Systemic lupus erythematosus blood test diagnostics. Treatment of systemic lupus
Diagnosis of lupus erythematosus
General principles for diagnosing the disease
Diagnosis of systemic lupus erythematosus is exhibited on the basis of special developed diagnostic criteria, proposed by the American Association of Rheumatology or the domestic scientist Nasonova. Next, after making a diagnosis based on diagnostic criteria, additional examinations are performed - laboratory and instrumental, which confirm the correctness of the diagnosis and allow one to assess the degree of activity pathological process and identify affected organs.Currently, the most commonly used diagnostic criteria are American Association rheumatologists, 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 mucous membrane oral cavity(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:
| Large diagnostic criteria | Minor diagnostic criteria |
| "Butterfly on the Face" | Body temperature above 37.5 o C, lasting longer than 7 days |
| Arthritis | Unreasonable weight loss of 5 or more kg per short term and tissue nutritional disorders |
| Lupus pneumonitis | Capillaritis on the fingers |
| LE cells in the blood (less than 5 per 1000 leukocytes – single, 5 – 10 per 1000 leukocytes – moderate amount, and more than 10 per 1000 leukocytes – a large number) | Skin rashes such as hives or rashes |
| ANF in high credits | Polyserositis (pleurisy and carditis) |
| Werlhoff syndrome | Lymphadenopathy (enlarged lymph ducts and nodes) |
| Coombs-positive hemolytic anemia | Hepatosplenomegaly (enlarged liver and spleen) |
| Lupus jade | Myocarditis |
| Hematoxylin bodies in pieces of tissue from various organs taken during biopsy | CNS damage |
| A characteristic pathomorphological 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 | |
| Acceleration of ESR more than 200 mm/hour | |
| Decrease in the number of leukocytes in the blood to less than 4*10 9 /l | |
| Anemia (hemoglobin level below 100 mg/ml) | |
| Decrease in platelet count below 100*10 9 /l | |
| Increase in the amount of globulin proteins by more than 22% | |
| ANF in low credits | |
| Free LE bodies | |
| Positive Wasserman reaction in the confirmed absence of syphilis |
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. Based only on laboratory tests and instrumental methods 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 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 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
Because the exact causes of lupus are unknown, there are no treatments that can completely cure the disease. As a result, only pathogenetic therapy is used, the purpose of which is to suppress inflammatory process, preventing relapses and achieving stable remission. In other words, the treatment of lupus erythematosus is to slow down the progression of the disease as much as possible, lengthen periods of remission and improve a person’s quality of 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 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 options and 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 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 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 restoring normal metabolism. For lupus erythematosus, you can and should additionally use any drugs that improve general health 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.);
- 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 smears bone marrow and peripheral blood patients with SLE discovered during incubation at 37°C, leukocytes with special inclusions, which were called LE cells. 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 identified in the acute period. LE cells are not specific for SLE, but the more often they reproduce positive test with 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 calf thymus cells. 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. Special meaning probably have adenosine and thymidine. 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 appropriate processing and the use of indirect immunofluorescence, only DNA antibodies can be detected. 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 with 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. With enough help 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 SLE patients, 65% of discoid lupus patients, and other diseases connective tissue in 0-7% of patients. 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. Noted high content 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. Extremely low level the latter, with a fairly high titer of complement-fixing antibodies to DNA, indicates an active phase of the disease with involvement of the kidneys in the process. A decrease in complement titer often precedes clinical crisis. With activity immune reactions in SLE, the level of IgG antibodies (to DNA and RNA) is especially correlated.
Therapy with corticoids and immunosuppressants often leads to rapid decline DNA-binding abilities, which can 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.
Belonging to the group of large collagenoses, which is characterized by diffuse damage connective tissue and blood vessels. Early diagnosis This pathology is a serious problem, since SLE can begin under the “mask” of other diseases. Since SLE is an autoimmune disease, the mechanism of its clinical manifestations, according to modern ideas, is explained from the following positions:
- circulating immune complexes (CIC), which include antinuclear antibodies, deposited in the microcirculatory link, lead to the development of vasculopathies and tissue damage;
- autoantibodies to blood cells lead to leuko-, lymphothrombopenia and anemia;
- antiphospholipid antibodies lead to the development of antiphospholipid syndrome (APS).
Modern methods of immunological laboratory diagnostics make it possible to identify all components of the pathogenesis of SLE and thereby verify the diagnosis of the disease with extraordinary, almost 100% accuracy. However, the presence of any changes in the analyzes allows them to be interpreted only taking into account the individual clinical picture.
It should be noted that the previous method of diagnosing SLE by the presence of LE cells in the blood did not stand the test of time, showing extremely low sensitivity and specificity, and therefore it was abandoned. LE cells are not even included in the SLE criteria system.
The main markers of SLE are:
Indications for prescribing a blood test for markers of systemic lupus erythematosus
- cutaneous lupus;
- drug-induced lupus;
- thrombocytopenic purpura;
- erythroderma;
- severe liver damage;
- CREST syndrome;
- polymyositis;
- dermatomyositis;
- chronic juvenile arthritis;
- autoimmune hepatitis;
- sclerosing cholangitis;
- polyneuropathy;
- myelitis;
How is the procedure done?
Blood is drawn from the ulnar vein on an empty stomach in the morning.
Preparing for analysis
Lupus anticoagulant
Lupus anticoagulants (LA) is one of the important screening and confirmatory tests for diagnosing APS. VAs are formed in the body as a result of the development of autoimmune processes after infectious influences and suppress the reaction of conversion of prothrombin into thrombin in the blood. When these antibodies are detected in the blood by prolongation of coagulation tests, they are defined as “lupus anticoagulant”.
- tumors;
Antinuclear factor
Antinuclear factor on the HEp-2 cell line (ANF HEp-2, titers; ANA IF, titers). A positive result of ANF is observed in more than 90% of patients with SLE and cutaneous forms of this disease, scleroderma, mixed connective tissue disease, Sjogren's syndrome. The result of the determination of ANF is the titer, which is the value of the final dilution of the serum at which significant nuclear fluorescence remains. The higher the denominator of the fraction, the greater the dilution of the serum, the more antibodies in the patient’s serum. The sensitivity of this test for SLE is 95%.
High ANF titers (1/640 and above):
- high probability systemic rheumatic disease;
- high probability of autoimmune liver disease;
- an increase in ANF titers over time indicates an exacerbation of a systemic disease;
- in SLE, the titer correlates with the severity of the disease and decreases with effective therapy.
Low ANF titers (up to 1/160):
- in 1-2% of healthy individuals;
- in relatives of patients with systemic diseases;
- many autoimmune, infectious and oncological diseases.
Antibodies to nucleosomes
Nucleosome antibodies (NCAs) are one of the first antibodies to form in the body during the development of SLE. NCA titers correlate with disease activity. The specificity of determining these autoantibodies for diagnosing SLE is more than 95%.
Decoding the analysis result
High levels of antibodies to nucleosomes (positive):
- drug-induced lupus;
- active SLE accompanied by nephritis.
- low probability of SLE;
- low risk of kidney damage in SLE.
IgG antibodies to double-stranded DNA
The presence of IgG antibodies to double-stranded DNA (anti-dsDNA IgG; anti-dsDNA IgG) is highly specific for SLE, and to a lesser extent for other diffuse connective tissue diseases or drug-induced SLE. The sensitivity of the test for SLE is 85%. Quantitative determination of anti-dsDNA IgG antibodies most suitable for monitoring the condition, prognosis and control of therapy in patients with SLE, as it correlates with its activity and the severity of glomerulonephritis.
Decoding the analysis result
Level up:
- Epstein-Barr virus infection;
Downgrade:
- norm.
Anti-cardiolipin IgG antibodies
Anticardiolipin IgG antibodies (aCL IgG) are one of the types of autoimmune antiphospholipid antibodies included in the pathogenesis of antiphospholipid syndrome. Their presence in the blood is manifested by the prolongation of phospholipid-dependent coagulogram tests (prothrombin, aPTT), which is referred to as “lupus anticoagulant”.
Decoding the analysis result
- drug-induced lupus;
- hepatitis C;
- borelliosis;
- HIV infection.
Antibodies to cardiolipin IgM
Antibodies to cardiolipin IgM (aCL IgM), when detected, indicate a high risk of developing SLE; aCL IgM are detected in 20-50% of patients with systemic lupus erythematosus and 3-20% of patients with other systemic rheumatic diseases.
Interpretation
Positive (antibodies detected):
- hepatitis C;
- borelliosis;
- HIV infection;
- systemic connective tissue diseases.
Norms
| Index | Norm | |
| Lupus anticoagulant (LA, Lupus anticoagulants, LA) | negated | |
| Antinuclear factor on the HEp-2 cell line (ANF HEp-2, titers; ANA IF, titers) | < 1:160 | |
| Antibodies to nucleosomes | < 20 отн. ед./мл | |
| IgG antibodies to double-stranded DNA | < 20 МЕ/мл (отрицательно) | |
| Anticardiolipin IgG antibodies (aCL IgG) | negative or< 12 GPL-ед./мл | |
| Anticardiolipin IgM antibodies (aCL IgM) | < 12 MPL-ед./мл | |
The main tests for lupus are the determination of antinuclear antibodies (ANA) and complement; a supporting role is played.
Blood analysis
In a blood test for lupus, pathology of any blood element is possible. Therefore, a complete blood count is an important component of the initial and subsequent assessment of all lupus patients. In the absence of appropriate medications, the decrease in cell number is usually secondary to peripheral destruction rather than bone marrow suppression.
Autoimmune hemolytic anemia is found in less than 10% of cases. The Coombs test, both direct and indirect, can be positive in the absence of active hemolysis. Nonspecific, indicating a chronic disease, develops in 80% of cases, leukopenia - in 50%. Absolute lymphopenia occurs more often than neutropenia. Unfortunately, the criterion for lymphopenia (
Thrombocytopenia can be moderate (50-100×109/l), chronic and completely asymptomatic or severe (
Erythrocyte sedimentation rate is often elevated in SLE and is not generally considered a reliable marker of clinical activity. An increase in C-reactive protein may indicate infection, but this sign is not absolute.
Test for antinuclear antibodies and complement
Determination of serological parameters is part of the basic tests for lupus and monitoring of patients with SLE. The term covers studies performed using blood serum, although plasma can be used for antibody detection (but not functional complement assays). For example, determining the ability of serum complement to lyse sheep red blood cells (CH50 test) cannot be carried out using plasma, since it is believed that activation of complement in plasma with ethylenediaminetetraacetic acid and citrate does not occur due to their chelation of calcium.
Detection of ANA during primary analysis for lupus is key, since differential diagnosis in this situation comes down to autoimmune diseases. It should be remembered that 2% of healthy young women also have ANA, so this test should be considered indicative. After identifying them once, subsequent measurements are not considered indicative of assessing the activity of the process. Antibodies to double-stranded DNA - not only the main one diagnostic analysis for lupus, but also in some cases (especially with kidney damage) - a marker of poor prognosis and high activity. Anti-BT antibodies that recognize determinants on proteins associated with small nucleoproteins involved in transfer RNA processing. have diagnostic value, but are not specific only for lupus. Antibodies to ribonucleoproteins also do not correlate with disease activity. They are often found in patients with one (or more) of the following symptoms: photosensitivity, dry eyes and mouth [Sjögren's syndrome], subacute skin lesions, risk of having a child with neonatal lupus. Antibodies to the SSA/Ro antigen, depending on the method of their detection, stain the cytoplasmic component of the cell in the corresponding color and therefore some cases of ANA-negative lupus may be associated with them. If ANA-negative lupus is suspected, the diagnosis is quite difficult to make, since there are no detectable autoantibodies.
Proteins of the complement system, autoantibodies and integral components of immune complexes can be examined both functionally (CH50) and for antigenic structure (C3, C4). Most laboratories determine the content of C3 and C4, since they are stable and do not require special processing, unlike CH50. CH50 reveals the ability of serum complement to lyse sheep red blood cells; this ability decreases as the serum is diluted, resulting in the lysis of 50% of sheep red blood cells coated with antibodies. A decrease in CH50 is observed with a deficiency or increased consumption of certain complement components. In fact, none of these methods for assessing the complement system makes it possible to distinguish increased consumption from reduced synthesis of its components. Such differentiation requires the identification of complement breakdown products (for example, C3). Such studies have diagnostic value, but they are not performed in most commercial laboratories.
The basis of management tactics for patients with SLE is the identification of tests for lupus, which determine the risk of exacerbations of the disease, especially those leading to irreversible damage to vital organs. It is likely that early treatment of patients with high risk further influences morbidity and mortality. Interest in assessing the complement system and identifying antibodies to DNA when examining patients with lupus arose after long-term observation, which revealed a decrease in complement levels and an increase in the level of antibodies to DNA in severe cases of the disease.
These test results for lupus are explained by the fact that immune complexes cause activation of complement, which are present locally or in the circulating blood and are capable of stimulating inflammatory cells, which leads to vascular damage. Determination of DNA antibodies and complement is an important part of the basic examination, but treatment depends more on the clinical picture rather than on serological data. Over time, it usually becomes clear whether serological changes in each specific case foreshadow and accompany exacerbations of the disease or not. It is known that in some cases low content complement and high levels of anti-DNA antibodies with relative clinical remission. Conversely, there are patients who are repeatedly found to have consistent clinical and serological activity in lupus tests. In such cases, the indication for treatment is a change in serological parameters before the onset of clinical symptoms, which helps prevent relapse. These data were obtained in a clinical study examining clinically stable patients with serological signs of activity, and also aiming to determine whether antibodies to DNA, C3, C4 and complement breakdown product C3 are harbingers of exacerbation, and whether a short course of glucocorticoids can prevent the occurrence of diseases. Although the study was relatively small, it showed that prophylactic glucocorticoids prevented recurrence. At the very least, the frequency of lupus urine dipstick testing should be increased in patients with increasing levels of anti-DNA antibodies and decreased complement. It has been suggested that some antinuclear antibodies are selective biological markers of active SLE (especially lupus nephritis).
Systemic lupus erythematosus (SLE)– a chronic autoimmune disease caused by a disruption of the immune mechanisms with the formation of damaging antibodies to one’s own cells and tissues. SLE is characterized by damage to joints, skin, blood vessels and various organs (kidneys, heart, etc.).
Cause and mechanisms of disease development
The cause of the disease is not clear. It is assumed that viruses (RNA and retroviruses) serve as the trigger for the development of the disease. In addition, people have a genetic predisposition to SLE. Women get sick 10 times more often, which is due to the characteristics of their hormonal system (high concentration estrogen in the blood). Proven protective effect regarding SLE male sex hormones (androgens). Factors that can cause the development of the disease can be a viral, bacterial infection, or medications.The mechanisms of the disease are based on dysfunction 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, and serous membranes internal organs(heart, lungs, etc.) causing inflammatory reactions.
Symptoms of the disease
SLE is characterized by a wide range of symptoms. The disease occurs with exacerbations and remissions. The onset of the disease can be either immediate or 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, the joints of the fingers, wrists, and knee joints are most 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%)
Damage to mucous membranes and skin
- Skin lesions at the onset of the disease appear in only 20-25% of patients, in 60-70% of patients they appear later, in 10-15% 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. The lesions have the appearance of erythema (reddish plaques with peeling), dilated capillaries at 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) occurs rarely, usually affecting the temporal areas. Hair falls out in a limited area.
- Increased sensitivity of the skin to sunlight (photosensitization) occurs in 30-60% of patients.
- Damage to the mucous membranes occurs in 25% of cases.
- Redness, decreased pigmentation, impaired nutrition of lip tissue (cheilitis)
- Pinpoint hemorrhages, ulcerative lesions of the oral mucosa
Respiratory system damage
Lesions from the respiratory system in SLE are 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). Characterized by chest pain, 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 blood vessels of the lungs, leading to pulmonary hypertension. Against the background of SLE, they often develop infectious processes in the lungs, and it is also possible to develop serious condition like a blockage pulmonary artery thrombus (pulmonary embolism).Damage to the cardiovascular system
SLE can affect all structures of the heart, the outer lining (pericardium), the inner layer (endocardium), the heart muscle itself (myocardium), valves and coronary vessels. The most common lesion occurs in the pericardium (pericarditis).- Pericarditis - inflammation serous membranes covering the heart muscle.
- Myocarditis is inflammation of the heart muscle.
- Damage to the heart valves, most often the mitral and aortic valves are affected.
- Defeat 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 developing atherosclerosis. Peripheral vascular damage manifests itself:
- Livedo reticularis ( blue spots on the skin creating a grid pattern)
- Lupus panniculitis (subcutaneous nodules, often painful, may ulcerate)
- Thrombosis of blood vessels of the extremities and internal organs
Kidney damage
The kidneys are most often affected in SLE; in 50% of patients, lesions of the renal apparatus are detected. A common symptom is the presence of protein in the urine (proteinuria); red blood cells and casts are usually not detected at the onset of the disease. The main manifestations of kidney damage in SLE are: proliferative glomerulonephritis and mebranous nephritis, which manifests itself as nephrotic syndrome (proteins in the urine more than 3.5 g/day, decreased protein in the blood, edema).Damage to the central nervous system
It is assumed that disorders of the central nervous system are caused by damage to the blood vessels of the brain, as well as the formation of antibodies to neurons, to the cells responsible for protecting and nourishing neurons (glial cells), and to immune cells (lymphocytes).Main manifestations of the lesion nerve structures and cerebral vessels:
- Headache and migraine, most frequent symptoms for SLE
- Irritability, depression – rare
- Psychoses: paranoia or hallucinations
- Brain stroke
- Chorea, parkinsonism – rare
- Myelopathies, neuropathies and other disorders of nerve sheath (myelin) formation
- Mononeuritis, polyneuritis, aseptic meningitis
Damage to the digestive tract
Clinical lesions of the digestive tract are diagnosed in 20% of patients with SLE.- Damage to the esophagus, impaired swallowing, dilatation 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 leukocytes in the blood. Caused by a decrease in lymphocytes and granulocytes (neutrophils, eosinophils, basophils).
- Thrombocytopenia is a decrease in platelets in the blood. 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 on data from laboratory and instrumental studies. The American College of Rheumatology has developed special criteria that can be used 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.
| Characteristics: without erosion, peripheral, manifested by pain, swelling, accumulation of slight fluid in the joint cavity |
| Red in color, oval, round or ring-shaped, plaques with uneven contours there are scales on their surface, dilated capillaries nearby, the scales are difficult to separate. 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 butterfly rash |
| Constant loss of protein in urine 0.5 g/day, release of cell casts |
| Pleurisy is inflammation of the membranes of the lungs. It manifests itself as pain in the chest, intensifying with inspiration. Pericarditis – inflammation of the heart lining |
| Convulsions, Psychosis - in the absence of drugs that can provoke them or metabolic disorders (uremia, etc.) |
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| Increased antinuclear antibodies (ANA) |
The degree of disease activity is determined using 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 summed up. The maximum is 105 points, which corresponds to very high disease activity.
Disease activity indices bySLEDAI
| Manifestations | Description | Punctuation |
| Pseudoepileptic seizure(development of seizures without loss of consciousness) | It is necessary to exclude metabolic disorders, infections, and medications that could provoke it. | 8 |
| Psychoses | Impaired ability to perform actions as usual, impaired perception of reality, hallucinations, decreased associative thinking, disorganized behavior. | 8 |
| Organic changes in the brain | Changes in logical thinking, impaired spatial orientation, decreased memory, intelligence, concentration, incoherent speech, insomnia or drowsiness. | 8 |
| Eye disorders | Inflammation of the optic nerve, excluding arterial hypertension. | 8 |
| Damage to cranial nerves | Damage to the cranial nerves detected for the first time. | |
| Headache | Severe, constant, may be migraine, not responding to narcotic analgesics | 8 |
| Cerebral circulatory disorders | Newly identified, excluding the consequences of atherosclerosis | 8 |
| Vasculitis-(vascular damage) | Ulcers, gangrene of the limbs, painful nodes on the fingers | 8 |
| Arthritis-(inflammation of joints) | Involvement of 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 |
| Casts in urine | Hyaline, granular, erythrocyte | 4 |
| Red blood cells in urine | More than 5 red blood cells in the field of view, exclude other pathologies | 4 |
| Protein in urine | More than 150 mg per day | 4 |
| Leukocytes in urine | More than 5 white blood cells per field of view, excluding infections | 4 |
| Skin lesions | Damage inflammatory in nature | 2 |
| Hair loss | Increased lesions or complete hair loss | 2 |
| Ulcers of the mucous membranes | Ulcers on the mucous membranes and 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, EchoCG | 2 |
| Declining compliment | Decreased C3 or C4 | 2 |
| AntiDNA | Positively | 2 |
| Temperature | More than 38 degrees C, excluding infections | 1 |
| Decreased platelets in the blood | Less than 150 10 9 /l, excluding medications | 1 |
| Decreased white blood cells | Less than 4.0 10 9 /l, excluding medications | 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, detected in 95% of patients, does not confirm the diagnosis in the absence of clinical manifestations of systemic lupus erythematosus
- Anti DNA– antibodies to DNA, detected 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 RNAs, 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 (cell energy station)
- Antihistones– antibodies against proteins necessary for packaging DNA into chromosomes, characteristic of drug-induced SLE.
- Markers of inflammation
- ESR – increased
- C – reactive protein, increased
- Compliment level reduced
- C3 and C4 are reduced as a result of excessive formation of immune complexes
- Some people have a reduced level of compliment from birth, this is a predisposing factor to the development of SLE.
- General blood analysis
- Possible decrease in red blood cells, white blood cells, lymphocytes, platelets
- Analysis of urine
- Protein in urine (proteinuria)
- Red blood cells in 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 system
- X-ray of joints
- X-ray and CT scan chest
- Nuclear magnetic resonance and angiography
- Echocardiography
Specific procedures
- A spinal tap can rule out infectious causes of neurological symptoms.
- A kidney biopsy (analysis of organ tissue) 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 main reason the disease was not found, just as the cause itself was not found. Thus, the principle of treatment is aimed at eliminating the mechanisms of disease development, reducing provoking factors and preventing complications. - Eliminate physical and mental stress conditions
- Reduce sun exposure and use sunscreen
- Glucocorticosteroids the most effective drugs in the treatment of SLE.
Dosage 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
- Intravenous administration of methylprednisolone in large doses (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, lesion 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 refractory to treatment with corticosteroids
- The need to reduce corticosteroid doses
- High SLE activity
- Progressive or fulminant course of SLE
- Cyclophosphamide during pulse therapy is 1000 mg, then 200 mg every day until a total dose of 5000 mg is reached.
- Azathioprine 2-2.5 mg/kg/day
- Methotrexate 7.5-10 mg/week, orally
- Anti-inflammatory drugs
- Naklofen, nimesil, airtal, katafast, etc.
- Aminoquinoline drugs
- delagil, plaquenil, etc.
- Biological drugs 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
- Extracorporeal treatment methods
- Plasmapheresis is a method of purifying blood outside the body, in which part of the blood plasma is removed, and with it antibodies causing disease SCV.
- 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- 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, alternating periods of exacerbations and remissions, predominance common symptoms(weakness, weight loss, low-grade fever (up to 38 0
C) and others), damage to internal organs and complications occur gradually, no earlier than 2-4 years after the onset of the disease.
3.
Chronic course– the most favorable course of SLE, there is a gradual onset, damage mainly to the skin and joints, more long periods remissions, 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 we can highlight 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 structures of the body.
2. Drug-induced lupus erythematosus– unlike the systemic type of lupus erythematosus, a completely reversible process. Drug-induced lupus develops as a result of exposure to certain medications:
- Medicines 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;
- herbal preparations for the treatment of venous diseases (thrombophlebitis, varicose veins of the lower extremities, and so on): horse chestnut, venotonic Doppelgerz, 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 with systemic lupus erythematosus, but blood test parameters (biochemical and immunological) do not have changes characteristic of SLE, and this will be the main criterion 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 differentiate from diseases that are similar in appearance (eczema, psoriasis, cutaneous form of sarcoidosis, and others).
4. Neonatal lupus erythematosus occurs in newborns whose mothers suffer from systemic lupus erythematosus or other systemic autoimmune diseases. At the same time, the mother SLE symptoms There may not be any, but when they are examined, autoimmune antibodies are detected.
Symptoms of neonatal lupus erythematosus In a child, they usually appear before the age of 3 months:
- changes on the skin of the face (often have the appearance of a butterfly);
- congenital arrhythmia, which is often determined by ultrasound of the fetus in the 2nd-3rd trimesters of pregnancy;
- lack of blood cells in a general blood test (decrease in the level of red blood cells, hemoglobin, leukocytes, platelets);
- identification of autoimmune antibodies specific for SLE.
5. The term “lupus” is also used for tuberculosis of the facial skin - tuberculous lupus . Skin tuberculosis is very similar in appearance to systemic lupus erythematosus. The diagnosis can be established by histological examination of the skin and microscopic and bacteriological examination of scrapings - mycobacterium tuberculosis (acid-fast bacteria) is detected.
Photo:
This is what tuberculosis of the facial skin or tuberculous lupus looks like.
Systemic lupus erythematosus and other systemic connective tissue diseases, how to differentiate?
Group systemic diseases connective tissue:- Systemic lupus erythematosus.
- Idiopathic dermatomyositis (polymyositis, Wagner's disease)– damage by autoimmune antibodies to smooth and skeletal muscles.
- Systemic scleroderma is a disease in which normal tissue is replaced by connective tissue (not bearing 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, etc.), 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 |
| Onset of the disease |
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 Photo: Raynaud's syndrome |
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| Temperature | Prolonged fever, body temperature above 38-39 0 C. | Long-term low-grade fever(up to 38 0 C). | Moderate prolonged fever (up to 39 0 C). |
| Patient's appearance (at the onset of the disease and in some of its forms, the patient’s appearance may not change in all these diseases) | Damage to the skin, mostly the face, “butterfly” (redness, scales, scars). The rash can be all over the body and on the mucous membranes. Dry skin, loss of hair and nails. Nails are deformed, striated nail plates. There may also be hemorrhagic rashes (bruises and petechiae) throughout the body.  | The face may acquire a “mask-like” expression without facial expressions, tense, the skin is shiny, deep folds appear around the mouth, the skin is motionless, tightly fused to deep-lying tissues. Often there is a disruption of the glands (dry mucous membranes, as in Sjögren's syndrome). Hair and nails fall out. On the skin of the limbs and neck there are dark spots against the background of “bronze skin”.  | A specific symptom is swelling of the eyelids, their color can be red or purple; on the face and décolleté there is a variety of rashes with redness of the skin, scales, hemorrhages, and scars. As the disease progresses, the face acquires a “mask-like appearance”, without facial expressions, tense, may be skewed, and drooping of the upper eyelid (ptosis) is often detected.  |
| Main symptoms during the period of disease activity |
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| Forecast | Chronic course, over time, more and more organs are affected. Without treatment, complications develop that threaten the patient's life. With adequate and regular treatment, it is possible to achieve long-term, stable remission. | ||
| Laboratory indicators |
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| Principles of treatment | Long-term hormonal therapy (Prednisolone) + cytostatics + symptomatic therapy and other drugs (see section of the article "Treatment 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. It is often enough for experienced rheumatologists to evaluate the skin manifestations of the disease to diagnose systemic lupus erythematosus (if present).
Systemic lupus erythematosus in children, what are the symptoms and treatment?
Systemic lupus erythematosus is less common in children than in adults. IN childhood The most common autoimmune disease is rheumatoid arthritis. SLE predominantly (in 90% of cases) affects girls. Systemic lupus erythematosus can occur in infants and young children, although it is rare. greatest number cases of this disease occur during puberty, namely at the age of 11-15 years. Considering the nature of the immune system, hormonal background, growth rate, systemic lupus erythematosus in children occurs with its own characteristics.
Features of the course of systemic lupus erythematosus in childhood:
- more severe course of the disease , high activity of the autoimmune process;
- chronic course the disease occurs in children 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 lightning-fast course SLE is an almost simultaneous lesion of 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 complications and high mortality;
- the most common complication is bleeding disorder in the form of internal bleeding, hemorrhagic rashes (bruises, hemorrhages on the skin), as a result - the development of a shock state of DIC syndrome - disseminated intravascular coagulation;
- Systemic lupus erythematosus in children often occurs in the form of vasculitis – inflammation of 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.
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, sudden loss of body weight.
2.
Skin changes in the form of a “butterfly” are relatively rare in children. But, given the development of a lack of blood platelets, it is more common hemorrhagic rash all over the body (bruises for no reason, petechiae or pinpoint hemorrhages). Also one of characteristic features systemic diseases are hair loss, eyelashes, eyebrows, up to complete baldness. The skin becomes marbled and very sensitive to sunlight. There may be various rashes on the skin, characteristic of allergic dermatitis. In some cases, Raynaud's syndrome develops - a violation of blood circulation in the hands. In the oral cavity there may be ulcers that do not heal for a long time - stomatitis.
3.
Joint pain– typical syndrome of active systemic lupus erythematosus, pain is periodic. Arthritis is accompanied by the accumulation of fluid in the joint cavity. Over time, joint pain is combined with muscle pain and stiffness of movement, starting with the small joints of the fingers.
4.
For children formation of exudative pleurisy is characteristic(liquid in pleural cavity), pericarditis (fluid in the pericardium, the lining of the heart), ascites and other exudative reactions (dropsy).
5.
Heart damage in children it usually manifests itself as myocarditis (inflammation of the heart muscle).
6.
Kidney damage or nephritis It develops much more often in childhood than in adulthood. Such nephritis relatively quickly leads to the development of acute renal failure (requiring intensive care and hemodialysis).
7.
Lung damage It is rare in children.
8.
In the early period of the disease in adolescents, in most cases there is damage to the gastrointestinal tract(hepatitis, peritonitis and so on).
9.
Damage to the central nervous system in children it is characterized by capriciousness, irritability, and in severe cases, seizures 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, timely treatment is the key to success in transitioning the active process into a period of stable remission.
Diagnostic principles systemic lupus erythematosus are the same as in adults, based mainly on immunological research(detection of autoimmune antibodies).
IN general analysis blood in all cases and from the very beginning of the disease, a decrease in the number of all formed elements of blood (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 child to the hospital (rheumatology department, with development severe complications– in the intensive care unit or intensive care unit).
In a hospital setting, a complete examination of the patient is carried out and the necessary therapy is selected. Depending on the presence of complications, symptomatic and intensive therapy is carried out. Given the presence of bleeding disorders in such patients, Heparin injections are often prescribed.
If started on time and regular treatment can be achieved stable remission, while children grow and develop according to their 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 treatment features?
As already mentioned, systemic lupus erythematosus most often affects young women, and for any woman the issue of motherhood is very important. But SLE and pregnancy are always a big risk for both the mother and the unborn baby. Risks of pregnancy 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. It is strictly forbidden to become pregnant while taking cytostatics (Methotrexate, Cyclophosphamide and others).
,
since these drugs will affect germ cells and embryonic cells; pregnancy is possible only no earlier than six months after discontinuation of these drugs.
3. Half
cases of pregnancy with SLE ends in birth healthy, full-term baby
. In 25%
cases such babies are born premature
, A in a quarter of cases
observed miscarriage
.
4. Possible complications of pregnancy with systemic lupus erythematosus,
in most cases associated with damage to the blood vessels of the placenta:
- fetal death;
- . Thus, in a third of cases, a worsening of the disease develops. The risk of such deterioration is greatest in the first weeks of the first or third trimester of pregnancy. And in other cases, there is a temporary retreat of the disease, but most of it is to be expected severe exacerbation 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 systemic lupus erythematosus. Pregnancy can also provoke the transition of discoid (cutaneous) lupus erythematosus to SLE.
7. A mother with systemic lupus erythematosus can pass the genes on to her baby , predisposing him to develop a systemic autoimmune disease during his life.
8. The child may develop neonatal lupus erythematosus associated with the circulation of maternal autoimmune antibodies in the baby’s blood; this condition is temporary and reversible.- It is necessary to plan a pregnancy under the supervision of qualified doctors , namely a rheumatologist and gynecologist.
- It is advisable to plan a pregnancy during a period of stable remission chronic course SCV.
- At acute course systemic lupus erythematosus with the development of complications, pregnancy can have a detrimental effect not only on the health, but also lead to the death of the woman.
- And if, nevertheless, pregnancy occurs in period of exacerbation, then the question of its possible preservation is decided by doctors, together with the patient. After all, exacerbation of SLE requires long-term use drugs, some of which are absolutely contraindicated during pregnancy.
- It is recommended to become pregnant no earlier than 6 months after discontinuation of cytotoxic drugs (Methotrexate and others).
- For lupus damage to the kidneys and heart There is no talk of pregnancy; this can lead to the death of a woman from kidney and/or heart failure, because these organs are under enormous stress when carrying a baby.
1. Necessary throughout pregnancy be observed by a rheumatologist and obstetrician-gynecologist , the approach to each patient is individual.
2. It is necessary to adhere to the following regime: don’t overwork, don’t be nervous, eat normally.
3. Be attentive to any changes in your health.
4. Delivery outside the maternity hospital is unacceptable , since there is a risk of developing severe complications during and after childbirth.
7. Even at the very beginning of pregnancy, the rheumatologist prescribes or adjusts 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 prescribe cytostatics and other drugs for the treatment of SLE - pulse therapy, since the postpartum period is dangerous for the development of severe exacerbations of the disease.Previously, all women with systemic lupus erythematosus were not recommended to become pregnant, and if they conceived, everyone was recommended to have an induced termination of pregnancy (medical abortion). Now doctors have changed their opinion on this matter; a woman cannot be deprived of motherhood, especially since there is a considerable chance of giving birth to a normal, healthy baby. But everything must be done to minimize the risk for mother and baby.
Is lupus erythematosus contagious?
Of course, any person who sees strange rashes on their face thinks: “Could it be contagious?” Moreover, people with these rashes walk for so long, feel unwell and constantly take some kind of medication. Moreover, doctors previously assumed that systemic lupus erythematosus was transmitted sexually, by contact, or even by airborne droplets. But having studied the mechanism of the disease in more detail, scientists have 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: the main cause is the presence of certain genes. But still, not all carriers of these genes suffer from systemic autoimmune diseases.
The trigger 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 irradiation).
Only tuberculous lupus can be contagious (facial skin tuberculosis), since a large number of tuberculosis bacilli are detected on the skin, and 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, microelements and biological active substances.The main characteristic of a diet for SLE is a balanced and proper diet.
1. foods containing unsaturated fatty acids (Omega-3):
- sea fish;
- many nuts and seeds;
- vegetable oil in small quantities;
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. Products 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);
- high fat dairy products and so on.
Photo: alfalfa grass.
3. Garlic – powerfully stimulates the immune system.
4. Salty, spicy, smoked dishes that retain fluid in the body.If diseases of the gastrointestinal tract occur against the background of SLE or taking medications, then the patient is recommended to eat frequent meals according to the therapeutic diet - table No. 1. All anti-inflammatory drugs are best taken with or immediately after meals.
Treatment of systemic lupus erythematosus at home is possible only after selecting an individual treatment regimen in a hospital setting and correcting conditions that threaten the patient’s life. 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 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 may simply waste valuable time. Folk remedies can be effective 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. You have to be careful with such drugs; any poison is a medicine as long as it is used in small doses.Photos of what the symptoms of lupus erythematosus look like?
Photo: Butterfly-shaped changes on the facial skin in SLE.
Photo: skin lesions on 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 striations of the nail plate.
Lupus lesions of the oral mucosa . By clinical picture very similar to infectious stomatitis, which does not heal for a long time.
And this is what they might look like first 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, resembles measles rashes, and leaves pigment spots that do not go away for a long time.
