Does not always bring the expected result. First of all, because it is rarely possible to recognize the causes of this autoimmune disease that affects blood vessels and connective tissues. Specialists from various medical fields are studying this problem. It is almost impossible to establish a diagnosis without high-quality diagnostics, since doctors are usually confused by secondary diseases that develop against the background of systemic lupus erythematosus. This article is devoted to the symptoms and treatment of this ailment.

Causes of the disease

Judging by most of the photos, women are more likely to need treatment for lupus erythematosus. This fact is also indicated by medical statistics: men suffer from this disease much less often, it is extremely rare that the disease is diagnosed among young guys.

Some researchers argue that hereditary predisposition is the main cause of lupus erythematosus. Treatment of a disease provoked by mutated genes, in their opinion, will not bring a stable result. Disorders that have arisen at the genetic level negatively affect the immune system, forcing it to act not in defense, but against the body.

Other experts believe that the main factor in this pathology is infection with a viral infection. The arguments of this version are numerous laboratory experiments and tests of scientists carried out in last years... It is believed that a virus that has entered the body stimulates the production of "wrong" antibodies: instead of destroying the pathogenic microbiota, they begin to actively fight their own tissues. The need for treatment of lupus erythematosus is difficult to overestimate. Without appropriate therapy, the disease can lead to the appearance of dangerous diseases of the nervous, respiratory, cardiovascular systems, and hematopoietic organs.

There is another form of lupus erythematosus - discoid. The treatment of this pathology differs from the therapy that is resorted to in case of diagnosis. systemic lupus... The discoid form is currently recognized as an infectious-allergic autoimmune disease, despite the fact that the pathogenesis of the disease is not fully understood. An excessive amount of gamma globulins is determined in the blood of patients with this disease. At the same time, in the conclusions of specialists on laboratory studies of the bone marrow, it is often mentioned about the presence of specific pathological cells. Such patients need urgent treatment - discoid lupus erythematosus inhibits the functions of the adrenal cortex, causes disturbances in the reproductive, endocrine systems, metabolic processes.

How it manifests itself externally

Diseases develop according to the same scenario for all patients, regardless of its true cause. The symptoms of systemic lupus erythematosus and the treatment of this disease largely depend on the individual characteristics of the patient's body, his age, the presence of additional chronic diseases and other factors.

The severity of signs of pathology affects not only the well-being, but also the patient's lifestyle. The patient's condition deteriorates rapidly without proper treatment. Symptoms of systemic lupus erythematosus that occur early in the development of the disease:

• Inflammation of small joints. Outwardly, the disease resembles arthritis, which is characterized by swelling, strong pain in the arms and legs, the hands are deformed, swollen and reddened. Large joints (hip, knee) are much less likely to be involved in the pathological process.
• Severe osteoporosis. Calcium entering the body is practically not absorbed. Experts learn about the deficiency of its content in the bone tissue from an X-ray.
• A rash on the epidermis is another symptom of lupus erythematosus in adults. Treatment of the rash is usually not required. Changes in the skin become visually noticeable after the patient's exposure to the sun. As the disease progresses, small foci grow, merging into a single large spot, covered with scales of peeling skin. The epidermis becomes thinner, small scars form on it, which are later quite difficult to eliminate.

In addition to damage to joints, cartilage and bones, patients often complain of a subfebrile increase in body temperature, fatigue, which does not go away even after rest, general weakness, rapid weight loss. With lupus erythematosus on the cheeks, nose, scalp, erythema may appear.

In addition to external symptoms, which give the patient psychological rather than physical discomfort, it is worth noting others. Clinical signs of this autoimmune disease. These include manifestations of myocarditis, pericarditis, pleurisy - inflammatory processes occurring in the heart and lungs. Against the background of these violations, arrhythmia occurs, chronic heart failure develops. Often, pathologies are accompanied by disorders of the central nervous system and the gastrointestinal tract.

Diagnostic methods

The treatment of systemic lupus erythematosus must be preceded by a comprehensive examination. The "standard" triad of manifestations in a patient will be quite enough for the doctor to suspect an ailment. This is about:

• rashes on the skin;
• inflammatory processes in the heart, lungs;
• osteoporosis and joint damage.

Without laboratory and instrumental studies, it is impossible to confirm the diagnosis and begin treatment. Early diagnosis of lupus erythematosus includes:

• Clinical blood test. The acute stage of the disease is characterized by an increase in the erythrocyte sedimentation rate (ESR), a decrease in leukocyte and lymphocyte counts. A patient with lupus erythematosus is sometimes found hemolytic or hypochromic anemia, which is caused by chronic inflammation, intoxication, internal bleeding.
• General analysis urine. In patients with lupus, protein, blood, leukocytes in varying degrees of severity are detected in the urine, indicating a change in the functioning of the kidneys.
• Blood chemistry. Such a study is usually carried out to objectively assess the degree of functionality. internal organs and systems.

In addition to laboratory methods, instrumental diagnostic methods are no less important:

• X-ray and CT of organs chest;
• EchoCG to detect pulmonary hypertension;
• electrocardiogram, Holter ECG monitoring;
• Ultrasound of the abdominal organs, esophagogastroduodenoscopy;
• electroencephalography, CT, MRI of the brain.

Basic principles of therapy

Just a few decades ago, the prognosis for people with lupus was not reassuring. But in recent years, doctors have made a huge breakthrough. Subject to early diagnosis, appointment and reception effective drugs patients have a good chance of leading a fulfilling life.

The treatment regimen for lupus erythematosus with medicines is compiled purely individually for each patient, depending on the course of the disease, the staging of the disease, the severity of symptoms. Therapy is carried out on an outpatient basis, but the patient may need hospitalization if:

• for a long time, there is a persistent fever, which is not knocked down by antipyretic drugs;
• he has a pre-infarction or pre-stroke condition, suspicion of pneumonia, dangerous disorders of the central nervous system;
• the patient's consciousness is depressed;
• the level of leukocytes in the blood is rapidly falling;
• other symptoms progress.

Treatment often involves the participation of highly specialized specialists (cardiologist, nephrologist, pulmonologist, rheumatologist). The main goal of therapy for this disease is not only to eliminate symptoms, but also to maintain the full vitality of the body. On this moment the life expectancy of patients with this autoimmune disease is much longer than what could have been achieved, for example, 20 or 30 years ago. Success depends to a large extent on the adequacy of therapy and the patient's responsible approach to the implementation of all medical prescriptions.

Hormone therapy

Since the pathology is based on a pathological autoimmune reaction of the body, it is possible to achieve more or less stable results and improve the patient's condition only by suppressing it. Treatment of lupus erythematosus in adults involves the use of drugs from several groups. One of them is hormone-containing drugs.

It is believed that glucocorticosteroids have helped make a huge leap forward in the treatment of lupus erythematosus. Hormonal drugs are excellent at fighting inflammation and suppressing the immune system. If you believe the statistics, then long before the introduction of corticoids into the therapeutic regimen, patients did not even overcome the five-year survival threshold after the diagnosis was made.

Hormones can help with sudden exacerbations of the disease that negatively affect the functionality of the kidneys. However, corticosteroids have a host of side effects, including bad mood, weight loss, and endocrine disruption. In addition, hormone-containing drugs with prolonged use are addictive, they also increase the risk of bone damage and the development of osteoporosis, arterial hypertension, diabetes mellitus. Steroids used to treat lupus erythematosus are taken by mouth.

The main indicator of the effectiveness of hormone therapy is the duration of remission when maintained with small doses of drugs, a decrease in the activity of the pathological process, and a stable satisfactory state of health. The most common corticosteroid drug prescribed for systemic and discoid lupus erythematosus is Prednisolone. At the stage of exacerbation, it is prescribed in a daily dosage of no more than 50 mg per kilogram of body weight of an adult patient. During the period of remission, the dose is reduced to 15 mg.

For some reason, hormone treatment is ineffective. In particular, the effect of drugs is neutralized if the tablets are taken irregularly. Steroids will not be beneficial even if the dose was incorrectly selected or treatment was started too late.

Side effects from hormones

Since lupus is predominantly female, many of them worry about the likely side effects of these steroid medications. More often, patients are worried about the risk of possible weight gain. It is important to understand here that without hormone treatment, the prognosis will not inspire optimism. In addition, very often fears and speculations about taking hormones are exaggerated. Many people are forced to take steroids for more than one decade in a row, while side effects not everyone develops.

In addition to weight gain, the more likely complications after taking steroids can be considered:

• peptic ulcer of the gastrointestinal tract;
• increased risk infection;
• the development of arterial hypertension;
• increased blood sugar levels.

Cytostatics

According to reviews, the treatment of lupus erythematosus is not complete without the use of drugs of this pharmacological group, but they are prescribed in combination with hormones in the event that the use of corticosteroids alone is not enough for a positive dynamics of recovery. Cytostatics, like corticoids, have immunosuppressive properties. The doctor makes a decision on the use of these funds in case of lupus with a progressive course, as well as in the case of diagnosing nephritic or nephrotic syndromes, indicating the involvement of the kidneys in the pathological process.

Cytostatics can serve as an alternative method of treatment when the effectiveness of isolated hormone therapy is low or the need to reduce the dose of steroids caused by their poor tolerance or the sudden development of side effects. Often, patients with lupus are prescribed "Azathioprine", "Cyclophosphamide", "Imuran".

Non-steroidal anti-inflammatory drugs

Such drugs are prescribed to patients with severe inflammation, swelling, and joint pain. Diclofenac, Indomethacin, Aspirin, Paracetamol, Ibuprofen helps to minimize the severity of these symptoms. Taking drugs from the NSAID group can take longer than hormones. In addition, they have fewer contraindications and side effects. The course of treatment with these drugs continues until the articular syndrome disappears and the body temperature stabilizes.

The choice of a drug or a combination of drugs depends on each individual case. For some patients, non-steroidal anti-inflammatory drugs alone are sufficient to control the course of the disease and suppress symptoms.

Traditional therapy

With the help of unconventional methods of treating lupus erythematosus, you can achieve good results. Quite often, in addition to drug therapy, experts advise herbal teas and homemade recipes. Alternative treatment of lupus erythematosus is a good alternative to the conservative one in the presence of contraindications, but, despite this, it is impossible to self-medicate and mindlessly take all the means in a row. Before resorting to non-traditional methods of therapy, it is necessary to consult with your doctor.

Some medicinal herbs have immunomodulatory and anti-inflammatory properties, other plants have a diuretic and wound healing effect, stimulate the production of hormones in the body, and reduce high blood pressure. With a competent combination of components, it is possible to reduce the severity of symptoms and enrich the body with vitamins and essential trace elements. Several recipes for effective folk remedies for the treatment of lupus erythematosus are especially popular.

Herbal infusion

To prepare this tool you will need:

• motherwort (2 tbsp. l.);
• St. John's wort (2 tbsp. l.);
• celandine (1 tbsp. l.);
• rosehip (3 tbsp. l.);
• white willow bark (1 tbsp. l.);
• birch buds (2 tbsp. l.);
• burdock root (1 tbsp. l.).

The mixture must be thoroughly grinded by passing it through a meat grinder or coffee grinder, mix and send to a dark, dry place. Before each meal, it is necessary to prepare a fresh infusion, which will require 10 g of this herbal collection. Raw materials are poured into 500 ml of boiling water and, covered with a lid, left for 5-7 hours. After the time has elapsed, you need to strain the drink and add a teaspoon of alcohol tincture of Sophora to enhance the therapeutic effect. Take 250 ml of infusion on an empty stomach and before dinner. The course of treatment is 2 weeks. You need to drink the drink regularly for six days, then take a one-day break and continue treatment.

St. John's wort oil

Lupus erythematosus treatment folk remedies involves not only oral intake of decoctions and infusions. For the treatment of skin rashes on the face, use It can be prepared at home. You will need a couple of tablespoons of the plant's flowers and a glass of olive or sunflower oil. To infuse the product, it is necessary to remove it in a remote cool place for 2-3 weeks, but shake the contents every day. When the oil of St. John's wort is ready, it is applied to the affected areas of the skin in the morning and before bed. In a similar way, you can prepare sea buckthorn oil - it also copes well with problem areas on the epidermis.

Other folk recipes

• For joint pain caused by systemic lupus erythematosus, chestnut tincture can be used. Such a remedy is sold in a pharmacy and is inexpensive. To relieve puffiness and pain, you need to rub the tincture into the joint every day, after which it is imperative to bandage or wrap it with a warm cloth. The course of treatment is 1-2 weeks.
• Another option for a folk remedy that helps with joint damage. To prepare it, you will need dried cherries (100 g of fruits), parsley root (20 g), black elderberry flowers (2 tbsp. L.). All ingredients are mixed and brewed with a liter of hot boiled water, then put on low heat and brought to a boil. Once the broth has cooled, it must be well filtered. You need to take the remedy half an hour before a meal in a glass.
• Patients with impaired kidney function can use the following herbal collection: 100 g of currant leaves, the same corn silk and rose hips. A decoction is prepared in the same way as the previous remedy.

How to live with this diagnosis

However, in order to successfully overcome exacerbations of the disease, it is important to follow the primitive, but at the same time very important recommendations of specialists:

• Avoid stressful situations, psycho-emotional stress, anxiety and anxiety.
• Eat a balanced diet.
• Limit exposure to the sun, refuse to visit the solarium.
• Exercise but avoid excessive physical activity.
• Do not start chronic diseases, cure colds to the end.
• Do not use hormonal contraception.
• Lead a healthy lifestyle in which there is no place for alcohol and smoking.
• Give preference to natural cosmetics.

In general, it is impossible to predict a complete recovery from lupus erythematosus. The percentage of deaths among patients with this disease is still high. But in most cases, the cause of death is not lupus itself, but complications caused by infection or deep damage to internal organs. In the case of timely detection of the disease and drawing up a competent treatment plan, lupus can be kept under control, not allowing it to destroy health and life.

Treatment for systemic lupus erythematosus includes educating patients, protecting against ultraviolet radiation, maintaining physical fitness, getting adequate immunizations, and identifying and managing risk factors for other diseases. Standard treatment for extra-organ manifestations of systemic SLE includes NSAIDs, glucocorticoids, and antimalarial drugs.

Patient education with an explanation of the nature of the disease and the therapy being performed is an essential component in the treatment of any chronic disease. Many patients independently study information about the disease, mainly gleaned from the Internet. The task of the staff is to reassure a patient who has learned about severe cases of lupus from the Internet resources, from friends and family members.

Fatigue in patients with systemic lupus erythematosus occurs very often. Its cause is probably multifactorial and includes concomitant diseases (hypothyroidism, depression,) and deterioration in physical condition due to chronic illness. Thus, treatment depends on the cause of the fatigue. In patients with photosensitivity, fatigue and exacerbation of the disease after exposure to ultraviolet radiation are also possible. Photoprotection eliminates exposure to the sun at noon, requires regular use of sunscreen and wearing protective clothing. Special protective and luminescent screens on the windows reduce exposure to UV radiation and reduce the risk of exacerbations of SLE in the presence of photosensitivity. Patients should also be wary of drug photosensitivity, often associated with antibiotic use. A sedentary lifestyle is the second distinguishing feature of SLE patients. This problem can lead to obesity, deterioration of the physical status and the quality of the heart. It was found that with SLE, the ability to engage in therapeutic exercises decreases. Dosed with hydrotherapy and walking should be part of the non-drug treatment.

The high frequency of infections in SLE is due to dysregulation of the immune system and prolonged immunosuppression. Patients should be advised to see a doctor in case of unexplained fever (any increase in body temperature cannot be explained by an exacerbation of lupus). Rational use of glucocorticoids and immunosuppressive drugs, immunization against influenza and pneumococcal infections can reduce the risk of infections.

Women are at high risk of dysplasia and (due in part to infection with the human papillomavirus). A recent international study found that people with lupus increase the risk of malignant neoplasms, especially non-Hodgkin's lymphoma. Whether the indicated increase in risk is a consequence of the disease itself or its treatment is unknown. A regular, age-appropriate medical examination is recommended, including examination and.

Modern methods of treatment

The choice of treatment for systemic lupus erythematosus depends on the results of examination of the affected organs and the severity of the disease. Almost all drugs have side effects.

Non-steroidal anti-inflammatory drugs

NSAIDs are effective for pain, therefore they are widely used for various symptoms: arthritis, myalgia, serositis, etc. The choice of NSAIDs is determined by cost, effectiveness, and side effects. The effectiveness of these drugs in different patients is not the same, it can also vary in the same patient. Patients with renal impairment on the background of lupus nephritis are not prescribed both selective and non-selective NSAIDs, since their inhibition of cyclooxygenase (COX) disrupts renal blood flow and maintenance of tubular transport by reducing the amount of prostaglandins and prostacyclins. The side effects on the kidneys, liver and central nervous system of non-selective COX inhibitors and selective COX-2 are approximately the same. It can be mistaken for active lupus. A common side effect of NSAIDs is a slight reversible increase in liver enzymes, in addition, aseptic meningitis, headache, cognitive impairment and even psychosis occur. Selective COX-2 inhibitors have a less pronounced effect on gastrointestinal tract, less often cause peptic ulcers and bleeding. However, due to the risk of cardiovascular complications in connection with the use of COX-2 inhibitors, drugs in this group should not be prescribed to patients suffering from ischemic disease hearts. Only one COX-2 inhibitor (celecoxib) is currently on the market.

Glucocorticoids

Glucocorticoids are effective in treating lupus and various inflammatory rheumatic diseases. They allow you to quickly stop some manifestations of SLE. Topical glucocorticoids are often used in dermatological practice. Systemic administration of glucocorticoids at a dose of 5-30 mg (in terms of prednisone) once or during the day is effective in the treatment of mild to moderate lupus erythematosus (with skin lesions, arthritis and serositis). More severe organ damage (nephritis, pneumonitis, hematological disorders, involvement of the central nervous system and systemic vasculitis) requires the introduction of oral or intravenous high doses of glucocorticoids (in terms of prednisone - 1-2 mg / kg per day). If these severe lesions are life threatening, intravenous pulse therapy with methylprednisolone is performed - 1 g per day for 3 days.

Systemic glucocorticoids act as a preparatory therapy for slow-acting immunosuppressive drugs. With the appearance of the effect of these drugs, the dose of glucocorticoids is gradually reduced. As symptoms control is achieved, glucocorticoids are discontinued completely or prescribed at a minimum dose (prednisone 5 mg / day or less) every day or every other day as maintenance therapy. The goal of a gradual decrease in the dose of glucocorticoids is to reduce the number of possible side effects of long-term glucocorticoid therapy in the absence of exacerbations or relapses of the disease. Common side effects of systemic glucocorticoid therapy include emotional lability, cataracts, glaucoma, peptic ulcers, osteoporosis, osteonecrosis, high risk of infections, and cushingoid symptoms (central obesity, striae, hypertension, diabetes, and dyslipidemia).

Topical treatment of systemic lupus erythematosus

When hormonal drugs are used for topical treatment of lupus, their dosage can be adjusted and then completely withdrawn or used as needed while slowly acting immunomodulators or immunosuppressants are prescribed. Clobetasol (highly effective) in solution or foam is used to treat alopecia caused by a lupus-specific rash. Due to the high risk of skin atrophy and telangiectasias in the facial area, as well as in the area of ​​diaper rash, topical application of highly active or fluorinated glucocorticoids should be avoided. In addition, glucocorticoids do not need to be applied topically continuously as they induce tachyphylaxis. Typically, patients apply topical glucocorticoids on weekdays and not on weekends, while other drugs that reduce the dose of glucocorticoids (for example, tacrolimus or pimecrolimus) are prescribed on days when the patient is not using steroids. With hypertrophic lupus changes, triamcinolone can be administered directly to the altered areas. Tacrolimus and pimecrolimus ointments are FDA approved for topical use in atopic dermatitis. The drugs inhibit T cell proliferation and cytokine release. Unlike steroids, they have no effect on keratinocytes, endothelial cells and fibroblasts, and therefore do not cause skin atrophy. When applied topically, retinoids, including tretinoin and tazarotene, have anti-inflammatory effects and are successfully used in the treatment of chronic cutaneous lupus erythematosus. Localized skin irritation is a common side effect.

Antimalarial drugs

Antimalarial drugs are often the mainstay of treatment for systemic lupus erythematosus. Hydroxychloroquine (HCQ) is the most commonly prescribed drug in the United States, followed by chloroquine and quinacrine. Antimalarial drugs are often used as first-line treatment for mild lupus, including constitutional symptoms, cutaneous and musculoskeletal changes. GHX is prescribed at 200 mg / day, then gradually increased to 200 mg twice a day or 400 mg / day. The response to GC is slow, with improvement occurring after about 6 months. The maximum effectiveness is sometimes noted after 4 months of treatment for systemic lupus erythematosus. GCh showed clinical efficacy in a randomized study: with discontinuation of the drug, relapses of mild degree developed 2.5 times more often than with continued use. Long-term follow-up of study participants revealed a tendency towards a decrease in the number of relapses with continuous administration of GC. Moreover, HCX promotes the achievement of remission with lupus erythematosus within a year in patients receiving mycophenolate mofetil (MMF) for glomerulonephritis. Two studies found that smoking affects the effectiveness of antimalarial drugs for discoid lupus and subacute cutaneous lupus. The effect was poorer in smokers than in nonsmokers, with the worst antimalarial prescriptions among those who smoked the most.

Chloroquine is prescribed at 3.5 mg / kg per day, the effect develops after 4 weeks (faster than with the appointment of GCS). The mechanism of action of quinacrine is similar to that of chloroquine. The dose of quinacrine is 2.5 mg / kg per day. Combination therapy with HCX (or chloroquine) and quinacrine usually gives a good result if monotherapy with these drugs is ineffective.

Side effects are often reported. They are usually transient, decrease with decreasing the dose of antimalarial drugs, as well as with the appointment of branded drugs, rather than generic ones. The most common complaints include abdominal pain, less commonly nausea, vomiting, bloating, and diarrhea. Chloroquine is less likely to cause disturbances, while HCX and quinacrine more often. Chloroquine is more likely than GC to act on the retina, causing visual field defects. Therefore, HCX and chloroquine must be administered concomitantly with caution, as the risk of retinopathy increases when combined. Other visual symptoms include impaired distance vision, difficulty reading, photophobia, and glare in front of the eyes. Long-term follow-up revealed a low incidence of HCX-associated retinopathy (0.5%) in 400 patients who received the recommended doses for more than 6 years. Antimalarial drugs can cause hyperpigmentation of nails, skin on the front of the legs, face, and (rarely) mucous membranes, mainly in areas exposed to sunlight. A change in skin color from blue-gray to dark purple occurs with the appointment of GC, a yellow color - when taking quinacrine. Hair hypopigmentation or freckles are observed with chloroquine treatment. These violations disappear after discontinuation of the drug. With the appointment of HCC and chloroquine, severe cardiotoxicity with myocardial dysfunction is sometimes revealed (confirmed by biopsy in less than 50% of cases. The risk of cardiotoxicity is higher in older women receiving antimalarial therapy for a long time. Cases of drug myopathy while taking HCC with the appearance of bent corpuscles in skeletal muscles have also been reported. ...

HCX has a hypoglycemic effect, which helps to control blood glucose concentration in patients with poorly controlled blood glucose levels in type 2 diabetes. In addition, HCX reduces the need for insulin in type 2 diabetes, if the patient is receiving insulin preparations, which increases the risk of hypoglycemia. Therefore, the patient should be aware of the hypoglycemic effects of HCH. Antimalarial drugs can also cause hemolytic activity in patients with G6PDH deficiency, which is more common in the Mediterranean region, the Middle East, Africa and India. Therefore, the physician should consider the origin of the patient when treating systemic lupus erythematosus. HCX is safe during pregnancy. The safety of HCX, chloroquine and quinacrine during lactation has not been proven.

Dapsone

Dapsone is sulfonic. Used to treat leprosy and prevent Pneumocystis jirpvecci pneumonia (formerly known as Pneumocystis carinii pneumonia). Dapsone additionally has an immunomodulatory effect, especially against neutrophils. It is used for various bullous diseases, erythema nodosum, Sweet's syndrome, cutaneous vasculitis and cutaneous lupus. Dapsone (100 mg / day), alone or in combination with glucocorticoids or antimalarial agents, is the drug of choice for bullous SLE and skin lesions involving small dermal vessels such as leukocytoclastic vasculitis.

The most severe and rare side effect is hypersensitivity syndrome, characterized by fever, rash, lymphadenopathy, hepatitis, and hepatosplenomegaly. Another severe side effect is bone marrow suppression, an idiosyncratic response to dapsone that is exacerbated by concomitant administration with antagonists folic acid... Taking dapsone, as well as antimalarial drugs, with G6PDH deficiency is accompanied by a high risk of hemolytic anemia. Dapsone is not teratogenic, but it may increase the risk of methemoglobinemia and cyanosis in neonates as well as in adults. In order to minimize the risk of bilirubin encephalopathy in a newborn, it is recommended to cancel the drug one month before the expected date of birth. Breastfeeding while taking dapsone is not recommended.

Azathioprine

Azathioprine (2 mg / kg per day) is often prescribed as a treatment for systemic lupus erythematosus, which allows for lower glucocorticoid doses in patients with mild to moderate disease activity, as an alternative maintenance treatment for systemic lupus erythematosus in patients with lupus nephritis and severe lesions other organs. This drug is a purine analogue, a mercaptopurine immunosuppressant that inhibits the synthesis of nucleic acids and, therefore, impairing cellular and humoral immunity. Azathioprine can be used in pregnant women with insufficient immunomodulatory effects of antimalarial drugs. Azathioprine passes into milk, breastfeeding is contraindicated.

The main side effect of azathioprine is acute myelotoxicity, manifested by pancytopenia in patients with a deficiency of the enzyme thiopurine methyltransferase, which inactivates azathioprine. Another side effect is a toxic effect on the gastrointestinal tract, similar to the action of antimalarial drugs.

Methotrexate

There is evidence of the effectiveness of methotrexate in the treatment of systemic lupus erythematosus. However, only a few randomized trials have been conducted on the treatment of SLE with methotrexate, the results of which have been conflicting. In some cases, as well as in some prospective studies, a good effect was obtained (allowing a gradual decrease in the dose of glucocorticoids) when prescribing methotrexate for the treatment of cutaneous or articular manifestations of lupus.

Methotrexate is an analogue of dihydrofolic acid that inhibits dehydrofolate reductase. In low doses, the drug has an immunomodulatory effect without the cytotoxic and antiproliferative effects observed with the administration of high doses (with chemotherapy). Side effects are common: gastrointestinal disorders, stomatitis, alopecia, increased liver enzymes, infections (especially at high doses). These effects can be reduced if the drug is prescribed at a dose of 7.5-15 mg / week. The addition of folic acid (daily) or folinic acid (weekly) reduces the incidence of oral ulcers and alopecia. Injection of methotrexate improves bioavailability and reduces gastrointestinal complaints (nausea, vomiting, diarrhea and abdominal pain). Elevations in hepatic enzymes are significant if persistent, but are not a reliable predictor of the severity of hepatotoxicity on a study. Patients taking methotrexate are not advised to consume alcohol, as this combination further increases the risk of hepatotoxicity. A rare, potentially life-threatening complication is methotrexate-induced pneumonitis. Such a side effect is early or late. If pneumonia or methotrexate-induced pneumonitis is suspected, the drug is discontinued. Methotrexate is teratogenic. therefore, six months before the planned pregnancy, it is canceled for both women and men.

Cyclosporine

Cyclosporine inhibits the proliferation of T lymphocytes and selectively inhibits T cell responses at the transcriptional level in naive T cells. SLE is considered a B-cell mediated autoimmune disease, but there is evidence that T cells play a primary role in development. Patients tolerate cyclosporine well at 2.5-5 mg / kg per day, the dose of glucocorticoids can be reduced: the activity of the disease decreases, becomes less, the content of leukocytes, platelets and complement increases. Limited data on the course of pregnancy (mainly in women who underwent transplantation) showed that the incidence of adverse outcomes while taking cyclosporine did not increase. The drug is non-teratogenic in experiments on animals. Cyclosporine is prescribed for pregnant women with SLE when the benefits outweigh the risks. Mothers taking cyclosporine are not advised to breastfeed because the drug passes into milk.

Most of the side effects are dose-dependent and reversible. These include hypertension, increased creatinine levels, tremors, hypertrichosis, gingival hypertrophy, paresthesias, gastrointestinal disturbances, and infections. Cyclosporine can also cause hyperkalemia, dyslipidemia, and exacerbate hyperuricemia, causing flare-ups of gout. Although cyclosporine is effective in the treatment of refractory nephrotic syndrome and membranous glomerulonephritis (World Health Organization class V), long-term treatment can cause structural changes in the kidneys.

Cyclophosphamide

Cyclophosphamide is an alkylating and cytotoxic agent that cross-binds to DNA and DNA-linked proteins. Used to treat systemic lupus erythematosus in severe cases, including lupus nephritis, central nervous system lesions, pulmonary hemorrhage and systemic vasculitis. There is a "gold standard" for the treatment of patients with diffuse proliferative glomerulonephritis. The standard regimen for prescribing cyclophosphamide for diffuse glomeruloniphritis is pulse therapy for 6 months with cyclophosphamide alone or simultaneously with pulse therapy with methylprednisolone at the beginning of treatment. Then pulse therapy with cyclophosphamide is performed every 3 months for 2 years. Intravenous cyclophosphamide has advantages over oral administration because the bladder can be protected with intravenous mesna (mercaptoethanesulfonic acid) along with active fluid intake to prevent hemorrhagic cystitis and cancer Bladder under the influence of acrolein (a toxic metabolite of cyclophosphamide). Studies to reduce the duration and / or reduce the dose of this drug have had varying results. The toxicity of long-term therapy with cyclophosphamide determines active attempts to reduce the course of treatment for systemic lupus erythematosus and switch to intermittent treatment regimens.

Side effects of cyclophosphamide include nausea and vomiting, alopecia, bone marrow suppression, high risk of infections, and bladder cancer. Cyclophosphamide increases the risk of cervical cancer. Nausea and vomiting are prevented by antiemetic drugs such as ondansterone and dilasterone given as needed. Dose-dependent maximum leukopenia occurs 8-12 days after the administration of cyclophosphamide. The most dangerous side effect is that caused by the gonadotoxicity of cyclophosphamide. The main risk factors for ovarian failure include initiation of treatment in old age and high cumulative doses of the drug. The appointment of cyclophosphamide during pregnancy and lactation is prohibited.

Mycophenolate mofetil (MMF)

MMF is an inactive prodrug of mycophenolic acid, which inhibits inosine monophosphate dehydrogenase, T and B cell functions. Many studies have shown the effectiveness of MMF in the treatment of lupus nephritis. MMF is as effective as cyclophisfamide in inducing short-term remission of lupus nephritis and is safer. There are high hopes for MMF in the treatment of lupus nephritis, especially in young women of reproductive age. There are limited data on the safety of using MMF during pregnancy.

MMF is generally well tolerated at a dosage of 500-1500 mg twice daily. Side effects include nausea, vomiting and diarrhea, cytopenia, and an increased risk of infections. Gastrointestinal reactions can be reduced by gradually increasing the dose of MMF or by prescribing it in capsules of 250 mg.

Leflunomide

Leflunomide reduces the proliferation of T and B cells. Several small studies have shown that leflunomide is well tolerated in SLE patients. Due to its relatively low nephrotoxicity and preferential metabolism in the liver and gastrointestinal tract, leflunomide is more preferable than cyclosporine or methotrexate for impaired renal function.

The most common side effect is diarrhea, which usually disappears with dose reduction. Other side effects include elevated liver enzymes, hypertension, and transient leukopenia. Cases of subacute cutaneous lupus erythematosus caused by leflunomide have been described. The drug is teratogenic. Breastfeeding while taking the drug is not recommended. Before planning pregnancy, it is necessary to check the plasma concentration of the active metabolite (A77 1726), which should be less than 0.2 mg / l in two measurements taken at intervals of 2 weeks or more. In case of pregnancy or toxicity, the drug can be withdrawn with cholestyramine. Therefore, the use of leflunomide should not be recommended for young women of reproductive age.

Hormonal treatment for systemic lupus erythematosus

Dehydroepiandrosterone is an adrenal steroid hormone with a slight androgenic effect, effective in the treatment of mild to moderate systemic lupus erythematosus. Prasterone (dehydroepiandrosterone) maintains bone mineral density and significantly increases it in women who are regularly receiving glucocorticoids. The drug is well tolerated. The most common side effect is acne. For the treatment of systemic lupus erythematosus, another hormonal agent is used - bromocriptine, a dopamine analogue and a selective inhibitor of the secretion of the immunostimulating hormone of the anterior pituitary gland - prolactin. Treatment with bromocriptine remains experimental. Danazol is a weak androgen effective in the treatment of autoimmune cytopenias.

Thalidomide

The attitude towards the appointment of thalidomide is controversial due to its well-known teratogenic effect. The drug is highly effective at a dose of 50-400 mg / day for the treatment of refractory chronic cutaneous lupus erythematosus, but the exact mechanism of action is still unknown. The relapse rate after drug withdrawal is high (approximately 68%). A common side effect is peripheral neuropathy. Neuropathy is not dose-dependent and can be irreversible if the drug is not discontinued in time. An important complication of thalidomide therapy is deep vein thrombosis.

Immunoglobulin

The mechanism of action in the treatment of systemic lupus erythematosus includes blockade of Pc receptors, inhibition of complement, immunomodulation of T and B cell functions. The drug is effective for thrombocytopenia, arthritis, nephritis and immunological disorders. Intravenous administration of immunoglobulin provides protection against infections in patients with immunodeficiency, therefore, this treatment is preferable for acute infectious diseases in patients with SLE. Immunoglobulin is administered intravenously at a dose of 2 g / kg per day (up to 5 injections). Common side effects include fever, myalgias, arthralgias, and headache... Rarely, aseptic meningitis and thrombocytopenia develop. Before intravenous administration of the drug, a study is required quantitative composition immunoglobulins in a patient to exclude a deficiency A. Patients with hypercoagulability (for example, with antiphospholipid syndrome) immunoglobulin therapy should be carried out with caution due to the risk of thromboembolism.

Plasmapheresis

Plasma replacement (plasmapheresis) is an effective but expensive method of treating systemic lupus erythematosus, which quickly removes immune complexes from the circulation. Also, the method is associated with a high risk of infection and anaphylactic reactions. Indications for plasmapheresis in SLE: thrombotic thrombocytopenic purpura, requiring expensive treatment, severe antiphospholipid syndrome, cryoglobulinemia and hyperviscosity syndrome. Other life-threatening complications of SLE are also treated with plasmapheresis if standard treatment fails.

Immunoablation with autologous stem cell transplant

In severe cases of SLE, the mainstay of treatment is cyclophosphamide, the dose of which is limited depending on myelosuppression. Immunoablation with the appointment of cyclophosphamide and subsequent transplantation of stem cells is performed to restore the patient's bone marrow with autologous stem cells after the administration of a high myelosuppressive dose of cyclophosphamide. In addition, high doses of cyclophosphamide imply restoration of the naive immune response through the destruction of autoreactive lymphocytes.

A recent open-label study found decreased disease activity after nonmyeloablative autologous hematopoietic stem cell transplantation in refractory SLE. Immunoablation carries a high risk of infection and mortality.

Immunoablation without stem cell transplant

High-dose cyclophosphamide without stem cell transplant is another therapy. Rapid recovery of hematopoiesis is achieved with the introduction of granulocyte colony-stimulating factor (G-CSF) after such therapy, an improvement in the condition of patients with refractory SLE was noted. Against the background of such treatment for systemic lupus erythematosus, persistent complete remission was observed in some patients with moderate and high degree of activity. The studies were not randomized, so the results are preliminary, which necessitates confirmation by controlled randomized trials.

Hemodialysis and kidney transplant

Hemodialysis and kidney transplants significantly increase the survival rate of SLE patients. They tolerate hemodialysis well, but the procedure is accompanied by a high risk of infection. Long-term survival and engraftment of a kidney transplant in SLE are approximately the same as in non-SLE transplant patients. However, the risk of thrombotic complications, such as early graft thrombosis, is higher in SLE patients, especially in the presence of antiphospholipid antibodies. The outcome of a kidney transplant depends on the clinical condition of the patient at the time of the transplant. The risk of developing lupus nephritis in a transplanted kidney varies from 2 to 30%.

New treatments for systemic lupus erythematosus

In connection with the change in the view of immunosuppression as a standard treatment for SLE, “drugs of the future” were created, characterized by higher efficiency and lower toxicity, acting on specific stages of the pathogenesis of SLE, without affecting the immune defense. Many new drugs are currently being developed and are in clinical trials.

The article was prepared and edited by: surgeon

This is a multifactorial disease that develops on the basis of a genetic imperfection of the immune system and is characterized by the production of a wide range of autoantibodies to the components of the cell nucleus. The molecular genetic basis of the disease has been studied rather poorly, and therefore no specific treatment has yet been created, and the pathogenetic therapy carried out in the clinic is based on immunosuppressants - glucocorticosteroids and cytostatics. And so, after more than 50 years of trying to develop a specific treatment for lupus, there has been a shift: FDA food products and Medicines, the United States has officially approved Benlysta, a monoclonal antibody that specifically blocks B-lymphocyte-stimulating protein (BLyS), as a lupus drug.

Systemic lupus erythematosus (SLE) is one of the most common autoimmune diseases, which is based on a genetically determined complex violation of immunoregulatory mechanisms. With the disease, a wide range of autoantibodies to various components of the cell nucleus and the formation of immune complexes are formed. The immune inflammation developing in various organs and tissues leads to extensive lesions of the microcirculatory bloodstream and systemic disorganization. connective tissue , .

In the pathogenesis of SLE, an important place is given to immune mechanisms, many aspects of which, despite intensive study, remain unclear. SLE is characterized by a discouraging "variegation" of immunological phenomena, which is associated with changes in almost all known functions of immunocompetent cells (Fig. 1).

Figure 1. Pathogenesis of SLE

Lupus is largely associated with abnormalities in the proliferation of various clones of B cells, activated by numerous antigens, which can be drugs, bacterial or viral DNA, and even phospholipids of the mitochondrial membrane. The interaction of antigens with leukocytes is associated either with the absorption of antigens by antigen-presenting cells (APCs), or with the interaction of antigen with an antibody on the surface of a B-cell.

As a result of alternate activation of either T- or B-cells, the production of antibodies (including autoantibodies) increases, hypergammaglobulinemia occurs, immune complexes are formed, T-helpers differentiate excessively and uncontrollably. Various defects in immunoregulation inherent in SLE are also associated with the overproduction of Th2-type cytokines (IL-2, IL-6, IL-4, IL-10 IL-12).

One of the key points in impaired immune regulation in SLE is the hindered cleavage (clearance) of immune complexes, possibly due to their insufficient phagocytosis, associated, in particular, with a decrease in the expression of CR 1 complement receptors on phagocytes and with functional receptor defects.

The prevalence of SLE ranges from 4–250 cases per 100,000 population; the peak incidence occurs at the age of 15–25 years, with the ratio of sick women to men 18: 1. Most often, the disease develops in women of reproductive age with an increased risk of exacerbation during pregnancy, in postpartum period, as well as after sun exposure and vaccination.

SLE is a common cause of disability. In developed countries, on average 3.5 years after diagnosis, 40% of SLE patients stop working completely, mainly due to neurocognitive dysfunctions and increased fatigue. Discoid lupus and lupus nephritis most often cause disability.

The clinical manifestations of SLE are extremely diverse: damage to the skin, joints, muscles, mucous membranes, lungs, heart, nervous system, etc. In one patient, you can observe various alternating variants of the course and activity of the disease; in most patients, periods of exacerbation of the disease alternate with remission. More than half of the patients have signs of kidney damage, accompanied by a deterioration in the rheological properties of the blood.

Because the molecular and genetic mechanisms underlying the disease are still not well understood, there was no specific treatment for lupus until recently. Basic therapy is based on the use of anti-inflammatory drugs, the action of which is aimed at suppressing the immune complex inflammation, both during an exacerbation and during remission. The main drugs for the treatment of SLE are:

1. glucocorticoids(prednisolone, methylprednisolone);
2. cytotoxic drugs(cyclophosphamide, azathioprine, methotrexate, mycophenolate mycophenolate, cyclosporine).

For the treatment of SLE, a monoclonal antibody preparation that selectively acts on CD20 + B-lymphocytes, rituximab, registered by the FDA for the treatment of non-Hodgkin's lymphoma, is also used. However, the high price of this drug did not allow it to be widely used in the treatment of SLE in our country.

"I know the password, I see the landmark"

In the late 1990s, a molecular pathway was discovered at the biopharmaceutical company Human Genome Sciences (Rockville, Maryland, USA), by "narrowing" which, to some extent, the development of SLE could be contained. This pathway involves a protein called the B-lymphocyte stimulator (or BLyS), a cytokine from the tumor necrosis factor family. It was found that inhibition of BLyS allows for some restraint of the enacted immune system and a decrease in the number of colonies of B-lymphocytes, which produce autoantibodies that attack healthy tissues.

Researchers, wishing to specifically block BLyS, relied on a human monoclonal antibody, developed jointly with the British biotechnology firm Cambridge Antibody Technology, called belimumab. In early March 2011, the US Food and Drug Administration (FDA) approved a drug for the specific treatment of systemic lupus erythematosus for the first time in 56 years. The drug was Benlista, the commercial name for the Belimumab antibody, already manufactured by GlaxoSmithKline. Prior to that, the FDA had approved hydroxychloroquine, a malaria drug, for the treatment of SLE; it was in 1956.

Figure 2. A person with systemic lupus erythematosus(1902 watercolor by Mabel Green). The disease got its name back in the Middle Ages, when it seemed to people that the characteristic lupus rash on the bridge of the nose resembled wolf bites.

The road to this achievement was long because until 2009, when belimumab successfully passed the first two phases of clinical trials, no lupus drug made it to Phase III trials - a randomized multicenter trial involving a large population of patients. (About the drug development process and clinical trials see "Drag-design: how new drugs are created in the modern world." candidates ”, which turned out to be simply ineffective or hazardous to the health of patients.

"It was simply not possible to get funding for projects to develop drugs against lupus, because everyone knew that these developments were failing as one.", says Richard Fury ( Richard Furie), a New York-based rheumatologist who led the clinical trials of belimumab. - “People said openly: 'you will never succeed[in clinical trials] “» .

Targeted therapy

When researchers at Human Genome Sciences (HGS) discovered the cytokine BLyS based on the analysis of the genetic activity of white blood cells, the complete sequence of the human genome was not yet available. "It was a wonderful time", - said David Gilbert ( David Hilbert), the former head of research for this company. - “Every day we sat over lymphocytes and received sequences of more and more new genes, about which it was absolutely not clear what they were” .

During the BLyS study, HGS researchers found that the amount of this cytokine is greatly increased during inflammation, and especially in patients with lupus. This was a very important clue, although it was clear from the outset that the road would not be easy, given the number of drug clinical trials that had already failed. The situation was especially complicated by the fact that the clinical manifestations of SLE are extremely varied - from mild discomfort in some to a heavy burden for life in others - which probably prompted the authors of House Dr. to include lupus in the series in such an exaggerated context.

By the way, there is even a monument to the cytokine BLyS, and in the process of its synthesis on the ribosome: the daughter of the founder of the HGS company, who is fond of molecular sculpture, "borrowed" protein from her father for sculpting. The sculpture is installed at the American Research Institute Cold Spring Harbor.

The action of drugs that selectively "turn off" some branches of the immune system at the molecular level must be very precise. For example, in 2008, clinical trials of atacicept ( atacicept), which inhibits not only BLyS, but also another related protein. Testing in patients with severe lupus - lupus nephritis - had to be urgently stopped due to abnormal high number side infections in those taking the medicine. A similar situation was with the antibody ocrelizumab ( ocrelizumab), which blocked the work of B-lymphocytes by a different mechanism.

Next in line

Belimumab is only the first drug in the pipeline for testing by various pharmaceutical companies (such as Anthera, Eli Lilly and others). Some of the drugs being developed also act on BLyS, others inhibit the work of T-lymphocytes, "attacking" the protein under the "scientific" name B7-related protein, another drug inhibits the inflammatory mediator interferon-γ. Belimumab itself is predicted a bright future - from the point of view of the pharmaceutical giants, this means billions of sales, bringing the drug to the coveted list of "blockbusters". By the way, this does not at all mean a complete cure for the disease for millions of patients - the effectiveness of the drug is not so high (according to

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Systemic lupus erythematosus treatment

Causes of systemic lupus erythematosus

(SLE) is a systemic connective tissue disease that develops mainly in young women and girls against the background of genetically determined imperfection of immunoregulatory processes. This leads to uncontrolled production of antibodies to its own cells and their components with the development of autoimmune and immunocomplex chronic inflammation, which results in damage to the skin, musculoskeletal system and internal organs.

The trend towards an increase in the incidence of SLE in the last decade has been observed everywhere, and its prevalence in various geographic zones ranges from 4 to 250 (in Ukraine - 16.5) cases per 100 thousand of the population, mainly in women of childbearing age. At the same time, the incidence is growing due to the expansion of the age range of the onset of the disease: more and more often it shifts to 14-15 years, and also overcomes the 40-year milestone, especially in men, whose number among patients with SLE has already reached 15% (as is known from classical works, the ratio of men and women with SLE was 1:10). Mortality among patients with SLE is 3 times higher than in the general population.

The etiology of SLE remains not fully understood, despite the fact that strong evidence has been obtained for the role of RNA-containing viruses and retroviruses (measles and measles-like) in pathogenesis. Revealed significant violations of antiviral humoral immunity, as well as a kind of tubuloreticular virus-like formations in the cells of the endothelium of the capillaries of the affected tissues of the kidneys, skin, synovium, muscles, blood cells. The identification of hybridization of the measles virus genome and the DNA of the patient's cells gives reason to classify SLE in the group of integration diseases, where the virus and the cell are in a peculiar state of integration.

The viral etiology of SLE is confirmed by the frequent detection both in patients and in their environment of lymphocytotoxic antibodies, which are markers of persistent viral infection. In addition, the identification of serological signs of infection with the Epstein-Barr virus in SLE patients significantly more often than in the general population, the "molecular mimicry" of viral proteins, the ability of bacterial DNA to stimulate the synthesis of antinuclear autoantibodies are a side confirmation of the etiological (or trigger) role of infection. The similarity of immune disorders in SLE and AIDS also confirms the viral etiology of the process.

The genetic predisposition of SLE is evidenced by:

• an increased risk of developing SLE in patients with complement deficiency, as well as in those with false-positive Wassermann reactions;
• frequent development of the disease in the presence of HLA antigens - A1, B8, B35, DR2, DR3, as well as selective B-cell alloantigens;
• genetic heterogeneity leading to clinical SLE polymorphism;
• family nature of the disease, noted in 5-10% of patients with SLE;
• pronounced associative links between the carriage of HLA-Cw6, HLA-Cw7 and the chronic nature of the course of SLE, a high degree of consistency;
• high probability of rapid progression of lupus nephritis in men with the phenotype HLA-A6 and HLA-B18;
• certain features of the course of SLE in individuals of different nationalities belonging to different ethnic groups.

Hormonal factors are of great importance in the development of SLE. This is confirmed by:

• a significantly higher incidence rate in women;
• a negative effect on the course of estrogen disease, as evidenced by the prevalence of SLE in women of childbearing age, as well as a significant deterioration in the condition of patients in the premenstrual period, during pregnancy and after childbirth.

Trigger trigger factors are:

• insolation,
• hypothermia
• acute infections
• mental and physical trauma,
• pregnancy, childbirth,
• vaccination, drug intolerance (hydralazine, antibiotics, sulfonamides, vitamins, serums, oral contraceptives, etc.).

The most important factors in the pathogenesis of SLE include disturbances in the processes that ensure the development of tolerance to autoantigens, the natural consequence of which is the pathological production of a wide range of autoantibodies. Possible reasons for the development of tolerance defects can be both T- and B-dependent disorders. At the same time, among the first, one can distinguish:

• violation of intrathymic selection and destruction of autoreactive T cells;
• disturbances in the development of peripheral T-cell anergy;
• defects in the function of T-suppressors;
• hyperactivity of T-helpers, which leads to the overproduction of factors that activate B-cells.

Among the B-cell defects that lead to impaired tolerance, the following are considered the main ones:

• excessive response of B-cells to immunostimulatory signals and excessive production of such signals by B-lymphocytes;
• decreased response to tolerogenic signals and decreased production of tolerogenic signals due to their polyclonal activation.

In the pathogenesis of SLE, which occurs with damage to small-caliber arteries, the formation of autoantibodies to antigens of the cytoplasm of neutrophils (ANCA) with the subsequent development of neutrophil-modulated damage to endothelial cells is of certain importance. The term ANCA refers to autoantibodies specific to proteins found within the cytoplasmic granules of neutrophils and monocyte lysosomes. Damage to various organs in SLE has a mixed cytotoxic, immunocomplex and thrombotic genesis and depends on the action of such main pathogenetic factors:

• the formation of immune complexes of antigen with an antibody with the consumption of complement, the deposition of complexes in certain places and subsequent inflammation and tissue damage;
• autoimmune disorders associated with the formation of tissue-specific autoantibodies;
• late manifestation as a result of the deposition of immune complexes;
• complications of the prescribed treatment.

The predominance of young women among SLE patients, the frequent onset of the disease after childbirth or abortion, impaired metabolism of estrogens with an increase in their activity, the presence of hyperprolactinemia indicate the participation of hormonal factors in the pathogenesis of the disease. Often, SLE patients show symptoms that indicate a decrease in the function of the adrenal cortex. Provocative factors in the development of SLE can be colds, childbirth, abortion, pregnancy, ultraviolet radiation, intolerance to drugs, vaccines, serums, etc.

The clinical manifestations of SLE are directly related to the development of vasculitis, which is due to the deposition of deposits of immune complexes in the vascular wall and thrombosis. In addition, cytotoxic antibodies can lead to the development of autoimmune hemolytic anemia and thrombocytopenia.

The development of a detailed clinical picture of SLE, as a rule, is preceded by a long prodromal period, which does not have clear criteria. However, signs such as polyarthritis or polyarthralgia, myalgia, aggravated by various nonspecific factors, especially in conditions of increased insolation, various skin rashes, weight loss (up to 20%), asthenia, low-grade body temperature (for no apparent reason), unspecified complaints associated with with the heart, the periodic appearance of protein in the urine, especially if this is combined with a steady increase in ESR and leukopenia, may suggest the possible development of SLE. Mostly young women (20-30 years old) are ill, but more and more often the disease is detected in adolescents and in people over 40 years old, especially in men.

The clinical picture of SLE is characterized by significant polymorphism. The disease begins mainly with the gradual development of articular syndrome, which resembles rheumatoid arthritis, malaise and weakness (asthenovegetative syndrome), fever, various skin rashes, trophic disorders, rapid weight loss.

The course of the disease can be acute, subacute and chronic.

The acute course of SLE is characterized by an acute onset, acute polyarthritis, serositis of the "glomerulus", after 3-6 months, pronounced polysyndromism, lupus nephritis, lesions of the central nervous system. The duration of the disease without treatment does not exceed 1-2 years. The prognosis improves with treatment.

The subacute course of SLE is characterized by arthralgia, recurrent arthritis, skin lesions, undulating course, after 2-3 years polysyndromism, lupus nephritis, encephalitis, and often chronic renal failure develop.

Chronic course of SLE long time manifested by relapses of polyarthritis, polyserositis, syndromes of discoid lupus, Raynaud, Verlhof, epilepsy. In the 5-10th year, nephritis, pulmonitis join, severe lupus nephritis and CNS damage rarely develop, recurrent arthritis leads to joint deformation (20%). In recent decades, there has been a change in the nature of the course of SLE: the disease becomes chronic due to a decrease in the frequency of subacute and especially acute forms of the disease, which to a certain extent is associated with the timeliness and adequacy of treatment.

The criteria for the degree of SLE activity are: the severity of the onset, the degree of polysyndromism, the rate of progression, the intensity of clinical manifestations, the severity of changes in laboratory parameters.

Skin changes are a typical sign of SLE, but the classic erythematous rash on the dorsum of the nose and cheeks (lupus butterfly) occurs in less than half of patients. An inflammatory rash on the nose and cheeks, reminiscent of the outline of a butterfly, is of great diagnostic value and comes in different versions:

• vascular (vasculitic) "butterfly" - unstable, pulsatile, diffuse redness of a cyanotic hue in the middle zone of the face, aggravated by external factors (insolation, wind, cold, etc.) or excitement;
• "butterfly" type of centrifugal erythema - persistent erythematous-edematous spots, sometimes with slight desquamation;
• "persistent erysipelas of Kaposi" - a bright pink spilled dense swelling of the skin of the face, especially the eyelids, reminiscent of erysipelas;
• discount "butterfly" - typical foci of a discount type in the middle zone of the face.

In SLE patients, local or diffuse alopecia is often observed, less often cicatricial changes in the scalp. Hair becomes coarse, dry, brittle, dystrophic changes in nails are also noted. Alopecia, one of the most significant diagnostic signs of SLE, may be the only clinical manifestation of disease activity. Sometimes, during a period of pronounced activity, subcutaneous nodes may appear. Other forms of skin lesions:

• panniculitis - inflammation of the subcutaneous fatty tissue,
• various manifestations of cutaneous vasculitis - purpura, urticaria, periungual or subungual microinfarctions,
• livedo reticularis - branchy reticular bluish-purple spots on the skin of the lower extremities, less often the trunk and upper extremities, associated with blood stagnation in the superficial capillaries or microthrombosis of venules.

How is systemic lupus erythematosus treated?

A complex set of procedures. The complexity of the mechanisms of the development of the disease, the impossibility of conducting etiotropic therapy justify the use of complex pathogenetic treatment aimed at suppressing immunocomplex pathology. To choose the most effective treatment many factors should be borne in mind, the primary ones of which are:

• the nature of the course of the disease (acute, subacute or chronic);
• process activity (minimal, moderate, pronounced);
• localization of the lesion (mainly skin, joints, serous membranes, lungs, heart, kidneys, nervous system, etc.);
• tolerance of glucorticosteroids or cytostatics;
• the presence (or absence) of complications of immunosuppressive therapy.

The first stage of treatment of SLE patients takes place in a specialized rheumatological hospital, where the patient is examined in order to confirm and clarify the diagnosis, the peculiarities of the course of SLE are established, and concomitant diseases are detected, the tactics and treatment plan are developed, and the appropriate drugs and doses are selected.

Patients are prescribed bed rest. In the dietary regimen, a sufficient amount of vitamins, polyunsaturated fatty acids should be provided, which leads to an increase in the synthesis of prostaglandins and leukotrienes, which have anti-inflammatory and anti-fibrosis effects.

The basis of drug therapy is glucocorticosteroid hormones, which are absolutely indicated after a reliable diagnosis has been established. You can prescribe prednisolone, methylprednisolone (medrol, urbazone), triamcinolone (polcortolone), dexamethasone (dexazone), betamethasone.

Taking into account the peculiarities of the biological effect of these funds on the body and possible side effects, methylprednisolone and prednisolone are more often used in the treatment of SLE. For long-term therapy of SLE, a drug from the group of glucocorticoid hormones methylprednisolone (medrol) is best suited. In the case of oral therapy with medium or high doses of corticosteroids, various options for their use are used - continuous (daily) and intermittent (alternating and intermittent). The dose of corticosteroid hormones is selected individually for each patient. It depends on the severity of the pathological process, the degree of activity, the nature of the visceral lesions.

Inadequate intermittent treatment of corticosteroids is accompanied by the development of a withdrawal syndrome with subsequent exacerbations. The individual dose is selected taking into account the variant of the course of the disease, the degree of its activity, the nature of the organ pathology, the age of the patients, and the previous treatment.

Indications for the appointment of GCS:

• acute and subacute course,
• chronic course with II-III degrees of activity.

Absolute indications for the administration of corticosteroids are:

• lupus nephritis,
• heavy course,
• severe lesions of the central nervous system,
• autoimmune thrombocytopenia with very low platelet counts
• autoimmune hemolytic anemia,
• acute lupus pneumonitis.

The duration of the use of corticosteroids is on average 3-6 months, sometimes longer. It is advisable to use GCS therapy throughout the patient's life: from large doses to active phase illness before supporting during the period of remission.

The use of corticosteroid hormones for a long time, especially in excessive dosage, causes the development of side effects of these drugs.

In addition to corticosteroid hormones, most SLE patients are prescribed aminoquinolone drugs (delagil, plaquenil, hingamin, chloroquine). They are most indicated for patients with SLE with skin lesions and with a chronic course of the disease. If GCS does not give an effect, drugs of the 11th line are prescribed - cytostatic immunosuppressants. Indications:

• high activity of the process and rapid progression of the course,
• active nephrotic and nephritic syndromes,
• lesions of the nervous system like neurolupus,
• insufficient efficiency of GCS,
• the need to quickly reduce the effective dose of corticosteroids due to poor tolerance and severity of side effects,
• the need to reduce the maintenance dose of prednisolone,
• corticosteroid dependence.

The most commonly used drugs are azathioprine (imuran) and cyclophosphamide in combination with prednisolone. You can use chlorbutin, methotrexate, cyclosporin A. In the case of high immunological activity of SLE, you can start treatment with parenteral use of cyclophosphamide to obtain a faster therapeutic effect, and after 2-3 weeks switch to the use of azathioprine.

Immunosuppressive drugs are canceled with severe cytopenia. In the case of the development of hematological complications simultaneously with the abolition of cytostatics, it is necessary to increase the dose of glucocorticosteroids to 50-60 mg per day, and sometimes more, until the initial blood counts are restored.

Ascorbic acid and B vitamins must be added to the complex treatment of SLE patients in courses for 2-3 months, especially during periods of severe vitamin deficiency (winter, spring), as well as during exacerbations of the disease, if necessary, increase the dose of hormones

The presence of lupus nephritis (lupus nephritis) requires special therapeutic tactics, which significantly aggravates the course of SLE and often determines the prognosis of the disease. With its severe course, the ineffectiveness of previous treatment in combination with high activity, the presence of systemic vasculitis, progressive lupus nephritis, cerebrovasculitis, the method of choice is the early prescription of shock doses of GCS (pulse therapy). With pulse therapy or after it, patients continue to use the same oral dose of GCS as before the procedure. The indication for pulse therapy is fast development renal pathology (nephrotic syndrome), disease progression, high maintenance dose of corticosteroids. Combined pulse therapy is performed with methylprednisolone and cyclophosphamide. Heparin is added to the dropper. To improve the action of glucocorticoids and cytostatics, stimulate and regulate the phagocytic activity of cells, suppress the formation of pathological immune complexes, systemic enzyme therapy preparations (wobenzym, phlogenzym

Plasmapheresis and hemosorption are the procedures of choice for patients in whom conventional GCS therapy is ineffective (with active lupus nephritis, persistent articular syndrome, skin vasculitis, inability to increase the GCS dose due to the development of complications). The appointment of GCS synchronously with cyclophosphamide and plasmapheresis for a year or more gives a good clinical effect.

In severe forms of SLE, local X-ray irradiation of supra- and subphrenic lymph nodes is prescribed (for a course of up to 4000 rad). This makes it possible to reduce extremely high activity disease that cannot be achieved with other methods of treatment. In the presence of persistent arthritis, bursitis, or polymyalgia, nonsteroidal anti-inflammatory drugs (diclofenac, meloxicam, nimesulide, celecoxib) may be the drugs of choice. Patients with skin lesions are prescribed Delagil or Plaquenil alone or in combination with GCS.

What diseases can it be associated with

A feature of systemic lupus erythematosus is the presence of morphological phenomena associated with the pathology of the nuclei (the appearance of hematoxylin bodies). Deposits of immunoglobulins and CEC are observed in kidney tissues and skin. The most characteristic symptom is lupus nephropathy (immunocomplex nephritis) with the phenomenon of wire loops and deposition of fibrinoid and hyaline thrombi in the loops of the glomeruli, the formation of hematoinsulin bodies.

Pathomorphologically, there are:

• focal proliferative lupus nephritis,
• diffuse proliferative lupus nephritis,
• membranous lupus nephritis,
• mesangial lupus nephritis,
• glomerulosclerosis.

Skin lesions:

• atrophy of the epidermis,
• hyperkeratosis,
• dystrophy of the cells of the basal layer,
• atrophy and hair loss,
• disorganization of the dermis,
• connective tissue,
• fibrinous swelling of collagen fibers, the upper layers of the dermis, Ig deposits in the area of ​​the dermo-epidermal junction.

Synovium lesions:

• acute, subacute and chronic synovitis,
• productive and destructive vasculitis,
• thrombovasculitis.

Heart damage:

• lupus pancarditis,
• Liebman-Sachs endocarditis,
• focal myocarditis.

Lesions of the central nervous system and peripheral nervous system:

• alterative-exudative meningoencephalomyelitis,
• alterative-productive radiculitis,
• neuritis,
• plexitis with the involvement of the vessels of the microcirculation system in the process.

With SLE, generalized lymphadenopathy, splenomegaly, hepatomegaly with follicular atrophy, perivascular sclerosis, necrosis and plasma cell infiltration, and antiphospholipid syndrome also develop. Skin lesions are manifested by atrophy of the epidermis, hyperkeratosis, vacuolar degeneration of cells, deposition of immunoglobulins G and M.

Target organ damage in SLE can lead to irreversible changes and life-threatening conditions. Life-threatening conditions and target organ damage in SLE:

• cardiac - coronary vasculitis / vasculopathy, Liebman-Sachs endocarditis, myocarditis, pericardial tamponade, malignant hypertension;
• hematological - hemolytic anemia, neutropenia, thrombocytopenia, thrombocytopenic purpura, arterial or venous thrombosis;
• neurological - convulsions, acute states of confusion, coma, stroke, transverse myopathy, mono-, polyneuritis, optic neuritis, psychosis;
• pulmonary - pulmonary hypertension, pulmonary hemorrhage, pneumonitis, pulmonary embolism / infarction, pulmonary fibrosis, interstitial fibrosis.
• gastrointestinal - mesenteric vasculitis, pancreatitis;
• renal - persistent nephritis, glomerulonephritis, nephrotic syndrome;
• muscle - myositis;
• cutaneous - vasculitis, diffuse rash with ulceration or blistering;
• general - high body temperature (with prostration) in the absence of signs of infection.

Home treatment for systemic lupus erythematosus

Systemic lupus erythematosus treatment lasts for months, years, and sometimes for life. During periods of exacerbation, the patient is shown hospitalization, the rest of the time, therapy is carried out at home. In this case, the patient must comply with all protective measures recommended to prevent the development of the disease. Equally important is the patient's compliance with certain recommendations on the mode of the nature of work and rest.

You should consult a doctor in a timely manner at the first signs of a change in well-being, the onset or exacerbation of concomitant diseases. In case of stressful situations, the patient must independently increase the dose of corticosteroid hormones for a short period, adhere to dietary recommendations, avoid overload, and, if possible, rest during the day for 1-2 hours. It is recommended to engage in physiotherapy exercises or sports that are not very tiring. Properly organized dispensary observation plays an important role in the prevention of SLE. With a probable diagnosis of SLE, an outpatient examination is carried out 2 times a year, and in the event of new manifestations, immediately.

What are the drugs to treat systemic lupus erythematosus?

• - 10-120 mg per day, depending on the nature of the disease and the activity of this process;
• - in the evening after meals, 1-2 tablets (0.25-0.5 g per day); the course of treatment lasts for many months and even years;
• - 0.2-0.4 g per day; the course of treatment lasts for many months and even years;
• - 100-120 mg per day in combination with 30 mg of prednisone for 2-2.5 months, and then switch to a maintenance dose of 50-100 mg per day for many months and even years.

Treatment of systemic lupus erythematosus with alternative methods

Systemic lupus erythematosus treatment folk remedies have low efficacy and can only be considered as an addition to the main therapy, which is prescribed and monitored by a professional physician. Any traditional medicine should be discussed with your doctor. Self-medication is unacceptable.

Treatment of systemic lupus erythematosus during pregnancy

Pregnancy is one of the factors contributing to the onset of SLE, since the disease is largely subject to the hormonal background. Activation and relapses of lupus are possible at any stage of pregnancy, therefore a woman with an already established diagnosis or suspicion of it should be under medical supervision. The diagnosis is not a contraindication to the onset of pregnancy or to the need to terminate it, but it can aggravate its course.

For pregnancy, it is better to choose a period of remission of the disease, the course of medications taken is regulated by the attending physician. There is a risk of premature birth and some organ dysfunctions in the newborn, but most of these can be normalized during treatment.

Which doctor should you contact if you have systemic lupus erythematosus

Laboratory diagnostics, determination of a large number of Le-cells and antinuclear antibodies in a high titer are of great diagnostic value. Le-cells are mature neutrophilic granulocytes, the cytoplasm of which contains round or oval inclusions, consisting of depolymerized DNA and stained in a bright purple color. If the test is performed thoroughly enough, Le cells are detected in about 80% of SLE patients. They are absent in those with globulinemia or severe kidney damage. The disadvantage of the Le test is the need for a long and thorough search, but even under this condition, Le cells may not be detected.

With the introduction of the immunofluorescence method into practice, methods for direct detection of antinuclear activity have appeared. Antinuclear antibodies are found in the blood serum of almost 100% of people with active SLE, so their determination is the best screening test for diagnosing the disease. The disadvantage of this sensitive test is that it is less specific than Le cell tests.

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease. SLE can only be diagnosed by a specialist with sufficient experience. Difficulties in diagnosing the disease are associated with a varied clinical picture, when during the course of the disease new signs of the disease appear, reflecting the damage to various organs and systems.

When making a diagnosis of SLE, MEDSI specialists are based on a combination of clinical manifestations of the disease and data laboratory diagnostics, in addition, blood and urine tests, ultrasound, and X-ray examinations can accurately determine the nature and degree of damage to internal organs, the phase of disease activity.

In the Clinic of Innovative Rheumatology of the Clinical and Diagnostic Center MEDSI on Belorusskaya, diagnostics is carried out using modern laboratory and instrumental research methods - determination of autoantibodies, complement, rheumatoid factor titer, biochemical blood test, MRI, MSCT, ultrasound, radiography, functional tests are performed. Treatment of the disease is carried out in accordance with international standards and recommendations of the rheumatological associations of Europe and the United States, together with specialists from the Center for Diagnostics and Innovative Medical Technologies MEDSI and the only one in Russia who apply the world's best innovative methods of diagnosis and treatment. The specialists of the EML Department have developed their own high-tech method of treating lupus erythematosus - immunosorption, which has no analogues in the world.

In the Clinical and Diagnostic Center on Belorusskaya, a well-known doctor of medical sciences, honored doctor is receiving Russian Federation... Sergey Konstantinovich - the founder of the national school intensive care rheumatic diseases, an expert in the diagnosis and treatment of systemic lupus erythematosus, severe forms rheumatoid arthritis, systemic vasculitis and other connective tissue diseases.

The methods developed by the Professor for the treatment of autoimmune rheumatic diseases using methods of extracorporeal therapy and genetically engineered biological drugs allow to ensure not only maximum survival, but also a high level of quality of life, the ability to minimize the intake of hormonal drugs or even their complete cancellation. Early recognition of the disease, timely and personalized therapy, professional monitoring are the basic principles that Sergey Konstantinovich is guided by in his daily practice.