumonia, with signs of inflammatory infiltration syndrome of lung tissue (it should be noted that the process is characterized by 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; physical changes are practically absent, so it is almost impossible to judge such lung damage at the second stage of the diagnostic search.
Damage to the digestive tract is manifested mainly by subjective signs identified at stage I. On physical examination, vague tenderness in the epigastrium and in the area of the pancreas, as well as stomatitis, can sometimes be detected. In some cases, hepatitis develops: during examination, an enlarged liver and its pain are noted.
Most often, SLE affects the kidneys (lupus glomerulonephritis or lupus nephritis), the evolution of which determines the future fate of the patient. Kidney damage in SLE can occur in various ways, so the data from direct examination
The patient's condition may vary widely. With isolated pathology of urinary sediment, no changes are detected during physical examination; with glomerulonephritis occurring with nephrotic syndrome, massive edema and often hypertension are detected. In the case of the formation of chronic nephritis with constant hypertension, an enlargement of the left ventricle is detected, an accent of the second tone in the second intercostal space to the right of the sternum.
Autoimmune thrombocytopenia (Werlhoff syndrome) manifests itself as typical hemorrhagic rashes of varying sizes on the skin inside limbs, chest, abdomen, on mucous membranes. Bleeding is also observed after minor injuries, for example after tooth extraction, nosebleeds, which are rarely profuse in nature and lead to anemia. Skin hemorrhages acquire different colors over time (blue-greenish, brown, yellow). SLE can manifest itself for a long time only as Werlhoff syndrome without other clinical symptoms typical of SLE.
Damage to the nervous system is expressed to varying degrees in many patients in all phases of the disease, since almost all parts of the nervous system are involved in the pathological process. Patients complain of migraine-type headaches and may have seizures. Possible cerebral circulation disorders (up to the development of a stroke). Upon direct examination of the patient, signs of polyneuritis are detected with impaired sensitivity, pain in the nerve trunks, decreased tendon reflexes, and paresthesia. Organic brain syndrome is characterized by emotional lability, episodes of depression, memory impairment, and dementia.
There is an increase in all groups of lymph nodes, spleen, liver (usually moderate) with generalization of the process.
Damage to the organ of vision manifests itself in the form of dry keratoconjunctivitis, which is caused by pathological changes in the lacrimal glands and disruption of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.
With antiphospholipid syndrome, in addition to the indicated clinical picture, thrombosis may be detected - venous (in the deep veins of the lower extremities with repeated pulmonary embolisms), arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks). On the part of the heart, valve defects, intracardiac thrombi (simulating cardiac myxoma), and coronary artery thrombosis with the development of myocardial infarction can be detected. Skin lesions in antiphospholipid syndrome are varied, the most common of which is livedo reticularis.
Thus, after the second stage of the study, multiple organ damage is revealed, and the degree of organ damage is very different: from barely noticeable clinical (even subclinical) to pronounced, significantly prevailing over the rest, which creates the preconditions for diagnostic errors due to the interpretation of these changes as a manifestation of independent diseases (eg, glomerulonephritis, myocarditis, arthritis).
Stage III of the diagnostic search for SLE is very important, since: 1) it helps to make a final diagnosis; 2) demonstrates the severity of immune disorders and the degree of damage to internal organs; 3) reveals the degree of activity of the pathological (lupus) process.
At stage III, the greatest importance is laboratory research blood. There are two groups of indicators:
1) directly having diagnostic value (detecting pronounced immune disorders):
A) LE cells (lupus erythematosus cells) - mature neutrophils that phagocytose nuclear proteins of other blood cells that have decayed under the influence of antinuclear factor;
B) antinuclear factor (ANF) - a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in a high titer - 1:32 and higher, detected in 95% of patients); the absence of ANF in the vast majority of cases does not confirm the diagnosis of SLE;
C) antibodies to native (i.e., to the whole molecule) DNA; an increase in their concentration correlates with disease activity and the development of lupus nephritis;
D) antibodies to Sm-nuclear antigen, Ro/La ribonucleoprotein; these antibodies are considered to be specific for SLE (they are detected by immunofluorescence in 30% of cases, and by hemagglutination in 20% of cases);
D) the “rosette” phenomenon - lying freely modified nuclei in tissues (hematoxylin bodies), surrounded by leukocytes;
E) diagnosis of antiphospholipid syndrome in SLE is based on the determination of “lupus anticoagulants” - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (increased thromboplastin time) and antibodies to cardiolipin using an enzyme-linked immunosorbent method. The term “lupus anticoagulant” itself is incorrect, since the main clinical manifestation of the presence of these antibodies is thrombus (and not bleeding).
These antibodies are also detected in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis, and autoimmune hemolytic anemia are observed.
2) Nonspecific acute phase indicators, which include:
A) dysproteinemia with an increase in the content of oc2- and γ-globulins in the blood serum;
B) the appearance of C-reactive protein;
B) increase in fibrinogen content;
D) increase in ESR.
With severe articular lesions, a small titer of RF (rheumatoid factor) - an antibody to the Fc fragment of IgG - can be detected. RF is detected using the Waaler-Rose reaction or latex test.
When examining peripheral blood, leukopenia can be detected, often pronounced (1-1.2109/l of blood), with a shift in the leukocyte formula of the blood to metamyelocytes and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Moderate hypochromic anemia is detected, in some cases - hemolytic anemia (with jaundice, reticulocytosis, positive Coombs test). Thrombocytopenia, manifested by hemorrhagic syndrome, is also rarely observed.
Kidney damage is characterized by changes in the urine, which can be classified as follows [Tareeva I.E., 1983]:
1) subclinical proteinuria (protein content in urine 0.5 g/day, often in combination with slight leukocyturia and erythrocyturia);
2) more pronounced proteinuria, which is an expression of nephritic syndrome accompanying subacute or active lupus nephritis. Very high proteinuria (as in amyloidosis) is rare. Moderate hematuria is noted. Leukocyturia can be a consequence of both the lupus inflammatory process in the kidneys and the frequent addition of a secondary infection urinary tract. Very high leukocyturia is a consequence of a secondary urinary infection.
A puncture biopsy of the kidneys reveals nonspecific mesangio-membranous changes, often with a fibroplastic component. Characteristic is: 1) detection in the preparations of altered nuclei (hematoxylin bodies) freely lying in the renal tissue; 2) the capillary membranes of the glomeruli take the form of “wire loops”; 3) deposition of immune complexes in the form of electron-dense deposits on the glomerular basement membrane in “wire loops”, fibrinoid
Sediments.
X-ray examination reveals: 1) changes in the joints with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints; Only with chronic arthritis and deformities is a narrowing of the joint space with subluxations noted; 2) changes in the lungs with the development of pneumonitis; with a long course of the disease - disc-shaped atelectasis, strengthening and deformation of the pulmonary pattern, which is combined with a high position of the diaphragm; 3) development of “lupus” heart disease or exudative pericarditis.
An electrocardiographic study helps detect nonspecific changes in the final part of the ventricular complex (T wave and segment 57), similar to those previously described for myocarditis and pericarditis.
Computed tomography (CT) of the brain and magnetic resonance imaging (MRI) can detect pathological changes in patients with central nervous system damage.
When conducting a diagnostic search, it is necessary to determine the degree of activity of the lupus process (Table 21).
Diagnostics. In cases of the classic course of SLE, the diagnosis is simple and is based on the detection of “butterfly”, recurrent polyarthritis and polyserositis, which constitute the clinical diagnostic triad, complemented by the presence of LE cells or antinuclear factor in diagnostic titers. Of auxiliary importance are the young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation, and infection. It is much more difficult to establish a diagnosis in other cases, especially if the classic diagnostic signs listed above are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 help (Table 22).
The diagnosis is reliable if four or more criteria are present. If there are fewer than four criteria, then the diagnosis of SLE is questionable and dynamic monitoring of the patient is required. This approach is justified: it clearly warns the doctor against prescribing corticosteroids to patients, since other diseases (including paraneoplastic syndrome) may occur with the same symptoms, for which corticosteroids are contraindicated.
Differential diagnosis. SLE should be differentiated from a number of diseases. As large as the list of organs and systems involved in the pathological process in SLE is, the list of diseases that can be erroneously diagnosed in SLE is equally extensive.
Table 22. Diagnostic criteria for SLE
To a greater degree, it can imitate various diseases™ ppi ™ ™ Particularly common at the onset of the disease, and about 1-2 organs (systems) are affected. For example, IR nSS? ™* b°L "Knowledge of pleural lesions can be considered
Or HSULZI^^I etiolop™; myocarditis - as a rheumatic butiouet r^rnt^f II^°SOBENNt,° MN0G0 errors occur if SLE de- ™GRU^ IN SIMILAR CASES DIAGNOSIS03 ONLY
It is often necessary to differentiate from rheumatism, in- schgic hepatitis, chronic hepatitis (CAH), hemorrhagic group (thrombocytopenic purpura), and other diseases from
The need to differentiate from rheumatism occurs, as a rule, in adolescents and young men at the onset of the disease in the presence of arthritis and fever. Rheumatoid arthritis differs from lupus in the greater severity of manifestations, predominant damage to large joints, and transience. One should not attach differential diagnostic significance to a previous infection - sore throat, since it may be a nonspecific factor causing clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic carditis) appear; subsequent dynamic observation makes it possible to identify an emerging heart defect, whereas in SLE, if mitral valve insufficiency occurs, it is mildly expressed, without clear hemodynamic disturbances, mitral regurgitation is not pronounced. In contrast to SLE, leukocytosis is observed in the acute stage of rheumatism; LE cells and ANF are not detected.
Differential diagnosis between SLE and rheumatoid arthritis is difficult in the initial stage of the disease due to the similarity of clinical symptoms: symmetrical damage to small joints of the hand, involvement in
Process of other joints, “morning stiffness”. Differentiation is based on the predominance of the proliferative component in the affected joints in RA, the early development of wasting of the muscles that move the affected joints, and the persistence of joint damage. Erosion of the articular surfaces is absent in SLE, but is a characteristic feature of RA. Rheumatoid factor (RF) in high titer is characteristic of RA; in SLE it is rarely detected and in low titer. Exceptionally complex differential diagnosis SLE and visceral form of RA. A mitigating factor is that the refined diagnosis in both cases does not affect the nature of treatment (corticosteroid therapy).
With chronic active hepatitis (CAH), systemic manifestations may develop in the form of fever, arthritis, pleurisy, skin rashes, glomerulonephritis; Leukopenia, thrombocytopenia, LE cells, and ANF are detected. When differentiating, one should take into account: 1) CAH develops more often in middle age; 2) patients with CAH have a history of acute viral hepatitis; 3) with CAH, pronounced changes in the structure and function of the liver are detected - cytolytic and cholestatic syndromes, signs of liver failure, hypersplenism, and then portal hypertension; 4) in SLE, liver damage is not too frequent and occurs in the form of mild hepatitis (with moderate signs of cytolytic syndrome); 5) with CAH, various markers of viral liver damage are detected (antiviral antibodies and the viral antigen itself).
In infective endocarditis (primary), heart damage (aortic or mitral valve insufficiency) is quickly detected, a clear effect of antibiotic therapy, LE cells, antibodies to DNA, and ANF are usually not detected. Timely blood culture can detect the growth of pathogenic microflora.
In thrombocytopenic purpura (idiopathic or symptomatic), many of the syndromes observed in SLE are absent, there is no fever, and there are no typical laboratory signs (LE cells, ANF, anti-DNA antibodies).
The most difficult differentiation is with other nosological forms from the DTD group. Diseases such as systemic scleroderma and dermatomyositis may share many features with SLE; The difficulty of diagnosis is aggravated by the possibility of detecting ANF and LE cells in these diseases (albeit in a lower titer). The basis of differentiation is the more frequent and more pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin damage in SSc, and a clear myopathic syndrome in DM. However, in some cases, only long-term follow-up of the patient allows a correct diagnosis to be made. Sometimes this takes many months and even years, especially in chronic cases of SLE with minimal activity.
The formulation of a detailed clinical diagnosis of SLE takes into account all the headings given in the working classification of the disease; the diagnosis should reflect: 1) the nature of the disease (acute, subacute, chronic). In case of chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated; 2) process activity; 3) clinical and morphological characteristics of damage to organs and systems, indicating the stage of functional failure (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the presence or absence of heart failure, with lung damage - the presence or absence of respiratory failure, etc.); 4) indicate
Knowledge of ongoing therapy (eg, corticosteroids); 5) complications of therapy (if any).
Treatment. Taking into account the pathogenesis of the disease, complex pathogenetic therapy is indicated for patients with SLE, the objectives of which are: 1) suppression of immune inflammation and immune complex pathology (uncontrolled immune response); 2) prevention of complications of immunosuppressive therapy; 3) treatment of complications arising during immunosuppressive therapy; 4) impact on individual, pronounced syndromes; 5) removal of circulating immune complexes and antibodies from the body.
First of all, it is necessary to exclude psycho-emotional stress, insolation, actively treat concomitant infections, consume food with low content fat and high content of polyunsaturated fatty acids, calcium and vitamin D. During exacerbation of the disease and during treatment with cytostatic drugs, active contraception is necessary. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.
To suppress immune inflammation and immune complex pathology in the treatment of SLE, the main immunosuppressants are used: corticosteroids, cytotoxic drugs, aminoquinoline derivatives. The duration of treatment, magnitude, choice of drug, as well as maintenance doses are determined by: 1) the degree of disease activity; 2) the nature of the flow (severity); 3) the extent of involvement of internal organs in the pathological process; 4) tolerability of corticosteroids or cytostatics and the presence (or absence) of complications of immunosuppressive therapy; 5) the presence of contraindications.
In the initial stages of the disease with signs of minimal activity of the process and the predominance of joint damage in the clinical picture, NSAIDs can be prescribed, however, even with minimal activity of the pathological process, corticosteroids are the drug of choice. Patients should be monitored at the dispensary so that at the first signs of exacerbation of the disease, the doctor can promptly prescribe corticosteroid therapy.
In the chronic course of the disease with predominantly skin lesions, 0.25 g/day of hingamine (Delagil, Resoquin) or hydroxychloroquine (Plaquenil) can be used for many months. If signs of generalization of the process appear (involvement of internal organs in the pathological process), as well as signs of activity, it is necessary to immediately switch to more effective immunosuppressive therapy with GCS.
Thus, the mainstay of treatment for SLE is corticosteroid therapy; when carrying out it, the following principles should be adhered to:
1) start treatment only if there is a definite diagnosis of SLE (if SLE is suspected, corticosteroids should not be prescribed);
2) the dose of GCS should be sufficient to suppress the activity of the pathological process;
3) treatment with a “suppressive” dose should be carried out until a pronounced clinical effect occurs (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes), usually this requires approximately 2 months;
4) after achieving the effect, you should gradually switch to maintenance doses;
5) prevention of complications of corticosteroid therapy is mandatory.
GCS therapy is indicated for II and III degrees of activity of the pathological process, which always happens in subacute and acute SLE. Patients with degree II of activity are prescribed medium doses (
For grade III, large doses are prescribed. The duration of taking large doses is 4-12 weeks. Dose reduction should be carried out slowly, under close clinical and laboratory control, and maintenance doses of drugs (10-15 mg) should be taken for many years.
To prevent side effects of GCS, the following are used: 1) potassium preparations (potassium orotate, potassium chloride, panangin); 2) anabolic drugs (methandrostenolone 5-10 mg); 3) diuretics (saluretics); 4) antihypertensive drugs (ACE inhibitors); 5) antacid drugs.
If severe complications develop, the following are prescribed: 1) antibiotics (for secondary infection); 2) anti-tuberculosis drugs (with the development of tuberculosis, most often of pulmonary localization); 3) insulin preparations, diet (with the development of diabetes mellitus); 4) antifungal agents (for candidiasis); 5) a course of antiulcer therapy (if a “steroid” ulcer appears).
During corticosteroid therapy, situations arise when it is necessary to administer extra-high doses of prednisolone (1000 mg intravenously drip over 30 minutes for 3 days): 1) a sharp increase (“burst”) in the activity of the process (III degree), despite, it would seem, adequately administered therapy; 2) resistance to doses that previously achieved a positive effect; 3) pronounced organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).
It is believed that such pulse therapy stops the formation of immune complexes by inhibiting the synthesis of antibodies to DNA. The decrease in the level of antibodies to DNA caused by corticosteroids leads to the formation of smaller immune complexes due to the dissociation of larger ones.
Significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of corticosteroids. Pulse therapy is most successful in young patients with a short duration of the disease.
Treatment with GCS is not always successful, which is due to: 1) the need to reduce the dose when complications develop (although such therapy is effective in this patient); 2) drug intolerance; 3) resistance to corticosteroid therapy (usually detected quite early). In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (bolus administration at a dose of 0.5-1 g/m2 intravenously monthly for at least 6 months, and then every 3 months in for 2 years) in combination with 10-30 mg/day of prednisolone. In the future, you can return to GCS therapy, since resistance to them usually disappears.
For the treatment of less severe but GCS-resistant manifestations of the disease, azathioprine or methotrexate (approximately 15 mg/week) and cyclosporine [less than 5 mg/day] are prescribed in combination with low doses of prednisolone (10-30 mg/day).
The criteria for assessing the effectiveness of the use of cytostatics are: 1) reduction or disappearance of clinical signs; 2) disappeared
Low steroid resistance; 3) persistent decrease in process activity; 4) preventing the progression of lupus nephritis.
Complications of cytostatic therapy: 1) leukopenia; 2) anemia and thrombocytopenia; 3) dyspeptic symptoms; 4) infectious complications.
If leukopenia (leukocytes less than 3.0 109/l) appears, the dose of the drug should be reduced to 1 mg/kg, and if leukopenia further increases, the drug is discontinued and the dose of prednisolone is increased by 50%.
In recent years, extracorporeal treatment methods - plasmapheresis, hemosorption - have become widespread. These methods make it possible to remove circulating immune complexes from the body, increase the sensitivity of cellular receptors to GCS, and reduce intoxication. They are used for generalized vasculitis, severe organ damage (lupus nephritis, pneumonitis, cerebrovasculitis), as well as for severe immune disorders that are difficult to respond to corticosteroid therapy.
Typically, extracorporeal methods are used in combination with pulse therapy or alone if pulse therapy is ineffective. It should be noted that in case of cytopenic syndrome, extracorporeal methods are not used.
In patients with high levels of antiphospholipid antibodies in the blood serum (but without clinical manifestations of antiphospholipid syndrome), small doses of acetylsalicylic acid (75 mg/day) are used. With significant antiphospholipid syndrome (with clinical manifestations) prescribe heparin and low doses of aspirin.
Forecast. In recent years, due to effective methods treatment, the prognosis has improved (approximately 90% of patients achieve remission). However, in 10% of patients, especially with kidney damage (death occurs due to the progression of chronic renal failure) or with cerebrovasculitis, the prognosis is unfavorable.
Prevention. Timely adequate therapy provides prevention of relapse of the disease. For primary prevention, a group of “threatened” persons is identified, which includes primarily relatives of patients, as well as persons suffering from isolated skin lesions (discoid lupus). These persons should avoid insolation, hypothermia, should not be vaccinated, and they should not undergo mud therapy or other balneological procedures.
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