Diagnosis of lupus erythematosus

General principles for diagnosing the disease

Currently, the most commonly used diagnostic criteria are the American Rheumatology Association, not Nasonova. But we will present both schemes of diagnostic criteria, since in a number of cases domestic doctors use Nasonova’s criteria to diagnose lupus.

American Rheumatology Association Diagnostic Criteria the following:

• Rash in the area of ​​the cheekbones on the face (there are red elements of the rash that are flat or slightly raised above the surface of the skin, spreading to the nasolabial folds);
• Discoid rashes (raised plaques above the surface of the skin with “black dots” in the pores, peeling and atrophic scars);
• Photosensitivity (the appearance of skin rashes after exposure to the sun);
• Ulcers on the oral mucosa (painless ulcerative defects localized on the mucous membrane of the mouth or nasopharynx);
• Arthritis (affecting two or more small joints, characterized by pain, swelling and swelling);
• Polyserositis (pleuritis, pericarditis or non-infectious peritonitis in the 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 red blood cells and casts (erythrocyte, hemoglobin, granular, mixed) in the urine);
• Neurological disorders: seizures or psychosis (delusions, hallucinations) not caused by medications, 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 anti-lupus coagulant);
• Increased titer of ANA (antinuclear antibodies) in the blood.

Nasonova's criteria for lupus erythematosus include major and minor diagnostic criteria, which are listed in the table below:

The diagnosis of lupus erythematosus is considered accurate and confirmed when any three large diagnostic criteria are combined, one of them 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, data is required to confirm it laboratory tests and additional instrumental examinations.

The above criteria of Nasonova and the American Association of Rheumatology 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 examination methods are only additional, allowing one to assess the degree of activity of the process, the number of affected organs and the general condition of the human body. A diagnosis of lupus erythematosus is not made based only on laboratory tests and instrumental examination methods.

Currently, ECG, echocardiography, MRI, and x-rays of organs can be used as instrumental diagnostic methods for lupus erythematosus chest, ultrasound, etc. All these methods make it possible to assess the degree and nature of damage in various organs.

Blood (test) for lupus erythematosus

• Antinuclear factors (ANF) – with lupus erythematosus are found in the blood in high titers no higher than 1: 1000;
• Antibodies to double-stranded DNA (anti-dsDNA-AT) – with lupus erythematosus are found in the blood of 90–98% of patients, but are normally absent;
• Antibodies to histone proteins - in lupus erythematosus are found in the blood, but 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 detected in the blood if there is lymphopenia, thrombocytopenia, photosensitivity, pulmonary fibrosis or Sjögren's syndrome;
• Antibodies to La/SS-B – in lupus erythematosus are detected in the blood under the same conditions as antibodies to Ro/SS-A;
• Complement level – with lupus erythematosus, the level of complement proteins in the blood is reduced;
• The presence of LE cells - with lupus erythematosus they are found in the blood of 80 - 90% of patients, but are normally absent;
• Antibodies to phospholipids (lupus anticoagulant, antibodies to cardiolipin, positive Wasserman test in the confirmed absence of syphilis);
• Antibodies to coagulation factors VIII, IX and XII (normally absent);
• Increased ESR by 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 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

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 severity general condition people 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 it 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 the dosages of Prednisolone. The list below shows dosages of other glucocorticoids equivalent to 5 mg 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 its use is never completely canceled. The dosage is first reduced by 5 mg per week, then by 2.5 mg per week, and after some time by 2.5 mg every 2 to 4 weeks. In total, the dosage is reduced so that 6–9 months after starting Prednisolone, its maintenance dose becomes 12.5–15 mg per day.

During a lupus crisis, involving 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 medications are used additionally, selecting them depending on the severity clinical symptoms and from the affected organ.

Thus, 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 skin lesions 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 a maintenance dose: 0.5 - 1 mg per 1 kg of body weight per day. Azathioprine is taken in a maintenance dosage for several years.

For severe lupus nephritis and pancytopenia(decrease total number platelets, erythrocytes and leukocytes in the blood) Cyclosporine is used in 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 m2 of body surface once a month for six months. Then, for two years, the drug continues to be administered in 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 damage skin and joints Aminoquinoline drugs (Chloroquine, Hydroxychloroquine, Plaquenil, Delagil) are used in the treatment of lupus erythematosus. In the first 3 to 4 months, the 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 from the group of anticoagulants and antiplatelet agents (Aspirin, Curantil, etc.) are used. Acetylsalicylic acid is mainly used in small doses - 75 mg per day for a long time.

Medicines from the group of non-steroidal 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 medications, for the treatment of lupus erythematosus, methods of plasmapheresis, hemosorption and cryoplasmasorption are used, which make it possible to remove antibodies and inflammatory 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.

To treat skin manifestations of lupus, it is necessary to externally use sunscreens with UVA and UVB filters and ointments with topical steroids (Fluorcinolone, Betamethasone, Prednisolone, Mometasone, Clobetasol, etc.).

Currently, in addition to these methods, drugs from 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 today they are not 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 requires the use of vitamins, potassium compounds, diuretics and antihypertensive drugs, tranquilizers, antiulcers and other drugs that reduce the severity of clinical symptoms in various organs, as well as restorative normal exchange substances. For lupus erythematosus, you can and should additionally use any medications that improve a person’s overall well-being.

Drugs for 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.);
• TNF alpha blockers (Infliximab, Adalimumab, Etanercept);
• Non-steroidal anti-inflammatory drugs (Diclofenac, Nimesulide,

Antibodies to nucleoproteins can be determined using immunological reactions.

1. Test to detect LE cells. In 1948, Hargraves et al. In bone marrow and peripheral blood smears of SLE patients, leukocytes with special inclusions, which were called LE cells, were found during incubation at 37°C. Haserick et al. showed that similar cells appear in cases where leukocytes from healthy individuals are incubated with serum or plasma from SLE patients. The LE cell test is positive in 75% of cases. They are especially often defined in acute period. LE cells are not specific for SLE, but the more often a positive test is reproduced in repeated studies, the higher the likelihood of this diagnosis.

In a small percentage of cases, this phenomenon is also found in other diseases accompanied by the production of ANF. The latter belong to the IgG class antibodies. According to most authors, the responsible antigen is the structure of nucleoproteins; other researchers attach particular importance to antibodies to DNA.

There are two phases in the LE phenomenon:

A) immunological. Cell damage with deformation (swelling) of the nucleus and loss of chromatin, basophilia, which serves as a prerequisite for the manifestation of antibody activity. This is followed by the fixation of antibodies on the nucleus, which is masked due to the negative charge of nucleic acids;

B) nonspecific. The nuclear material in the form of a grayish-smoky mass is phagocytosed by cells that become typical for lupus erythematosus. Complement has a certain significance both during the influence of antibodies and during phagocytosis. The LE phenomenon is a consequence of both the antibody response and phagocytosis of opsonized material from cell nuclei. Phagocytes are primarily polymorphonuclear neutrophils, and less commonly eosinophilic and basophilic granulocytes. The so-called free particles have a variety of shapes. They can be homogeneously or inhomogeneously colored. In some cases, these are altered non-phagocytosed nuclei, and in others, they are nuclear structures that have already been phagocytosed and emerged from destroyed phagocytes. Large, hematoxylin-stained structures result from flocculation. The same happens in tissues.

In vivo, LE cells are present in peripheral blood, non-ricardial and pleural effusions, and in skin lesions.

The LE cell test has the following modifications:

Direct test using blood and bone marrow samples from the patient;

Indirect test using donor leukocytes as a substrate to analyze the patient's serum and assess phagocytosis.

In practice, a direct version of the test is usually used. The Rebuck method is also informative.

2. Rosette reaction. The observed rosettes consist of round or irregularly shaped LE particles surrounded by polymorphonuclear granulocytes. Probably, the central structures represent an intermediate stage between “loose bodies” and LE cells.

3. “B cells” according to Heller and Zimmermann resemble typical LE cells, but the inclusions are less homogeneous, so the differences in color between the inclusions and the nuclei of phagocytic cells are weakly expressed.

4. Nucleophagocytosis, i.e. detection of phagocytosis of nuclei without typical changes in their structures, which has no diagnostic value for SLE.

5. Other methods for detecting antibodies to nucleoproteins: RSC, Friou immunofluorescence, as well as agglutination of carrier particles conjugated with nucleoproteins. In general, there is a clear correlation with the test for LE cells.

The configuration of nucleoproteins acting as antigens is still unknown. Tan et al., using phosphate buffer, extracted the soluble fraction of nucleoprotein from cells thymus calves This antigen reacted with antibodies to nucleoproteins from SLE patients, as well as some RA patients. After treatment of the drug with trypsin and deoxyribonuclease, antigenicity was lost. The authors suggested that both histones and DNA are involved in the formation of antigenic determinants, but most antibodies to nucleoproteins react with insoluble nucleoproteins and give homogeneous fluorescence. Antibodies to the soluble fraction of nucleoproteins are characterized by predominantly peripheral coloring (binding), which is also characteristic of antibodies to DNA. Anti-DNA sera mostly contain antibodies to nucleoproteins.

Antibodies to DNA. As analysis of experimental data has shown, native DNA is a rather weak antigen. When using denatured DNA and an adjuvant, it is possible to induce the production of antibodies. This explains why anti-DNA antibodies studied in SLE react partly with denatured DNA, partly with native DNA, and sometimes with both. The latter are heterogeneous. Antigen binding sites include a sequence of five bases (among which guanosine plays a special role) and are obviously located in different areas of the macromolecule. Adenosine and thymidine are likely to be of particular importance. Antibodies to denatured DNA often react with denatured RNA.

Antibodies to DNA deserve close attention, as they are highly specific for SLE. To decide whether they are directed against native or denatured DNA, a passive agglutination reaction is used (the antigen is pre-conjugated to a carrier: latex or erythrocytes). This is a fairly sensitive method, giving a positive result in 50-75% of cases. Using direct precipitation in an agar gel, positive results are obtained only in 6-10% of cases, and with immunoelectrophoresis - in 35-80% of cases. Evidence of the production of antibodies to native DNA is of practical importance, since this phenomenon is highly specific for SLE. For this purpose, RIM or immunofluorescence is used. The first test uses labeled DNA. After the addition of Ab-containing serum, separation of free and bound DNA occurs, usually by ammonium sulfate or polyethylene glycol precipitation, filtration through millipore filters (cellulose), or using the double antibody technique. The latter method is more specific, since it eliminates the influence of nonspecific binding of the main protein on DNA. The ability to bind sera of patients with SLE can be 30-50 times higher than that of healthy individuals. Critical factors are the different molecular weight of DNA, as well as the presence of denatured DNA and other proteins. In practice, the “solid phase” technique is often used: DNA is fixed on the surface of plastic or cellulose. At the second stage, incubation with the test serum is carried out. To bind antibodies, labeled anti-Ig is used. The origin of DNA does not play a significant role in these reactions. When antigen-antibody complexes are separated, some denaturation always occurs. Conventional purification methods do not guarantee the complete elimination of this DNA. Bacteriophage DNA is much more stable. The ELISA technique can be used in a similar way.

Thanks to the use of trypanosomes or Crithidia luciliae, it is possible to detect antibodies to DNA by immunofluorescence. In these flagellates, DNA is localized in giant mitochondria. With proper handling and application indirect method Immunofluorescence can only detect DNA antibodies. The sensitivity of this test is slightly lower than RIM. Using anti-C3 serum labeled with fluorescein isothiocyanate, C-linked antibodies to DNA can be detected, which is obviously valuable for determining the activity of the process.

Antibodies to native DNA have diagnostic value almost only in SLE (in the acute period in 80-98%, in remission - 30-70%); only sometimes they are found in certain forms of uveitis. In other diseases, the question is debated whether we are talking specifically about antibodies to native DNA. A high titer is not always combined with pronounced activity of the process. A simultaneous change in complement concentration suggests kidney damage. IgG antibodies probably play a greater pathogenetic role than IgM. A single positive test for detecting antibodies to DNA allows making a diagnostic, but not a prognostic conclusion, and only maintenance over a long period of time higher level These antibodies can be regarded as a prognostically unfavorable sign. A decrease in level predicts remission or (sometimes) death. Some authors note a more pronounced correlation between the activity of the process and the content of complement-fixing antibodies.

When immunofluorescence, antibodies to DNA are detected mainly along the periphery of the nucleus, but sometimes they are distributed in other areas in the form of a delicate mesh formation. Using fairly sensitive methods, it is possible to detect DNA in serum with a concentration of up to 250 mg/l.

Antibodies to RNA, or antiribosomal antibodies, are found in 40-80% of SLE patients. Their titer does not depend on the level of antibodies to DNA and the degree of activity of the process. Much less frequently, antibodies to RNA are detected in Myasthenia gravis, scleroderma, rheumatoid arthritis, including Sjögren's syndrome, as well as among relatives of the patient and in healthy individuals. They react with both native and synthetic RNA. In other diseases they almost never occur. In Sharp's syndrome, antibodies predominantly to RNP are detected. Antibodies in SLE are relatively heterogeneous and react predominantly with uridine bases, and in scleroderma - with uracil bases of RNA. Antibodies to synthetic polyriboadenylic acid are found in 75% of patients with SLE, 65% of patients with discoid lupus, and 0-7% of patients with other connective tissue diseases. Antibodies are often detected in relatives of patients with SLE (mainly IgM). Ribosomal antibodies react in some cases with free ribosome RNA.

Antibodies to histone. Histones are a mixture of low molecular weight proteins that bind DNA through their base structures. Antihistone Abs are detected in lupus (primarily drug-induced) and RA. They exhibit somewhat different specificities. Thus, in SLE, these antibodies are directed mainly against HI, H2B and H3. They are detected in 30-60%, and in low titers even in 80% of patients. Antibodies to H2B are associated with photosensitivity. In prokainamid-induced lupus, the detected ANFs are directed primarily against histones. In clinical manifestations, these are mainly IgG antibodies to the H2A-H2B complex; in asymptomatic conditions, these are IgM antibodies, in which their specificity to a certain class of histones cannot be recognized. The highest titer of antihistone antibodies has been described in rheumatoid vasculitis (this is only partly due to cross-reacting RF). Highly sensitive methods, such as immunofluorescence, RIM, ELISA, immunoblotting, allow analysis using the most purified histones. Antibodies to histones are not species or tissue specific.

Antibodies to non-histone proteins- to extractable nuclear antigens. The antigen responsible is heterogeneous. Its main fragments are Sm and RNP antigens. There are probably other fractions, as evidenced by immunoelectrophoresis data using rabbit and calf thymus extracts.

Immunofluorescence demonstrates the pattern of the spot. The localization of antibodies is quite difficult to establish. The entire pool of antibodies to non-histone proteins can be determined in the passive agglutination test and RSK. Positive results were obtained for SLE in 40-60%, for rheumatoid arthritis - in 15.5% and for other connective tissue diseases - in 1% of cases. Sharpe's syndrome occupies a special place.

The antigen is extracted from the cell nuclear fraction using phosphate buffer. It is stable to ribo- and deoxyribonucleases, trypsin, ether, and heating to 56 °C. Chemically, it is a glycoprotein. In SLE, antibodies to the Sm antigen are detected in almost 30% of cases through precipitation in the gel and passive agglutination, and vice versa: when these antibodies were detected, 85% of the subjects had systemic lupus erythematosus.

Sm antibodies precipitate five small RNAs (U1, U, U4-U6). RNP antibodies recognize the 5s nucleotide sequence along with a specific polypeptide structure. In fact, splicing can be blocked using antibodies, but there is still no data indicating a pathogenetic role for these mechanisms. According to new research, the binding sites for two types of antibodies are located on the same molecule, with different epitopes. Sm-Ar may also be present in free form. Sm antibodies bind to a nucleotide sequence close to the protein structure.

Antibodies to centromere antigens directed against the kinetostructures of the centromere. The antigen is detected in metaphase. For its detection, rapidly dividing cell lines are most suitable, for example, the HEp-2 line obtained from cultured laryngeal carcinoma cells.

RM-1-complex. Apparently, this is a heterogeneous antigen that is sensitive to heat and trypsin treatment. A high content was noted in the thymus gland of calves, in particular, also in the nucleoli. Antibodies to this antigen are found in the combination of polymyositis and scleroderma in 12% of cases, with polymyositis in 9% and scleroderma in 8% of cases. Sometimes PM-1 antibodies are the only type of autoantibodies detected and thus are of particular diagnostic value. Previously reported high levels of these antibodies were caused by the presence of impurities.

PCNA. Antibodies to this antigen were detected by polymorphic immunofluorescence using a cell line.

Mi-system. As relatively new studies have shown, IgG functions as an antigen, but in a slightly modified form, but an attempt to identify antibodies using rheumatoid factor in reactions was unsuccessful. The question of the diagnostic value of antibodies can be considered unfounded.

Antibodies to nucleoli also detected in SLE (approximately 25% of cases), but much more often (more than 50%) and in high titer in the generalized form of scleroderma, in addition, in almost 8% of patients with rheumatoid arthritis.

To assess the immune system of SLE patients, it is advisable to determine the level of antibodies to DNA and complement activity. An extremely low level of the latter with a fairly high titer of complement-fixing antibodies to DNA indicates an active phase of the disease involving the kidneys. A decrease in complement titer often precedes clinical crisis. The level of IgG antibodies (to DNA and RNA) is especially correlated with the activity of immune reactions in SLE.

Treatment with corticoids and immunosuppressants often results in a rapid decrease in DNA-binding capacity, which may be explained not only by a decrease in antibody production. Anti-DNA antibodies are sometimes detected in dosage forms, particularly in hydralazine treatment.

In RA, SLE-like forms of the disease are often identified, in which LE cells are detected. In accordance with this, immunofluorescence is observed and antibodies to nucleoproteins are determined. In exceptional cases, antibodies to DNA are detected, in which case a combination of two diseases is possible. ANF ​​in rheumatoid arthritis most often belong to class M immunoglobulins.

In scleroderma, ANF is also quite often detected (60-80%), but their titer is usually lower than in RA. The distribution of immunoglobulin classes corresponds to that in SLE. In 2/3 of cases, fluorescence is spotty, in 1/3 - homogeneous. The fluorescence of the nucleoli is quite characteristic. In half of the observations, antibodies bind complement. Noteworthy is a certain discrepancy between the positive results general definition ANF ​​and the absence or production of low titre antibodies to nucleoproteins and DNA. This shows that ANF are mainly directed against substances that do not contain chromatin. There is no relationship between the presence of ANF and the duration or severity of the disease. Most often, correlations are found in those patients whose serum also contains rheumatoid factor.

In addition to rheumatic diseases, ANF is found in chronic active hepatitis (30-50% of cases). Their titer sometimes reaches 1:1000. According to various authors, with discoid lupus erythematosus, ANF is detected in a maximum of 50% of patients.

Immunofluorescence is an almost ideal screening method. When the Ab titer is below 1:50, it is not very informative (especially in elderly people). Titers above 1:1000 are observed only in SLE, lupoid hepatitis and sometimes in scleroderma. Antibodies to nucleoproteins are most often detected (94%). An informative test is the detection of antibodies to DNA.

Laboratory data and blood tests confirm the diagnosis made on the basis of the clinical picture of systemic lupus erythematosus. The classic laboratory sign of systemic lupus erythematosus is antinuclear antibodies in the blood. Since they are present in almost all patients, if the test results are negative, the diagnosis of systemic lupus erythematosus is unlikely.

However, antinuclear antibodies are detected not only in systemic lupus erythematosus, but also in other autoimmune and inflammatory diseases (for example, rheumatoid arthritis, chronic autoimmune hepatitis, interstitial lung diseases), as well as in healthy elderly people.

When assessing the result of determining antinuclear antibodies, it is necessary to take into account their titer, as well as clinical data.

• If the titer is below 1:160, the result is most likely false-positive or associated with a nonspecific increase in immunological reactivity.
• A titer of 1:1280 and higher, on the contrary, indicates an autoimmune disease, and not necessarily SLE.

A test for antinuclear antibodies reveals a combination of antibodies to different nuclear antigens. To clarify the diagnosis, it is necessary to determine a specific antigen (for example, Sm antigen, ribonucleoproteins, Ro/SS-A or La/SS-B). Unlike other autoimmune diseases, in which antibodies to a single antigen often predominate, in SLE antibodies to different nuclear antigens are detected.

Antibodies to double-stranded DNA and Sm antigen are of greatest importance. The former are pathognomonic for SLE. In addition, an increase in their titer may be a sign of exacerbation or severe complications, especially glomerulonephritis.

Other laboratory indicators are also important.

Laboratory signs of systemic lupus erythematosus (detection rate, %)

• Antinuclear antibodies - 99%
• Antibodies to double-stranded DNA - 40-60%
• Antibodies to Sm antigen - 15-30%
• Reduced level of complement components C3 or C4 - 50-70%
• Positive direct Coombs test - 40-60%
• Leukopenia, lymphopenia - 60-80%
• Thrombocytopenia - 20-40%
• Antiphospholipid antibodies - 20-40%
• Proteinuria - 30-50%
• Cellular casts in urine - 20-30%

Complement levels may decrease in any immune complex disease, but the simultaneous detection of antinuclear antibodies speaks in favor of systemic lupus erythematosus.

Approximately 60% of patients have a positive direct Coombs test, although severe hemolytic anemia is extremely rare.

Normocytic normochromic anemia, detected in most patients, is not specific for SLE, since it develops with any chronic inflammation. At the same time, lymphopenia and thrombocytopenia are usually mediated by antibodies to lymphocytes and platelets, reflecting an increase in immunological reactivity so characteristic of SLE. Other autoantibodies may also be detected, and the more of them, the more likely the diagnosis of SLE.

To detect antiphospholipid antibodies, three different approaches are now used: non-treponemal reactions to syphilis, determination of lupus anticoagulant and antibodies to cardiolipin. False-positive nontreponemal reactions have long been regarded as a marker of SLE. The presence of lupus anticoagulant is judged by the prolongation of APTT, which persists with the addition of normal plasma. Antibodies to cardiolipin are detected using ELISA. The appearance of antiphospholipid antibodies, especially lupus anticoagulant, is associated with a high risk of thrombosis, which can lead to thrombophlebitis, stroke and spontaneous abortion.

Antiphospholipid antibodies and their clinical significance

1. Detection methods

• Nontreponemal reactions to syphilis
• Lupus anticoagulant
• Antibodies to cardiolipin

2. Clinical manifestations

• Thrombosis of arteries and veins (can lead to thrombophlebitis and strokes)
• Spontaneous abortion
• Livedo
• Thrombocytopenia

3. Diseases

• Drug-induced lupus syndrome
• Primary antiphospholipid syndrome

These antibodies are characteristic not only of SLE, but also of primary antiphospholipid syndrome, which manifests itself in similar ways. vascular complications. In antiphospholipid syndrome, thrombocytopenia and a low titer of antinuclear antibodies are sometimes detected, which can cause an erroneous diagnosis of SLE.

If systemic lupus erythematosus is suspected, it is necessary to carry out general analysis urine and serum creatinine levels are determined to detect kidney damage.

If serum creatinine levels increase, new proteinuria (protein excretion more than 500 mg/day), hematuria, or cell casts are detected in the urinary sediment, a kidney biopsy may be required. Similar changes in patients with recent onset arterial hypertension, hypo-complementemia or antinuclear antibodies in the serum indicate glomerulonephritis and require consultation with a nephrologist or rheumatologist.

A kidney biopsy reveals morphological changes and is therefore much more informative than conventional ones laboratory research. In addition, with the help of a biopsy, it is possible to assess the activity of glomerulonephritis, determine treatment tactics and prognosis.

Prof. D. Nobel

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 Advanced Training for Physicians, 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 of the regional Center for 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"

• Ultraviolet irradiation 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, less commonly UV-A), which provokes exacerbation of SLE, the role of other environmental factors in the pathogenesis of the disease has not been established. Increased sensitivity 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 the high incidence rate in individuals exposed to frequent viral diseases. It is known that viruses can not only damage cells of organs and systems, causing the formation of numerous autoantigens, but also influence the genome of immunocompetent cells, which leads to disruption of the mechanisms of immunological tolerance and the synthesis of antibodies.
• Data have been obtained on the role of measles and measles-like viruses in the origin of the disease. RNA-containing defective viruses have been discovered.
• “Molecular mimicry” of viral proteins and “lupus” autoantigens (Sm, etc.) has been revealed. Indirect confirmation of the etiological (or “trigger”) role of 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 are capable of causing changes in the interactions of lymphocytes and influencing the manifestations of the disease. However, there is no direct evidence that the occurrence of SLE in humans is caused by infectious pathogens.

Environmental factors

• Family and twin studies suggest a genetic predisposition to SLE. The disease often appears in families with a deficiency of certain 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 haplotypes HLA-A1, B8, DR3. 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 patients with SLE have relatives (parents or siblings) suffering from this disease in their families, and only 5% of children born in families where one of the parents has SLE develops 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 autoantigens is considered a central link in the pathogenesis of SLE. Patients tend to develop autoantibodies, increased B-lymphocyte activity, and T-lymphocyte dysfunction.

• SLE occurs primarily in women of childbearing age, but hormonal factors may have a greater influence on the manifestations of the disease than on its occurrence.
• In women of reproductive age suffering from SLE, there is an excess 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 towards hypoandrogenemia and hyperproduction of prolactin.
• It is believed that estrogens promote polyclonal activation of B lymphocytes. In addition, as already mentioned, it should be noted that the clinical and laboratory signs diseases can occur in some patients with long-term use of various medications (antibiotics, sulfonamides, anti-tuberculosis drugs and others).

Pathogenesis

• At the early stage of the disease, polyclonal (B-cell) immune activation predominates.
• Subsequently, antigen-specific (T-cell) immune activation 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 in SLE, autoantibodies are produced in only 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. Various defects in cellular immunity are characteristic, characterized by hyperproduction of Th2 cytokines (IL-6, IL-4 and IL-10). The latter are autocrine factors activating B lymphocytes that synthesize antinuclear 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 patients with SLE 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 patients with SLE, the proliferation of certain clones of B lymphocytes that produce high-affinity autoantibodies may be increased.

• According to most studies of experimental mouse models of SLE, vital role T lymphocytes play a 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.

• The search and study of the structure of antigens to which autoantibodies are produced continues. 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, for example, to the surface antigens of erythrocytes and platelets. Other autoantibodies cross-react with multiple antigens—for example, anti-DNA antibodies may bind to laminin in the glomerular basement membrane. 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, thereby 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.

• The development of lupus nephritis is not associated with the deposition of circulating immune complexes (as in some forms of systemic vasculitis), but with local (in situ) formation of immune complexes. First, nuclear antigens (DNA, nucleosomes, etc.) bind to the components of the glomeruli of the kidney, and then interact with the corresponding antibodies. Another possible mechanism is cross interaction antibodies to DNA with glomerular components.
• Dysfunction of the reticuloendothelial system (RES). Prolonged circulation of immune complexes contributes to their pathogenic effects, since over time the RES loses the ability to remove immune complexes. It has been revealed that SLE is more often observed in individuals with a defective C4a gene.
• Autoantibodies can cause a number of disorders:

• Lymphocyte dysfunction. In patients with SLE, various combinations of B-lymphocyte hyperactivity and dysfunction 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.

1. 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 especially important in affecting those organs that are inaccessible to immune complexes (for example, the central nervous system).

Morphological changes

• A characteristic sign of kidney damage in SLE is periodic changes in the histological picture of nephritis, depending on the activity of the disease or the therapy performed. A kidney biopsy allows one to assess the activity of the process (acute inflammation) and its chronicity (glomerulosclerosis and fibrotic interstitial changes). Acute kidney damage is more treatable.
• Mesangial nephritis occurs due to Ig deposition in the mesangium and is considered the most common and mild damage kidneys in SLE.
• Focal proliferative nephritis is characterized by involvement of only glomerular segments in less than 50% of the glomeruli, but may progress to the development of diffuse glomerular involvement.
• Diffuse proliferative nephritis occurs with cellular proliferation of most glomerular segments in more than 50% of glomeruli.
• Membranous nephritis is a consequence of Ig deposition in the epithelium and peripheral capillary loops without proliferation of glomerular cells; it is rare, although in some patients there are combinations of proliferative and membranous changes. Membranous nephritis has a better prognosis than proliferative nephritis.
• Interstitial inflammation can be observed in all of the disorders described above.

• Nonspecific synovitis and lymphocytic muscle infiltration often occur.
• Non-bacterial endocarditis is often encountered, and in typical cases it is asymptomatic. However, in half of the patients, non-bacterial warty endocarditis (Libman-Sachs) is detected, usually affecting the mitral and tricuspid valves and the formation of their insufficiency, serous-fibrinous pericarditis, and myocarditis.

• Spicy.
• Subacute.
• Chronic.

• Idegree,
• IIdegree,
• IIIdegree.

• Discoid lesions with telangiectasia (more often with chronic course SCV).
• On the skin side, erythematous rashes on the face in the area of ​​the wings of the nose, cheekbones, resembling a “butterfly” are typical.

• Facial erythema may not be persistent, but periodically intensifies, especially after sun exposure or exposure to cold.

• Sometimes blistering or maculopapular elements, urticaria, polymorphic exudative erythema, rash, and panniculitis are observed.
• There are reports of non-scarring psoriasis-like eruptions with telangiectasia 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 (even baldness). Unlike discoid lupus erythematosus, in SLE, lost hair can grow back. It takes several months for them to start up 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 areas along the hairline.
• Skin vasculitis is possible, which manifests itself as: hemorrhagic papulonecrotic rashes, nodular-ulcerative vasculitis of the legs, hyperpigmentation, infarction of the nail folds, gangrene of the fingers.
• Sometimes the so-called lupus cheilitis occurs - 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-ulcerative lesions of the nasopharynx.

• Every third patient with SLE experiences Raynaud's phenomenon, 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. Typical is the two- or three-phase nature of blood flow disturbances, when, following whitening and/or cyanosis of the fingers, reactive hyperemia develops. Trophic disorders of the skin of the fingers arise gradually, and, as a rule, are limited to the fingertips.
• SLE is characterized by vascular aneurysms and thrombosis (fibrinoid changes in the walls of blood vessels in combination with a cellular reaction).
• Sometimes, mainly on the skin lower limbs, hemorrhagic pinpoint-sized rashes the size of a pinhead are observed, which may be due to either thrombocytopenia or hemorrhagic vasculitis. In some cases, especially with secondary antiphospholipid syndrome, livedo reticularis (a marbled pattern of the skin in the extremities and trunk) is noted.
• On the periphery - thromboangiitis obliterans syndrome with intermittent claudication and migratory phlebitis - Buerger's syndrome.
• Although thrombosis can develop in the setting of vasculitis, increasing evidence suggests that antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies) cause thrombosis in the absence of inflammation. In addition, long-term exposure to immune complexes on the vascular wall and hyperlipoproteinemia, which develops during treatment with glucocorticoids, predispose to the development of ischemic heart disease, therefore, for some patients, anticoagulant therapy is more important than immunosuppressive therapy

• in acute progressive SLE, vasculitis is possible coronary vessels, however, the main cause of myocardial infarction in patients with SLE is atherosclerosis due to long-term steroid therapy;
• in SLE, the endocardium may also be involved in the pathological process, a feature of the lesion is the development of septic Libman-Sachs endocarditis, which occurs with thickening of the parietal endocardium in the area of ​​the atrioventricular ring, less often - the aortic valve; usually asymptomatic and detected during ecocardiographic examination; very rarely leads to the development of hemodynamically significant heart defects. These pathomorphological changes are usually detected at autopsy. In secondary adhesive phospholipid syndrome, cases of thrombotic valvulitis and thrombosis of the heart chambers have been described. It is believed that non-bacterial endocardial damage (Liebman-Sachs endocarditis) is more associated with the presence of AT to phospholipids. Endocarditis may be accompanied by embolism, dysfunction of the valves and infection;
• Premenopausal women with SLE have a high risk of developing atherosclerosis, the mechanism of which is probably the deposition of immune complex deposits in the vascular wall. Long-term therapy with GCS may have an additional effect on the formation of atherosclerosis due to hyperlipidemia and hyperglyceridemia.

• Pleurisy is found in 30% of patients. Pleurisy (dry or effusion, often bilateral, sometimes in combination with pericarditis). Pleural friction noise (with dry pleurisy).

• Diffuse interstitial lung lesions are rare (like Hamman-Rich syndrome). Interstitial pneumonitis - in the early stages it is curable, but if pulmonary fibrosis develops, treatment is ineffective.
• Severe, although rare, manifestations of SLE include pulmonary hypertension, usually as a consequence of recurrent pulmonary embolisms in APS; RDSV and massive pulmonary hemorrhage. The last two complications often lead to death.

• Gastrointestinal disorders in SLE most often manifest themselves as nausea, diarrhea, and abdominal discomfort. 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 vasculitis of the mesenteric vessels, manifested by acute cramping abdominal pain, vomiting and diarrhea. Intestinal perforation is possible, usually requiring emergency surgery.
• Abdominal pain and radiographically detectable stretching of the loops of the small intestine and, sometimes, swelling of its wall may be manifestations of intestinal pseudo-obstruction; in this case surgical intervention not shown. For all of the listed gastrointestinal disorders, glucocorticoids are effective.
• Some patients experience gastrointestinal motility disorders similar to what is observed with 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 difficult.
• Increased amylase activity in SLE may be due not only to pancreatitis, but also to inflammation of the salivary glands or macroamylasemia.
• During exacerbation of SLE, serum aminotransferase activity often increases in the absence of significant liver damage; when the exacerbation subsides, the activity of aminotransferases decreases.
• However, liver enlargement sometimes occurs. It is possible to develop toxic drug-induced hepatitis while taking aspirin, other non-steroidal anti-inflammatory drugs, hydroxychloroquine, azathioprine and others. Progression of autoimmune hepatitis to cirrhosis is extremely rare. Interstitial and parenchymal 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 damage and is often asymptomatic. Slight proteinuria and hematuria are detected in the urine. Usually no specific treatment is carried out. CRF develops after 7 or more years.
• Focal proliferative nephritis is also a relatively benign variant of kidney damage and in typical cases responds to steroid therapy.
• Diffuse proliferative nephritis - severe kidney damage, often accompanied arterial hypertension, widespread edematous syndromes, significant proteinuria, erythrocyturia and signs of renal failure. Glucocorticoids and cytostatics are used to protect the kidneys.
• 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 cytostatics in this form of lupus nephritis has not been proven. With a rapidly progressing variant of glomerulonephritis without treatment, patients die within 6-12 months from the onset of the first clinical manifestations.

• pericarditis occurs in approximately 20% of patients with SLE, of whom 50% have echocardiographic evidence of fluid effusion, but cardiac tamponade is rare;
• myocarditis (with conduction disturbances, arrhythmias and heart failure) is somewhat less common, and the changes can be reversible with adequate hormonal therapy;

• The most common manifestations are mild cognitive impairment and headache, which may resemble a migraine. Headache(often of a migraine nature, resistant to non-narcotic and even narcotic analgesics, often combined with other neuropsychiatric disorders, often with APS).
• Generalized manifestations are possible:

• Depression and anxiety disorders are often observed, the cause of which is usually not the disease itself, but the reaction of patients to it.
• Laboratory and instrumental studies do not always allow detection of CNS damage 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 rarely develop. 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 can also occur.

• One of the serious complications of SLE is choroiditis, which can lead to blindness within a few days and therefore requires treatment with high doses of immunosuppressants.
• Episcleritis, conjunctivitis, corneal ulcers, xerophthalmia.
• Fundus: whitish and grayish lesions around the vessels - cytoid bodies, varicose hypertrophy and degeneration of the nerve fiber, optic neuritis.

• Charlie-Frommel syndrome is a syndrome of persistent lactation and amenorrhea after childbirth, which is apparently associated with damage to the hypothalamic centers in SLE. Atrophy of the uterus and ovaries is possible.
• Autoimmune thyroiditis Hashimoto's.

• Antileukocyte ATs cause the development of autoimmune lymphopenia and, less commonly, 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 been quite often described antiphospholipid syndrome in chronic SLE. This is a symptom complex characterized by a triad of signs - venous or arterial thrombosis, obstetric pathology (intrauterine fetal death, recurrent spontaneous abortions), thrombocytopenia that occurs against the background of overproduction 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 SLE patients.

• As a result of immune complex activity in patients with SLE, low levels of complement components C3 and C4 are noted, and in many cases this indicator is associated with the degree of lupus activity.
• Hypergammaglobulinemia results in hyperactivity of B lymphocytes.
• However, autoantibodies are the most common finding in SLE.
• The diagnosis of SLE is considered confirmed when characteristic autoantibodies are detected. The best method of preliminary diagnosis is determination 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 serum healthy people(usually in low titre), 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 medications. Thus, the detection of these antibodies does not confirm, and their absence does not exclude, the diagnosis of SLE. ANAT is determined using immunofluorescent methods. When components of epithelial cell nuclei isolated by freezing and thawing are added to the test 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.

• In SLE, it is often determined antibodies to membrane and cytoplasmic components: AT to transfer RNA and ribosomal nucleoproteins. Other cytoplasmic ATs apparently interact with phospholipids cell membranes and cause cytotoxic reactions in some organs and tissues (AT to the parietal cells of the stomach, epithelial cells of the thyroid gland and cellular elements of the blood)

• Circulating immune complexes

• general blood analysis;
• general urine analysis;
• biochemical studies;
• kidney biopsy (to determine the morphological variant of glomerulonephritis and identify patients with active lupus nephritis who require aggressive cytostatic therapy);
• immunological examination detecting 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 patients with SLE (usually in high titer), and the absence of ANF in most cases allows us to exclude the diagnosis of SLE. The appearance of immunofluorescence to some extent reflects the specificity various types AHA: in SLE, the most common type is homogeneous (antibodies to DNA, histone), less often peripheral (antibodies to DNA) or speckled (antibodies to Sm, RNP, Ro/La). To detect autoantibodies to certain nuclear and cytoplasmic autoantigens, various immunological methods are used (enzyme immunoassay, radioimmunoassay, immunobotting, immunoprecipitation).

• unexplained fever, malaise, weight loss, anemia,
• photodermatitis,
• arthralgia, arthritis,
• Raynaud's phenomenon
• serositis,
• nephritis and nephrotic syndrome,
• neurological disorders (seizures or psychosis),
• alopecia,
• thrombophlebitis,
• recurrent spontaneous abortions.

1. With the development of SLE from lupus nephritis it is important to use the entire complex of clinical laboratory parameters, to clarify whether there were transient arthritis or arthralgia, trophic disorders, but the most important is the identification of LE cells, ANA, as well as electron microscopic and immunofluorescent examination of a kidney biopsy. The same approach is useful in autoimmune cytopenias.

1. 6. Fibromyalgia with ANF.
2. 7. Idiopathic thrombocytopenic purpura.
3. 8. Systemic vasculitis.
4. Neonatal lupus syndrome can develop in children whose mothers have high titers of AT to Ro, IgG. Maternal ATs 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 condition is considered to be damage to the conduction system of the child’s heart, which may require permanent cardiac stimulation. 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

1. Local application of corticosteroids.

• severity of the course: the highest doses for acute course and exacerbation of subacute course;
• activity of the pathological process: 40-60 mg of prednisolone per day or pulse therapy in grade III, 30-40 mg per day in grade II and 15-20 mg per day in grade I.
• predominant organ pathology (hormonal therapy should be especially suppressive 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/heart attack
• 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 progressing nephritis
• Nephrotic syndrome

• Vasculitis
• Diffuse rash with ulceration

• Myositis

• High fever in the absence of infection

• progressive course with the development of new symptoms and syndromes, despite the use of high doses of GCS for 1 - 1.5 months;
• lupus nephritis with the formation of nephrotic syndrome;
• severe damage to the central nervous system (acute psychosis, the appearance of focal symptoms, transverse myelitis, status epilepticus);
• development of life-threatening complications (exudative pericarditis; pneumonitis with increasing respiratory failure, recurrent thrombosis, etc.).

• Thus, to prevent the development of peptic ulcers, patients are recommended to eat regularly: it is necessary to exclude spicy, irritating dishes, food should be mechanically gentle; It is advisable to use alkalizing agents, especially in cases of developed dyspeptic symptoms, and antispasmodics (papaverine, no-spa, etc.).
• In the presence of focal strepto-and staphylococcal infection Anti-infective therapy should be included in complex treatment. In case of infectious complications, the dose of corticosteroid drugs should not only not be reduced, but connection with 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 antituberculosis drugs (isothiazide, streptomycin, etc.).
• Developed local or general candidomycosis is not a contraindication to continued therapy with glucocorticosteroids, provided that antifungal drugs are taken.
• In order to prevent disturbances in mineral and water metabolism (release of potassium, calcium, phosphorus and sodium and water retention), often accompanied by edema, it is necessary to control the potassium content in blood. For hypokalemia, potassium chloride is given orally, 1-2 g 3-4 times a day, after 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 usually manifests itself in SLE as diffuse osteoporosis.

• An undoubted contraindication to continued treatment with corticosteroids is steroid psychosis or increased seizures (epilepsy). It is necessary to differentiate with cerebral vasculitis. Excitement (insomnia, euphoria) is not an indication for stopping treatment: this condition can be controlled with sedatives.
• pericarditis occurs in approximately 20% of patients with SLE, of whom 50% have echocardiographic evidence of fluid effusion, but cardiac tamponade is rare;

• myocarditis (with conduction disturbances, arrhythmias and heart failure) is somewhat less common, and the changes can be reversible with adequate hormonal therapy;

Use of NSAIDs for SLE

• 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, and increased blood pressure;
• NSAIDs may cause gastrointestinal damage.

• a high degree of disease activity involving many organs and systems, and especially the kidneys, in proliferative and membranous lupus nephritis (both nephrotic and nephritic syndrome); renal syndrome occupies a special place in the indications for immunosuppressive therapy; Thus, even in the absence of other clinical signs of SLE activity, kidney damage requires early, massive and longer-term 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 control clinical manifestations refractory to high-dose glucocorticoid monotherapy (thrombocytopenia, central nervous system lesions, pulmonary hemorrhages, interstitial pulmonary fibrosis, systemic vasculitis);
• insufficient effectiveness of GCS when it is necessary to reduce the “suppressive dose” of corticosteroids due to severe side effects (rapid significant weight gain, arterial hypertension, steroid diabetes, severe osteoporosis, spondylopathy, etc.) or due to the individual characteristics of patients (constitutional obesity, teenage and menopause), when it is necessary to reduce the maintenance dose, if it is >15-20 mg, for corticosteroid dependence.

• Currently, cyclophosphamide and azathioprine (Imuran) are more commonly used in doses of 2-3 mg/kg (usually 100 to 200 mg per day). In recent years, when carrying out 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 simultaneously receive from 10 to 40 mg of prednisolone per day (in cases diffuse glomerulonephritis with nephrotic syndrome).
• Pulse therapy with cyclophosphamide (10-15 mg/kg IV once every 4 weeks) less often leads to hemorrhagic cystitis than daily oral administration of the drug, but is accompanied by pronounced inhibition of hematopoiesis.
• Treatment with cyclophosphamide (intravenous bolus administration at a dose of 0.5-1 g/m2 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 GC 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:

• inhibition of hematopoiesis,
• frequent opportunistic infections (for example, caused by the varicella-zoster virus),
• irreversible ovarian failure,
• hepatotoxic effect (azathioprine),
• hemorrhagic cystitis (cyclophosphamide),
• alopecia and carcinogenic effect.

Plasmapheresis

Hemosorption

• continued activity of SLE, despite large doses of glucocorticoids and cytostatics;
• active lupus nephritis;
• stubborn joint syndrome;
• skin vasculitis with ulcerations;
• impossibility of increasing the dose of glucocorticoids due to complications that have developed.

Calcium channel blockers and other vasodilators

Vitamin therapy

Exercise therapy and massage

Prevention of SLE

• eliminate psycho-emotional stress;
• reduce sun exposure and use sunscreen;
• actively treat (and, if possible, prevent) the development of infection, including through vaccination;
• consume food with low content fat and high content of polyunsaturated fatty acids, calcium and vitamin D;
• observe effective contraception during the period of exacerbation of the disease and during treatment with cytotoxic drugs (you should not take oral contraceptives with a high content of estrogen, since exacerbation of SLE is possible);
• in the absence of severe, life-threatening complications, prescribe the least toxic drugs in effective doses;
• when involved in a pathological process, it is vital important organs and a high risk of irreversible lesions, immediately prescribe aggressive therapy, including pharmacological and non-pharmacological treatment methods;
• avoid surgical interventions, do not administer vaccines and serums;
• in case of stable remission, glucocorticoids can be discontinued, but patients should be under dynamic observation for 3 years and spring-autumn period receive anti-relapse treatment with one of the aminoquinoline drugs, antihistamines, vitamins.

• arterial hypertension,
• antiphospholipid syndrome,
• high disease activity,
• high values damage index,
• addition of infection,
• complications of drug therapy.

Lupus is a fairly common autoimmune disease: for example, it affects approximately one and a half million people in the United States. This disease affects various organs, such as the brain, skin, kidneys and joints. Symptoms of lupus can be easily confused with those of other diseases, making it difficult to diagnose. It's helpful to know the symptoms and diagnosis of lupus so it doesn't catch you by surprise. You should also be aware of the causes of lupus to avoid potential risk factors.

Attention: The information in this article is for informational purposes only. If you experience any of the following symptoms, consult your doctor.

Steps

Lupus symptoms

Check to see if you have a butterfly wing rash on your face. On average, 30 percent of people with lupus develop a characteristic rash on their face, which is often described as being shaped like a butterfly or a wolf bite. The rash covers the cheeks and nose and sometimes extends all the way to the eyes.

• Also check for disc-shaped rashes on your face, scalp and neck. This rash appears as red, raised spots and can be so severe that it leaves scars.
• Pay special attention to rashes that appear or worsen when exposed to sunlight. Sensitivity to natural or artificial ultraviolet radiation can cause a rash on sunlit areas of the body and worsen the butterfly rash on the face. This rash is more abundant and appears faster than with a regular sunburn.

1. Check for ulcers in the mouth and nasal cavity. If you often have ulcers on the roof of your mouth, the corners of your mouth, your gums, or your nose, this is another a worrying sign. Pay special attention to painless sores. Typically, with lupus, sores in the mouth and nose do not hurt.

   • Photosensitivity of ulcers, that is, their aggravation by exposure to sunlight, is another sign of lupus.

2. Look for signs of inflammation. People with lupus often experience inflammation of the joints, lungs, and tissues around the heart (the pericardial sac). Usually the corresponding blood vessels. Inflammation can be identified by swelling of the feet, legs, palms and eyes.

   Pay attention to your kidney function. Although it is difficult to assess the condition of the kidneys at home, it can still be done based on some signs. If lupus causes your kidneys to be unable to filter urine, your feet may become swollen. Moreover, the development of renal failure may be accompanied by nausea and weakness.

   Take a closer look at possible problems with the brain and nervous system. Lupus can affect the nervous system. Some symptoms, such as anxiety, headaches and vision problems, are also observed in many other diseases. However, lupus can also cause very serious symptoms such as seizures and personality changes.

   • Although lupus is often accompanied by headaches, this pain is very difficult to identify the disease. Headache is a common symptom and can be caused by a variety of reasons.

3. See if you feel tired more often than usual. Extreme fatigue is another sign of lupus. Although feeling tired can have a variety of causes, often those causes are related to lupus. If fatigue is accompanied by a fever, this is another sign of lupus.

   Look for other unusual signs. When exposed to cold, fingers and toes may change color (turn white or blue). This phenomenon is called Raynaud's disease, and it often accompanies lupus. Dry eyes and difficulty breathing may also occur. If all of these symptoms occur at the same time, you may have lupus.

   Learn about tests that use imaging techniques. If your doctor suspects that lupus may be affecting your lungs or heart, he may order a test to see internal organs. To find out the health of your lungs, you may be referred for a standard chest x-ray, while an echocardiogram will provide insight into the health of your heart.

   • A chest x-ray sometimes shows shadowed areas in the lungs, which may indicate fluid accumulation or inflammation.
   • Echocardiography uses sound waves to measure the heartbeat and identify possible heart problems.

4. Find out about biopsy. If your doctor suspects that lupus has caused kidney damage, he or she may order a kidney biopsy. A sample of your kidney tissue will be taken for analysis. This will allow you to assess the condition of the kidneys, the degree and type of damage. A biopsy will help your doctor determine the best treatment options for lupus.