Differential diagnosis. SLE should be differentiated from a number of diseases

Laboratory data. All patients with active systemic lupus erythematosus certainly have antinuclear antibodies. The method for identifying them is the best screening test for SLE; assertions about the existence of " systemic lupus erythematosus without antinuclear antibodies» require careful verification. Antibodies to DNA are relatively specific and are combined with active form diseases, especially with nephritis; thus, DNA antibodies may serve as an indicator of the severity and activity of systemic lupus erythematosus. In patients with severe active systemic lupus erythematosus, especially in patients with nephritis, there is a decrease in the level of hemolytic complement in the serum, as well as some of its components (the level of S3 is most often measured); Therefore, serum complement levels serve as another useful indicator of the activity and severity of systemic lupus erythematosus. Other antibodies are detected using biological tests for syphilis and Coombs tests. Serum gamma globulin levels are usually elevated; Alpha 2 globulin levels may be elevated and albumin levels may be decreased. Levels of one or more classes of immunoglobulins may be elevated. According to some studies, patients with systemic lupus erythematosus have an increased frequency of HLA-B8, DW3/DR3, DW2/DR2 antigens.

Anemia associated with chronic inflammation or hemolysis is often noted. The presence of antibodies to erythrocyte antigens makes it difficult to determine the blood group of patients and select appropriate donors. Thrombocytopenia and leukopenia are often observed. Some patients have platelet antibodies; Sometimes the first manifestation of SLE is idiopathic thrombocytopenic purpura. Red blood cells, white blood cells, protein, and casts may be present in the urine. Renal failure is manifested by an increase in blood urea nitrogen and creatinine, as well as abnormalities in renal function tests.

Diagnosis and differential diagnosis. Systemic lupus erythematosus can occur under the mask of any rheumatic disease, as well as many other diseases. The diagnosis is based on clinical data and is confirmed using laboratory tests. Were suggested diagnostic criteria. Antinuclear antibodies have no diagnostic value, despite the fact that they are detected in all patients with systemic lupus erythematosus; the absence of these antibodies in a given patient makes the diagnosis systemic lupus erythematosus doubtful. Antibodies to double-stranded DNA are almost pathognomonic, but they are present only in severe or widespread forms of the disease. LE cells cannot be detected in all patients. Signs such as hypergamma globulinemia, a positive Coombs test, and false positive test for syphilis, anemia, leukopenia or thrombocytopenia and signs of nephritis - all of these criteria support the diagnosis of SLE. Some patients with active SLE have reduced serum levels of hemolytic complement and some of its components. Non-detection hemolytic activity complement indicates its hereditary deficiency. The diagnosis can be confirmed by examining renal biopsies, but histological changes are not entirely specific.

Thrombocytopenic purpura and hemolytic anemia; When differentially diagnosing these clinical manifestations, it is necessary to remember systemic lupus erythematosus.

Criteria for diagnosing systemic lupus erythematosus.

Butterfly rash on the face
Discoid rash
Photosensitivity
Ulcerations of the oral mucosa
Arthritis of two or more joints
Serositis (pleurisy or pericarditis)
Renal symptoms (persistent proteinuria or cylindruria)
Neurological disorders(seizures or psychosis)
Blood changes (hemolytic anemia or leukopenia or lymphopenia or thrombocytopenia)
Immunological abnormalities (detection of LE cells or anti-DNA antibodies or anti-Sm antibodies, or false-positive reactions for syphilis)
Antinuclear antibodies

Note. We can talk about systemic lupus erythematosus if the patient has four or more criteria out of 11 listed, both simultaneously and sequentially throughout any observation period.
(From: TanE.M, Cohen A. S., Fries J. F. et al.The 1982 revised criteria for the classification of systemic lupus erythematosus.ArthritisRheum. 25:1271, 1992.)

Treatment. Therapy should be carried out taking into account the prevalence and severity of the disease in a given patient. Patients must be examined most carefully, especially with regard to the condition of the kidneys. In patients with clinical symptoms of nephritis, the nature and severity of renal lesions should be assessed by examining biopsy specimens.

Specific treatment systemic lupus erythematosus does not exist; For therapy, drugs are used that suppress the inflammatory process and, possibly, the formation of immune complexes, as well as the functional ability of immunologically active effector cells (the latter mechanism of action of drugs has not been proven). Overall therapy patients with SLE should be aimed at maintaining clinical well-being and normal serum complement levels.

As a rule, taking into account a specific case, the following options are possible in the treatment of systemic lupus erythematosus: extracorporeal pharmacotherapy using sparing doses of anti-TNF, prednisolone, diclofenac sodium, plasmasorption, cryoprecipitation, immunosorption, leukocytapheresis, blastapheresis.

In patients mild form systemic lupus erythematosus, occurring without nephritis, to relieve arthritis and other symptoms, causing discomfort, salicylates or other non-steroidal drugs. Important acquires careful monitoring of the patient for the purpose of early detection of nephritis. Chloroquine and hydroxychloroquine have been used for the treatment of discoid lupus and SLE for many years, but due to the possible toxic effects of these drugs on the retina, they should be used with great caution. Topical steroid medications can be used to treat facial rashes. For mild lupus nephritis (for example, lupus glomerulitis), therapy is also symptomatic; it should be accompanied by careful monitoring of the patient's condition. Corticosteroids should be used initially in doses sufficient to suppress symptoms, followed by a reduction to the lowest dose required to suppress symptoms. Helpful aids may include antimalarial drugs. In severe lupus nephritis (lupus glomerulonephritis or membranous glomerulonephritis with nephrotic syndrome), treatment should be aimed not only at maintaining the clinical well-being of the patient, but also at suppressing the pathological process in the kidneys, which can be judged by the normalization of serum complement levels and a decrease in the number of circulating antibodies to DNA. This may require long-term use of large doses of corticosteroids; The initial dose of prednisone is usually 1-2 mg/(kg-day). Long-term use of large doses of corticosteroids may cause any known unwanted side effects of these drugs. Sometimes other steroid administration regimens are used, including high-dose intravenous pulse therapy or taking them every other day.

Drugs such as azathioprine, cyclophosphamide, and chlorambucil can effectively suppress severe systemic lupus erythematosus; however, such therapy is still experimental and should be used with extreme caution. Long-term consequences the use of these drugs, especially in children, is still poorly studied; Side effects of these drugs include increased sensitivity to severe viral and other infections, inhibition of gonadal function and, possibly, induction of malignant neoplasms. Such drugs should not be used to treat mild systemic lupus erythematosus, or in cases where the disease activity can be effectively suppressed with corticosteroids alone.

Convulsions and other manifestations of damage to the central nervous system it is necessary, with caution, to treat with large doses of prednisone; As a rule, such symptoms are observed in severe active systemic lupus erythematosus, occur sporadically and may never appear again if the patient, thanks to treatment, has successfully survived acute attack and if disease activity can subsequently be effectively controlled.

Given the existence of drug-induced lupus, it is necessary to ask the patient whether he has taken medications that can induce lupus; Medicines that can cause lupus should not be used to treat patients with systemic lupus erythematosus.

Careful monitoring is essential for the proper management of all patients with SLE; To do this, it is necessary to periodically evaluate clinical condition the patient, his serological status and renal function. Any signs of worsening of the condition should be recognized quickly and appropriate treatment provided promptly. Since the disease is incurable and persists throughout life, patients must be monitored for many years.

Forecast. It was generally accepted that systemic lupus erythematosus, especially in children, was almost inevitably fatal. However, at present, in some children the disease is relatively mild, and not in all cases severe nephritis occurs. Systemic lupus erythematosus occurs with spontaneous exacerbations and remissions, but long-term remissions are not typical for children. Treatment with antibiotics, corticosteroids and, possibly, cytotoxic drugs can prolong the life of many patients with SLE and significantly improve the short-term prognosis. The proportion of children with systemic lupus erythematosus who survive for 5 years is very high. However, many patients still die from this disease in more late dates. Currently, the main causes of death in patients with systemic lupus erythematosus are nephritis, complications of the central nervous system, infections, lung damage, and possibly myocardial infarction. It remains to be seen whether active therapy can improve the final prognosis of severe forms of systemic lupus erythematosus.

The content of the article

Systemic lupus erythematosus- systemic autoimmune disease, occurring predominantly in women young and characterized by a progressive course.

Etiology and pathogenesis of systemic lupus erythematosus

The etiology of the disease is unknown. In its development, the role of viral infection, as well as genetic, endocrine and metabolic factors is assumed. Lymphocytotoxic antibodies and antibodies to double-stranded RNA, which are markers of persistent viral infection, are detected in patients and their relatives. Virus-like inclusions are detected in the endothelium of capillaries of damaged tissues (kidneys, skin); the virus has been identified in experimental models.
The fact that SLE is genetically determined is supported by the fact that its prevalence in families is significantly higher than in the population, and the presence of other diseases in relatives of patients connective tissue(rheumatoid arthritis, systemic scleroderma), as well as hypergammaglobulinemia, antinuclear antibodies and false-positive Wasserman reaction, cases of the disease in identical twins. An association has been established between SLE and the carriage of certain HLA antigens, as well as a connection with genetically determined deficiency of the enzyme N-acetyltransferase, which metabolizes many medications, and complement component deficiency.
The predominance of young women among patients, the frequent development or exacerbation of the disease after childbirth or abortion, disruption of estrogen metabolism in patients with an increase in their activity, and an increase in cases of SLE among patients with Klinefelter syndrome make it obvious that sex hormones are involved in the pathogenesis of the disease. Among the environmental factors that influence the course of the disease, UV irradiation is important; patients often indicate the appearance skin erythema, fever, arthralgia after prolonged exposure to the sun, however, an increase in the incidence of SLE in areas with increased insolation is not observed. A disease similar to SLE can be caused by some drugs that change double-stranded DNA - hydralazine, procainamide.
The disease is based on a decrease immune tolerance to one’s own antigens, leading to the uncontrolled production of many antibodies (autoantibodies) to components of the body’s cells, mainly nuclear antigens. A decrease in immune tolerance occurs due to a defect (genetically determined or developed as a result of a viral infection) in both the T-system (decreased activity of T-suppressors, decreased production of interleukin-2) and the system (polyclonal activation). Antibodies have both a direct damaging effect (for example, on red blood cells, platelets, T cells) and indirectly through the formation of immune complexes, the elimination of which is impaired.
The most studied pathogenetic significance of antibodies to native DNA and circulating immune complexes consisting of native DNA, antibodies to it and complement, which are deposited on the basement membranes of the capillaries of the glomeruli of the kidneys, skin, in the vascular wall and have a damaging effect, accompanied by an inflammatory reaction. In the process of inflammation and destruction of connective tissue, new antibodies are released, in response to which new immune complexes are formed, etc. Thus, SLE is a typical autoimmune immune complex disease that develops with the participation of various factors of the external and internal environment of the body.

Characteristic changes in connective tissue with an increase in the number of fibroblasts and sclerosis, generalized vascular damage and nuclear pathology. In vessels - capillaries, arterioles and venules - productive vasculitis is observed, with high activity of the process - fibrinoid necrosis of the walls, sometimes with the formation of microaneurysms. Nuclear pathology is characterized by deformation of nuclei (karyopyknosis), their disintegration (karyorrhexis) with accumulation of nuclear material in the form of “hematoxylin bodies” - round, structureless formations that are a tissue analogue of LE cells. The synovium of the joints may be edematous and contain fibrinoid deposits. Quite specific changes are observed during the development of Libman-Sachs endocarditis, which are characterized by the imposition of thrombotic masses along the edge of the valve, as well as on its surface and in the places where the valvular endocardium transitions to the parietal endocardium. Pathognomonic for SLE are changes in the vessels of the spleen with the development of perivascular (concentric) sclerosis (the “onion skin” phenomenon).
The most characteristic changes are detected in the kidneys, where immune complex glomerulonephritis develops. Proliferation of glomerular cells, membranous changes, tubular involvement and interstitial tissue, as well as signs considered specific specifically for lupus glomerulonephritis: fibrinoid necrosis, karyorrhexis (cellular detritus in the glomeruli), hyaline thrombi in the lumen of the capillaries, sharp focal thickening of the basement membranes of the glomerular capillaries in the form of “wire loops”. An immunomorphological study reveals the fixation of immunoglobulins and complement on the basement membrane of the glomerulus. Electron microscopy reveals deposits - subendothelial, intramembranous and subepithelial, virus-like inclusions.

Systemic lupus erythematosus clinic

SLE occurs predominantly in young (20-30 years old) women, but cases of the disease are not uncommon in adolescents and older people (over 40-50 years old). Among those affected, only 10% are men, but the disease is more severe in them than in women. Provoking factors are often insolation, drug intolerance, stress; for women - childbirth or abortion.
The first signs of the disease are usually fever, malaise, joint pain, skin rashes, and weight loss. Less commonly, the disease begins with one or another visceritis, for example, pleurisy, glomerulonephritis. The most common manifestations of SLE are joint pain and skin rashes (which may be limited to clinical picture diseases), the most severe are damage to the kidneys and central nervous system.

Skin lesions

The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose (“butterfly”), which occur under the influence of insolation. Often there are capillaritis - superficial vasculitis on the fingertips - on the flesh and around the nail bed, on the palms and soles. Livedo reticularis is often observed on the extremities (in patients with antiphospholipid antibodies), and less commonly, purpura. A third of patients experience photosensitivity - the appearance of diffuse erythema on the face and open areas of the body under the influence of UV rays, exacerbation of the disease after insolation. Characterized by increased hair loss, up to focal or complete baldness, thinning and brittle hair, trophic changes in the skin and nails. Benign option The disease is discoid lupus, in which skin lesions are often the only sign, although systemic manifestations may develop over time. There is a rash on the face characteristic appearance- clearly defined erythematous plaques, which subsequently undergo scarring and pigmentation.
Characteristic is erythema on the mucous membrane of the hard palate, cheeks, gums, tongue in the form of erythematous spots with sharp boundaries, damage to the red border of the lips (cheilitis).

Joint damage

Arthralgia or arthritis are observed in 90% of patients. Mostly small joints of the hands, wrists, and ankles are affected, but damage may also occur. large joints. The pain is often severe, but externally the joints may be little changed, although they are often swollen, and deformation rarely develops. Myalgia is often observed, and myositis sometimes develops. X-ray examination reveals epiphyseal osteoporosis, mainly of the interphalangeal joints of the hands. In 5-10% of patients, aseptic necrosis of bones, mainly the femoral and humeral heads, is noted. At the core aseptic necrosis vasculitis with thrombosis, ischemia and tissue destruction lies. Gradually, pain in the affected joint appears and increases, intensifying with movement, restriction of movements in the joint increases, and a peculiar “duck” gait appears. X-ray examination reveals flattening of the heads of the femoral or humeral bones and uneven structure of the spongy substance. Later the heads become sharply deformed.

Damage to the serous membranes

It is observed in 80-90% of patients. The pleura and pericardium are especially often affected, less often the peritoneum. Involvement of the pleura in the process is an early sign of the disease. Pleurisy is usually bilateral, recurrent, often dry or with a small amount of effusion, which is rich in fibrin. Pain with pleurisy is sharp, especially with diaphragmatitis; As effusion develops, shortness of breath and cough appear. Previous pleurisy is indicated by pleural adhesions, thickening of the pleura and a high position of the diaphragm on radiographs chest.
The peritoneum is rarely affected, although limited damage may develop - perihepatitis and perisplenitis, which are manifested only by slight pain in the right or left hypochondrium.

Damage to the heart and blood vessels

With lupuscarditis, all the membranes of the heart are affected. More often, pericarditis is observed, which manifests itself as chest pain and shortness of breath. On auscultation - dullness of tones; Pericardial friction rub is rarely heard. An ECG reveals a decrease in wave voltage, amplitude, or a negative T wave. The effusion is usually small and can be detected by echocardiography. Lupus myocarditis is accompanied by pain in the heart, tachycardia, and shortness of breath. The examination reveals an increase in the size of the heart, dullness of sounds, systolic murmur at the apex, and rhythm disturbances. Myocarditis is often combined with myopathic syndrome, and a high level of creatine phosphokinase is detected.
With Libman-Sachs endocarditis, a characteristic, although rare, manifestation of SLE, there is a rough systolic murmur and a weakening of the first sound over the apex of the heart, an increase in the second sound over the pulmonary artery, sometimes a heart defect is formed, usually mitral valve insufficiency.
In 20-30% of patients, Raynaud's syndrome is observed - a suddenly developing disturbance in the blood supply to the hands and feet with coldness and pallor (with a clear boundary) of the fingertips, and skin paresthesia. This syndrome occurs more often in patients with a chronic benign course of the disease. Livedo reticularis, recurrent thrombophlebitis, and chronic leg ulcers are also characteristic.

Lung damage

Lupus pneumonitis is characterized by the development of fibrosing interstitial lung and pleural lesions with restrictive respiratory failure. X-rays reveal persistent enhancement and deformation of the pulmonary pattern, disc-shaped atelectasis (striped shadows located parallel to the diaphragm).

Kidney damage

Lupus glomerulonephritis is the most severe visceritis in SLE, which, along with central nervous system damage, determines the prognosis.
Depending on the severity of clinical manifestations, course, and prognosis, the following variants of lupus glomerulonephritis are distinguished:
1) rapidly progressive with nephrotic syndrome, arterial hypertension and progressive renal failure, often complicated by disseminated intravascular coagulation syndrome;
2) active with nephrotic syndrome, often occurring with arterial hypertension;
3) active with pronounced urinary syndrome (proteinuria in this option does not exceed 3.5 g/day, erythrocyturia and leukocyturia are moderate);
4) latent nephritis - subclinical (up to 0.5 g per day) proteinuria without changes in urine sediment and arterial hypertension; in these patients renal symptoms recedes into the background in the clinical picture, the leading manifestations are articular syndrome, serositis, etc. Isolated erythrocyturia and gross hematuria are very rare.
Arterial hypertension often accompanies severe kidney damage; at the same time, glomerulonephritis of the hypertensive type practically does not occur. Active glomerulonephritis is characterized by periodic exacerbations and remissions; in the absence of adequate treatment, renal failure gradually develops.
The prognosis is very severe for lupus cerebrovasculitis, which is accompanied by psychotic reactions (which should be differentiated from steroid psychoses), convulsions, and epileptiform seizures. Sometimes polyneuritis, transverse myelitis with pelvic disorders, in severe cases -itis. Most patients have a pronounced asthenovegetative syndrome: weakness, fatigue, depressed mood.
In SLE, an increase in all groups may be observed lymph nodes, sometimes enlarged spleen. Often there is an enlargement of the liver (usually due to its fatty degeneration). Abdominal pain can be caused by vasculitis of the mesenteric vessels, and extremely rarely by splenic infarction. Acute and chronic pancreatitis(as a manifestation of disease activity or a complication of glucocorticoid therapy). Sometimes there is a pronounced hemorrhagic syndrome associated with autoimmune thrombocytopenia (Werlhoff syndrome) or disseminated intravascular coagulation.
SLE is characterized by leukopenia, often with a shift in the blood count to promyelocytes, myelocytes in combination with lymphopenia. There is a tendency towards eosinopenia. Hypochromic anemia is often detected, less often - autoimmune hemolytic anemia, thrombocytopenia, the severity of which reflects the activity of the disease. An increase in ESR (usually not very sharp) and an increase in the levels of fibrinogen, a2- and y-globulins are noted. Pathognomonic for SLE is the detection of LE cells - mature neutrophils, in the cytoplasm of which round or oval inclusions of a homogeneous nuclear matrix are found. LE cells are found in 70% of patients. Great diagnostic importance is attached to the detection of antinuclear antibodies - antibodies to DNA, deoxyribonucleoprotein, and whole nuclei. In some patients, circulating lupus anticoagulant (antiphospholipid antibodies) and a false-positive Wasserman reaction are detected in the serum.
In case of severe kidney damage, there is a decrease in the titer of complement and its components (C3, C4), the level of fibrinogen can be reduced as a result of disseminated intravascular coagulation syndrome.
The course of the disease can be acute, subacute or chronic. In the acute course, high fever, polyarthritis, pleurisy, pericarditis suddenly develop, after a few months organ damage occurs, life expectancy without treatment does not exceed 1-2 years. This option is currently rare. In the subacute course, the disease begins gradually, with general symptoms, arthralgia, and subsequently proceeds in waves, with gradual involvement various organs and systems; a characteristic polysyndromic picture develops over 2-3 years. Chronic forms are characterized by a long-term recurrent course of polyarthritis, skin lesions, and polyserositis. Organ pathology, if associated, occurs late, in the 5-10th year of illness. Raynaud's syndrome is characteristic.
As separate variants of the course, the following can be distinguished: 1) SLE with features of scleroderma and dermato(poly)myositis, hyperglobulinemia and hyperproteinemia; 2) option with circulating lupus anticoagulant; 3) monoorgan “masks” of SLE. The presence of lupus anticoagulant in the blood is combined with certain clinical and biological manifestations: 60% of patients develop venous and arterial thrombosis, thrombocytopenia, and livedo reticularis. Women experience spontaneous miscarriages, the cause of which is thrombosis of the placental vessels. The presence of lupus anticoagulant may be combined with pulmonary hypertension(prolonged thromboembolism of branches pulmonary artery). In 40% of patients a false-positive Wasserman reaction is detected, in 75% a positive Coombs reaction is detected. Among monoorgan “masks” of SLE, renal masks are more common. The possibility of lupus etiology should always be kept in mind when a young woman develops glomerulonephritis with nephrotic syndrome. A carefully collected anamnesis and a careful examination of the patient make it possible in such cases to identify certain symptoms that did not previously attract attention - joint pain, the onset of the disease after pregnancy or sun exposure, signs of previous pleurisy, leukopenia, etc. The diagnosis is confirmed by identifying LE cells or antinuclear antibodies. Sometimes the development of SLE is long preceded by autoimmune thrombocytopenia, Werlhoff syndrome.

Diagnosis and differential diagnosis of systemic lupus erythematosus

With a comprehensive picture of SLE, the diagnosis is rarely difficult. In 90% of cases, LE cells and (or) antinuclear factor (which can be observed in some cases in rheumatoid arthritis, systemic scleroderma, chronic active hepatitis) and more specific antibodies to native DNA are found in the blood.
IN clinical practice Diagnostic criteria developed by the American Rheumatological Association (1982) may be useful:
1) fixed erythema on the face, in the malar area, with a tendency to spread to the nasolabial folds;
2) discoid rashes - erythematous plaques protruding above the skin with keratosis and follicular plugs, followed by skin atrophy;
3) photosensitivity;
4) ulcers in the mouth and nose;
5) nonerosive arthritis affecting two or more peripheral joints;
6) pleurisy or pericarditis;
7) persistent proteinuria more than 0.5 g per day;
8) psychosis or seizures;
9) hematological disorders: hemolytic anemia, leukopenia, lymphopenia or thrombocytopenia;
10) positive lupus cell phenomenon, anti-DNA antibodies or false-positive Wasserman reaction;
11) increase in the titer of antinuclear antibodies.
If any 4 criteria are present (including anamnestic data), the diagnosis of SLE is quite reliable.
Differential diagnosis should be carried out with other systemic diseases - periarteritis nodosa, hemorrhagic vasculitis, medicinal disease, chronic active hepatitis, rheumatoid arthritis, multiple myeloma, primary and hereditary amyloidosis, subacute infective endocarditis, tuberculosis, tumors. When worn out systemic signs sometimes it is necessary to differentiate the disease from chronic nephritis.
Particular care should be taken when diagnosing SLE with atypical clinical and laboratory data - development of the disease in men, absence of arthralgia, refractoriness of fever to medium-high doses of steroids (50-60 mg/day prednisolone), absence of LE cells and antibodies to DNA, etc.
Periarteritis nodosa occurs predominantly in men, occurs with peripheral polyneuritis, arthralgia, abdominal crises, leukocytosis, and sometimes (in women) bronchial asthma and hypereosinophilia. Kidney damage is characterized by vasculitis of the renal vessels with the development of persistent (often malignant) arterial hypertension with moderate urinary syndrome, often with predominant hematuria.
Hemorrhagic vasculitis accompanied by damage to the joints, skin, and fever. Symmetrical rashes on the legs are characteristic; glomerulonephritis, which is rare in SLE, is often hematuric in nature, with macrohematuria unusual for SLE.
It is sometimes very difficult to differentiate SLE from drug-induced disease, as well as chronic active hepatitis.
A similar clinical picture can be observed in rheumatoid arthritis with kidney damage, especially taking into account the possibility of the development of other systemic manifestations in this disease (lymphadenopathy, damage to the heart, lungs) and the detection of LE cells in some cases. Rheumatoid arthritis is characterized by a long-term course with the development of persistent joint deformities and atrophy of the interosseous muscles, ulnar deviation of the hand, severe radiographic changes joints, high titers of rheumatoid factor in serum (in SLE, rheumatoid factor is often detected, but in low titers). Kidney biopsy reveals amyloidosis in almost half of cases of rheumatoid nephropathy (and almost all cases of nephrotic syndrome), which is practically not found in SLE.
In some cases, it is necessary to differentiate the disease from myeloma, which is usually accompanied by bone pain, a sharp increase in ESR, anemia, and proteinuria in older women. The diagnosis can be clarified using electrophoresis (immunoelectrophoresis) of protein fractions of blood serum and urine, sternal puncture, and x-ray examination of bones.
It is necessary to exclude the possibility of infectious diseases requiring massive antibiotic therapy, primarily subacute infective endocarditis or renal tuberculosis with paraspecific reactions. Subacute infective endocarditis occurs with fever, leukopenia, anemia, increased ESR, and sometimes glomerulonephritis. Glomerulonephritis is most often hematuric (focal embolic), but nephrotic syndrome can also develop. It should be remembered that aortic regurgitation is rare in SLE. In doubtful cases, blood cultures and trial treatment are necessary. high doses antibiotics. It is also important to exclude tuberculosis (which can join SLE after massive therapy with immunosuppressants) and tumors, especially kidney cancer, which often occurs with paraspecific reactions.

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SYSTEMIC LUPUS ERYTHEMATOSUS

Introduction

1 Etiology

2 Pathogenesis

3 Classification

4 Clinical picture

5 Diagnostics

6 Differential diagnosis

7 Treatment

8 Forecast

INTRODUCTION

Systemic lupus erythematosus(SKV) - a chronic polysyndromic 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 their own cells and their components, with the development of autoimmune and immunocomplex chronic damage. The essence of the disease is immunoinflammatory damage to the connective tissue and microvasculature of the skin, joints and internal organs (with visceral lesions being the leading ones, determining the course and prognosis of the disease).

Systemic lupus erythematosus, according to various authors, occurs with a frequency of 2.7-4.8 per 100,000 population, the ratio of affected women to men is 9:1.

1 ETIOLOGY

Specific etiological factor in SLE has not been established, but 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 of other rheumatic or allergic diseases in families, various violations immunity allow you to think about possible meaning family genetic predisposition.

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

2 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 humoral immunity. In the body of patients, uncontrolled production of antibodies to various tissues, cells, and proteins of the body (including cellular organelles) occurs. Subsequently, the formation of immune complexes occurs and their deposition in various organs and tissues (mainly in the microvasculature). 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.

3 CLASSIFICATION

Working classification clinical options SCR flow takes into account:

The nature of the current;

Activity of the pathological process;

Clinical and morphological characteristics of damage to organs and systems.

There are acute, subacute and chronic course of the disease.

Acute course: sudden onset - patients can indicate the day when fever, polyarthritis began, and changes appeared on the skin. In the next 3-6 months, polysyndromy, 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 complete remission can be achieved with corticosteroids and long-term maintenance therapy. 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 current is distinct. A detailed picture of the disease is formed after 2-3, less often - after 3-4 years.

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

Activity is the severity of potentially reversible immunoinflammatory damage to internal organs, which determines the nature of therapy in a particular patient. There are three degrees of activity according to the following criteria:

systemic lupus erythematosus

Index	I degree	IIdegree	IIIdegree
Body temperature	Normal		38°C and above
Weight loss	Minor	Moderate	Expressed
Skin lesions	Discoid lesions		"Butterfly", capillarites
Pericarditis	Adhesive		Vypotnoy
Myocarditis	Cardiosclerosis	Moderate	Expressed
	Adhesive		Vypotnoy
Glomerulonephritis	Urinary syndrome	Nephritic syndrome	Nephrotic syndrome
	120 or more
g-Globulins,%
LE cells, per 1000 leukocytes	Single or "-"
Antinuclear antibodies, titers
Type of glow during immunofluorescence test	Homogeneous	Homogeneous and peripheral	Peripheral

4 CLINICAL PICTURE

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

Ha initial stage diagnostic search receive information on the basis of which you can formulate an idea:

About the variant of onset of the disease;

About the nature of the disease;

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

About previous treatment and its effectiveness, as well as possible complications treatment.

The onset of the disease can be very diverse. Most often, the disease can begin as 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. The diagnostic value of certain syndromes increases when they are combined. IN early period In SLE, the most common syndromes are lesions of the joints, skin, serous membranes, and fever. Thus, the most “suspicious” combinations regarding SLE will be:

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

Polyarthritis, fever, pleural damage (pleurisy);

Fever, trophic skin disorders, pleural lesions.

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 above combinations.

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

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

Information about previous treatment allows us to judge:

About its adequacy;

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 in medical complex cytostatics for severe immune disorders, high activity of lupus nephritis, etc.; 3) about the presence of complications of corticosteroid and cytostatic therapy.

At the initial stage, certain conclusions can be drawn regarding the diagnosis when long term disease, however, at the onset of the disease, the diagnosis is established at subsequent stages of the study.

During a physical examination, you can obtain a lot of data indicating the damage to organs and the degree of their functional failure.

Damage to the musculoskeletal system manifests itself as polyarthritis, reminiscent of rheumatoid arthritis, a symmetrical lesion small joints hands (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. Articular damage may be accompanied by muscle damage in the form of diffuse myalgia, very rarely - true polymyositis with swelling and muscle weakness. Sometimes the lesion manifests itself only as arthralgia.

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:

Vascular (vasculitic) “butterfly” - unstable, pulsating, diffuse redness of the skin with a cyanotic tint in the middle zone of the face, increasing with exposure to external factors(insolation, wind, cold) or excitement;

- “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 development of atrophy on the skin of the face, limbs and trunk. Finally, some patients experience nonspecific exudative erythema on the skin of the limbs, chest, signs of photodermatosis on exposed parts of the body.

To defeat skin include capillarites - small punctate hemorrhagic rash on the pads of the fingers, nail beds, 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). Particularly common are lesions of the pleura, pericardium, and, less commonly, the peritoneum. Features for SLE:

Dry pleurisy and pericarditis are more common;

In effusion forms, the amount of exudate is small;

Damage to the serous membranes lasts a short time and is usually diagnosed retrospectively by pleuropericardial adhesions or thickening of the costal, interlobar, mediastinal pleura during X-ray examination;

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 is pericarditis, which tends to recur. Much more often than previously thought, the endocardium is affected in the form of development warty endocarditis(lupus endocarditis) on the cusps of the mitral, as well as the aortic or tricuspid valves. If the process lasts for a long time, signs of insufficiency of the corresponding valve can be identified (signs of stenosis of the orifice, as a rule, are not noted).

Focal myocarditis is almost never recognized, but diffuse myocarditis, especially severe, produces certain symptoms.

Vascular damage can manifest itself in the form of Raynaud's syndrome: paroxysmal developing disorders of the arterial blood supply to the hands and/or feet, arising under the influence of cold or excitement. During an attack, paresthesia is noted, the skin of the fingers becomes pale and/or cyanotic, and the fingers are cold. 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 similarly to pneumonia with signs of inflammatory infiltration syndrome lung tissue(it is worth noting the peculiarity of the process in the form of an unproductive cough combined with shortness of breath). Another option for lung damage is chronic interstitial changes (inflammation of perivascular, peribronchial and interlobular connective tissue), manifested by slowly progressive shortness of breath and changes in the lungs during X-ray examination; There are practically no physical changes.

Damage to the digestive tract is manifested mainly by subjective signs detected at the initial stage. On physical examination, vague tenderness in the epigastrium and in the area of the pancreas, as well as signs of 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, 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 pathology of urinary sediment, no changes are detected during physical examination; with glomerulonephritis occurring with nephrotic syndrome, massive edema is detected, often arterial hypertension(AG). In case of formation 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 various sizes on the skin of the inner side of the extremities, the skin of the chest and abdomen, and on the mucous membranes. Bleeding is also observed after minor injuries, for example, after tooth extraction, nosebleeds, which are occasionally 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 neuropsychic sphere is expressed to varying degrees in many patients in all phases of the disease. At the initial stage, asthenovegetative syndrome is detected. Upon direct examination of the patient, signs of polyneuritis are detected with impaired sensitivity, pain in the nerve trunks, decreased tendon reflexes, and paresthesia.

Damage to the reticuloendothelial system is expressed in polyadenopathy (enlargement of all groups of lymph nodes, not reaching significant degrees) - early symptom generalization of the process, as well as enlargement of the spleen and liver (usually moderate).

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.

Thus, after a physical examination, multiple organ lesions are revealed, and the degree of organ damage is very different: from barely clinically noticeable (even subclinical) to pronounced, significantly prevailing over the others, which creates the preconditions for diagnostic errors - interpretation of these changes as manifestations independent diseases(eg, glomerulonephritis, myocarditis, arthritis).

The final stage of the diagnostic search for SLE is very great importance, because:

Helps make a final diagnosis;

Demonstrates the severity of immune disorders and the degree of damage to internal organs;

Reveals the degree of pathological (lupus) process.

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

1. Having direct diagnostic value (detecting 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 antinuclear factor;

Antinuclear factor (ANF) - a complex of antinuclear antibodies circulating in the blood (in a high titer - 1: 32 and higher);

Antibodies to native (i.e., to the whole molecule) DNA;

Antibodies to Sm-nuclear antigen; 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);

The “rosette” phenomenon is freely lying modified nuclei in tissues (hematoxylin bodies), surrounded by leukocytes.

2. Nonspecific acute phase indicators, which include:

Dysproteinemia with increased levels of b 2 - and g-globulins;

The appearance of C-reactive protein;

Increased fibrinogen content;

Increase in ESR.

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

When examining peripheral blood, leukopenia can be detected, often of a pronounced degree (1-1.2 * 10 9 / l of blood), with a shift leukocyte formula blood to young forms 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 combined with Werlhoff syndrome is also rarely observed.

Kidney damage is characterized by changes in urine, which can be classified as follows:

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

More pronounced proteinuria, which is an expression of nephrotic syndrome accompanying subacute or active lupus nephritis. Very high proteinuria (such as that seen in amyloidosis) is rare. 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 infection urinary tract. Very high leukocyturia is a consequence of a secondary urinary infection.

Morphologically - with puncture biopsy of the kidneys - reveal nonspecific mesangiomembranous changes, often with a fibroplastic component. Characteristic is:

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

The capillary membranes of the glomeruli take the form of “wire loops”;

Deposition of immune complexes in the form of electron-dense deposits on the glomerular basement membrane in “wire loops”, fibrinoid deposits.

X-ray examination reveals:

Changes in the joints with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints; Only in cases of chronic arthritis and deformities are narrowing of the joint space with subluxations observed;

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 are observed, which is combined with a high position of the diaphragm;

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

An electrocardiographic study helps detect nonspecific changes in the terminal part of the ventricular complex (T wave and ST segment).

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

5 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 classical diagnostic signs are missing. In this situation, diagnostic criteria developed by the American Rheumatological Association (ARA) help:

Symptom	Characteristic
1. Rash on the cheekbones (lupoid “butterfly”)	Fixed erythema (flat or raised), tending to extend to the nasolabial area
2. Discoid rash	Erythematous raised plaques with adjacent scales and follicular plugs; old lesions may have atrophic scars
3. Photodermatitis	Skin rash resulting from exposure to sunlight (history or doctor's observation)
4. Erosion and ulcers in the oral cavity	Ulcerations of the mouth or nasopharynx, usually painless (must be reported by a physician)
	Non-erosive arthritis of 2 or more peripheral joints, characterized by tenderness, swelling, and effusion
6. Serositis	Pleurisy: pleural pain, pleural friction rub and/or presence of effusion; pericarditis on echocardiography or a pericardial friction rub heard by the doctor
7. Kidney damage	Persistent proteinuria more than 0.5 g/day or casts (erythrocyte, tubular, granular, mixed), hematuria
8. Damage to the central nervous system	Seizures - in the absence of medication or metabolic disorders(uremia, ketoacidosis, electrolyte imbalance); psychosis - in the absence of intake
9. Hematological disorders	Leukopenia less than 410 9 /l, registered at least 2 times; lymphopenia less than 1.510 9 /l, registered at least 2 times; thrombocytopenia less than 100*10 9 /l, not associated with medication
10. Immunological disorders	Anti-DNA: antibodies to native DNA in increased titer; anti-Sm: AT to nuclear Sm-Ag; detection of antiphospholipid antibodies based on elevated levels of serum IgG or IgM antibodies to cardiolipin; detection of lupus coagulant; false-positive Wassermann reaction for at least 6 months with confirmed absence of syphilis
11. Antinuclear antibodies	Increasing their titer, in the absence of taking drugs that cause lupus-like syndrome

The diagnosis is reliable if 4 or more criteria are present. If less than 4 criteria are present, then the diagnosis of SLE is questionable and requires dynamic observation for the sick. This approach has a basis: it clearly warns against prescribing corticosteroids to such patients, since other diseases (including paraneoplastic syndrome) may occur with the same symptoms, for which corticosteroids are contraindicated.

6 DIFFERENTIAL DIAGNOSTICS

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 diseases. These problems are especially common at the onset of the disease, as well as with dominant damage to 1-2 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 regarded 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 rheumatism, infective endocarditis, chronic active hepatitis (CAH), hemorrhagic diathesis (thrombocytopenic purpura), and other diseases from the DCT group.

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. A previous infection (sore throat) should not be given differential diagnostic significance, since it may be a nonspecific factor, causing the appearance clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment signs of heart damage (rheumatic carditis) appear; subsequent dynamic observation allows us to identify an emerging heart defect, while in SLE, if mitral valve insufficiency occurs, it is mildly expressed, without clear hemodynamic disturbances, mitral regurgitation is not pronounced. Unlike SLE in acute stage In rheumatism, leukocytosis is noted, LE cells, and ANF are not detected.

Differential diagnosis between SLE and rheumatoid arthritis difficult in the initial stage of the disease due to the similarity of clinical symptoms: symmetrical damage to the small joints of the hand, involvement of new joints, the presence of “ morning stiffness" Differentiation is based on the predominance of the proliferative component in the affected joints in rheumatoid arthritis, 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 feature of rheumatoid arthritis. Rheumatoid factor (RF) in high titer is characteristic of rheumatoid arthritis; in SLE it is rarely found and in low titer. The differential diagnosis of SLE and visceral form rheumatoid arthritis. A mitigating factor is that the refined diagnosis in both cases does not affect the nature of treatment (corticosteroid therapy).

With CAH, systemic manifestations may develop in the form of fever, arthritis, pleurisy, skin rashes, glomerulonephritis; Leukopenia, thrombocytopenia, LE cells, and ANF may be detected. When differentiating, you should consider:

CAH develops more often in middle age;

Patients with CAH have a history of acute viral hepatitis;

With CAH, pronounced changes in the structure and function of the liver are detected - cytolytic and cholestatic syndromes, signs liver failure, hypersplenism, and then portal hypertension;

In SLE, liver damage is not very common and occurs in the form of hepatitis mild course(with moderate signs of cytolytic syndrome);

When CAH is detected various markers viral infection liver (antiviral antibodies and the viral antigen itself).

For infective endocarditis ( we're talking about about primary IE), cardiac damage is quickly detected (development of aortic or mitral valve insufficiency), a clear effect of antibiotic therapy; LE cells, antibodies to DNA, and ANF are usually not detected. Timely blood culture reveals 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 complexity is compounded by the possibility of detecting ANF and LE cells in these diseases (albeit in lower titers). 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 systemic scleroderma, and a clear myopathic syndrome in dermatomyositis. However, in some cases, only long-term dynamic observation of the patient makes it possible to diagnose correct diagnosis. Sometimes this takes many months and even years, especially in chronic cases of SLE with minimal activity.

The wording of the expanded clinical diagnosis SLE takes into account all categories given in the working classification of the disease; the diagnosis should reflect:

The nature of the course of the disease (acute, subacute, chronic). In case of chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated;

Process activity;

Clinical and morphological characteristics of damage to organs and systems, indicating the stage of functional failure (for example, with lupus nephritis - stage renal failure, with myocarditis - the presence or absence of heart failure, with lung damage - the presence or absence respiratory failure etc.);

Indication of therapy (eg, corticosteroids);

Complications of therapy (if any).

7 TREATMENT

Taking into account the pathogenesis of the disease, complex pathogenetic therapy is indicated for patients with SLE, the objectives of which are:

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

Prevention of complications of immunosuppressive therapy;

Treatment of complications arising during immunosuppressive therapy;

Impact on individual, pronounced syndromes;

Removal of circulating immune complexes and antibodies from the body.

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:

The degree of disease activity;

The nature of the flow (severity);

The extensive involvement of internal organs in the pathological process,

Tolerability of corticosteroids or cytostatics and the presence (or absence) of complications of immunosuppressive therapy;

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, non-steroidal anti-inflammatory drugs (NSAIDs) are not prescribed; corticosteroids, even with minimal activity of the pathological process, remain 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, Resoquine, Chloroquine) or hydroxychloroquine (Plaquenil) can be used for many months. If signs of generalization of the process (involvement of internal organs in the pathological process), as well as signs of activity, appear, it is necessary to immediately switch to more effective immunosuppressive therapy with corticosteroids.

From the above it follows that the main method of treatment for SLE is corticosteroid therapy. When conducting corticosteroid therapy, the following principles should be adhered to:

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

The dose of corticosteroids should be sufficient to suppress the activity of the pathological process;

Treatment with a “suppressive” dose should be carried out before the onset of pronounced clinical effect(improvement general condition, normalization of body temperature, improvement of laboratory parameters, positive dynamics of organ changes), this usually takes approximately 2 months;

After achieving the effect, you should gradually switch to maintenance doses;

Prevention of complications of corticosteroid therapy is mandatory.

Corticosteroid therapy is indicated for grades II and III of the pathological process, which always happens in subacute and acute SLE. Patients with degree II of activity are prescribed 30-50 mg, with degree III - 50-90 mg/day. If after 24-48 hours the patient’s condition does not improve, then the initial dose is increased by 25-30%, and if an effect is noted, then the dose is left unchanged. After achieving a clinical effect (which usually happens after 2 months of corticosteroid therapy, with nephrotic syndrome or signs of kidney damage - after 3-5 months), the dose of prednisolone is gradually reduced, while certain rules should be followed. At a dose of 50-80 mg, reduce by 5 mg per week, at a dose of 20-50 mg - 2.5 mg every 2 weeks, then 1/4 tablet every 3-4 weeks until the maintenance dose (5 mg - for women ; 7.5 mg - for men), which has been taken for years.

For warning side effects corticosteroids are used:

Potassium preparations (potassium orotate, potassium chloride, panangin);

Anabolic drugs (methandrostenolone 5-10 mg);

Diuretics (saluretics);

Antihypertensive drugs (ACE inhibitors, peripheral vasodilators);

Antacid drugs.

During development severe complications prescribe:

Antibiotics (for secondary infection);

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

Insulin preparations, diet (for the development of diabetes mellitus);

Antifungal agents (for candidiasis);

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 daily for 3 days):

A sharp increase (“burst”) in the activity of the process (III degree), despite seemingly adequate therapy;

Resistance to doses that previously achieved a positive effect;

Severe organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).

It is believed that such pulse therapy (sometimes adding 1000 mg of a cytostatic, such as cyclophosphamide, intravenously) 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 corticosteroids is not always successful due to:

The need to reduce the dose if complications develop (although such therapy is effective in this patient);

Intolerance to corticosteroids;

Resistance to corticosteroid therapy (usually detected quite early).

In such cases, cytostatics are prescribed - cyclophosphamide or azathioprine (imuran) at a dose of 1-3 mg per 1 kg of body weight in combination with 10-30 mg of prednisolone for 4-6 months until lasting improvement. Then the dose is reduced to maintenance and treatment is continued for 1/2 -3 years. In the future, you can return to corticosteroid therapy, as resistance to them usually disappears.

The criteria for assessing the effectiveness of the use of cytostatics are:

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 are:

Leukopenia;

Anemia and thrombocytopenia;

Dyspeptic symptoms;

Infectious complications.

If leukopenia appears below 3.0 * 10 9 / l, the dose of the drug should be reduced to 1 mg per 1 kg of body weight, 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 corticosteroids, 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 the presence of cytopenic syndrome, extracorporeal methods are not used.

8 FORECAST

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

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12. Treatment of well.

Goal of treatment- achieving induced remission, which

assumes the absence of any clinical manifestations of SLE (at the same time, there may be signs that arose as a result of damage to one or another organ or system during previous exacerbations), the absence of cytopenic syndrome, immunological studies should not reveal AHA and other organ-specific antibodies. In case of exacerbation of SLE, treatment should be carried out in a hospital(!)

diet with limited salt, liquid, spicy and salty foods

regime with limited physical activity for 3-4 weeks

drug therapy

NGTVP is used to relieve constitutional and musculoskeletal manifestations of SLE, as well as moderate serositis. Patients with SLE are more likely than other patients to develop renal dysfunction and unusual side effects (hepatitis, aseptic meningitis) when using NSAIDs.

Antimalarial (aminoquinoline) drugs:

effective for skin lesions, joints, constitutional disorders

prevent exacerbation in patients with moderate disease activity

reduce lipid levels and reduce the risk of thrombotic complications.

In the first 3-4 months, the dose of hydroxychloroquine is 400 mg/day (6.5 mg/kg), then 200 mg/day. The most dangerous side effect is retinopathy, so it is necessary 1 time during treatment | Perform a full ophthalmological examination annually.

Glucocorticosteroids (GCS) short acting are the main medicine treatment of SLE. The most commonly used are prednisolone and methylprednisolone. The dose of GCS depends on the activity of the disease:

small doses (<10 мг/сут) назначают при низкой активности (в случае неэффективности НПВП и антималярийных ЛС)

High doses (1 mg/kg/day or more) are indicated for high SLE activity. The duration of taking high doses of GCS, depending on the clinical effect, ranges from 4 to 12 weeks. The dose reduction should be carried out gradually under close clinical and laboratory control, and maintenance doses (5-10 mg/day) should be taken for many years.

Pulse therapy (1000 mg methylprednisolone intravenously over at least 30 minutes for three days in a row) is an effective treatment method that allows for rapid control of many manifestations of SLE, and further management of patients at lower doses. However, there is no convincing data on the benefits of pulse therapy over oral administration of high corticosteroids. The mechanism of action of loading doses of methylprednisolone during intravenous administration has not yet been fully disclosed, but available data indicate a significant immunosuppressive effect of the drug already on the first day. A short course of intravenous administration of methylprednisolone causes a significant and long-term decrease in serum IgG levels due to increased catabolism and decreased synthesis. It is believed that loading doses of methylprednisolone suspend the formation of immune complexes and cause a change in their mass by interfering with the synthesis of antibodies to DNA, which in turn leads to a redistribution of the deposition of immune complexes and their release from the subendothelial layers of the basement membrane. It is also possible that the action of lymphotoxins is blocked. Currently, a category of patients has been identified (young age, rapidly progressing lupus nephritis, high immunological activity) in whom this type of therapy should be used at the onset of the disease.

Cytotoxic PM.

The choice of cytotoxic drugs depends on the characteristics of the course, severity of the disease, the nature and effectiveness of previous therapy. Cyclophosphamide (CP) is the drug of choice for:

Proliferative lupus nephritis

Membranous VN

Severe damage to the central nervous system that cannot be controlled by high doses of corticosteroids

Treatment with CP (intravenous bolus administration at a dose of 0.5-1 g/m2 monthly for at least 6 months, and then every 3 months for 2 years) in combination with oral GC and pulse therapy increases the survival of patients with proliferative lupus nephritis .

Azathioprine(1-4 mg/kg/day), methotrexate(15"mg/week) and cyclosporine A(<5 мг/кг/сут) показаны:

For the treatment of less severe but GCS-resistant manifestations of SLE

As a component of maintenance therapy, allowing patients to be managed on lower doses of GCS (“steroid-sparing” effect)

Intensive therapy SLE, i.e. the use of loading doses of GCS and cytostatics to suppress activity was first used in our country 20 years ago and showed high effectiveness in severe cases of the disease.

Main indications for intensive care:

Active lupus nephritis (especially with nephritic syndrome, hypertension, rapid increase in creatinine)

Acute severe damage to the central nervous system (meningoencephalitis,is, transverse myelitis)

Hematological crisis, severe thrombocytopenia

Ulcerative necrotizing cutaneous vasculitis

Pulmonary vasculitis

High disease activity, resistant to previous, previously considered adequate therapy

The most common intensive care techniques:

Classic pulse therapy with methylprednisolone: 1000 mg/day intravenously for 3 consecutive days (3000 mg per course)

IV administration of methylprednisolone in reduced doses (250-300 mg/day) until a total dose of about 3000 mg per course is achieved

Monthly IV administration of 1000 mg methylprednisolone for 6-12 months

Combined pulse therapy: intravenous administration of 1000 mg of methylprednisolone for 3 days in a row and 1000 mg of cyclophosphamide on the 1st or 2nd day (the drugs are administered sequentially)

Monthly IV administration of 1000 mg methylprednisolone and 1000 mg cyclophosphamide for 12 months

It should be noted that quickly reduce the daily dose of prednisoloneper os Immediately after pulse therapy is not recommended. If the disease activity is high, after pulse therapy, which is usually used in the morning, it is left for the evening. 1 A daily dose per os, since methylprednisolone administered intravenously in the morning is no longer detectable in the blood after 4;+-7 hours and withdrawal syndrome may develop.

Intravenous immunoglobulin has been used for more than 15 years to treat SLE, but no controlled randomized trials have been conducted. The effectiveness of the drug against the following manifestations of SLE has been demonstrated: I

Thrombocytopenia

Pleurisy
Vasculitis
Fevers

Currently, the only absolute indication for IV immunoglobulin in SLE is severe refractory thrombocytopenia, especially if there is a risk of bleeding.

Mycophenolate mofetil. In patients with lupus nephritis refractory to cyclophosphamide, treatment with mycophenolate leads to a decrease or stabilization of serum creatinine and proteinuria, a decrease in the activity of SLE and doses of GCS.

Extracorporeal procedures.

Plasmapheresis used to treat the most severe patients with rapidly increasing dysfunction of vital organs in combination with active therapy with cyclophosphamide and GCS. It is effective for:

Cytopenia

Cryoglobulinemia

Vasculitis

Damage to the central nervous system

Thrombotic thrombocytopenic purpura

Efficiency pulse synchronization, consisting in inducing an exacerbation of the disease by interrupting treatment (rebound syndrome) followed by three sessions of intensive plasmapheresis in combination with pulse therapy with cyclophosphamide and 1) GCS requires further study.

With the development of chronic renal failure, indicated program hemodialysis and kidney transplantation.

Diagnosis systemic lupus erythematosus (SLE) consists of a complex of clinical and laboratory data. There are characteristic signs of the disease that allow a diagnosis to be made very quickly. In typical SLE with skin lesions, the presence of LE cells or antibodies to native DNA, and high titers of antinuclear factor, the diagnosis is not problematic.

However, there are often cases of unusual onset of the disease with the absence of skin manifestations, a monosymptomatic course of the disease and the absence of characteristic laboratory signs, when a definite diagnosis is established months and even years later.

An attempt to develop diagnostic criteria for SLE was made more than four decades ago. In 1970 American Rheumatology Association (ARA) created a group of scientists to develop criteria distinguishing systemic lupus erythematosus from rheumatoid arthritis (RA). After testing 74 clinical and laboratory signs in large groups of patients with SLE and RA, 14 criteria were selected, which, as the authors believed, were most characteristic of SLE.

The criteria included:

1) “butterfly” erythema;
2) discoid lesions of lupus;
3) Raynaud's syndrome;
4) alopecia;
5) photosensitivity;
6) ulcers in the mouth or nose;
7) non-deforming arthritis;
8) presence of LE cells;
9) false-positive Wasserman reaction;
10) proteinuria more than 3.5 g/day;
11) the presence of cylinders in the urine;
12) detection of pleurisy during examination or history, radiologically confirmed, or pericarditis by pericardial noise or ECG data;
13) the presence of psychosis or seizures according to the clinical picture or anamnesis;
14) one or more of the laboratory signs: hemolytic anemia, leukopenia less than 4·10 9 /l, thrombocytopenia less than 100·10 9 /l.

Subsequently, it turned out that the criteria are quite specific and sensitive for identifying systemic lupus erythematosus, but only in the presence of a polysyndromic picture at the very beginning of the disease, and for cases of SLE with an erased picture, the sensitivity of the criteria was no more than 67%.

At the Institute of Rheumatology of the USSR Academy of Medical Sciences in 1972-1978. An attempt was made to create criteria for systemic lupus erythematosus.

For each criterion, sensitivity, specificity and information content were calculated. Symptoms with a negative value of the information content index were transferred to a separate group of signs that are more characteristic of diseases similar to SLE.

Threshold values for sums of information content were established that reliably indicate that the patient belongs to one or another nosological form. Only in a very small percentage of cases did patients end up in the wrong class. Based on the found threshold values, a table of conventional units was developed, which allows us to formalize the decisive diagnostic rule (Table 4.5).

Using the table of diagnostic criteria is quite simple. After examining the patient, the sum of the information content of the patient’s symptoms belonging to the first group (positive symptoms) and the sum of the information content of the symptoms belonging to the second group (negative symptoms) are calculated. For each of these amounts, according to table. 4.5 determine the number of conventional units. With a sum of arbitrary units equal to 3, a diagnosis of SLE can be assumed with a probability of 93.4%; with a sum of arbitrary units equal to 4, the diagnosis of systemic lupus erythematosus is reliable with a probability of 98.6%.

Table 4.5. Threshold intervals for symptom assessment

Positive		Negative		General	Diagnosis
symptoms		Symptoms		sum
				conditional
				units
sum	number	Sum	number
Bit	conditional	Bit	conditional
	units		units
0-4	0	0-2	-2	1	SLE-like disease
4,1-6,5	2	2,1-4	-1	2	Diagnosis unclear
6,6-10	3	4,1-7,5	0	3	SLE with a probability of 93.4%
10	4	7,5	-1	4	» » » 98.6%
and more

Let us give an example of the practical application of the obtained criteria for the diagnosis of systemic lupus erythematosus.

Patient B., 22 years old, the following symptoms of the first group turned out to be: transient flexion contractures of the fingers - the information content was 0.3; migratory nature of arthritis - 0.7; arthritis without deformation - 0.7; paroxysmal development of articular syndrome - 1.0; erythema on the face - 1.1; alopecia - 1.0, ulcers in the mouth and nasopharynx - 0.4; photosensitivity - 0.2; cylindruria - 1.9; pleurisy - 0.7, pericarditis - 1.9, leukopenia (4 10 /l) - 1.1; LE cells in the blood - 2.6; complement CH 50 - 1.5.

This patient also exhibited the following symptoms of the second group: morning stiffness - information content 2.1; skin pigmentation disorder - 3.6; Raynaud's syndrome - 1.6.

According to the decision rule, the information content values corresponding to the patient’s signs of the disease are summed up. In the first group of symptoms, the sum of information content is 15.1, in the second - 7.3. According to the table 4.5 we evaluate the obtained sums of criteria in conventional units in accordance with threshold values.

In the first group of symptoms, the sum is 15.1 and is estimated at 4 conventional units. The amount of information content in the second group of symptoms (7.3) falls into the threshold interval of 4.1-7.5, i.e. it gives 0 arbitrary units. Thus, the total algebraic sum of conventional units is equal to 4, which with a high degree of probability confirms the diagnosis of SLE, which was made to the patient in the clinic.

The results of recognizing SLE using the criteria table were very encouraging. In a group of 87 patients with a definite diagnosis of systemic lupus erythematosus, correct classification was achieved in 97.7% of cases; the diagnostic error was 2.3%. Among 219 patients suffering from diseases similar to SLE, the diagnosis of lupus was correctly rejected in 97.3%.

Symptoms

An important advantage of these criteria is the possibility of differentiated quantitative assessment of each symptom. Thus, if in the APA criteria photosensitivity and LE cells are equivalent for diagnosis, then in the developed criteria the information content of these symptoms differs (0.2 and 2.6, respectively). The use of these criteria helps to improve the quality of diagnosis of SLE in the early stages of the disease, when differentiation from RA, the onset of dermatomyositis, scleroderma or other rheumatic diseases is required.

In 1982, the American Rheumatological Association revised the diagnostic criteria for systemic lupus erythematosus, conducting research primarily to improve the diagnosis. The high specificity of certain laboratory parameters, among which new ones were identified (for example, Sm antigen), re-evaluation of old ones (antibodies to double-stranded DNA, antibodies to ribonucleoprotein, hypocomplementemia) in combination with a complex of the most characteristic clinical symptoms made the new criteria more suitable for accurate diagnosis of the disease. The combination of four or more signs made the diagnosis quite reliable (67-80%).

The number of criteria was reduced to 11, indicating the frequency of occurrence of each of them: 1) erythema in the “butterfly” zone - 57%; 2) discoid lesions of lupus - 18%; 3) photosensitivity - 43%; 4) ulcers in the mouth or nose - 27%; 5) non-erosive arthritis - 86%; 6) pleurisy - 52% or pericarditis - 18%; 7) persistent proteinuria - 52% or casts in the urine - 36%; 8) convulsions or psychoses - 12-13%; 9) hemolytic anemia or leukopenia or thrombocytopenia - 18, 46 and 21%, respectively; 10) LE cells - 73% or DNA antibodies - 67%; Sm-antibodies - 31%, false-positive test for syphilis - 15%; 11) antinuclear antibodies - 99%.

In the early stage of the disease, differential diagnosis is made with rheumatoid arthritis, dermatomyositis, systemic scleroderma, isolated Raynaud's syndrome.

In addition to the listed clinical and laboratory signs, young age and female gender are of great importance in establishing the diagnosis of SLE. Sometimes the differential diagnosis should also include hemolytic anemia, thrombocytopenic purpura, idiopathic thrombocytopenia, Henoch-Schönlein disease, systemic vasculitis, lymphoma, leukemia and other diseases.

Recently, the need to differentiate CNS lupus from Sneddon syndrome, an antiphospholipid syndrome, has become apparent. In some cases, a differential diagnosis is necessary with bacterial endocarditis, meningitis of various etiologies, tuberculosis, sarcoidosis, serum sickness, angioimmunoblastic lymphadenopathy, arthritis due to Lyme borreliosis and acquired immunodeficiency syndrome. 4.5. Systemic lupus erythematosus and pregnancy

The issue of pregnancy and the possibility of having children with SLE remains relevant to this day. Long-term observation of patients has shown that in the absence of kidney damage, as a rule, pregnancy and childbirth proceed normally.

To prevent possible complications, it is important to note two points: 1) disease activity must be well suppressed before conception; 2) the maintenance dose of corticosteroids should be slightly increased (by approximately 25%) at the time of delivery and in the postpartum period. According to the Institute of Rheumatology of the Russian Academy of Medical Sciences, which included observation of more than 200 patients, pregnancy ended successfully in 90% of patients who did not have lupus nephritis. Corticosteroids do not interfere with fetal growth or cause any abnormalities in its development.

Moreover, it is known from the literature that from mothers not treated with corticosteroids, children are born with lower body weight, i.e. these drugs promote intrauterine growth of the fetus. With regard to continued use of cytostatics during pregnancy, the issue is complex, but there are cases of successful births with continued treatment with azathioprine during pregnancy. There are reports of this in the foreign literature, and our observations of two cases show that the children (both boys) are healthy for 12 and 20 years after birth.

Kidney function deteriorates by the 16th to 20th week of pregnancy in almost all patients with lupus nephritis. In such cases, there is a high risk of fetal death, premature birth, and perinatal death. Fetal death occurs not only as a result of renal failure in the mother and intoxication, but also as a result of deposition of immune complexes in the basement membrane of trophoblasts, penetration of anti-Co antibodies or lupus anticoagulant into the placenta.

Patients with systemic lupus erythematosus should avoid abortions and cesarean sections, which are accompanied by significant bleeding and additional stress. It is better to use mechanical contraceptives. Estrogen contraceptives are contraindicated, as they can cause serious complications (phlebitis, thrombosis) and exacerbation of the disease itself. For a successful pregnancy outcome, joint observation of the patient by a rheumatologist and an obstetrician-gynecologist, as well as close contact after childbirth with a pediatrician, is important.

Sigidin Ya.A., Guseva N.G., Ivanova M.M.