Systemic lupus erythematosus antibodies to DNA. Systemic lupus erythematosus (SLE)
Description
Material under study Serum
№ 997 Antibodies to cardiolipin class IgM
In systemic lupus erythematosus (SLE) and other systemic rheumatic diseases, the immune response is directed against nucleoprotein antigens, i.e. complexes of nucleic acids and proteins. Currently, about 200 varieties of antibodies to nucleoproteins and ribonucleic acids have been described, which are called antinuclear antibodies.
Antinuclear factor on the HEp-2 cell line (see description of the test) allows you to detect 90-95% of all antinuclear antibodies, since human cells contain all antinuclear antibody antigens, including structural, insoluble and conformational. Antinuclear factor on the HEp-2 cell line is found in SLE, other systemic rheumatic diseases and many autoimmune diseases, which makes it a universal test in the examination of patients with autoimmune pathology. Detection of antinuclear factor is of great importance in SLE, since its titers correlate with the severity of the disease and decrease with effective therapy.
Anti-nucleosome antibodies are among the first autoantibodies to form in the body during the development of SLE. Antibodies to nucleosomes, as well as antibodies to ds-DNA, may play an important role in the pathogenesis of kidney damage in lupus nephritis. A high level of antinucleosomal antibodies is characteristic only for patients with active SLE accompanied by nephritis, and their level positively correlates with indicators of disease activity. The level of antibodies to nucleosomes increases immediately before the outbreak of SLE in parallel with the development of glomerulonephritis.
Anticardiolipin antibodies of the IgG and IgM classes are the main representatives of the antiphospholipid antibody family. Along with antibodies to beta-2-glycoprotein, antibodies to cardiolipin are included in the laboratory criteria for antiphospholipid syndrome, and together with antibodies to double-stranded DNA and Sm antigen, in the immunological criteria for systemic lupus erythematosus.
Literature
- Lapin S.V. Totolyan A.A. Immunological laboratory diagnostics of autoimmune diseases / Publishing house "Chelovek", St. Petersburg - 2010. 272 p.
- Nasonov E.L., Aleksandrova E.N. Modern standards for laboratory diagnosis of rheumatic diseases. Clinical guidelines / BHM, M - 2006.
- Conrad K, Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Organ Specific Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden - 2011. 300 p.
- Conrad K, Schlosler W., Hiepe F., Fitzler M.J. Autoantibodies in Systemic Autoimmune Diseases: A Diagnostic Reference/ PABST, Dresden - 2007. 300 p.
- Gershvin ME, Meroni PL, Shoenfeld Y. Autoantibodies 2nd ed./ Elsevier Science - 2006. 862 p.
- Shoenfeld Y., Cervera R, Gershvin ME Diagnostic Criteria in Autoimmune Diseases / Humana Press - 2008. 598 p.
- Reagent Kit Instructions.
Preparation
It is preferable to withstand 4 hours after the last meal, there are no mandatory requirements.
Indications for appointment
The study is indicated for the diagnosis and monitoring of the following conditions:
- systemic lupus erythematosus;
- lupus glomerulonephritis;
- medicinal lupus;
- secondary antiphospholipid syndrome in systemic lupus erythematosus.
Interpretation of results
The interpretation of test results contains information for the attending physician and is not a diagnosis. The information in this section should not be used for self-diagnosis or self-treatment. An accurate diagnosis is made by the doctor, using both the results of this examination¤ and the necessary information from other sources: history, results of other examinations, etc.
Antinuclear factor, antibodies to nucleosomes, and antibodies to cardiolipin IgG and IgM classes play an important role in the diagnosis and monitoring of patients with SLE. Monitoring of antinuclear factor titers, anti-nucleosome antibodies and anti-ds-DNA antibodies is recommended every 3 months.
Systemic lupus erythematosus (SLE) is one of the most common chronic autoimmune systemic (non-organ-specific) diseases characterized by diffuse lesion connective tissue and blood vessels; belongs to the group of so-called large collagenoses.
The frequency of SLE varies from country to country; for example, in North America and Europe it averages 40 cases per 100,000 population. However, it has been established that the black population of America and the population of Spain are affected more often and their disease is more severe.
Women get sick with SLE much more often (9:1); up to 80% of women suffer from SLE during their childbearing years. In children and the elderly, the incidence of SLE is approximately 1 case per 100,000 population, with a female:male ratio of 3:1.
Quite often, in addition to the signs of this disease, patients with SLE also have signs of another pathology of the connective tissue - rheumatoid arthritis and scleroderma.
Immunopathogenesis. The development of SLE is associated with the influence of genetic and environmental factors, which lead to the development of immune regulation disorders, modification of autoantigens, breakdown of tolerance, and development of an autoimmune response.
The role of genetic factors is confirmed by the following data:
- It has been proven that SLE develops in 30% of monozygotic twins and only in 5% of dizygotic twins;
- An association has been established between predisposition to SLE and the HLA DR2/DR3 genes, Gm allotype and structural features of the alpha chain of the T-cell antigen-recognizing receptor;
- There are special inbred lines of mice in which SLE-like disease develops spontaneously;
- It was revealed that predisposition to SLE disease is encoded by more than 6 genes located on different chromosomes.
The role of environmental factors is confirmed by the following data:
- In 30% of patients, skin photosensitivity is noted, which is manifested by the development of a rash after exposure to the sun;
- It has been established that drug-induced SLE syndrome develops under the influence of hydralazine, procainamide, phenytoin, hydantoin, isoniazid, chlorpromazine, D-penicillin amine, etc.;
- Cases of SLE induction after past infections are well known.
The role of hormonal factors is confirmed by the higher incidence of SLE in women compared to men (ratio 9:1).
The role of autoantibodies, immune complexes and complement deficiency is supported by the following data:
- An increase in the concentration of IgG in the blood serum of patients;
- The presence of autoantibodies to autologous and foreign antigens;
- Identification of circulating immune complexes in 80% of patients;
- A decrease in the concentration of C2, C4 and C3 in the blood serum of patients;
- A decrease in the number of complement receptors (CR1) on erythrocytes;
- Deposition of IgG, M, C3 and C4 in the capillaries of the renal glomeruli and skin.
T- and B-lymphocyte disorders in SLE patients T-lymphocytes:
- Lymphopenia developing under the influence of anti-lymphocyte antibodies, including anti-T antibodies;
- Decreased number and function of suppressor cells;
- Reducing the number of "naive" T-lymphocytes (CD4V8 CD45RA +);
- Decrease in the number of memory T-cells (CD4 \ 8 CD29. CD45RO +);
- Increase in the number of activated T cells (CD4+DR+).
B-lymphocytes:
- Polyclonal activation of B-lymphocytes;
- Increased sensitivity to stimulating cytokine signals;
- The disruption of the cytokine profile in SLE patients includes a decrease in the ability of monocytes to produce IL-1, as well as a decrease in the ability of T-lymphocytes to respond to IL-2.
Upon activation of the disease, an increase in the level of cytokines that control the differentiation of B-lymphocytes and the production of humoral antibodies was also found: IL-6, IL-4, IL-5. One of the sensitive indicators indicating the activation of SLE is an increase in the amount of soluble receptors for IL-2 in the blood serum.
immune complexes. In patients with the active stage of SLE, an increase in the level of circulating immune complexes has been proven, which, being deposited in the vessels, cause tissue inflammation.
Under physiological conditions, antibodies that are produced in response to microbial infection form circulating immune complexes. The latter, after binding to serum complement, are fixed on erythrocytes due to the presence of a receptor for C3b on the erythrocyte membrane. Subsequently, immune complexes enter the liver and spleen, where they are removed from the blood.
In SLE, due to various disorders, conditions are created for the persistence of circulating immune complexes (CIC) in high titers. This leads to the fact that immune complexes are deposited in non-lymphoid tissues, for example, in the glomeruli of the kidney or in the vessels of the skin. Their deposition in tissues leads to complement activation, chemotaxis of polymorphonuclear leukocytes, which release inflammatory mediators, which causes vascular damage and the development of vasculitis.
Thus, the main clinical manifestations of SLE are explained by the following immune mechanisms:
- The presence of CEC, which include anti-nuclear antibodies; the latter, being deposited in the microvasculature, lead to the development of vasculopathy and, as a result, to tissue damage.
- The presence of autoantibodies to blood cells leads to leuko-, lympho-, thrombopenia and anemia.
- The presence of antiphospholipid antibodies leads to the development of the so-called antiphospholipid syndrome.
Clinic. The most common early manifestations of SLE are polyarthritis and dermatitis. It should be taken into account that; 1) in principle, any of the symptoms of SLE can be the first manifestation of the disease; 2) it may take many months or even years before it is installed final diagnosis SLE. In addition to the mentioned polyarthritis and dermatitis, early symptoms of SLE that should be paid attention to include chronic fatigue, various disorders of consciousness, affects, including anxiety and depression, pericarditis, thrombocytopenia, anemia, leukopenia and lymphopenia. Subsequently, signs of damage to the kidneys and central nervous system.
Diagnosis. Criteria for the diagnosis of SLE and other connective tissue diseases developed by the American Rheumatological Association and include 11 items. For their better memorization, F. Graziano and R. Lemanske (1989) suggest using a mnemonic device, highlighting the first letters of each item in such a way that a new phrase is formed - SOAP BRAIN MD (SOAP-soap; BRAIN-brain; MD - medical doctor):
- S - serositis, pleural or pericardial;
- 0-oral (or nasopharyngeal) ulceration of the mucous membrane, which can be detected during examination;
- A-arthritis, non-erosive, involving two or more joints, with soreness, swelling and effusion;
- P-photosensitivity (photosensitivity), leading to the appearance of a rash after exposure to the sun;
- B-blood (blood): hemolytic anemia, leukopenia (< 400 в 1 мл), лимфопения (< 1500 мм3), тромбоцитопения (< 100 000 в 1 мл);
- R - kidneys (renal): proteinuria (> 0.5 g / day) or cylindruria;
- A - antinuclear antibodies;
- I - immune tests: anti-dsDNA antibodies, anti-Sm antibodies, false positive reaction to syphilis, LE cells;
- N - neurological disorders: convulsive seizures or psychoses not related to the intake medicines or with metabolic disorders such as uremia, electrolyte balance or ketoacidosis;
- M - rash (malar) with fixed erythema in the form of a butterfly in the nasolabial region;
- D - discoid rash with erythematous patches.
The diagnosis is considered confirmed if 4 out of 11 criteria are present.
Laboratory diagnostics. Below are laboratory findings that may help in the diagnosis of SLE, and the percentage of their detection in untreated patients.
Laboratory signs of SLE
Antibodies to dsDNA > 80% (ds - double-stranded) Antinuclear antibodies (high titers; IgG) - 95% Increased serum IgG - 65% Decreased levels of C3 and C4 complement components - 60% Antiplatelet antibodies - 60% Cryoglobulinemia - 60%
Antibodies to extractable nuclear antigens:
Antibodies to phospholipids - 30-40%
rheumatoid factor (low titers) - 30%
Skin biopsy showing IgG, C3 and C4 deposits - 75%
Increase in ESR - 60%
Leukopenia - 45%
Lupus anticoagulant - 10-20%
False positive Wasserman reaction - 10%
An increase in the level of C-reactive protein, normal before the addition of infection (informative test for the detection of an attached infection)
Proteinuria - 30%
According to H. Chapel, M. Haeney (1995), the determination of LE cells is a non-specific, very insensitive and outdated method.
At laboratory examination The patient is found to have various hematological, serological and biochemical disorders that are a direct consequence of the disease, due to its complications or secondary and associated with treatment.
Many tests (eg, immunoglobulin levels, complement levels, presence of autoantibodies) alone are not diagnostic and must be interpreted in the context of the individual clinical picture.
One of the characteristic immunological laboratory signs of SLE is the presence in the circulating blood of autoantibodies directed to various components of the cell: nuclear, membrane structures, serum proteins. It has been proven that these autoantibodies largely determine the clinical features of the manifestation of SLE. Their participation in the pathogenesis of SLE may be associated either with a direct damaging effect on the cell, or with the induction of immune dysregulation, which, in turn, leads to the development of the disease.
Antinuclear (or antinuclear) autoantibodies react with nuclear antigens and are found in more than 95% of patients. They are best detected by indirect immunofluorescence. Various cells are used as substrates, for example, the transplanted cell line HEp2, etc. When determining antinuclear autoantibodies by this method, the most crucial moment is to establish the nature of the fluorescent glow. There are three main types of luminescence: homogeneous, annular (in the form of a rim) and granular (mottled).
Homogeneous luminescence is caused by autoantibodies to dsDNA, histones and deoxyribonucleoproteins. Granular luminescence is caused by autoantibodies directed to extractable nuclear antigens - Sm, UT-RNP, Scl 70 (topoisomerase 1 DNA), SS-A / Ro, SS-B / La, etc. Ring-shaped luminescence is found in a small number of patients with SLE complicated by hepatitis, cytopenia, vasculitis. Although the method of indirect immunofluorescence is very sensitive, its specificity is low, so it is used mainly as a screening method.
Autoantibodies to DNA are most common in patients with SLE. There are autoantibodies to native (double-stranded - ds) DNA and single-stranded (ss) DNA. To identify them, they are currently using following methods: radioimmunological, ELISE and immunofluorescent. autoantibodies to ss-DNA are found in various inflammatory and autoimmune diseases, so their detection is of little diagnostic value. In contrast, high titers of anti-ds-DNA autoantibodies are highly specific (98%) for SLE and often reflect disease activity. However, they are found only in 60% of patients with SLE. autoantibodies to ds-DNA play a pathogenic role in the development of SLE, and their presence is often associated with early involvement of the kidneys in the pathological process. Their determination is very useful for monitoring the activity of the disease and the effectiveness of therapy.
Autoantibodies to nonhistone structures.
1. autoantibodies to Sm (Smith) antigen and ribon-cleoprotein antigens. The term "extractable nuclear antigens" (ENA) includes two antigens - Sm and nuclear ribonucleoprotein (nRNP). These antigens are composed of five different uridylates, enriched ribonucleoproteins that are associated with proteins. They form a functional unit, the spliceosome, which is involved in post-translational changes in mDNA. Patients with SLE develop specific autoantibodies to these functional units. autoantibodies to U1-RNP are called anti-UIRNP autoantibodies; antibodies to the UI-U5RNP complex are called anti-Sm autoantibodies. To identify this heterogeneous group of autoantibodies, the method of immunodiffusion (Ouchterlony), quantitative immunofluorescence and immunoprecipitation are used. autoantibodies to UI-RNP and Sm are found in 40-50% and 10-30% of SLE patients, respectively. Anti-Sm antibodies are very specific for SLE. autoantibodies to UI-RNP are found in patients with SLE who have both Raynaud's syndrome and myositis or scleroderma and polymyositis. As a rule, anti-ds-DNA antibodies are not detected in patients with anti-UI-RNP autoantibodies, the underlying disease is not severe, kidney damage is detected infrequently.
2. Autoantibodies to SS-A/Ro and SS-B/La antigens. Another part of small nuclear ribonucleoproteins (SSA/Ro and SSB/La) are associated with RNA polymerase III during mRNA transcription. SSA/Ro antigen is a protein (molecular weight 6.0-5.2 104 KD) associated with one of the five cytoplasmic nucleoproteins; SSB/La antigen (molecular weight 4.8-104 KD) was initially found in the cytoplasm of SLE patients with Sjögren's syndrome. The expression of these antigens varies depending on the stage of the cell cycle, and their localization can be found in the cytoplasm or nucleus. The production of autoantibodies to SSA/Ro and SSB/La antigens is associated with the presence of certain antigens in the HLA-DQ locus in a patient. Anti-SS-A/Ro and anti-SS-B/La antibodies are found in 25-40% and 10% of SLE patients, respectively. Anti-SS-A/Ro antibodies can occur without anti-SS-B/La, while anti-SS-B/La occurs only together with anti-SS-A/Ro antibodies. Patients with anti-SS-A\Ro antibodies most often have photosensitivity, severe symptoms Sjögren's syndrome, rheumatoid factor and hypergammaglobulinemia. Anti-SS-A/Ro antibodies are also detected in healthy individuals (3%) and in relatives of patients with autoimmune diseases.
The issue of titers in which antinuclear antibodies are detected is very difficult in terms of diagnostic value. It is known that in different laboratories the dilutions of normal sera (i.e., the actual titers) at which antinuclear antibodies continue to be determined vary greatly. Therefore, it is necessary to adhere to the following rule: if the antibody titers in the blood serum of patients are less than 2 times higher than the antibody titers in the blood serum of healthy individuals (in control), such results should be considered doubtful. For example, if in the serum of healthy individuals the antibody titer is 1:16, then the results of a study of the serum of patients with antibody titers of 1:32 and even 1:64 should be considered doubtful. The higher the antibody titer, the higher the information content of their determination for diagnosis. It should be borne in mind that in approximately 2% of the healthy population, these antibodies can be detected in low titers.
The diagnosis of SLE is easily established if the patient has 3 or 4 typical symptoms, such as a characteristic rash, thrombocytopenia, serositis or nephritis, and antinuclear antibodies. However, unfortunately, in practice, most often you have to deal with such complaints as arthralgia or non-specific manifestations of arthritis, vague symptoms from the central nervous system, a history of skin rash or Raynaud's phenomenon, and a weakly positive test for antinuclear antibodies. In such cases, the diagnosis may be preliminary and such a patient should be under medical supervision.
One of the additional immunogenetic features, in some cases allowing to verify the diagnosis, is the determination of the HLA phenotype of the patient. It has been established that the production of certain antibodies in SLE patients is associated with certain HLA antigens. Drug-induced SLE. A sufficiently large number of cases have been described when, as a result of taking a particular drug, patients developed disorders resembling SLE. One such classic drug is procainamide. characteristic clinical features Such SLE syndrome consists of relatively mild symptoms, including arthralgia, maculopapular rash, serositis, fever, anemia, and leukopenia. autoantibodies in this form of SLE have certain features: 1) antinuclear antibodies, if they are detected, give a homogeneous glow in immunofluorescent studies; 2) as a rule, antihistone antibodies are detected; 3) antibodies to native DNA are never detected in drug-induced SLE.
After discontinuation of the suspicious drug, the symptoms disappear after 4-6 weeks, but autoantibodies continue to be detected for another 6-12 months.
Mention should be made of antiphospholipid antibodies, which are found in approximately 30% of patients with SLE. They are the cause of various types of thromboembolic complications, such as stroke, thrombosis of the vena cava (portal) vein, thrombophlebitis, pulmonary embolism at different levels, etc. The presence of antiphospholipid antibodies in SLE patients largely determines the outcome of the disease. However, the risk of thromboembolic complications is not the same in all patients with such antibodies. The risk is higher in cases where functional disorders in the blood coagulation system are detected simultaneously with antiphospholipid antibodies. The presence of antiphospholipid antibodies in SLE patients may be the cause of a positive Wasserman reaction. It follows that if a positive Wasserman reaction is detected for no apparent reason, then the presence of antiphospholipid antibodies should be suspected as an early sign of SLE.
The presence of antiphospholipid antibodies in women (including those without SLE) can be the cause of habitual miscarriages, therefore, if a woman has a history of repeated miscarriages in the second trimester of pregnancy, an analysis for antiphospholipid antibodies should be done (for some more details, see the section on this). Reproductive Immunology).
SLE patients have a very high risk of developing infectious complications, which are quite often the cause of death. This is most often observed in patients with kidney and central nervous system damage, who have to prescribe high doses of glycocorticoids and cytostatics; while infectious complications are caused by opportunistic infection. However, in more intact patients with SLE, the tendency to infections (eg, systemic lesions caused by Neisseria, Salmonella, Gram-positive cocci) is increased. The reason for this is antibody-induced leukopenia and dysfunction of granulocytes, a decrease in the level of complement, the so-called functional asplenia, etc.
Treatment. Unfortunately, there is no standard treatment that would suit any SLE patient. In each individual case, taking into account the individual clinical picture, the severity of the disease and laboratory parameters, one or another treatment tactic is determined. General recommendations include the following:
- Inclusion in the diet of unsaturated fatty acids;
- Smoking ban;
- Regular exercise program;
- Maintaining ideal body weight;
- Use of photoprotectors, including avoiding sun exposure in the middle of the day.
When SLE is detected, the main treatment should be aimed at solving two problems:
- prevention of antigenic stimuli or the influence of environmental factors that could serve as triggers for the activation of the disease;
- control over the production of autoantibodies using immunosuppressive effects.
It should be borne in mind that some drugs, as well as vaccines, can cause an exacerbation of the disease. Often, an exacerbation develops after infections, insolation, stress and other environmental factors.
Drugs and methods used in the treatment of patients with SLE
- Non-steroidal anti-inflammatory drugs
- Antimalarial drugs
- Hydroxychloroquine (plaquenil)
- Chloroquine
- Corticosteroids
- prednisone or prednisolone
- Methylprednisolone (i.v.)
- Immunosuppressive drugs (immunosuppressants)
- Azathioprine
- Cyclosporin A (sandimmun-neoral)
- Anticancer drugs with immunosuppressive action
- Methotrexate
- Cyclophosphamide
- Antibiotics
- Chlorambucil
- Androgens
- 19-Nortestosterone
- Danazol
- Efferent therapies
- Plasmapheresis, plasma sorption
- Lymphocytopheresis
- Diet
- Arachidonic acid analogues
- Immunotherapy
- Immunoadsorption of anti-DNA antibodies
Normal human immunoglobulin for intravenous administration monoclonal antibodies against CD4+ or CD5+ cells. Topical corticosteroids may be effective in controlling the skin manifestations of SLE. In the initial stages of the disease, treatment of polyarthralgia and polyarthritis is possible with the help of non-steroidal anti-inflammatory drugs. In case of their ineffectiveness, one should proceed to the appointment of antimalarial drugs. As a rule, it is hydroxychloroquine (plaquenil). This drug is less effective in the treatment of skin and joint manifestations, but may delay the development of systemic lesions. The starting dose is usually 400 mg/day with a gradual decrease to 200 mg/day, long-term. It is necessary to control possible complications from the eyes, since the drug has toxicity to the retina. Low-dose corticosteroids (prednisolone 5–10 mg/day) may be used to control difficult-to-treat skin and joint manifestations.
High doses of corticosteroids and immunosuppressive drugs are usually prescribed for disease progression and involvement of the kidneys and other organs. Usually, during an exacerbation of SLE (lupus crisis), oral prednisolone is prescribed at a dose of 50-100 mg / day or intermittent intravenous pulse therapy with methylprednisolone (500-1000 mg). When the effect is achieved (usually after a few weeks), the dose of corticosteroids is gradually reduced.
With resistance to glucocorticoids and the ineffectiveness of other therapy, cyclophosphamide is prescribed, intravenous administration which (in courses of 4-6 weeks; up to 6 courses or more) is more effective and less toxic than long-term daily intake per os. With prolonged oral administration, there is a risk of developing infectious complications (herpes zoster), infertility (especially in women), tumors, and toxicity to the bladder is less pronounced.
Azathioprine is less toxic than cyclophosphamide, but monotherapy with kidney damage is less effective. It is more often used as a second drug in combination with prednisolone, allowing the dose of the latter to be reduced. In these cases, the dose of corticosteroids should not be reduced below 12-15 mg/day without the risk of increased disease activity.
On the mechanism of action of cyclosporine. And in more detail it will be said in the section “Rheumatoid arthritis”. It should also be noted here that in recent years, the effectiveness of a new dosage form of cyclosporine, sandimmune-neoral, has been revealed in nephrotic syndrome.
Diagnosis of lupus erythematosus
General principles for diagnosing a disease
Diagnosis of systemic lupus erythematosus exhibited on the basis of special developed diagnostic criteria proposed by the American Association of Rheumatologists or Russian scientist Nasonova. Further, after the diagnosis is made on the basis of diagnostic criteria, additional examinations are performed - laboratory and instrumental, which confirm the correctness of the diagnosis and allow us to assess the degree of activity of the pathological process and identify the affected organs.Currently, the most commonly used diagnostic criteria are the American Rheumatology Association, and not Nasonova. But we will give both schemes of diagnostic criteria, since in a number of cases, domestic doctors use Nasonova's criteria to diagnose lupus.
Diagnostic criteria of the American Rheumatology Association the following:
- Rashes in the area of the cheekbones on the face (there are red elements of the rash that are flat or slightly rising above the surface of the skin, extending to the nasolabial folds);
- Discoid rashes (plaques raised above the skin surface with "black dots" in the pores, peeling and atrophic scars);
- Photosensitivity (the appearance of rashes on the skin after exposure to the sun);
- Ulcers on the mucous membrane oral cavity(painless ulcerative defects localized on the mucous membrane of the mouth or nasopharynx);
- Arthritis (damage to two or more small joints, characterized by pain, swelling and swelling);
- Polyserositis (pleurisy, pericarditis, or non-infectious peritonitis, present or past);
- Kidney damage (the constant presence of protein in the urine in an amount of more than 0.5 g per day, as well as the constant presence of erythrocytes and cylinders in the urine (erythrocyte, hemoglobin, granular, mixed));
- Neurological disorders: seizures or psychosis (delusions, hallucinations) not due to medication, uremia, ketoacidosis, or electrolyte imbalance;
- Hematological disorders (hemolytic anemia, leukopenia with the number of leukocytes in the blood less than 1 * 10 9, lymphopenia with the number of lymphocytes in the blood less than 1.5 * 10 9, thrombocytopenia with the number of platelets less than 100 * 10 9);
- Immunological disorders (antibodies to double-stranded DNA in an increased titer, the presence of antibodies to the Sm antigen, a positive LE test, a false positive Wasserman reaction to syphilis for six months, the presence of an antilupus coagulant);
- An increase in the titer of ANA (antinuclear antibodies) in the blood.
Criteria for lupus erythematosus Nasonova include major and minor diagnostic criteria, which are shown in the table below:
| Great diagnostic criteria | Minor diagnostic criteria |
| "Butterfly on the Face" | Body temperature above 37.5 o C, lasting longer than 7 days |
| Arthritis | Causeless weight loss of 5 or more kg in a short time and malnutrition of tissues |
| Lupus pneumonitis | capillaries on the fingers |
| LE cells in the blood (less than 5 per 1000 leukocytes - single, 5 - 10 per 1000 leukocytes - a moderate number, and more than 10 per 1000 leukocytes - a large number) | Rashes on the skin like urticaria or rash |
| ANF in high credits | Polyserositis (pleurisy and carditis) |
| Werlhof syndrome | Lymphadenopathy (enlarged lymphatic ducts and nodes) |
| Coombs-positive hemolytic anemia | Hepatosplenomegaly (enlargement of the liver and spleen) |
| Lupus Jade | Myocarditis |
| Hematoxylin bodies in pieces of tissues of various organs taken during a biopsy | CNS lesion |
| Characteristic pathological picture in the removed spleen ("bulbous sclerosis"), in skin samples (vasculitis, immunofluorescence of immunoglobulins on the basement membrane) and kidneys (glomerular capillary fibrinoid, hyaline thrombi, "wire loops") | Polyneuritis |
| Polymyositis and polymyalgia (inflammation and muscle pain) | |
| Polyarthralgia (joint pain) | |
| Raynaud's syndrome | |
| ESR acceleration over 200 mm/hour | |
| Decrease in the number of leukocytes in the blood less than 4 * 10 9 / l | |
| Anemia (hemoglobin level below 100 mg/ml) | |
| Reducing the number of platelets below 100 * 10 9 / l | |
| Increase in the amount of globulin proteins over 22% | |
| ANF in low credits | |
| Free LE bodies | |
| Positive Wassermann test with confirmed absence of syphilis |
The diagnosis of lupus erythematosus is considered accurate and confirmed by a combination of any of the three major diagnostic criteria, one of which must be either "butterfly" or LE cells in large numbers, and the other two must be any of the above. If a person has only minor diagnostic signs or they are combined with arthritis, then the diagnosis of lupus erythematosus is considered only probable. In this case, to confirm it, data from laboratory tests and additional instrumental examinations are required.
The above criteria of Nason and the American Association of Rheumatologists are the main ones in the diagnosis of lupus erythematosus. This means that the diagnosis of lupus erythematosus is made only on their basis. And any laboratory tests and instrumental methods of examination are only additional, allowing to assess the degree of activity of the process, the number of affected organs and the general condition of the human body. Based only on laboratory tests and instrumental methods of examination, the diagnosis of lupus erythematosus is not made.
Currently, ECG, EchoCG, MRI, chest X-ray, ultrasound, etc. can be used as instrumental diagnostic methods for lupus erythematosus. All these methods make it possible to assess the degree and nature of damage in various organs.
Blood (test) for lupus erythematosus
Among the laboratory tests to assess the degree of intensity of the process in lupus erythematosus, the following are used: - Antinuclear factors (ANF) - with lupus erythematosus are found in the blood in high titers not higher than 1: 1000;
- Antibodies to double-stranded DNA (anti-dsDNA-AT) - with lupus erythematosus are found in the blood in 90 - 98% of patients, and are normally absent;
- Antibodies to histone proteins - with lupus erythematosus are found in the blood, are normally absent;
- Antibodies to the Sm antigen - with lupus erythematosus are found in the blood, but are normally absent;
- Antibodies to Ro / SS-A - in lupus erythematosus are found in the blood if there is lymphopenia, thrombocytopenia, photosensitivity, pulmonary fibrosis, or Sjögren's syndrome;
- Antibodies to La / SS-B - in lupus erythematosus are found in the blood under the same conditions as antibodies to Ro / SS-A;
- Complement level - in lupus erythematosus, the level of complement proteins in the blood is reduced;
- The presence of LE cells - in lupus erythematosus, they are found in the blood in 80 - 90% of patients, and are normally absent;
- Antibodies to phospholipids (lupus anticoagulant, antibodies to cardiolipin, positive Wassermann test with confirmed absence of syphilis);
- Antibodies to coagulation factors VIII, IX and XII (normally absent);
- Increase in ESR more than 20 mm/hour;
- Leukopenia (decrease in the level of leukocytes in the blood less than 4 * 10 9 / l);
- Thrombocytopenia (decrease in the level of platelets in the blood less than 100 * 10 9 / l);
- Lymphopenia (decrease in the level of lymphocytes in the blood is less than 1.5 * 10 9 / l);
- Increased blood concentrations of seromucoid, sialic acids, fibrin, haptoglobin, C-reactive protein of circulating immune complexes and immunoglobulins.
Diagnosis of lupus erythematosus, tests. How to distinguish lupus erythematosus from psoriasis, eczema, scleroderma, lichen and urticaria (recommendations from a dermatologist) - video
Treatment of systemic lupus erythematosus
General principles of therapy
Since the exact causes of lupus erythematosus are unknown, there are no therapies that can completely cure this disease. As a result, only pathogenetic therapy is used, the purpose of which is to suppress the inflammatory process, prevent relapses and achieve stable remission. In other words, the treatment of lupus erythematosus is to slow down the progression of the disease as much as possible, lengthen the periods of remission and improve the quality of human life. The main drugs in the treatment of lupus erythematosus are glucocorticosteroid hormones.(Prednisolone, Dexamethasone, etc.), which are used constantly, but depending on the activity of the pathological process and the severity of the general condition of the person, they change their dosage. The main glucocorticoid in the treatment of lupus is Prednisolone. It is this drug that is the drug of choice, and it is for him that the exact dosages are calculated for various clinical variants and the activity of the pathological process of the disease. Dosages for all other glucocorticoids are calculated based on prednisolone dosages. The list below shows dosages of other glucocorticoids equivalent to 5 mg of prednisolone:
- Betamethasone - 0.60 mg;
- Hydrocortisone - 20 mg;
- Dexamethasone - 0.75 mg;
- Deflazacort - 6 mg;
- Cortisone - 25 mg;
- Methylprednisolone - 4 mg;
- Paramethasone - 2 mg;
- Prednisone - 5 mg;
- Triamcinolone - 4 mg;
- Flurprednisolone - 1.5 mg.
So, at the first degree of activity pathological process Prednisolone is used in therapeutic dosages of 0.3 - 0.5 mg per 1 kg of body weight per day, at the second degree of activity- 0.7 - 1.0 mg per 1 kg of weight per day, and at the third degree- 1 - 1.5 mg per 1 kg of body weight per day. In the indicated doses, Prednisolone is used for 4 to 8 weeks, and then the dosage of the drug is reduced, but it is never completely canceled. The dosage is first reduced by 5 mg per week, then by 2.5 mg per week, after a while, by 2.5 mg in 2 to 4 weeks. In total, the dosage is reduced so that 6-9 months after the start of taking Prednisolone, its dose becomes maintenance, equal to 12.5-15 mg per day.
With a lupus crisis, capturing several organs, glucocorticoids are administered intravenously for 3 to 5 days, after which they switch to taking drugs in tablets.
Since glucocorticoids are the main means of treating lupus, they are prescribed and used without fail, and all other drugs are used additionally, selecting them depending on the severity of clinical symptoms and on the affected organ.
So, with a high degree of activity of lupus erythematosus, with lupus crises, with severe lupus nephritis, with severe damage to the central nervous system, with frequent relapses and instability of remission, in addition to glucocorticoids, cytostatic immunosuppressants are used (Cyclophosphamide, Azathioprine, Cyclosporine, Methotrexate, etc.).
For severe and widespread lesions skin Azathioprine is used at a dosage of 2 mg per 1 kg of body weight per day for 2 months, after which the dose is reduced to maintenance: 0.5-1 mg per 1 kg of body weight per day. Azathioprine at a maintenance dosage is taken for several years.
For severe lupus nephritis and pancytopenia(decrease in the total number of platelets, erythrocytes and leukocytes in the blood) use Cyclosporine at a dosage of 3-5 mg per 1 kg of body weight.
With proliferative and membranous lupus nephritis, with severe damage to the central nervous system Cyclophosphamide is used, which is administered intravenously at a dosage of 0.5 - 1 g per m 2 of body surface once a month for six months. Then, for two years, the drug continues to be administered at the same dosage, but once every three months. Cyclophosphamide ensures the survival of patients suffering from lupus nephritis and helps control clinical symptoms that are not affected by glucocorticoids (CNS damage, pulmonary hemorrhage, pulmonary fibrosis, systemic vasculitis).
If lupus erythematosus does not respond to glucocorticoid therapy, then Methotrexate, Azathioprine or Cyclosporine are used instead.
With low activity of the pathological process with lesions skin and joints in the treatment of lupus erythematosus, aminoquinoline drugs are used (Chloroquine, Hydroxychloroquine, Plaquenil, Delagil). In the first 3-4 months, drugs are used at 400 mg per day, and then at 200 mg per day.
With lupus nephritis and the presence of antiphospholipid bodies in the blood(antibodies to cardiolipin, lupus anticoagulant) drugs of the group of anticoagulants and antiaggregants (Aspirin, Curantil, etc.) are used. Basically, acetylsalicylic acid is used in small doses - 75 mg per day for a long time.
Drugs of the group of nonsteroidal anti-inflammatory drugs (NSAIDs), such as Ibuprofen, Nimesulide, Diclofenac, etc., are used as drugs to relieve pain and relieve inflammation in arthritis, bursitis, myalgia, myositis, moderate serositis and fever.
In addition to drugs, plasmapheresis, hemosorption and cryoplasmosorption methods are used to treat lupus erythematosus, which allow you to remove antibodies and inflammation products from the blood, which significantly improves the condition of patients, reduces the degree of activity of the pathological process and reduces the rate of progression of the pathology. However, these methods are only auxiliary, and therefore can only be used in combination with taking medications, and not instead of them.
For the treatment of skin manifestations of lupus, it is necessary to externally use sunscreens with UVA and UVB filters and ointments with topical steroids (Ftorcinolone, Betamethasone, Prednisolone, Mometasone, Clobetasol, etc.).
Currently, in addition to these methods, drugs of the group of tumor necrosis factor blockers (Infliximab, Adalimumab, Etanercept) are used in the treatment of lupus. However, these drugs are used exclusively as a trial, experimental treatment, since they are not currently recommended by the Ministry of Health. But the results obtained allow us to consider tumor necrosis factor blockers as promising drugs, since the effectiveness of their use is higher than that of glucocorticoids and immunosuppressants.
In addition to the described drugs used directly for the treatment of lupus erythematosus, this disease shows the intake of vitamins, potassium compounds, diuretics and antihypertensive drugs, tranquilizers, antiulcers and other drugs that reduce the severity of clinical symptoms from various organs, as well as restoring normal exchange substances. With lupus erythematosus, you can and should additionally use any drugs that improve general well-being person.
Drugs for lupus erythematosus
Currently, the following groups of drugs are used to treat lupus erythematosus: - Glucocorticosteroids (Prednisolone, Methylprednisolone, Betamethasone, Dexamethasone, Hydrocortisone, Cortisone, Deflazacort, Paramethasone, Triamcinolone, Flurprednisolone);
- Cytostatic immunosuppressants (Azathioprine, Methotrexate, Cyclophosphamide, Cyclosporine);
- Antimalarial drugs - aminoquinoline derivatives (Chloroquine, Hydroxychloroquine, Plaquenil, Delagil, etc.);
- Alpha TNF blockers (Infliximab, Adalimumab, Etanercept);
- Non-steroidal anti-inflammatory drugs (Diclofenac, Nimesulide,
systemic lupus erythematosus
Irina Aleksandrovna Zborovskaya – Doctor of Medical Sciences, Professor, Professor of the Department of Hospital Therapy with a Course of Clinical Rheumatology, Faculty of Postgraduate Medical Education, Volgograd State Medical University, Director of the Federal Budgetary State Institution "Research Institute of Clinical and Experimental Rheumatology" of the Russian Academy of Medical Sciences, Head regional center on osteoporosis, member of the Presidium of the Association of Rheumatologists of Russia, member of the editorial boards of the journals Scientific and Practical Rheumatology and Modern Rheumatology
Definition Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease pathogenetically associated with such disorders of immunoregulation that cause hyperproduction of a wide range of organo-nonspecific autoantibodies to various components of the nucleus and immune complexes, in which an immunoinflammatory process develops in various organs and tissues, leading as the disease progresses to the formation of multiple organ failure. SLE is one of the most severe diffuse diseases of the connective tissue, characterized by systemic autoimmune damage to the connective tissue and blood vessels. Epidemiology 1. The incidence of SLE is approximately 15-50:100,000 of the population. Women of childbearing age suffer 8-10 times more often than men.2. The disease often develops in relatives of SLE patients, concordance in twins reaches 50%.3. The prevalence of the disease among representatives of different races and ethnic groups is not the same: it occurs most often in blacks, somewhat less often in Hispanics and Asians, and least often in whites. Etiology. No single cause of SLE has been identified. It is believed that the complex relationship of environmental factors, genetic features immune response and hormonal background can influence the onset and clinical manifestations of the disease. 1. Many patients have indications of increased sensitivity of the skin to sunlight, or photosensitivity. With developed SLE, even a short exposure to the sun can lead not only to the appearance of skin changes, but also to an exacerbation of the disease as a whole. It is known that ultraviolet rays can cause changes in the genome of skin cells, which become a source of autoantigens that trigger and maintain the immune-inflammatory process.- Ultraviolet radiation stimulates apoptosis (programmed death) of skin cells. This leads to the appearance of intracellular autoantigens on the membrane of “apoptotic” cells and thereby inducing the development of an autoimmune process in genetically predisposed individuals.
- With the exception of ultraviolet radiation (usually UV-B, rarely UV-A), which provokes exacerbations of SLE, the role of other environmental factors in the pathogenesis of the disease has not been established. Hypersensitivity to sunlight is detected in 70% of patients.
- viral and/or bacterial infection, environmental factors;
- hereditary predisposition;
- hormonal regulation disorders.
- The possibility of a viral etiology of SLE is evidenced by a high incidence rate in individuals prone to frequent viral diseases. It is known that viruses can not only damage the cells of organs and systems, causing the formation of numerous autoantigens, but also affect the genome of immunocompetent cells, which leads to a violation of the mechanisms of immunological tolerance and the synthesis of antibodies.
- Data on the role of measles and measles-like viruses in the origin of the disease have been obtained. RNA-containing defective viruses were found.
- “Molecular mimicry” of viral proteins and “lupus” autoantigens (Sm and others) has been revealed. An indirect confirmation of the etiological (or “trigger”) role of a viral infection is the more frequent detection of serological signs of infection with the Epstein-Barr virus in SLE patients than in the population, the ability of bacterial DNA to stimulate the synthesis of antinuclear autoantibodies.
- Theoretically, viruses can cause opinions in the interactions of lymphocytes and influence the manifestations of the disease. However, there is no direct evidence that the occurrence of SLE in humans is caused by infectious agents.
environmental factors
genetic factors.- Family and twin studies suggest a genetic predisposition to SLE. The disease often appears in families with a deficiency of individual complement components. Some alloantigens (Ar HLA-DR2, HLA-B8 and HLA-DR3) are much more common in SLE patients than in the general population.
- The incidence of SLE increases in the presence of HLA-A1, B8, DR3 haplotypes. This hypothesis is also confirmed by the fact that if one of the twins develops SLE, then the risk of developing the disease in the second increases by 2 times. Although, in general, only 10% of SLE patients have relatives (parents or siblings) in their families who suffer from this disease, and only 5% of children born in families where one of the parents is sick with SLE develop this disease. Moreover, to date, it has not been possible to identify the gene or genes responsible for the development of SLE.
- Autoimmunity. Loss of tolerance to self-antigens is considered a central link in the pathogenesis of SLE. Patients tend to develop autoantibodies, increased activity B-lymphocytes and dysfunction of T-lymphocytes.
- SLE develops mainly in women of childbearing age, but hormonal factors may have more influence on the manifestations of the disease than on its occurrence.
- In women of reproductive age suffering from SLE, there is an excessive synthesis of estrogens and prolactin, which stimulate the immune response, and a lack of androgens, which have immunosuppressive activity. In men suffering from SLE, there is a tendency to hypoandrogenemia and hyperproduction of prolactin.
- It is believed that estrogens contribute to the polyclonal activation of B-lymphocytes. In addition, as already mentioned, it should be noted that the clinical and laboratory signs of the disease characteristic of SLE may occur in some patients with long-term use of various drugs (antibiotics, sulfanilamide, anti-tuberculosis drugs, and others).
Pathogenesis
It has been established that the underlying cause of the disease is uncontrolled production of antibodies and loss of tolerance to self-antigens, tissue damage by autoantibodies and immune complexes . Pronounced disturbances in the immune response to antigens are characteristic, including excessive activation of T- and B-lymphocytes and a violation of the mechanisms of its regulation.- At an early stage of the disease, polyclonal (B-cell) activation of immunity predominates.
- In the future, antigen-specific (T-cell) activation of immunity predominates.
- The fundamental immune disorder underlying SLE is congenital or induced defects in programmed cell death (apoptosis).
- The role of antigen-specific mechanisms is evidenced by the fact that autoantibodies are produced in SLE only in about 40 of more than 2 thousand potentially autoantigenic cellular components, the most important of which are DNA and multivalent intracellular nucleoprotein complexes (nucleosomes, ribonucleoproteins, Ro/La, etc.). .). The high immunogenicity of the latter is determined by the ability to cross-link B cell receptors and accumulate on the surface of “apoptotic” cells. A variety of defects cellular immunity, characterized by hyperproduction of Th2 cytokines (IL-6, IL-4 and IL-10). The latter are autocrine activation factors for B-lymphocytes synthesizing anti-nuclear autoantibodies. At the same time, estrogens have the ability to stimulate the synthesis of Th2 cytokines.
- Immunoglobulin genes that would be responsible only for the synthesis of autoantibodies in SLE patients have not been found. However, it has been shown that immunoglobulins with similar variable regions predominate in the serum of these patients. This suggests that in SLE patients, the proliferation of individual clones of B-lymphocytes that produce high-affinity autoantibodies may increase.
- According to most studies of experimental models of SLE in mice, T-lymphocytes play the most important role in the pathogenesis of the disease. It has been shown that the production of autoantibodies is stimulated not only by CD4 lymphocytes, but also by other populations of T-lymphocytes, including CD8 lymphocytes and T-lymphocytes that do not express either CD4 or CD8.
Activation of autoreactive B- and T-lymphocytes in SLE is due to many reasons, including impaired immunological tolerance, apoptosis mechanisms, production of anti-idiotypic antibodies, excretion of immune complexes, and proliferation of cells that control the immune response. Autoantibodies are formed that destroy the body's own cells and lead to a violation of their function. - The search and study of the structure of antigens to which autoantibodies are produced does not stop. Some antigens are components of the body's own cells (nucleosomes, ribonucleoproteins, surface antigens of erythrocytes and lymphocytes), others are of exogenous origin and are similar in structure to autoantigens (for example, the protein of the vesicular stomatitis virus, similar to the cSm antigen)
- The damaging effect of some autoantibodies is due to their specific binding to antigens, such as the surface antigens of erythrocytes and platelets. Other autoantibodies cross-react with multiple antigens - for example, DNA antibodies can bind to glomerular basement membrane laminin. Finally, autoantibodies carry a positive charge and can therefore bind to negatively charged structures such as the glomerular basement membrane. Antigen-antibody complexes can activate complement, leading to tissue damage. In addition, the binding of antibodies to the cell membrane can lead to disruption of cell functions even in the absence of complement activation.
- Circulating immune complexes and autoantibodies cause tissue damage and organ dysfunction.
Lesions of the skin, mucous membranes, central nervous system, kidneys and blood are typical. The autoimmune nature of the disease is confirmed by the determination of ANAT (antinuclear antibodies) in the blood and the detection of immune complexes in tissues. All clinical manifestations of SLE are a consequence of impaired humoral (synthesis of antinuclear antibodies) and cellular immunity. - The development of lupus nephritis is not associated with the deposition of circulating immune complexes (as in some forms of systemic vasculitis), but with the local (in situ) formation of immune complexes. First, nuclear antigens (DNA, nucleosomes, etc.) bind to the components of the kidney glomeruli, and then interact with the corresponding antibodies. Another possible mechanism is the cross-reaction of anti-DNA antibodies with glomerular components.
- Dysfunction of the reticuloendothelial system (RES). Long-term circulation of immune complexes contributes to their pathogenic effects, as over time, RES loses its ability to remove immune complexes. It was found that SLE is more often observed in individuals with a defective C4a gene.
- Autoantibodies can cause a number of disorders:
- Lymphocyte dysfunction. In SLE patients, various combinations of hyperactivity of B-lymphocytes and impaired function of CD8+ and CD4+ cells are observed, which leads to the production of autoantibodies and the formation of a large number of these immune complexes.
- Systemic immune inflammation may be associated with cytokine-dependent (IL-1 and TNF-alpha) damage to the endothelium, activation of leukocytes and the complement system. It is assumed that the latter mechanism is of particular importance in the defeat of those organs that are inaccessible to immune complexes (for example, the central nervous system).
Morphological changes
Characteristic microscopic changes . Hematoxylin bodies . In the foci of damage to the connective tissue, amorphous masses of nuclear substance are determined, stained with hematoxylin in a purple-blue color. Neutrophils that have engulfed such bodies in vitro are called LE cells. fibrinoid necrosis . We observe immune complexes in the connective tissue and vessel walls, consisting of DNA, AT to DNA and complement, they form a picture of “fibrinoid necrosis”. Sclerosis. The “bulb peel” phenomenon “ observed in the vessels of the spleen of patients with SLE with a characteristic perivascular concentric deposition of collagen. Vascular changes - fibrinoid changes, thickening of the endothelium develop in the intima. Tissue changes. Leather. With minor skin lesions, only nonspecific lymphocytic infiltration is observed. In more severe cases, deposition of Ig, complement, and necrosis (the area of the dermoepidermal junction) occurs. Classical discoid areas have follicular plugs, hyperkeratosis, and epidermal atrophy. Meet and open damage to the walls of small vessels of the skin (leukoclastic vasculitis). Kidneys. The deposition and formation of immune complexes in the mesangium and glomerular basement membrane lead to the development of glomerulonephritis in SLE. The prognosis of the disease and the tactics of treatment depend on the localization of deposits of immune complexes, the morphological type, the degree of activity and the severity of irreversible changes.- A characteristic sign of kidney damage in SLE is a periodic change in the histological picture of nephritis, depending on the activity of the disease or the therapy being carried out. A kidney biopsy allows you to assess the activity of the process (acute inflammation) and its chronicity (glomerulosclerosis and fibrous interstitial changes). Acute kidney injury responds better to treatment.
- Mesangial nephritis occurs due to the deposition of Ig in the mesangium, is considered the most frequent and mild kidney damage in SLE.
- Focal proliferative nephritis is characterized by involvement of only glomerular segments in less than 50% of glomeruli, but may progress to diffuse glomerular involvement.
- Diffuse proliferative nephritis occurs with cellular proliferation of most glomerular segments in more than 50% of the glomeruli.
- Membranous nephritis is a consequence of the deposition of Ig in the epithelium and peripheral capillary loops without proliferation of glomerular cells, is rare, although in some patients there are combinations of proliferative and membranous changes. With membranous nephritis, the prognosis is better than with proliferative.
- Interstitial inflammation can be observed in all of the disorders described above.
- Nonspecific synovitis and lymphocytic muscle infiltration often occur.
- Non-bacterial endocarditis is not uncommon and is typically asymptomatic. However, in half of the patients, non-bacterial verrucous endocarditis (Libman-Sachs) is found with damage to the usually mitral, tricuspid valves and the formation of their insufficiency, serous-fibrinous pericarditis, myocarditis.
Classification
flow options
Taking into account the nature of the onset of the disease, the speed of progression, its total duration, the degree of involvement of organs and systems in the process, as well as the response to treatment, three variants of the course are distinguished: - Acute.
- Subacute.
- Chronic.
According to clinical and laboratory data, 3 degrees of activity are distinguished:
- Idegree,
- IIdegree,
- IIIdegree.
- Discoid foci with telangiectasias (more often in chronic SLE).
- From the side of the skin, erythematous rashes on the face in the region of the wings of the nose, zygomatic bones, resembling a "butterfly" are typical.
on the ears, fingertips (finger capillaries), alopecia. 
- Erythema of the face may be unstable, but periodically increases, especially after insolation or exposure to cold.
- Sometimes blistering or maculopapular elements, urticaria, polymorphic exudative erythema, rash, panniculitis are observed.
- There are reports of non-scarring psoriasis-like rashes with telangiectasias and hyperpigmentation. Sometimes, it is even difficult to differentiate from psoriasis (observed in subacute cutaneous lupus erythematosus).
- Possible erythematous rashes on the scalp and hair loss (up to baldness). Unlike discoid lupus erythematosus, hair that has fallen out can grow back in SLE. It takes several months for them to branch out again. In some cases, the hair on the head begins to break at a distance of 1-3 cm from the surface of the skin in the frontal and temporal regions along the hairline.
- Possible vasculitis of the skin, which manifests itself: hemorrhagic papulonecrotic rashes, nodular-ulcerative vasculitis of the legs, hyperpigmentation, infarction of the nail folds, gangrene of the fingers.
- Sometimes there is a so-called lupus-cheilitis - swelling and congestive hyperemia of the red border of the lips with dense dry scales, crusts, erosions, followed by cicatricial atrophy.
- Sometimes enanthema is found on the mucous membrane of the hard palate, cheeks, lips, gums, tongue in the form of erythematous-edematous spots, erosive-ulcerative stomatitis, erosive and ulcerative lesion nasopharynx.
- Every third patient with SLE Raynaud's phenomenon is observed, which is characterized by changes in the color of the skin of the hands or feet (whitening and / or cyanosis) that are not permanent, but paroxysmal in nature. Typical is a two - or three-phase nature of blood flow disorders, when, after whitening and / or cyanosis of the fingers, reactive hyperemia. Trophic disorders of the skin of the fingers occur gradually, and, as a rule, are limited to the fingertips.
- SLE is characterized by vascular aneurysms, thrombosis (fibrinoid changes in the walls of blood vessels in combination with a cellular reaction).
- Sometimes, mainly on the skin of the lower extremities, there are hemorrhagic punctate rashes the size of a pinhead, which may be due to either thrombocytopenia or hemorrhagic vasculitis. In some cases, especially with secondary antiphospholipid syndrome, livedo reticularis (marble pattern of the skin in the extremities and torso) is noted.
- On the periphery - thromboangiitis obliterans syndrome with intermittent claudication and migrating phlebitis - Buerger's syndrome.
- Although thrombosis can develop in the presence of vasculitis, there is increasing evidence that antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies) cause thrombosis in the absence of inflammation. In addition, the long-term effect of immune complexes on the vascular wall and hyperlipoproteinemia, which develops during treatment with glucocorticoids, predispose to the development of coronary artery disease, therefore, for some patients, anticoagulant therapy is more important than immunosuppressive therapy.
- in acute progressive course of SLE, vasculitis of the coronary vessels is possible, however, the main cause of myocardial infarction in patients with SLE is atherosclerosis due to long-term steroid therapy;
- in SLE, the pathological process may also involve the endocardium, a feature of the lesion of which is the development of Libman-Sachs septic endocarditis, which occurs with a thickening of the parietal endocardium in the region of the atrioventricular ring, less often in the aortic valve; usually asymptomatic and detected by ecocardiographic examination; very rarely leads to the development of hemodynamically significant heart defects. These pathomorphological changes are usually found at autopsy. In secondary adgiphospholipid syndrome, cases of thrombotic valvulitis and thrombosis of the heart chambers are described. It is believed that non-bacterial damage to the endocardium (Libman-Sacks endocarditis) is more associated with the presence of AT to phospholipids. Endocarditis may be accompanied by embolism, valve dysfunction and infection;
- women with SLE in the premenopausal period have a high risk of developing atherosclerosis, the mechanism of which is probably the deposition of deposits of immune complexes in the vascular wall. An additional effect on the formation of atherosclerosis can have long-term therapy with corticosteroids due to hyperlipidemia and hyperglyceridemia.
- Pleurisy is found in 30% of patients. Pleurisy (dry or effusion, often bilateral, sometimes in combination with pericarditis). Rubbing noise of the pleura (with dry pleurisy).
Lupus pneumonitis is often difficult to distinguish from acute pneumonia. In the R-th study, infiltrates in SLE are bilateral, have a clear border, “volatile”. It is noted high standing of the diaphragm, increased pulmonary pattern, focal mesh deformity of the lower and middle sections of the lungs, symmetrical focal shadows in combination with one- or two-sided discoid atelectasis. Often this picture is accompanied by fever, shortness of breath, cough, hemoptysis. Pain during breathing, weakening of breathing, unvoiced wet rales in the lower parts of the lungs are noted. 
- Diffuse interstitial lung lesions are rare (like Hamman-Rich syndrome). Interstitial pneumonitis - in the early stages it is curable, but with the development of pulmonary fibrosis, treatment is ineffective.
- Severe, although rare, manifestations of SLE include pulmonary hypertension, usually as a consequence of recurrent pulmonary embolism in APS; rdsv and massive pulmonary hemorrhage. The last two complications often lead to death.
- Gastrointestinal disorders in SLE are most often manifested by nausea, diarrhea, and discomfort in the abdomen. The appearance of these symptoms may be due to lupus peritonitis and indicate an exacerbation of SLE. The most dangerous gastrointestinal complication of SLE is mesenteric vasculitis, manifested by acute cramping abdominal pain, vomiting, and diarrhea. Intestinal perforation is possible, usually requiring emergency surgery.
- Abdominal pain and X-ray evidence of small bowel distension and sometimes swelling of the bowel wall may be manifestations of bowel pseudo-obstruction; in this case, surgery is not indicated. For all of these gastrointestinal disorders, glucocorticoids are effective.
- In some patients, there is a violation of gastrointestinal motility, similar to that observed in systemic scleroderma. In this case, glucocorticoids do not help.
- In some patients, exacerbation of SLE or treatment with glucocorticoids and azathioprine leads to acute pancreatitis, which can be severe.
- An increase in amylase activity in SLE may be due not only to pancreatitis, but also to inflammation. salivary glands or macroamylasemia.
- Serum aminotransferase activity is often elevated in SLE exacerbations in the absence of severe liver damage; when the exacerbation subsides, the activity of aminotransferases decreases.
- However, sometimes there is an increase in the liver. It is possible to develop toxic drug-induced hepatitis while taking aspirin, other non-steroidal anti-inflammatory drugs, hydroxychloroquine, azathioprine and others. The progression of autoimmune hepatitis to cirrhosis is extremely rare. Interstitial and paranchymal hepatitis, sometimes necrosis of the parenchyma, due to thrombosis, are detected.
- Rapidly progressive lupus nephritis
- Nephritis with nephrotic syndrome,
- Nephritis with severe urinary syndrome,
- Nephritis with minimal urinary syndrome and subclinical proteinuria.
- Mesangial nephritis is the most common and relatively benign form of kidney disease, often asymptomatic. Mild proteinuria and hematuria are found in the urine. Usually specific treatment do not carry out. CRF is formed after 7 or more years.
- Focal proliferative nephritis is also a relatively benign variant of kidney disease and typically responds to steroid therapy.
- Diffuse proliferative nephritis - severe kidney damage, often accompanied by arterial hypertension, widespread edematous syndromes, significant proteinuria, erythrocyturia and signs of renal failure. To protect the kidneys, glucocorticoids and cytostatics are used.
- Membranous glomerulonephritis occurs with severe proteinuria, nephrotic syndrome, hypocomplementemia, slight changes in urine sediment and the absence of arterial hypertension. Over time, kidney failure develops. The effectiveness of the use of cytostatics in this form of lupus nephritis has not been proven. With a rapidly progressive variant of glomerulonephritis without treatment, patients die within 6-12 months from the onset of the first clinical manifestations.
- pericarditis is observed in approximately 20% of patients with SLE, of which 50% have echocardiographic signs of fluid effusion, but cardiac tamponade occurs rarely;
- myocarditis is somewhat less common (with conduction disturbances, arrhythmias and heart failure), and the changes can be reversible with adequate hormone therapy;
9. Defeat of the reticuloendothelial system It is manifested by an increase in all groups of lymph nodes, occurring in 30 - 70% of cases. They are soft, without inflammatory changes. The cubital lymph nodes are most commonly affected. In addition, an enlarged spleen is found (often correlated with activity). 10. Damage to the nervous system.
CNS: The disease can be accompanied by neuropsychiatric disorders in about 50% of cases, which include both acute and chronic disorders and are characterized by cerebral and focal symptoms.
CNS disorders in SLE are so diverse that they cover almost the entire spectrum of neurological disorders. SLE can affect all parts of the brain, as well as meninges, spinal cord, cranial and spinal nerves. Multiple lesions are possible; often neurological disorders are observed simultaneously with lesions of other organs. - The most common manifestations are mild cognitive impairment and headache, which may resemble a migraine. Headache(usually of a migraine nature, resistant to non-narcotic and even narcotic analgesics, often combined with other neuropsychiatric disorders, more often with APS).
- Possible generalized manifestations:
- Depression and anxiety disorders are often noted, the cause of which is usually not the disease itself, but the reaction of patients to it.
- Laboratory and instrumental studies do not always reveal CNS lesions in patients with SLE.
- symmetrical sensory (or motor),
- multiple mononeuritis (rare),
- Guillain-Barré syndrome (very rare)
- Arthralgias and symmetrical arthritis are classic manifestations of active lupus, but deformities are rare. Accompanied by tendovaginitis. Arthropathy (Jaccoud's syndrome) with persistent deformities occurs due to the involvement of ligaments and tendons, and not due to erosive arthritis.
- Inflammatory muscle lesions are often asymptomatic, although inflammatory myopathies may occur.
- One of the serious complications of SLE is choroiditis, which can lead to blindness in a few days and therefore requires treatment with high doses of immunosuppressive drugs.
- Episcleritis, conjunctivitis, corneal ulcers, xerophthalmia.
- Fundus: whitish and grayish lesions around the vessels - cytoid bodies, varicose hypertrophy and degeneration nerve fiber, optic neuritis.
- Syndrome, Charlie-Frommel is a syndrome of persistent lactation and amenorrhea after childbirth, which is apparently associated with damage to the centers of the hypothalamus in SLE. Possible atrophy of the uterus and ovaries.
- Autoimmune Hashimoto's thyroiditis.
| CLINICAL MANIFESTATIONS OF SLE General symptoms Fatigue, malaise, fever, loss of appetite, nausea, weight loss Lesions of the musculoskeletal system Arthralgia, myalgia Polyarthritis without erosion articular surfaces Hand deformity Myopathy Myositis Aseptic bone necrosis Skin lesions Butterfly erythema Discoid lupus erythematosus Hypersensitivity to sunlight Oral ulcers Other forms of rash: maculopapular, bullous, wheals, subacute cutaneous lupus erythematosus Alopecia Vasculitis Panniculitis Hematological disorders Normocytic normochromic anemia Hemolytic anemia Leukopenia (< 4000 мкл -1) Лимфопения (< 1500 мкл -1) Тромбоцитопения (< 100 000 мкл -1) Ингибиторные коагулопатии Спленомегалия Увеличение лимфоузлов Neurological disorders Cognitive impairment Psychosis Epileptic seizures Headache Neuropathy Other CNS symptoms | Frequency,% 95 95 95 95 60 10 40 5 15 80 50 15 70 40 40 40 20 5 85 70 10 65 50 15 10-20 15 20 60 50 10 20 25 15 15 |
Heart and lung damagePleurisy Pericarditis Myocarditis Aseptic thromboendocarditis Pleural effusion Lupus pneumonitis Interstitial pulmonary fibrosis Pulmonary hypertension ARDS, diffuse bleeding of the lung parenchymakidney damageProteinuria (> 500 mg/day) Cellular casts nephrotic syndrome kidney failureGastrointestinal lesionsNon-specific symptoms: loss of appetite, nausea, mild abdominal pain, diarrhea Vasculitis with gastrointestinal bleeding or intestinal perforation Ascites Change in liver enzyme activityThrombosisVenArteriesSpontaneous abortionEye lesionsChoroiditis Conjunctivitis, episcleritis Xerophthalmia |
Frequency, % 60 50 30 10 10 30 10 5 < 5 < 5 50 50 50 25 5-10 45 30 5 < 5 40 15 10 5 30 15 5 10 15 |
- Antileukocyte antibodies cause the development of autoimmune lymphopenia, less often neutropenia. Moreover, if leukopenia is not caused by the side effects of cytostatic drugs, then the risk of secondary infectious complications is low.
- Antiplatelet antibodies contribute to the development of acute or chronic immune thrombocytopenia.
- In recent years, it has often been described antiphospholipid syndrome in chronic SLE. This is a symptom complex characterized by a triad of signs - venous or arterial thrombosis, obstetric pathology (fetal death, recurrent spontaneous abortions), thrombocytopenia, arising against the background of hyperproduction of antibodies to phospholipids (i.e. lupus anticoagulant) antibodies to cardiolipin and / or a false positive reaction Wasserman). Antibodies to phospholipids are found in 30-60% of patients with SLE.
At this time, the chromatin network is gradually erased, the volume of the nucleus increases significantly; the cytoplasm breaks, expelling a homogeneous nuclear mass - free bodies of lupus erythematosus. Phase II - or rosette phenomenon, in which healthy white blood cells agglutinate around the affected cell. These leukocytes, due to chemotaxis with respect to the KB body that they surround, determine the formation of a rosette. 
Phase III - or the formation of LE cells, in which one of the living leukocytes surrounding the KB body phagocytes it, resulting in the formation of an LE cell (Hargraves cell). So, LE cells are mature neutrophils with a nucleus pushed to the periphery, in the cytoplasm of which round or oval large inclusions are found in the form of homogeneous amorphous clumps, consisting of depolymerized DNA and staining purple. LE cells are usually found in 70% of SLE patients. At the same time, single LE cells can be observed in other diseases. The test may be positive in 20% of patients with RA, Sjögren's syndrome, scleroderma, liver diseases. 5. Other immunological studies
- As a result of immunocomplex activity in SLE patients, a low level of complement components C3 and C4 is noted, and in many cases this indicator is associated with the degree of lupus activity.
- Hypergammaglobulinemia controls the hyperactivity of B-lymphocytes.
- However, autoantibodies are recognized as the most typical findings in SLE.
- The diagnosis of SLE is considered confirmed when autoantibodies characteristic of it are detected. The best method of preliminary diagnosis is the definition antinuclear antibodies(ANAT). When using human cells, these antibodies are found in 95% of SLE patients. They are not specific for SLE and may be present in the serum of healthy individuals (usually in low titer), especially in the elderly. Antinuclear antibodies also appear in other autoimmune diseases, as well as in viral infections, chronic inflammation and the use of certain drugs. Thus, the detection of these antibodies does not allow to confirm, and their absence - to exclude the diagnosis of SLE. ANAT is determined using immunofluorescent methods. When the components of the nuclei of epithelial cells isolated by freezing-thawing are introduced into the tested serum, the patient's ANAT interacts with them, forming fluorescent immune complexes. Diffuse, homogeneous immunofluorescent staining of specimens is most common, but ring-shaped staining is possible.
| Antibodies | Frequency detection % | Antigen | Diagnostic value |
| Antinuclear antibodies | 98 | Various nuclear antigens | The sensitivity of the method is higher when using human rather than mouse cells. With repeated negative results studies, the diagnosis of SLE is unlikely |
| Antibodies to DNA | 70 | native DNA | Unlike antibodies to single-stranded DNA, antibodies to native DNA are relatively specific for SLE. High antibody titer is a sign of glomerulonephritis and increased activity of SLE |
| Antibodies to SM antigen | 30 | Proteins associated with small nuclear RNAs U1, U2, U4/6 and U5 | specific to SLE |
| Antibodies to ribonucleoprotein | 40 | Proteins associated with U1 small nuclear RNA | Found in high titer in polymyositis, SLE, systemic scleroderma, and mixed connective tissue disease. The detection of these antibodies in SLE patients in the absence of antibodies to DNA indicates a low risk of glomerulonephritis. |
| Antibodies to the Ro/SS-A antigen | 30 | Proteins associated with RNA Y1-Y3 | They are found in Sjögren's syndrome, subacute cutaneous lupus erythematosus, congenital complement deficiency, SLE, not accompanied by the appearance of antinuclear antibodies, in elderly patients with SLE, in lupus syndrome in newborns, congenital AV blockade. May cause glomerulonephritis |
| Antibodies to antigen La/SS-B | 10 | Phosphoprotein | Along with these antibodies, antibodies to the Ro/SS-A antigen are always detected. Detection of antibodies to La/SS-B indicates a low risk of glomerulonephritis. Specific to Sjögren's syndrome |
| Antibodies to histones | 70 | Histones | In drug-induced lupus syndrome, they are detected more often (in 95% of patients) than in SLE |
| Antiphospholipid antibodies | 50 | Phospholipids | Lupus anticoagulant, antibodies to cardiolipin and antibodies detected by non-treponemal tests. Detection of lupus anticoagulant and antibodies to cardiolipin (especially IgG in high titer) indicates a high risk of thrombosis, spontaneous abortion, thrombocytopenia and heart defects |
| Antibodies to erythrocytes | 60 | red blood cells | A minority of patients with these antibodies present in their serum develop hemolytic anemia. |
| Antibodies to platelets | 30 | platelets | seen in thrombocytopenia |
| Antibodies to lymphocytes | 70 | Lymphocytes | Possibly cause leukopenia and T-lymphocyte dysfunction |
| Antibodies to neurons | 60 | Membranes of neurons and lymphocytes | According to a number of studies, a high titer of IgG antibodies to neurons is characteristic of SLE that occurs with diffuse CNS damage. |
| Antibodies to P-protein of ribosomes | 20 | P-protein ribosomes | A number of studies have shown that these antibodies are detected in SLE accompanied by depression and other psychiatric disorders. |
- In SLE, it is often determined antibodies to membrane and cytoplasmic components: AT to transfer RNA and ribosomal nucleoproteins. Other cytoplasmic AT apparently interact with phospholipids of cell membranes and cause cytotoxic reactions in some organs and tissues (AT to gastric parietal cells, thyroid epithelial cells and blood cells)
- Circulating immune complexes
- general blood analysis;
- general urine analysis;
- biochemical research;
- kidney biopsy (to determine the morphological variant of glomerulonephritis and identify patients with active lupus nephritis in need of aggressive cytostatic therapy);
- an immunological examination that detects antinuclear (ANF) or antinuclear factor. ANF is a heterogeneous population of autoantibodies (AHA) that react with various components of the cell nucleus. ANF is detected in 95% of SLE patients (usually in high titer), and the absence of ANF in most cases makes it possible to exclude the diagnosis of SLE. The type of immunofluorescence to some extent reflects the specificity of different types of AHA: in SLE, the homogeneous type (antibodies to DNA, histone) is most often detected, less often peripheral (antibodies to DNA) or mottled (antibodies to Sm, RNP, Ro/La). To detect autoantibodies to certain nuclear and cytoplasmic autoantigens, various methods are used. immunological methods(immunoenzymatic, radioimmunological, immunobotting, immunoprecipitation).
| 1. Butterfly erythema 2. Discoid lupus erythematosus 3. Increased sensitivity to ultraviolet radiation 4. Ulcers of the oral and nasal mucosa 5. Arthritis 6. Serositis 7. Kidney damage 8. CNS damage 9. Hematological disorders 10. Immunological disorders 11. Antinuclear antibodies | Persistent erythema or plaques on the cheekbones Raised-edged plaques covered with tight-fitting scales, horny plugs at the orifices hair follicles; atrophic scars may appear On examination Without erosion of the articular surfaces, with damage to ³ joints, manifested by swelling, tenderness and effusion Pleurisy or pericarditis (ECG changes, pericardial effusion or pericardial friction rub) Proteinuria (> 0.5 g / day or abruptly positive result rapid analysis of urine for protein) Epileptic seizures or psychoses that occur without apparent reason Hemolytic anemia, leukopenia (< 4000 мкл -1), лимфопения (< 1500 мкл -1) или тромбоцитопения (< 100 000 мкл -1), не связанные с применением лекарственных средств Наличие LE-клеток, антител к нативной ДНК или Sm-антигену или ложноположительные нетрепонемные serological reactions for syphilis A persistent increase in the titer of antinuclear antibodies detected by immunofluorescence, with the exclusion of drug-induced lupus syndrome |
- unexplained fever, malaise, weight loss, anemia,
- photodermatitis,
- arthralgia, arthritis,
- Raynaud phenomenon,
- serositis,
- nephritis and nephrotic syndrome,
- neurological disorders (convulsions or psychosis),
- alopecia,
- thrombophlebitis,
- recurrent spontaneous abortions.
- With the development of SLE with lupus nephritis it is important to use the whole complex of clinical and laboratory indicators, to clarify whether there were transient arthritis or arthralgia, trophic disorders, but highest value has the detection of LE cells, ANA, as well as electron microscopic and immunofluorescent examination of a kidney biopsy. The same approach is useful in autoimmune cytopenias.
- 6. Fibromyalgia with ANF.
- 7. Idiopathic thrombocytopenic purpura.
- 8. Systemic vasculitis.
- Neonatal lupus syndrome can develop in children whose mothers have high titers of AT to Ro, IgG. Maternal antibodies pass through the placenta and cause immune damage to the baby's tissues. Typical clinical signs include skin manifestations, transient thrombocytopenia, and hemolytic anemia. The most severe is the defeat of the conduction system of the child's heart, which may require constant pacing. Over time, most mothers develop some kind of autoimmune disease, including SLE.
- lyme borreliosis,
- tuberculosis
- secondary syphilis,
- infectious mononucleosis,
- hepatitis B,
- HIV infection, etc.;
- Chronic active hepatitis.
SLE treatment
SLE is incurable. Complete remission is also rarely achieved. Therefore, both the doctor and the patient must be aware that the main goals of treatment are: 1. Fighting severe exacerbations 2. Maintaining a satisfactory condition in the period between exacerbations, usually at the cost side effects used medicines. The goal of treatment should be to achieve induced remission, which implies the absence of any clinical manifestations of SLE (in this case, there may be signs that have arisen due to lesions of one or another organ or system during previous exacerbations), the absence of cytopenic syndrome, and immunological examination should not reveal antinuclear and other organ-specific antibodies. Treatment of SLE is carried out purely individually, not all patients are prescribed glucocorticosteroids. Patients are explained that the prognosis for this chronic disease is much more favorable than it is commonly thought, and properly administered therapy, with the exclusion of a number of provoking factors (ultraviolet rays, emotional stress), contribute to a more favorable course of the disease. It must be remembered that in case of exacerbations of the disease, surgical intervention may be necessary. Often an infection joins, complications of pregnancy and the postnatal period are possible. Sunscreens (with a protection factor of at least 15), containing para-aminobenzoic acid or benzophenones, effectively protect one third of SLE patients from photosensitivity. Corticosteroids .- Topical application of corticosteroids.
- severity of the course: the highest doses in acute course and exacerbation of subacute course;
- activity of the pathological process: 40-60 mg of prednisolone per day or pulse therapy for grade III, 30-40 mg per day for grade II, and 15-20 mg per day for grade I.
- predominant organ pathology (especially suppressive hormone therapy should be for lupus nephritis and lesions of the nervous system).
- age-related reactivity in adolescence and menopause, excitability, insomnia and other side effects quickly occur.
- coronary vasculitis
- Libman-Sachs endocarditis
- Myocarditis
- Tamponade
- malignant hypertension
- Pulmonary hypertension
- Pulmonary hemorrhages
- Pneumonitis
- Embolism/infarction
- Interstitial fibrosis
- Hemolytic anemia
- Neutropenia (< 1000/мм 3)
- Thrombocytopenia (< 50 000 мм 3)
- Thrombotic thrombocytopenic purpura
- Thrombosis (venous or arterial)
- mesenteric vasculitis
- pancreatitis
- convulsions
- Stroke
- Transverse myelitis
- mononeuritis, polyneuritis
- Optic neuritis
- Psychosis
- Demyelinating syndrome
- Persistent nephritis
- Rapidly progressive nephritis
- nephrotic syndrome
- Vasculitis
- Diffuse rash with ulceration
- Myositis
- High fever without infection
| Dose of prednisolone, mg | A week | |||||||
| 1st | 2nd | 3rd | 4th | 5th | 6th | 7th | 8th | |
| 75 | 70 | 65 | 60 | 55 | 50 | – | – | – |
| 50 | 47,5 | 45 | 45 | 42,5 | 42,5 | 40 | 40 | – |
| 40 | 37,5 | 37,5 | 35 | 35 | 32,5 | 32,5 | 30 | 30 |
| 30 | 27,5 | 27,5 | 25 | 25 | 22,5 | 22,5 | 20 | 20 |
Glucocorticoids are prescribed in combination with potassium preparations, vitamins, plasma and blood transfusions (carefully), and, if necessary, with anabolic drugs and others. symptomatic means(diuretic, hypotensive, ATP, cocarboxylase, etc.). In acute and subacute SLE treatment programs active forms SLE has its own characteristics due to the more aggressive course of the disease, which is accompanied by: - progressive course with the development of new symptoms and syndromes, despite the use of high doses of corticosteroids for 1-1.5 months;
- lupus nephritis with the formation of nephrotic syndrome;
- severe lesions of the central nervous system (acute psychosis, the appearance of focal symptoms, transverse myelitis, status epilepticus);
- the development of life-threatening complications (exudative pericarditis; pneumonitis with increasing respiratory failure, recurrent thrombosis, etc.).
- So, to prevent the development of peptic ulcers, patients are recommended regular meals: it is necessary to exclude spicy, irritating dishes, food should be mechanically gentle; it is desirable to use alkalizing agents, especially with developed dyspeptic symptoms and antispasmodics (papaverine, no-shpa, etc.).
- In the presence of focal strepto - and staphylococcal infections, anti-infective therapy should be included in the complex treatment. In infectious complications, the dose of corticosteroid drugs should not only not be reduced, but in connection with a temporary suppression of the function of the adrenal cortex in some patients, subject to reliable anti-infective protection, it should even be increased.
- If a patient has focal tuberculosis, corticosteroid hormones should be prescribed in combination with anti-tuberculosis drugs (isothiazide, streptomycin, etc.).
- The development of local or general candidiasis is not a contraindication to the continuation of glucocorticosteroid therapy, provided that antifungal drugs are taken.
- In order to prevent violations of mineral and water metabolism (release of potassium, calcium, phosphorus and retention of sodium and water), often accompanied by edema, it is necessary to control the content of potassium in blood. With hypokalemia, potassium chloride is given orally 1-2 g 3-4 times a day, previously dissolving it in water, usually up to 5 g per day or potassium acetate (15% solution, 3-4 tablespoons per day). Loss of calcium and phosphorus by the body is usually manifested in SLE with diffuse osteoporosis.
- A clear contraindication to continued corticosteroid treatment is steroid psychosis or increased seizures (epilepsy). It is necessary to differentiate with cerebral vasculitis. Excitation (insomnia, euphoria) is not an indication for discontinuation of treatment: this condition can be stopped with sedatives.
- pericarditis is observed in approximately 20% of patients with SLE, of which 50% have echocardiographic signs of fluid effusion, but cardiac tamponade occurs rarely;
- myocarditis is somewhat less common (with conduction disturbances, arrhythmias and heart failure), and the changes can be reversible with adequate hormone therapy;
Use of NSAIDs in SLE
Arthritis and arthralgia are among the frequent manifestations of SLE, with moderate severity of which, NSAIDs are used until inflammation in the joints subsides and body temperature normalizes. However, NSAIDs should be used with extreme caution in SLE due to the possibility of developing unusual severe side effects:- aseptic meningitis described during treatment with ibuprofen, tolmetin, sulindac (indomethacin);
- in SLE, NSAIDs often have a hepatotoxic effect (usually manifested by an isolated increase in transaminase levels) than in other diseases;
- in addition, these drugs can cause a weakening of glomerular filtration (especially in patients with previous kidney damage, congestive heart failure and cirrhosis of the liver);
- NSAIDs can reduce the effectiveness of furosemide and thiazide diuretics, cause fluid retention, increase blood pressure;
- NSAIDs can cause damage to the gastrointestinal tract.
- a high degree of disease activity involving many organs and systems, and especially the kidneys, in proliferative and membranous lupus nephritis (both in nephrotic and nephritic syndromes); renal syndrome occupies a special place in the indications for immunosuppressive therapy; so, even in the absence of others clinical signs activity of SLE, kidney damage requires early, massive and longer administration of immunosuppressants due to the autoimmune genesis of lupus nephritis, severe concomitant disorders of humoral and cellular immunity;
- the use of cyclophosphamide will often allow control of clinical manifestations refractory to monotherapy with high doses of glucocorticoids (thrombocytopenia, CNS lesions, pulmonary hemorrhages, interstitial pulmonary fibrosis, systemic vasculitis);
- insufficient effectiveness of corticosteroids when it is necessary to reduce the “overwhelming dose” of corticosteroids due to a pronounced side effect (rapid significant weight gain, arterial hypertension, steroid diabetes, severe osteoporosis, spondylopathy, etc.) or due to the individual characteristics of patients (constitutional obesity, adolescence and menopause), when it is necessary to reduce the maintenance dose, if it is> 15-20 mg, with corticosteroid dependence.
- Currently, cyclophosphamide and azathioprine (Imuran) are more commonly used at doses of 2-3 mg/kg (usually 100 to 200 mg per day). In recent years, when conducting pulse therapy with metipred, 1 g of cyclophosphamide is added to the system once, and then the patient is transferred to oral azathioprine. In this case, patients receive simultaneously from 10 to 40 mg of prednisolone per day (in cases of diffuse glomerulonephritis with nephrotic syndrome).
- Pulse therapy with cyclophosphamide (10-15 mg/kg IV once every 4 weeks) rarely leads to hemorrhagic cystitis than daily oral administration, but is accompanied by severe hematopoiesis suppression.
- Treatment with cyclophosphamide (intravenous bolus injection of 0.5-1 g/m 2 monthly for at least six months, and then every three months for two years) in combination with oral GC and pulse therapy increases the survival of patients with proliferative lupus nephritis to a greater extent than glucocorticoid monotherapy (including pulse therapy), or treatment with a combination of glucocorticoids and azathioprine.
- Azathioprine (1-4 mg / kg / day), methotrexate (15 mg / week) are indicated:
- Long-term treatment with azathioprine is used:
- hemopoiesis suppression,
- frequent opportunistic infections (for example, those caused by the varicella-zoster virus),
- irreversible ovarian failure
- hepatotoxicity (azathioprine),
- hemorrhagic cystitis (cyclophosphamide),
- alopecia and carcinogenic effects.
Plasmapheresis
The mechanisms of action of plasmapheresis are associated with an improvement in the functional activity of the reticuloendothelial system, the removal of autoantibodies, CEC and inflammatory mediators from the bloodstream. An important factor in extracorporeal methods of blood purification is an increase in the body's sensitivity to drugs and, first of all, GCS. In some patients resistant to cytotoxic drugs, the use of plasmapheresis in some cases gives an obvious clinical effect (from 3 to 5 plasmapheresis procedures with a single removal of 800-1000 mg of plasma). It is believed that plasmapheresis sessions in SLE are most justified in patients with cryoglobulinemia, increased blood viscosity, thrombotic thrombocytopenic purpura, severe vasculitis with forms of proliferative nephritis resistant to glucocorticoids and cytostatics, as well as autoimmune hemolytic anemia, antiphospholipid syndrome, hemorrhagic lupus pneumonitisHemosorption
Hemosorption is an extracorporeal method of blood purification by passing it through a column with activated carbon granules. The method has an immunocorrective effect, and also increases the sensitivity of cells and tissues to the action of glucocorticoids. Indications for hemosorption in SLE:- persistent SLE activity despite large doses of glucocorticoids and cytostatics;
- active lupus nephritis;
- persistent articular syndrome;
- vasculitis of the skin with ulceration;
- the impossibility of increasing the dose of glucocorticoids due to the developed complications.
Calcium channel blockers and other vasodilators
Calcium channel blockers (nifedipine) are used in the treatment of Raynaud's syndrome. With the development of severe tissue ischemia, vasodilators with antithrombotic potential (intravenous prostacyclin) are indicated. Photopheresis Sometimes extracorporeal photochemotherapy (photopheresis) is used to treat SLE. In some patients with SLE, a significant effect was noted, manifested in a decrease in the overall activity of the disease and especially a decrease in the skin manifestations of the disease and arthritis. In most patients, it was possible to reduce the dose of GCs and cytostatics. There are practically no side effects with this type of treatment. Some patients had a long-term clinical remission for 30 months. UVR application photosensitivity is good known complication SLE. The direct damaging effects of sunlight on the skin, especially evident in subacute cutaneous lupus erythematosus, may exacerbate the skin process in discoid lupus or exacerbate skin lesions in SLE. In addition, ultraviolet irradiation is potentially capable of exacerbating not only the skin syndrome, but also the systemic immunopathological process in SLE. However, there have recently been reports of a beneficial effect of UVR at specific wavelengths in SLE. This leads to a significant decrease in some parameters of SLE activity, including weakness, joint pain, stiffness, and fever. Attention is drawn to the effectiveness of UVR in relation to skin manifestations, including subacute cutaneous lupus erythematosus.vitamin therapy
The complex therapy of patients with SLE includes vitamins C and group B in courses lasting 2-3 months, especially during periods of severe vitamin deficiency (winter, spring), as well as during an exacerbation of the disease, if it is necessary to increase doses of hormones. However, vitamin therapy must be administered with caution due to the possibility of allergic reactions.Exercise therapy and massage
Due to the fact that a number of patients for a long time have pain in the joints and limitation of movements (mainly due to subluxations), when active visceritis subsides, exercise therapy and massage can be used under the control of the general condition and condition of the internal organs. Physiotherapy and spa treatment is not recommended. Often the onset of the disease or its exacerbations are provoked by UV - irradiation of the joints, the use of radon baths, insolation. X-Ray Exposure There are anecdotal reports of the potential effectiveness of X-ray exposure in SLE. Interestingly, in SLE, X-ray exposure usually causes a decrease in antibody titers to DNA and ANF (antinuclear factor). Use of monoclonal antibodies. Specific approaches to immunotherapy involve the use of monoclonal antibodies to a wide range of mononuclear cell and endothelial membrane antigens, antibodies to cytokines, natural cytokine receptor ligands, and soluble cytokine antagonists or chemicals with immunomodulatory activity. It is assumed that the introduction of antibodies can not only cause the elimination of the corresponding target cells, but also lead to a change in their functional activity. For example, the possibility of treating 4 patients with SLE with monoclonal antibodies to DM was revealed. Side effects are observed in most patients, but they are usually mild and do not lead to interruption of treatment. There are few data on the efficacy of recombinant DNase, a DNA-cleaving enzyme, in experimental lupus models. Immunomodulators Another area of SLE therapy in recent years is the use of certain immunomodulators, such as thalidomide, bindarit, nucleoside analogues (fludarabine 25-30 mg/m 2 /day IV for 30 minutes, mizoribine, leflunomide). At present, some experience has been gained in the use of these drugs in patients with SLE. Clinical trials of thalidomide were mainly conducted in patients with severe skin lesions resistant to antimalarial drugs and GKS. The vast majority of patients were able to achieve good effect and reducing the dose of corticosteroids, while drug withdrawal did not lead to an exacerbation of symptoms. The main limitation with the use of thalidomide is its teratogenicity. In addition, the development of irreversible peripheral neuropathy is described, depending on the dose and duration of treatment. Linomide is a new immunomodulatory drug. It has the ability to enhance the activity of natural killer cells (NK~cells), monocytes (macrophages and T-lymphocytes), inhibits the activity of the autoimmune process. The results indicate the possibility of using linomide in SLE. Autologous stem cell transplant (ATSC) Autologous stem cell transplantation is currently the most aggressive treatment for SLE. By 2000, a little more than 30 patients with SLE had gained experience in using ATSC. Preliminary positive results certainly need further confirmation. Long-term monitoring of patients is necessary, bearing in mind the possibility of induction against the background of treatment for the development of malignant tumors. Despite the impression that this type of therapy is effective in cases of refractory and severe SLE, due to the high mortality that accompanies it, ATSC can only be recommended in the most severe, hopeless cases. Vitamin E ( a -tocopherol) Tocopherol has antioxidant activity. Used to treat skin lesions in discoid and systemic lupus erythematosus. The drug is more active in newly developed superficial skin lesions and when used in high doses (800-2000 IU / day). Vitamin E gives a positive isotropic effect, it should be used with extreme caution in patients with arterial hypertension and diabetes mellitus.Prevention of SLE
I. Mainly secondary. 1. Secondary prevention SLE, aimed at preventing exacerbations and further progression of the disease, includes, first of all, timely complex long-term therapy of the disease, which is carried out under dynamic control. The patient should regularly undergo dispensary examinations, consult a doctor immediately if the state of health changes, strictly adhere to the prescribed medication regimen, diet, and observe the daily routine. 2. General recommendations:- exclude psycho-emotional stress;
- reduce sun exposure, use sunscreen;
- actively treat (and, if possible, prevent) the development of infection, including through vaccination;
- consume food with low content fat and high content polyunsaturated fatty acids, calcium and vitamin D;
- observe effective contraception during an exacerbation of the disease and in the treatment of cytotoxic drugs (you should not take oral contraceptives with a high content of estrogens, since an exacerbation of SLE is possible);
- in the absence of severe, life-threatening complications, prescribe the least toxic drugs in effective doses;
- if vital organs are involved in the pathological process and there is a high risk of irreversible lesions, immediately prescribe aggressive therapy, including pharmacological and non-pharmacological methods of treatment;
- avoid surgical interventions, do not administer vaccines and sera;
- with stable remission, glucocorticoids can be canceled, but patients should be under dynamic observation and in the spring-autumn period to receive anti-relapse treatment with one of the aminoquinoline drugs, antihistamines, vitamins.
- arterial hypertension,
- antiphospholipid syndrome,
- high disease activity
- high values of damage index,
- accession of infection,
- complications of drug therapy.
Systemic lupus erythematosus (SLE)- a chronic autoimmune disease caused by a malfunction of immune mechanisms with the formation of damaging antibodies to one's own cells and tissues. SLE is characterized by damage to the joints, skin, blood vessels and various organs (kidneys, heart, etc.).
The cause and mechanisms of the development of the disease
The cause of the disease has not been elucidated. It is assumed that the trigger mechanism for the development of the disease are viruses (RNA and retroviruses). In addition, people have a genetic predisposition to SLE. Women get sick 10 times more often, which is associated with the peculiarities of their hormonal system (high concentration of estrogen in the blood). The protective effect of male sex hormones (androgens) with respect to SLE has been proven. Factors that can cause the development of the disease can be a viral, bacterial infection, medications.The basis of the mechanisms of the disease is a violation of the functions of immune cells (T and B - lymphocytes), which is accompanied by excessive formation of antibodies to the body's own cells. As a result of excessive and uncontrolled production of antibodies, specific complexes are formed that circulate throughout the body. Circulating immune complexes (CIC) settle in the skin, kidneys, on the serous membranes of internal organs (heart, lungs, etc.) causing inflammatory reactions.
Symptoms of the disease
SLE is characterized by a wide range of symptoms. The disease proceeds with exacerbations and remissions. The onset of the disease can be both lightning fast and gradual. General symptoms
- Fatigue
- Weight loss
- Temperature
- Decreased performance
- Fast fatiguability
Damage to the musculoskeletal system
- Arthritis - inflammation of the joints
- Occurs in 90% of cases, non-erosive, non-deforming, joints of the fingers, wrists, knee joints are more often affected.
- Osteoporosis - decreased bone density
- As a result of inflammation or treatment with hormonal drugs (corticosteroids).
- Muscle pain (15-64% of cases), muscle inflammation (5-11%), muscle weakness (5-10%)
Mucosal and skin lesions
- Skin lesions at the onset of the disease appear only in 20-25% of patients, in 60-70% of patients they occur later, in 10-15% of the skin manifestations of the disease do not occur at all. Skin changes appear on areas of the body exposed to the sun: face, neck, shoulders. Lesions have the appearance of erythema (reddish plaques with peeling), dilated capillaries along the edges, areas with excess or lack of pigment. On the face, such changes resemble the appearance of a butterfly, as the back of the nose and cheeks are affected.
- Hair loss (alopecia) is rare, usually affecting the temporal region. Hair falls out in a limited area.
- Increased skin sensitivity to sunlight (photosensitivity) occurs in 30-60% of patients.
- Mucosal involvement occurs in 25% of cases.
- Redness, decreased pigmentation, malnutrition of the tissues of the lips (cheilitis)
- Small punctate hemorrhages, ulcerative lesions of the oral mucosa
Respiratory damage
Defeats from the side respiratory system SLE is diagnosed in 65% of cases. Pulmonary pathology can develop both acutely and gradually with various complications. The most common manifestation of damage to the pulmonary system is inflammation of the membrane covering the lungs (pleurisy). It is characterized by pain in the chest, shortness of breath. SLE can also cause the development of lupus pneumonia (lupus pneumonitis), characterized by: shortness of breath, cough with bloody sputum. SLE often affects the vessels of the lungs, leading to pulmonary hypertension. Against the background of SLE, infectious processes in the lungs often develop, and it is also possible to develop a serious condition such as blockage of the pulmonary artery by a thrombus (pulmonary embolism).Damage to the cardiovascular system
SLE can affect all the structures of the heart, the outer shell (pericardium), the inner layer (endocardium), directly the heart muscle (myocardium), valves and coronary vessels. The most common is the pericardium (pericarditis).- Pericarditis is an inflammation of the serous membranes that cover the heart muscle.
- Myocarditis is inflammation of the heart muscle.
- The defeat of the valves of the heart, the mitral and aortic valves are more often affected.
- Damage to the coronary vessels can lead to myocardial infarction, which can also develop in young patients with SLE.
- Damage to the inner lining of blood vessels (endothelium) increases the risk of atherosclerosis. Peripheral vascular disease is manifested by:
- Livedo reticularis (blue spots on the skin creating a grid pattern)
- Lupus panniculitis (subcutaneous nodules, often painful, may ulcerate)
- Thrombosis of the vessels of the extremities and internal organs
Kidney damage
Most often in SLE, the kidneys are affected, in 50% of patients lesions of the renal apparatus are determined. A frequent symptom is the presence of protein in the urine (proteinuria), erythrocytes and cylinders are usually not detected at the onset of the disease. The main manifestations of kidney damage in SLE are: proliferative glomerulonephritis and mebran nephritis, which is manifested by nephrotic syndrome (proteins in the urine are more than 3.5 g / day, a decrease in protein in the blood, edema).Damage to the central nervous system
It is assumed that CNS disorders are caused by damage to the cerebral vessels, as well as the formation of antibodies to neurons, to cells responsible for protecting and nourishing neurons (glial cells), and to immune cells (lymphocytes).The main manifestations of damage to the nervous structures and blood vessels of the brain:
- Headache and migraine, the most common symptoms in SLE
- Irritability, depression - rare
- Psychoses: paranoia or hallucinations
- brain stroke
- Chorea, parkinsonism - rare
- Myelopathy, neuropathy and other disorders of the formation of nerve sheaths (myelin)
- Mononeuritis, polyneuritis, aseptic meningitis
Digestive tract injury
Clinical lesion digestive tract are diagnosed in 20% of patients with SLE.- Damage to the esophagus, violation of the act of swallowing, expansion of the esophagus occurs in 5% of cases
- Ulcers of the stomach and 12th intestine are caused both by the disease itself and by the side effects of treatment.
- Abdominal pain as a manifestation of SLE, and can also be caused by pancreatitis, inflammation of the intestinal vessels, intestinal infarction
- Nausea, abdominal discomfort, indigestion
- Hypochromic normocytic anemia occurs in 50% of patients, the severity depends on the activity of SLE. Hemolytic anemia is rare in SLE.
- Leukopenia is a decrease in white blood cells. It is caused by a decrease in lymphocytes and granulocytes (neutrophils, eosinophils, basophils).
- Thrombocytopenia is a decrease in platelets in the blood. It occurs in 25% of cases, caused by the formation of antibodies against platelets, as well as antibodies to phospholipids (fats that make up cell membranes).
Diagnosis of SLE
Diagnosis of SLE is based on data from the clinical manifestations of the disease, as well as data from laboratory and instrumental studies. The American College of Rheumatology has developed special criteria by which it is possible to make a diagnosis - systemic lupus erythematosus.Criteria for the diagnosis of systemic lupus erythematosus
The diagnosis of SLE is made if at least 4 out of 11 criteria are present.
| Characteristic: without erosion, peripheral, manifested by pain, swelling, accumulation of insignificant fluid in the joint cavity |
| Red, oval, round or annular in shape, plaques with uneven contours on their surface there are scales, dilated capillaries nearby, the scales are separated with difficulty. Untreated lesions leave scars. |
| The oral mucosa or nasopharyngeal mucosa is affected in the form of ulcerations. Usually painless. |
| Increased sensitivity to sunlight. As a result of exposure to sunlight, a rash appears on the skin. |
| Specific rash in the form of a butterfly |
| Permanent loss of protein in the urine 0.5 g/day, excretion of cellular casts |
| Pleurisy is an inflammation of the membranes of the lungs. It is manifested by pain in the chest, aggravated by inhalation. Pericarditis - inflammation of the lining of the heart |
| Convulsions, Psychosis - in the absence of drugs that can provoke them or metabolic disorders (uremia, etc.) |
|
|
|
|
| Elevated anti-nuclear antibodies (ANA) |
The degree of disease activity is determined by special SLEDAI indices ( Systemic lupus erythematosus disease activity index). The disease activity index includes 24 parameters and reflects the state of 9 systems and organs, expressed in points that are summarized. Maximum 105 points, which corresponds to very high disease activity.
Disease activity indices bySLEDAI
| Manifestations | Description | Punctuation |
| Pseudo-epileptic seizure(development of convulsions without loss of consciousness) | It is necessary to exclude metabolic disorders, infections, medications that could provoke it. | 8 |
| psychoses | Violation of the ability to perform actions in the usual mode, impaired perception of reality, hallucinations, decreased associative thinking, disorganized behavior. | 8 |
| Organic changes in the brain | Changes logical thinking, orientation in space is disturbed, memory, intelligence, concentration, incoherent speech, insomnia or drowsiness are reduced. | 8 |
| Eye disorders | Inflammation of the optic nerve, excluding arterial hypertension. | 8 |
| Damage to the cranial nerves | Damage to the cranial nerves revealed for the first time. | |
| Headache | Severe, persistent, may be migraineous, not responding to narcotic analgesics | 8 |
| Cerebral circulatory disorders | First detected, excluding the consequences of atherosclerosis | 8 |
| Vasculitis-(vascular damage) | Ulcers, gangrene of the extremities, painful knots on the fingers | 8 |
| Arthritis- (inflammation of the joints) | Damage to more than 2 joints with signs of inflammation and swelling. | 4 |
| Myositis- (inflammation of skeletal muscles) | Muscle pain, weakness with confirmation of instrumental studies | 4 |
| Cylinders in the urine | Hyaline, granular, erythrocyte | 4 |
| erythrocytes in urine | More than 5 red blood cells in the field of view, exclude other pathologies | 4 |
| Protein in the urine | More than 150 mg per day | 4 |
| Leukocytes in urine | More than 5 white blood cells in the field of view, excluding infections | 4 |
| Skin lesions | Inflammatory damage | 2 |
| Hair loss | Enlargement of lesions or complete hair loss | 2 |
| Mucosal ulcers | Ulcers on the mucous membranes and on the nose | 2 |
| Pleurisy- (inflammation of the membranes of the lungs) | Chest pain, pleural thickening | 2 |
| Pericarditis-( inflammation of the lining of the heart) | Detected on ECG, echocardiography | 2 |
| Decreased compliment | Decreased C3 or C4 | 2 |
| AntiDNA | Positively | 2 |
| Temperature | More than 38 degrees C, excluding infections | 1 |
| Decrease in blood platelets | Less than 150 10 9 /l, excluding medicines | 1 |
| Decrease in white blood cells | Less than 4.0 10 9 /l, excluding medicines | 1 |
- Light activity: 1-5 points
- Moderate activity: 6-10 points
- High activity: 11-20 points
- Very high activity: more than 20 points
Diagnostic tests used to detect SLE
- ANA- screening test, specific antibodies to cell nuclei are determined, is determined in 95% of patients, does not confirm the diagnosis in the absence of clinical manifestations of systemic lupus erythematosus
- Anti DNA– antibodies to DNA, determined in 50% of patients, the level of these antibodies reflects the activity of the disease
- Anti-sm- specific antibodies to the Smith antigen, which is part of short RNA, are detected in 30-40% of cases
- Anti-SSA or Anti-SSB, antibodies to specific proteins located in the cell nucleus, are present in 55% of patients with systemic lupus erythematosus, are not specific for SLE, and are also detected in other connective tissue diseases
- Anticardiolipin - antibodies to mitochondrial membranes (energy station of cells)
- Antihistones- antibodies against proteins necessary for packaging DNA into chromosomes, characteristic of drug-induced SLE.
- Markers of inflammation
- ESR - increased
- C - reactive protein, elevated
- Compliment level lowered
- C3 and C4 are reduced as a result of excessive formation of immune complexes
- Some people are born with reduced compliment levels, a predisposing factor for developing SLE.
- General blood analysis
- Possible decrease in red blood cells, white blood cells, lymphocytes, platelets
- Analysis of urine
- Protein in the urine (proteinuria)
- Red blood cells in the urine (hematuria)
- Casts in the urine (cylindruria)
- White blood cells in urine (pyuria)
- Blood chemistry
- Creatinine - an increase indicates kidney damage
- ALAT, ASAT - an increase indicates liver damage
- Creatine kinase - increases with damage to the muscular apparatus
- X-ray of the joints
- X-ray and computed tomography of the chest
- Nuclear magnetic resonance and angiography
- echocardiography
Specific Procedures
- A lumbar puncture can help rule out infectious causes of neurological symptoms.
- A biopsy (analysis of organ tissue) of the kidneys allows you to determine the type of glomerulonephritis and facilitate the choice of treatment tactics.
- A skin biopsy allows you to clarify the diagnosis and exclude similar dermatological diseases.
Treatment of systemic lupus
Despite significant advances in the modern treatment of systemic lupus erythematosus, this task remains very difficult. Treatment aimed at eliminating the main cause of the disease has not been found, just as the cause itself has not been found. Thus, the principle of treatment is aimed at eliminating the mechanisms of the development of the disease, reducing provoking factors and preventing complications. - Eliminate physical and mental stress conditions
- Reduce sun exposure, use sunscreen
- Glucocorticosteroids the most effective drugs in the treatment of SLE.
Dosing regimens:
- Inside:
- Initial dose of prednisolone 0.5 - 1 mg / kg
- Maintenance dose 5-10 mg
- Prednisolone should be taken in the morning, the dose is reduced by 5 mg every 2-3 weeks
- High-dose intravenous methylprednisolone (pulse therapy)
- Dose 500-1000 mg/day, for 3-5 days
- Or 15-20 mg/kg body weight
Indications for pulse therapy: young age, fulminant lupus nephritis, high immunological activity, damage to the nervous system.
- 1000 mg methylprednisolone and 1000 mg cyclophosphamide on the first day
- Cytostatics: cyclophosphamide (cyclophosphamide), azathioprine, methotrexate, are used in the complex treatment of SLE.
- Acute lupus nephritis
- Vasculitis
- Forms resistant to treatment with corticosteroids
- The need to reduce doses of corticosteroids
- High SLE activity
- Progressive or fulminant course of SLE
- Cyclophosphamide with pulse therapy 1000 mg, then every day 200 mg until a total dose of 5000 mg is reached.
- Azathioprine 2-2.5 mg/kg/day
- Methotrexate 7.5-10 mg/week, by mouth
- Anti-inflammatory drugs
- Naklofen, nimesil, aertal, catafast, etc.
- Aminoquinoline drugs
- delagil, plaquenil, etc.
- Biologicals are a promising treatment for SLE
- Anti CD 20 - Rituximab
- Tumor necrosis factor alpha - Remicade, Gumira, Embrel
- Other drugs
- Anticoagulants (heparin, warfarin, etc.)
- Antiplatelet agents (aspirin, clopidogrel, etc.)
- Diuretics (furosemide, hydrochlorothiazide, etc.)
- Calcium and potassium preparations
- Methods of extracorporeal treatment
- Plasmapheresis is a method of blood purification outside the body, in which part of the blood plasma is removed, and with it antibodies disease-causing SLE.
- Hemosorption is a method of purifying blood outside the body using specific sorbents (ion exchange resins, Activated carbon and etc.).
What are the complications and prognosis for life with systemic lupus erythematosus?
The risk of developing complications of systemic lupus erythematosus directly depends on the course of the disease.Variants of the course of systemic lupus erythematosus:
1.
Acute course- is characterized by a lightning-fast onset, a rapid course and the rapid simultaneous development of symptoms of damage to many internal organs (lungs, heart, central nervous system, and so on). The acute course of systemic lupus erythematosus, fortunately, is rare, since this option quickly and almost always leads to complications and can cause the death of the patient.
2.
Subacute course- characterized by a gradual onset, a change in periods of exacerbations and remissions, a predominance of general symptoms (weakness, weight loss, subfebrile temperature (up to 38 0
C) and others), damage to internal organs and complications occur gradually, not earlier than 2-4 years after the onset of the disease.
3.
chronic course- most favorable course SLE, there is a gradual onset, damage mainly to the skin and joints, longer periods of remission, damage to internal organs and complications occur after decades.
Damage to organs such as the heart, kidneys, lungs, central nervous system, and blood, which are described as symptoms of the disease, in fact, are complications of systemic lupus erythematosus.
But it is possible to distinguish complications that lead to irreversible consequences and can lead to the death of the patient:
1. Systemic lupus erythematosus- affects the connective tissue of the skin, joints, kidneys, blood vessels and other body structures.
2. medicinal lupus erythematosus- unlike the systemic form of lupus erythematosus, a completely reversible process. Drug-induced lupus develops as a result of exposure to certain drugs:
- Medicinal products for the treatment of cardiovascular diseases: phenothiazine groups (Apressin, Aminazine), Hydralazine, Inderal, Metoprolol, Bisoprolol, Propranolol and some others;
- antiarrhythmic drug Novocainamide;
- sulfonamides: Biseptol and others;
- anti-tuberculosis drug Isoniazid;
- oral contraceptives;
- drugs plant origin for the treatment of vein diseases (thrombophlebitis, varicose veins of the lower extremities, and so on): horse chestnut, venotonic Doppelhertz, Detralex and some others.
3. Discoid (or cutaneous) lupus erythematosus may precede the development of systemic lupus erythematosus. With this type of disease, the skin of the face is affected to a greater extent. Changes on the face are similar to those in systemic lupus erythematosus, but blood tests (biochemical and immunological) do not have changes characteristic of SLE, and this will be the main criterion for differential diagnosis with other types of lupus erythematosus. To clarify the diagnosis, it is necessary to conduct a histological examination of the skin, which will help to differentiate from diseases similar in appearance (eczema, psoriasis, skin form of sarcoidosis, and others).
4. neonatal lupus erythematosus occurs in newborn babies whose mothers suffer from systemic lupus erythematosus or other systemic autoimmune diseases. At the same time, the mother may not have symptoms of SLE, but autoimmune antibodies are detected during their examination.
Symptoms of neonatal lupus erythematosus the child usually manifests itself before the age of 3 months:
- changes on the skin of the face (often look like a butterfly);
- congenital arrhythmia, which is often determined by ultrasound of the fetus in the II-III trimesters of pregnancy;
- flaw blood cells in the general blood test (decrease in the level of erythrocytes, hemoglobin, leukocytes, platelets);
- detection of autoimmune antibodies specific for SLE.
5. Also, the term "lupus" is used for tuberculosis of the skin of the face - tuberculous lupus. Tuberculosis of the skin is very similar in appearance to the systemic lupus erythematosus butterfly. The diagnosis will help to establish a histological examination of the skin and microscopic and bacteriological examination of the scraping - Mycobacterium tuberculosis (acid-resistant bacteria) is detected.
Photo:
this is what tuberculosis of the skin of the face or tuberculous lupus looks like.
Systemic lupus erythematosus and other systemic connective tissue diseases, how to differentiate?
Group of systemic connective tissue diseases:- Systemic lupus erythematosus.
- Idiopathic dermatomyositis (polymyositis, Wagner's disease)- defeat by autoimmune antibodies of smooth and skeletal muscles.
- Systemic scleroderma is a disease in which normal tissue is replaced by connective tissue (which does not carry functional properties), including blood vessels.
- Diffuse fasciitis (eosinophilic)- damage to the fascia - structures that are cases for skeletal muscles, while in the blood of most patients there is an increased number of eosinophils (blood cells responsible for allergies).
- Sjögren's syndrome- damage to various glands (lacrimal, salivary, sweat, and so on), for which this syndrome is also called dry.
- Other systemic diseases.
Differential diagnosis of systemic connective tissue diseases.
| Diagnostic criteria | Systemic lupus erythematosus | Systemic scleroderma | Idiopathic dermatomyositis |
| The onset of the disease |
|
 Photo: Raynaud's syndrome |
|
| Temperature | Prolonged fever, body temperature above 38-39 0 C. | Prolonged subfebrile condition (up to 38 0 C). | Moderate prolonged fever (up to 39 0 С). |
| Appearance of the patient (at the beginning of the disease and in some of its forms, the appearance of the patient may not be changed in all these diseases) | Skin lesions, mostly of the face, "butterfly" (redness, scales, scars). Rashes can be all over the body and on the mucous membranes. Dry skin, loss of hair, nails. Nails are deformed, striated nail plates. Also, throughout the body there may be hemorrhagic rashes (bruises and petechiae).  | The face can acquire a “mask-like” expression without facial expressions, stretched, the skin is shiny, deep folds appear around the mouth, the skin is motionless, tightly soldered to deep-lying tissues. Often there is a violation of the glands (dry mucous membranes, as in Sjögren's syndrome). Hair and nails fall out. Dark spots on the skin of the extremities and neck against the background of "bronze skin".  | A specific symptom is swelling of the eyelids, their color may be red or purple, on the face and in the décolleté area there is a varied rash with reddening of the skin, scales, hemorrhages, scars. With the progression of the disease, the face acquires a “mask-like appearance”, without facial expressions, stretched, may be skewed, omission is often detected upper eyelid(ptosis).  |
| The main symptoms during the period of disease activity |
|
|
|
| Forecast | Chronic course, over time, more and more organs are affected. Without treatment, complications develop that threaten the life of the patient. With adequate and regular treatment, it is possible to achieve a long-term, stable remission. | ||
| Laboratory indicators |
|
|
|
| Principles of treatment | Long-term hormonal therapy (Prednisolone) + cytostatics + symptomatic therapy and other drugs (see article section "Treatment of systemic lupus"). | ||
As you can see, there is not a single analysis that would completely differentiate systemic lupus erythematosus from other systemic diseases, and the symptoms are very similar, especially in the early stages. Experienced rheumatologists often need to evaluate the skin manifestations of the disease to diagnose systemic lupus erythematosus (if present).
Systemic lupus erythematosus in children, what are the features of symptoms and treatment?
Systemic lupus erythematosus is less common in children than in adults. In childhood, rheumatoid arthritis is more often detected from autoimmune diseases. SLE predominantly (in 90% of cases) affects girls. Systemic lupus erythematosus can occur in infants and young children, although rarely, the largest number of cases of this disease occurs during puberty, namely at the age of 11-15 years. Given the peculiarity of immunity, hormonal levels, growth intensity, systemic lupus erythematosus in children proceeds with its own characteristics.
Features of the course of systemic lupus erythematosus in childhood:
- more severe disease , high activity of the autoimmune process;
- chronic course disease in children occurs only in a third of cases;
- more common acute or subacute course diseases with rapid damage to internal organs;
- also isolated only in children acute or fulminant course SLE - almost simultaneous damage to all organs, including the central nervous system, which can lead to the death of a small patient in the first six months from the onset of the disease;
- frequent development of complications and high mortality;
- the most common complication is bleeding disorder in the form of internal bleeding, hemorrhagic eruptions (bruises, hemorrhages on the skin), as a result - the development of a shock state of DIC - disseminated intravascular coagulation;
- systemic lupus erythematosus in children often occurs in the form of vasculitis - inflammation of the blood vessels, which determines the severity of the process;
- children with SLE are usually malnourished , have a pronounced deficiency of body weight, up to cachexia (extreme degree of dystrophy).
1.
The onset of the disease acute, with an increase in body temperature to high numbers (over 38-39 0 C), with pain in the joints and severe weakness, a sharp loss of body weight.
2.
Skin changes in the form of a "butterfly" in children are relatively rare. But, given the development of a lack of blood platelets, it is more common hemorrhagic rash all over the body (bruising without cause, petechiae or pinpoint hemorrhages). Also, one of the characteristic signs of systemic diseases is hair loss, eyelashes, eyebrows, up to complete baldness. The skin becomes marbled, very sensitive to the sun's rays. The skin may have various rashes characteristic of allergic dermatitis. In some cases, Raynaud's syndrome develops - a violation of the circulation of the hands. In the oral cavity there may be long-term non-healing sores - stomatitis.
3.
Joint pain- a typical syndrome of active systemic lupus erythematosus, the pain is periodic. Arthritis is accompanied by the accumulation of fluid in the joint cavity. Pain in the joints over time is combined with pain in the muscles and stiffness of movements, starting with the small joints of the fingers.
4.
For children characterized by the formation of exudative pleurisy(fluid in the pleural cavity), pericarditis (fluid in the pericardium, the lining of the heart), ascites and other exudative reactions (dropsy).
5.
Heart failure in children, it usually manifests as myocarditis (inflammation of the heart muscle).
6.
Kidney damage or nephritis much more often develops in childhood than in adults. Such nephritis relatively quickly leads to the development of acute renal failure (requiring intensive care and hemodialysis).
7.
Lung injury is rare in children.
8.
In the early period of the disease in adolescents, in most cases, there is gastrointestinal tract injury(hepatitis, peritonitis, etc.).
9.
Damage to the central nervous system in children it is characterized by capriciousness, irritability, in severe cases, convulsions may develop.
That is, in children, systemic lupus erythematosus is also characterized by a variety of symptoms. And many of these symptoms are masked under the guise of other pathologies, the diagnosis of systemic lupus erythematosus is not immediately assumed. Unfortunately, after all, timely treatment is the key to success in the transition of an active process into a period of stable remission.
Diagnostic principles systemic lupus erythematosus are the same as in adults, based mainly on immunological studies (detection of autoimmune antibodies).
In a general blood test, in all cases and from the very beginning of the disease, a decrease in the number of all blood cells (erythrocytes, leukocytes, platelets) is determined, blood clotting is impaired.
Treatment of systemic lupus erythematosus in children, as in adults, involves long-term use of glucocorticoids, namely Prednisolone, cytostatics and anti-inflammatory drugs. Systemic lupus erythematosus is a diagnosis that requires urgent hospitalization of the child in a hospital (rheumatology department, with the development of severe complications - in the intensive care unit or intensive care unit).
In a hospital setting, full examination patient and select necessary therapy. Depending on the presence of complications, symptomatic and intensive therapy is carried out. Given the presence of bleeding disorders in such patients, injections of Heparin are often prescribed.
In the case of timely started and regular treatment, it is possible to achieve stable remission, while children grow and develop according to age, including normal puberty. In girls, a normal menstrual cycle is established and pregnancy is possible in the future. In this case forecast favorable for life.
Systemic lupus erythematosus and pregnancy, what are the risks and features of treatment?
As already mentioned, young women are more likely to suffer from systemic lupus erythematosus, and for any woman, the issue of motherhood is very important. But SLE and pregnancy is always a big risk for both the mother and the unborn baby. Pregnancy risks for a woman with systemic lupus erythematosus:
1. Systemic lupus erythematosus
In most cases does not affect the ability to get pregnant
,
as well as long-term use of prednisolone.
2. When taking cytostatics (Methotrexate, Cyclophosphamide and others), it is absolutely impossible to become pregnant
,
since these drugs will affect germ cells and embryonic cells; pregnancy is possible only not earlier than six months after the abolition of these drugs.
3. Half
cases of pregnancy with SLE ends with the birth of healthy, full-term baby
. At 25%
cases such children are born premature
, A in a quarter of cases
observed miscarriage
.
4. Possible Complications pregnancy with systemic lupus erythematosus,
in most cases associated with damage to the vessels of the placenta:
- fetal death;
- . So, in a third of cases, an aggravation of the course of the disease develops. The risk of such deterioration is maximum in the first weeks of I, or in the III trimester of pregnancy. And in other cases, there is a temporary retreat of the disease, but for the most part, one should expect a strong exacerbation of systemic lupus erythematosus 1-3 months after birth. No one knows which path the autoimmune process will take.
6. Pregnancy can be a trigger in the development of the onset of systemic lupus erythematosus. Also, pregnancy can provoke the transition of discoid (cutaneous) lupus erythematosus to SLE.
7. Mother with systemic lupus erythematosus can pass genes to her baby that predispose him to develop a systemic autoimmune disease during his lifetime.
8. The child may develop neonatal lupus erythematosus associated with the circulation of maternal autoimmune antibodies in the blood of the baby; this condition is temporary and reversible.- It is necessary to plan a pregnancy under the supervision of qualified doctors , namely a rheumatologist and a gynecologist.
- It is advisable to plan a pregnancy during a period of persistent remission chronic course of SLE.
- In case of acute systemic lupus erythematosus with the development of complications, pregnancy can adversely affect not only health, but also lead to the death of a woman.
- And if, nevertheless, pregnancy occurred during an exacerbation, then the question of its possible preservation is decided by the doctors, together with the patient. After all, exacerbation of SLE requires long-term use of drugs, some of which are absolutely contraindicated during pregnancy.
- Pregnancy is recommended no earlier than 6 months after discontinuation of cytotoxic drugs (Methotrexate and others).
- With lupus lesion of the kidneys and heart there can be no talk of pregnancy, this can lead to a woman's death from kidney and / or heart failure, because it is these organs that are under a huge load when carrying a baby.
1. Essential throughout pregnancy observed by a rheumatologist and an obstetrician-gynecologist , the approach to each patient is only individual.
2. Be sure to follow the rules: don’t overwork, don’t be nervous, eat normally.
3. Pay close attention to any changes in your health.
4. Delivery outside the maternity hospital is unacceptable , as there is a risk of developing severe complications during and after childbirth.
7. Even at the very beginning of pregnancy, a rheumatologist prescribes or corrects therapy. Prednisolone is the main drug for the treatment of SLE and is not contraindicated during pregnancy. The dose of the drug is selected individually.
8. Also recommended for pregnant women with SLE taking vitamins, potassium supplements, aspirin (up to the 35th week of pregnancy) and other symptomatic and anti-inflammatory drugs.
9. Mandatory treatment of late toxicosis and other pathological conditions of pregnancy in a maternity hospital.
10. After childbirth the rheumatologist increases the dose of hormones; in some cases, it is recommended to stop breastfeeding, as well as the appointment of cytostatics and other drugs for the treatment of SLE - pulse therapy, since it is the postpartum period that is dangerous for the development of severe exacerbations of the disease.Previously, all women with systemic lupus erythematosus were advised not to become pregnant, and in the event of conception, all were recommended artificial termination of pregnancy (medical abortion). Now doctors have changed their opinion on this matter, you can’t deprive a woman of motherhood, especially since there are considerable chances to give birth to a normal healthy baby. But everything must be done in order to minimize the risk to mother and baby.
Is lupus erythematosus contagious?
Of course, any person who sees strange rashes on the face thinks: “Maybe it’s contagious?”. Moreover, people with these rashes walk for so long, feel unwell and constantly take some kind of medication. Moreover, earlier doctors also assumed that systemic lupus erythematosus is transmitted sexually, by contact, or even by airborne droplets. But having studied the mechanism of the disease in more detail, scientists completely dispelled these myths, because this is an autoimmune process.The exact cause of the development of systemic lupus erythematosus has not yet been established, there are only theories and assumptions. It all boils down to one thing, that the underlying cause is the presence of certain genes. But still, not all carriers of these genes suffer from systemic autoimmune diseases.
The trigger mechanism for the development of systemic lupus erythematosus can be:
- various viral infections;
- bacterial infections (especially beta-hemolytic streptococcus);
- stress factors;
- hormonal changes (pregnancy, adolescence);
- environmental factors (for example, ultraviolet radiation).
Only tuberculous lupus can be contagious (tuberculosis of the skin of the face), since a large number of tuberculosis sticks are detected on the skin, while the contact route of transmission of the pathogen is isolated.
Lupus erythematosus, what diet is recommended and are there any methods of treatment with folk remedies?
As with any disease, nutrition plays an important role in lupus erythematosus. Moreover, with this disease, there is almost always a deficiency, or against the background of hormonal therapy - excess body weight, lack of vitamins, trace elements and biologically active substances.The main characteristic of the SLE diet is a balanced and proper diet.
1. foods containing unsaturated fatty acids (Omega-3):
- sea fish;
- many nuts and seeds;
- vegetable oil in a small amount;
3. juices, fruit drinks;
4. lean poultry meat: chicken, turkey fillet;
5. low-fat dairy , especially dairy products (low-fat cheese, cottage cheese, yogurt);
6. cereals and vegetable fiber (grain bread, buckwheat, oatmeal, wheat germ and many others).1. Foods with saturated fatty acids have a bad effect on blood vessels, which can aggravate the course of SLE:
- animal fats;
- fried food;
- fatty meats (red meat);
- dairy products with high fat content and so on.
Photo: alfalfa grass.
3. Garlic - powerfully stimulates the immune system.
4. Salty, spicy, smoked dishes holding fluid in the body.If diseases of the gastrointestinal tract occur against the background of SLE or medication, then the patient is recommended frequent fractional nutrition according to therapeutic diet- table number 1. All anti-inflammatory drugs are best taken with or immediately after meals.
Treatment of systemic lupus erythematosus at home is possible only after the selection of an individual treatment regimen in a hospital setting and the correction of conditions that threaten the life of the patient. Heavy drugs used in the treatment of SLE cannot be prescribed on their own, self-medication will not lead to anything good. Hormones, cytostatics, non-steroidal anti-inflammatory drugs and other drugs have their own characteristics and a bunch of adverse reactions, and the dose of these drugs is very individual. The therapy selected by doctors is taken at home, strictly adhering to the recommendations. Omissions and irregularity in taking medications are unacceptable.
Concerning traditional medicine recipes, then systemic lupus erythematosus does not tolerate experiments. None of these remedies will prevent the autoimmune process, you can just lose precious time. Folk remedies can give their effectiveness if they are used in combination with traditional methods of treatment, but only after consultation with a rheumatologist.
Some traditional medicines for the treatment of systemic lupus erythematosus:
Precautionary measures! All folk remedies containing poisonous herbs or substances must be kept out of the reach of children. One must be careful with such remedies, any poison is a medicine as long as it is used in small doses.Photo, what do the symptoms of lupus erythematosus look like?
Photo: changes on the skin of the face in the form of a butterfly in SLE.
Photo: skin lesions of the palms with systemic lupus erythematosus. In addition to skin changes, this patient shows thickening of the joints of the phalanges of the fingers - signs of arthritis.
Dystrophic changes in nails with systemic lupus erythematosus: fragility, discoloration, longitudinal striation of the nail plate.
Lupus lesions of the oral mucosa . According to the clinical picture, they are very similar to infectious stomatitis, which do not heal for a long time.
And this is what they might look like early symptoms of discoid or cutaneous lupus erythematosus.
And this is what it might look like neonatal lupus erythematosus, these changes, fortunately, are reversible and in the future the baby will be absolutely healthy.
Skin changes in systemic lupus erythematosus characteristic of childhood. The rash is hemorrhagic in nature, reminiscent of measles rashes, leaves pigment spots that do not go away for a long time.
