Treatment. How to treat lupus erythematosus using folk remedies? Diagnosis of lupus erythematosus

How to treat lupus erythematosus using folk remedies?

Lupus erythematosus is a systemic disease that is characterized by diffuse damage to connective tissue and microvasculature. A peculiar calling card of the disease is a rash on the face in the shape of butterfly wings. The systemic nature of the disease suggests that changes occur throughout the body. With lupus, the pathological process spreads to the joints, heart, kidneys, nervous system, and blood system. Such diverse manifestations make traditional methods of treating lupus erythematosus very popular. Both the course of the disease and the prognosis contribute to this.

Where does lupus erythematosus come from?

The cause of damage to various organs is a disrupted immune response mechanism. Antibodies, which are normally produced against foreign agents, in this case begin to be produced against the body’s own tissues. Circulating in the blood, these antibodies affect all systems. The microcirculatory system suffers especially severely. Specific lupus erythematosus cells appear in the blood: leukocytes, with remnants of other cells inside.

Why pathological antibodies begin to be produced is unknown. The tendency to the disease is inherited. The onset of lupus can be triggered by any infectious disease, sudden temperature change, psychological distress, trauma, etc.

Symptoms of lupus erythematosus

Lupus erythematosus can occur with predominant damage to the skin, or with predominant damage to internal organs. In the first option it will be discoid or disseminated lupus erythematosus, in the second – systemic lupus erythematosus.

In the case of predominantly skin lesions, the symptoms of lupus erythematosus appear mainly on the face: red spots appear, which over time turn into plaques, and later become covered with scales. The scales have spines on the reverse surface. The plaques are limited from the rest of the skin by a red, raised border. After some time, the inflammation begins to heal, the skin underneath atrophies, becoming pale and thin. Scars form. If the inflammation was on the scalp, then hair no longer grows in this place. The classic “butterfly” with lupus is a rash on the skin of the nose and cheeks.

With systemic lupus erythematosus, the symptoms of skin lesions fade into the background. Massive damage to internal organs leads to the development of multiple organ failure. The gradual increase in general symptoms is a kind of incubation period for lupus, when the main manifestations of the disease are not yet present. With the accumulation of a large number of antibodies, deviations in the body’s functioning intensify. A person feels chronic fatigue, his joints and muscles hurt, his appetite disappears, and his temperature rises. Against the background of these manifestations, it is not uncommon. Lymph nodes enlarge. According to internal changes, changes in the blood are observed: the number of red blood cells and leukocytes decreases, specific lupus cells appear, and the amount of protein decreases. In this case, protein is found in the urine.

Treatment of lupus with official methods

Since the cause of the occurrence of immune complexes in the body against itself is unknown, treatment regimens have been developed that act on the consequences of their actions, or prevent their effect on the body.

The main treatment method is hormonal drugs that inhibit the immune response. Cytostatics, inhibitors of inflammatory cytokines, and nonsteroidal anti-inflammatory drugs are also widely used. To remove damaging immune complexes from the body, plasmapheresis and hemosorption are used. If necessary, treatment is supplemented with drugs that affect various symptoms.

Lupus erythematosus treatment with traditional methods

Nature is rich in substances that can have a restorative effect and prevent the body from self-destruction, without violating the natural laws of its existence. The use of plant medicines for internal and external use allows you to naturally treat lupus erythematosus using traditional methods. In this case, it is necessary to undergo regular examinations to determine the amount of immune complexes in the blood and the condition of internal organs.

The use of traditional methods for the treatment of systemic lupus erythematosus goes well with modern drug therapy. This approach allows, if necessary, to enhance the effect of herbal preparations and soften the effect of hormones and cytostatics, which can be difficult to do without.

It is important to know that when treating lupus erythematosus, you cannot use drugs that stimulate the activity of the immune system, because. In this case, the disease will be even more aggressive.

Collection for the treatment of lupus erythematosus. In order for the folk treatment of systemic lupus erythematosus to be effective, it is necessary to take the following decoction daily. Prepare a collection of equal parts: burnet root, peony root, burdock root, calendula flowers, tartar herb, celandine herb. Pour four tablespoons into a liter of water, boil for half an hour over low heat, strain. Drink the decoction throughout the day, each time before meals.

Mistletoe infusion to combat systemic manifestations of lupus. To prepare this infusion, you need to prepare only mistletoe leaves in advance, collecting them in the cold season. Wash and dry the raw materials; chop and place in a glass bottle for storage. The blood-purifying properties of mistletoe will be stronger if it is collected from a birch tree. Pour two teaspoons of dried mistletoe leaves into one glass of water, boil over low heat for one minute, leave for half an hour. Strain the infusion and take after meals three times a day, dividing the portion into three doses.

Hemlock tincture for lupus. Prepare the tincture: pour 50 grams of dry raw material with half a liter of vodka, leave for two weeks in a dark place, strain. The scheme for taking the tincture is as follows: on the first day, add one drop of tincture to the water and drink on an empty stomach, on the second day - two drops, and so on until the fortieth day, until you reach forty drops; after that, stop taking the infusion in decreasing order, up to one drop per day. After you drink the tincture diluted with water in the morning, you should not eat anything for an hour.

Oil for treating affected skin with lupus. Place one glass of olive oil on low heat, add 1 tablespoon of fresh violets and one tablespoon of fresh string. Stir the mixture constantly for five minutes. Remove from heat, cover with a lid, leave for 24 hours. The dishes should not be metal. The next day, strain the oil and squeeze out the remaining liquid from the plants. The resulting oil should be lubricated on the affected areas of the skin three times a day.

Dead bees for external treatment of lupus. Dead bees are dead bees that regularly appear where there are apiaries. An experienced beekeeper will help you collect dead bees, and you will get a very effective remedy for treating lupus. This product should not be used if you are allergic to bee products. The collected bees need to be dried in the sun for an hour, crushed, poured with medical alcohol (1 tablespoon of raw material per glass of alcohol), close the container tightly and leave for three weeks in a dark place, stirring occasionally. The resulting tincture, diluted in half with water, should be moistened with the affected skin twice a day, and in between, treated with oil prepared according to the previous recipe. This tincture can also be taken internally: dissolve a teaspoon of tincture in 1 glass of water, drink three times a day before meals.

Restorative collection for lupus. Prepare a collection of equal parts: nettle, tansy, lingonberry leaves, birch leaves, St. John's wort, water pepper herb, plantain leaves, dandelion root, coltsfoot, oregano herb, yarrow, sweet clover. Grind all the raw materials well, mix until maximum homogeneity. Pour two tablespoons of the mixture into a thermos and pour half a liter of boiling water into it. Infuse the herbs in a thermos for eight hours. Strain, take a third of a glass three times a day.

Treatment of lupus erythematosus with licorice root. Pour 1 tablespoon of dry crushed licorice root into half a liter of water and boil over low heat for 15 minutes. Cool the broth and then strain. Take one or two sips of the medicine between meals throughout the day. Prepare the decoction every day for at least a month.

Treatment of lupus with walnut infusion, nightshade and chicory. Grind six green walnuts, mix with half a glass of chopped chicory root, and a third of a glass of black nightshade herb. Pour the mixture with a liter of boiling water and leave for three hours. Strain the infusion. It should be taken after meals for a month, a tablespoon three times a day. This medicine stops the formation of pathological immune complexes.

Collection for the prevention of exacerbations of lupus erythematosus. Prepare the mixture: 3 tablespoons of Leuzea root, 2 tablespoons of hop cones, 2 tablespoons of celandine herb, 1 tablespoon of fenugreek seeds, 1 tablespoon of licorice root. Mix everything into a homogeneous mass. Pour 1 tablespoon of the mixture into a glass of boiling water, leave for 30 minutes. Strain and drink half an hour before meals. Prepare this infusion twice a day.

Strengthening mixture for the treatment of lupus erythematosus. Mix 1 tablespoon of buckwheat, two dried apricots, two prunes, 10 raisins, the kernel of one walnut, 1 slice of lemon, two teaspoons of honey, two-thirds of a glass of melt water. Infuse this composition for eight hours in a porcelain bowl. In the morning, eat before breakfast 40 minutes (or instead). Take this dietary supplement continuously for several years.

Treatment of lupus erythematosus in children. The roots of young willow need to be harvested in early spring, when the buds on the tree begin to swell. Collect the roots, wash them well and dry them in the oven, chop them. Brew one tablespoon of roots with a glass of boiling water and leave to steep for 8 hours. After this, bring to a boil, strain. Take two tablespoons of the infusion at regular intervals throughout the day. For a child, the medicine can be sweetened with honey.

Ointment from birch buds for the treatment of skin inflammation due to lupus. Grind one glass of birch buds into powder and mix in half a liter of fresh interior fat. Put everything in a pot and simmer in the oven over low heat for three hours a day for a week. After everything is ready, you need to strain the fat and collect it in a separate container - this is medicine. Lubricate the affected areas with this fat three times a day. Simultaneous oral administration works well: three times a day before meals, take one teaspoon of this fat dissolved in milk (about half a glass).

Prevention of lupus erythematosus

There is no specific prevention. Today it is possible to identify antibodies in the body and systematically reduce their concentration through hemosorption and plasmapheresis. This tactic allows you to delay serious manifestations of the disease. However, the opportunity to start treatment on time appears only with the patient’s alertness and regular examination, which is almost impossible. Similar actions can be recommended for people who have a family history of lupus.

Nonspecific prevention of lupus erythematosus consists of following the rules of a healthy lifestyle, measured and balanced nutrition, and giving up bad habits. Avoid direct sunlight, do not go to the solarium. Be careful with cosmetic procedures, especially facial cleansing. Use high-quality cosmetics.

Treatment for systemic lupus erythematosus includes patient education, protection from ultraviolet radiation, staying physically fit, appropriate immunizations, and identifying and managing risk factors for other diseases. Standard treatment for extraorgan manifestations of systemic SLE includes NSAIDs, glucocorticoids, and antimalarials.

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

Fatigue occurs very often in patients with systemic lupus erythematosus. Its cause is likely multifactorial and includes concomitant diseases (hypothyroidism, depression, etc.) and deterioration in physical condition due to chronic disease. Thus, treatment depends on the cause of fatigue. In patients with photosensitivity, fatigue and exacerbation of the disease after exposure to ultraviolet radiation are also possible. Photoprotection excludes exposure to the sun at midday and requires regular use of sunscreen and wearing protective clothing. Special protective and fluorescent screens on windows reduce exposure to ultraviolet radiation and reduce the risk of exacerbations of SLE in the presence of photosensitivity. Patients should also be wary of drug photosensitivity, which often develops while taking antibiotics. A sedentary lifestyle is the second distinguishing feature of SLE patients. This problem can lead to obesity, deterioration of somatic status and the quality of heart function. It has been found that with SLE, the ability to engage in therapeutic exercises is reduced. Part of the non-drug treatment should be dosed with hydrotherapy and walking.

The high incidence of infections in SLE is due to dysregulation of the immune system and long-term immunosuppression. Patients should be advised to consult a doctor if they have an unexplained fever (any increase in body temperature cannot be attributed to 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 (partly due to infection with the human papillomavirus). A recent international study found that lupus increases the risk of cancer, especially non-Hodgkin's lymphoma. Whether this increased risk is a consequence of the disease itself or its treatment is unknown. 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.

Nonsteroidal anti-inflammatory drugs

NSAIDs are effective for pain, so they are widely used for various symptoms: arthritis, myalgia, serositis, etc. The choice of NSAID is determined by cost, effectiveness and side effects. The effectiveness of these drugs varies from patient to patient and may also vary within the same patient. In patients with renal impairment due to lupus nephritis, the use of both selective and non-selective NSAIDs is not indicated, since their inhibition of cyclooxygenase (COX) impairs renal blood flow and the 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 inhibitors are approximately the same. It can be mistaken for manifestations of 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 the gastrointestinal tract and are less likely to cause peptic ulcers and bleeding. However, due to the risk of cardiovascular complications in connection with taking COX-2 inhibitors, drugs in this group should not be prescribed to patients suffering from coronary heart disease. Only one COX-2 inhibitor (celecoxib) currently remains on the market.

Glucocorticoids

Glucocorticoids are effective in the treatment of lupus and various inflammatory rheumatic diseases. They allow you to quickly stop some manifestations of SLE. Local glucocorticoids are often used in dermatological practice. Systemic administration of glucocorticoids in a dose of 5-30 mg (in terms of prednisone) once or throughout the day is effective in the treatment of mild or moderate lupus (skin lesions, arthritis and serositis). More severe organ damage (nephritis, pneumonitis, hematological disorders, central nervous system involvement and systemic vasculitis) requires oral or intravenous administration of 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 preparatory therapy for slow-acting immunosuppressive drugs. When the effect of these drugs appears, the dose of glucocorticoids is gradually reduced. As symptoms are controlled, glucocorticoids are discontinued completely or prescribed at a minimal dose (prednisone 5 mg/day or less) every day or every other day as maintenance therapy. The goal of gradually reducing 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 features (central obesity, striae, hypertension, diabetes, and dyslipidemia).

Local treatment of systemic lupus erythematosus

When using hormonal drugs for topical treatment of lupus, their dosage can be adjusted and then completely discontinued or used as needed while prescribing slow-acting immunomodulators or immunosuppressives. Clobetasol (high potency) as a solution or foam is used to treat alopecia caused by a lupus-specific rash. Due to the high risk of skin atrophy and telangiectasia in the facial area, as well as in the area of ​​diaper rash, topical use of highly active or fluorinated glucocorticoids should be avoided. In addition, glucocorticoids do not need to be applied topically continuously because they cause tachyphylaxis. Typically, patients apply topical glucocorticoids on weekdays and not on weekends, while other glucocorticoid dose-reducing agents (eg, tacrolimus or pimecrolimus) are prescribed on days when the patient is not using steroids. For hypertrophic lupus changes, triamcinolone can be injected directly into the affected 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 do not affect 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 have been successfully used in the treatment of chronic cutaneous lupus. A common side effect is local skin irritation.

Antimalarials

Antimalarials often form the basis of treatment for systemic lupus erythematosus. Hydroxychloroquine (HCQ) is the most commonly prescribed drug in the United States, followed by chloroquine and quinacrine. Antimalarials are often used as first-line therapy for the treatment of mild manifestations of lupus, including constitutional symptoms, skin and musculoskeletal changes. HQQ is prescribed at 200 mg/day, then gradually increased to 200 mg twice a day or 400 mg/day. The response to HCQ develops slowly, with improvement appearing after approximately 6 months. Maximum effectiveness is sometimes observed after 4 months of treatment for systemic lupus erythematosus. HCQ showed clinical efficacy in a randomized study: when the drug was discontinued, mild relapses were 2.5 times more likely to develop than with continued use. Long-term follow-up of study participants revealed a trend towards a decrease in the number of relapses with constant use of HCQ. Moreover, HCQ helps achieve remission of lupus erythematosus within a year in patients receiving mycophenolate mofetil (MMF) for glomerulonephritis. Two studies found that smoking affected the effectiveness of antimalarials in discoid lupus and subacute cutaneous lupus. The effect was worse in smokers than in non-smokers, and the worst results of antimalarial treatment were among those who smoked the most.

Chloroquine is prescribed at 3.5 mg/kg per day, the effect develops after 4 weeks (faster than when prescribing HQQ). The mechanism of action of quinacrine is similar to the mechanism of action of chloroquine. The dose of quinacrine is 2.5 mg/kg per day. Combination therapy with HCQ (or chloroquine) and quinacrine usually gives good results when monotherapy with these drugs is ineffective.

Side effects are frequently reported. They are usually transient and decrease when the dose of antimalarial drugs is reduced, as well as when branded drugs are prescribed rather than generic ones. The most common complaints include abdominal pain and, less commonly, nausea, vomiting, bloating and diarrhea. Chloroquine is less likely to cause disturbances, while HQQ and quinacrine are more likely to cause problems. Chloroquine is more likely than HCQ to act on the retina, causing visual field defects. Therefore, HCQ and chloroquine should be coadministered with caution as the risk of retinopathy increases when they are combined. Other visual symptoms include blurred distance vision, difficulty reading, photophobia, and glare in front of the eyes. Long-term follow-up revealed a low incidence of HCQ-related retinopathy (0.5%) in 400 patients receiving recommended doses for more than 6 years. Antimalarials may cause hyperpigmentation of the nails, skin on the anterior surface 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 when taking HCQ, and a yellow color occurs when taking quinacrine. Hypopigmentation of hair or freckles has been observed with chloroquine treatment. These disorders disappear after discontinuation of the drug. When HCQ and chloroquine are prescribed, severe cardiotoxicity with myocardial dysfunction is sometimes detected (biopsy confirmed in less than 50% of cases. The risk of cardiotoxicity is higher in older women receiving long-term antimalarial therapy. Cases of drug-induced myopathy with HCQ, with the appearance of curved bodies in skeletal muscles, have also been reported .

HCQ has a hypoglycemic effect, which helps control blood glucose concentrations in patients with poorly controlled glucose levels in type 2 diabetes. In addition, HCQ 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 HCQ. Antimalarials may also cause hemolysis in patients with G6PD deficiency, which is more common in the Mediterranean region, the Middle East, Africa and India. Therefore, the physician must take into account the patient's background when treating systemic lupus erythematosus. HCQ is safe during pregnancy. The safety of HCQ, chloroquine and quinacrine during lactation has not been proven.

Dapsone

Dapsone is a sulfonic acid. Used to treat leprosy and prevent pneumonia caused by Pneumocystis jirpvecci (formerly known as pneumonia caused by Pneumocystis carinii). Dapsone additionally has an immunomodulatory effect, especially pronounced in relation to neutrophils. Used for various bullous diseases, erythema nodosum, Sweet's syndrome, cutaneous vasculitis and cutaneous lupus. Dapsone (100 mg/day), as monotherapy or in combination with glucocorticoids or antimalarials, is the drug of choice for bullous SLE and skin lesions involving small vessels of the dermis, 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 reaction to dapsone that is exacerbated by coadministration with folic acid antagonists. Taking dapsone, like antimalarials, with G6PD 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 in adults. In order to minimize the risk of bilirubin encephalopathy in a newborn, it is recommended to discontinue 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 glucocorticoid-reducing treatment for systemic lupus erythematosus in patients with mild to moderate disease activity, and as an alternative maintenance treatment for systemic lupus erythematosus in patients with lupus nephritis and severe disease. other organs. This drug is a purine analogue, a mercaptopurine immunosuppressant that inhibits the synthesis of nucleic acids and, therefore, disrupts cellular and humoral immunity. Azathioprine can be used in pregnant women if the immunomodulatory effect of antimalarial drugs is insufficient. 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 gastrointestinal toxicity, similar to the effects of antimalarials.

Methotrexate

There is evidence of the effectiveness of methoctrexate 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 were contradictory. In some cases, as well as in some prospective studies, a good effect (allowing a gradual reduction in the dose of glucocorticoids) was obtained when prescribing methotrexate for the treatment of cutaneous or joint 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 high doses (during chemotherapy). Side effects occur frequently: 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. Supplementation with 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 of liver enzymes are important if they are persistent, but they are not a reliable predictor of the severity of hepatotoxicity detected by testing. Patients taking methotrexate are not recommended to drink alcohol, since this combination further increases the risk of hepatotoxicity. A rare, potentially life-threatening complication is methotrexate-induced pneumonitis. This 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 T cell proliferation and selectively inhibits T cell responses at the transcriptional level in naïve T cells. SLE is considered an autoimmune disease mediated by B cells, but there is evidence that T cells play a primary role in development. Patients tolerate cyclosporine 2.5-5 mg/kg per day well; the dose of glucocorticoids can be reduced: disease activity decreases, becomes smaller, and the content of leukocytes, platelets and complement increases. Limited data on the course of pregnancy (mainly in women who have undergone transplantation) have shown that the incidence of adverse outcomes does not increase while taking cyclosporine. The drug is non-teratogenic in animal experiments. Cyclosporine is prescribed to pregnant women with SLE when the benefit outweighs the risk. Mothers taking cyclosporine are not recommended to breastfeed their babies because the drug passes into milk.

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

Cyclophosphamide

Cyclophosphamide is an alkylating and cytotoxic agent that cross-binds with DNA and DNA-bound 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 cyclophosphamide for diffuse glomerulonifritis 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 carried out once every 3 months for 2 years. Intravenous cyclophosphamide has advantages over oral administration because the bladder can be protected by intravenous mesna (mercaptoethanesulfonic acid) along with aggressive fluid intake to prevent hemorrhagic cystitis and bladder cancer caused by acrolein (a toxic metabolite of cyclophosphamide). Studies of shorter duration and/or lower dosage 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 tumors. Nausea and vomiting are prevented with antiemetic drugs such as ondansterone and dilasterone, given as needed. Dose-dependent maximum leukopenia occurs 8-12 days after administration of cyclophosphamide. The most dangerous side effect is caused by 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 use of cyclophosphamide during pregnancy and lactation is prohibited.

Mycophenolate mofetil (MMF)

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

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

Leflunomide

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

The most common side effect is diarrhea, which usually disappears after reducing the dose. Other side effects include elevated liver enzymes, hypertension, and transient leukopenia. Cases of subacute cutaneous lupus 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 an interval of 2 weeks or more. If pregnancy occurs or toxicity occurs, the drug can be removed with cholestyramine. Therefore, the use of leflunomide should not be recommended for young women of reproductive age.

Hormonal treatment of 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) preserves bone mineral density and significantly increases it in women chronically receiving glucocorticoids. The drug is well tolerated. The most common side effect is acne. To treat 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

Attitudes towards the use of thalidomide are controversial due to its well-known teratogenic effects. The drug is highly effective at a dose of 50-400 mg/day for the treatment of refractory chronic cutaneous lupus, but the exact mechanism of action is still unknown. The relapse rate after drug discontinuation is high (approximately 68%). A common side effect is peripheral neuropathy. Neuropathy is not dose-related and may be irreversible if the drug is not stopped promptly. 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, complement inhibition, immunomodulation of T and B cell functions. The drug is effective for thrombocytopenia, arthritis, nephritis and immunological disorders. Intravenous immunoglobulin provides protection against infections in patients with immunodeficiency, so 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, myalgia, arthralgia and headache. Aseptic meningitis and thrombocytopenia rarely develop. Before intravenous administration of the drug, it is necessary to study the quantitative composition of immunoglobulins in the patient to exclude A deficiency. In patients with hypercoagulability (for example, with antiphospholipid syndrome), immunoglobulin therapy should be carried out with caution due to the risk of thromboembolism.

Plasmapheresis

Plasma exchange (plasmapheresis) is an effective but expensive treatment for systemic lupus erythematosus, allowing the rapid removal of immune complexes from the circulation. The method is also associated with a high risk of infection and anaphylactic reactions. Indications for plasmapheresis in SLE: thrombotic thrombocytopenic purpura, severe antiphospholipid syndrome requiring expensive treatment, cryoglobulinemia and hyperviscosity syndrome. Other life-threatening complications of SLE are also treated with plasma exchange when standard treatment fails.

Immunoablation with autologous stem cell transplantation

In severe cases of SLE, the mainstay of treatment is cyclophosphamide, the dose of which is limited depending on myelosuppression. Immunoablation with cyclophosphamide and subsequent stem cell transplantation is performed to restore the patient's bone marrow with autologous stem cells after 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 showed a reduction in disease activity after nonmyeloablative autologous hematopoietic stem cell transplantation for 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 treatment option. Rapid restoration of hematopoiesis is achieved by administering 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 this treatment of systemic lupus erythematosus, persistent complete remission was observed in some patients with moderate and high levels of activity. The studies were not randomized, so their results are preliminary, which necessitates confirmation by controlled randomized trials.

Hemodialysis and kidney transplantation

Hemodialysis and kidney transplantation significantly increases the survival rate of patients with SLE. They tolerate hemodialysis well, but the procedure is accompanied by a high risk of infection. Long-term survival and kidney graft engraftment in SLE are approximately the same as among patients without SLE who undergo transplantation. However, the risk of thrombotic complications, such as early graft thrombosis, is higher in patients with SLE, especially in the presence of antiphospholipid antibodies. The outcome of kidney transplantation depends on the clinical condition of the patient at the time of transplantation. The risk of lupus nephritis in a transplanted kidney varies from 2 to 30%.

New treatments for systemic lupus erythematosus

In connection with a change in the view of immunosuppression as a standard treatment for SLE, “drugs of the future” were created, characterized by higher efficiency and less 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

Systemic lupus erythematosus is a chronic disease with many symptoms, which is based on constant autoimmune inflammation. Young girls and women aged 15 to 45 years are most often affected. Prevalence of lupus: 50 people per 100,000 population. Despite the fact that the disease is quite rare, knowing its symptoms is extremely important. In this article we will also talk about the treatment of lupus, which is usually prescribed by doctors.

Causes of systemic lupus erythematosus

Excessive exposure to ultraviolet radiation on the body contributes to the development of the pathological process.

1. Excessive exposure to ultraviolet radiation (especially “chocolate” tans and tans leading to sunburn).
2. Stressful situations.
3. Episodes of hypothermia.
4. Physical and mental overload.
5. Acute and chronic viral infection (herpes simplex virus, Epstein-Barr virus, cytomegalovirus).
6. Genetic predisposition. If one of your relatives has or is suffering from lupus in the family, then for everyone else the risk of getting sick increases significantly.
7. Deficiency of complement component C2. Complement is one of the “participants” of the body’s immune response.
8. Presence of HLA All, DR2, DR3, B35, B7 antigens in the blood.

A number of studies show that lupus does not have one specific cause. Therefore, the disease is considered multifactorial, that is, its occurrence is due to the simultaneous or sequential influence of a number of causes.

Classification of systemic lupus erythematosus

According to the development of the disease:

• Acute onset. Against the background of complete health, lupus symptoms suddenly appear.
• Subclinical onset. Symptoms appear gradually and may mimic another rheumatic disease.

Course of the disease:

• Spicy. Usually, patients can tell within a few hours when their first symptoms appeared: the temperature rose, typical redness of the facial skin (“butterfly”) appeared, and joint pain began. Without proper treatment, the nervous system and kidneys are affected within 6 months.
• Subacute. The most common course of lupus. The disease begins nonspecifically, the general condition begins to worsen, and skin rashes may appear. The disease occurs cyclically, with each relapse involving new organs in the process.
• Chronic. Lupus for a long time manifests itself as relapses of only those symptoms and syndromes with which it began (polyarthritis, skin syndrome), without involving other organs and systems in the process. The chronic course of the disease has the most favorable prognosis.

Symptoms of systemic lupus erythematosus

Joint damage

It is observed in 90% of patients. It manifests itself as migrating pain in the joints and alternating inflammation of the joints. It is very rare for the same joint to constantly hurt and become inflamed. Mainly the interphalangeal, metacarpophalangeal and wrist joints are affected, and less commonly the ankle joints. Large joints (for example, knees and elbows) are affected much less frequently. Arthritis is usually accompanied by severe muscle pain and inflammation.

Skin syndrome

The most common type of lupus “butterfly” is redness of the skin in the cheekbones and dorsum of the nose.

There are several options for skin damage:

1. Vasculitic (vascular) butterfly. It is characterized by unstable diffuse redness of the facial skin, with a blue discoloration in the center, intensified by cold, wind, excitement, and ultraviolet radiation. Foci of redness can be either flat or raised above the surface of the skin. After healing, no scars remain.
2. Multiple skin rashes due to photosensitivity. They appear on open areas of the body (neck, face, décolleté, arms, legs) under the influence of sunlight. The rash goes away without a trace.
3. Subacute lupus erythematosus. Areas of redness (erythema) appear after sun exposure. Erythemas are raised above the surface of the skin, can be ring-shaped, crescent-shaped, and almost always peel off. A patch of depigmented skin may remain at the site of the spot.
4. Discoid lupus erythematosus. First, patients develop small red plaques, which gradually merge into one large lesion. The skin in such places is thin, and excessive keratinization is noted in the center of the lesion. Such plaques appear on the face and extensor surfaces of the limbs. After healing, scars remain at the site of the lesions.

Skin manifestations may include hair loss (up to complete), changes in nails, and ulcerative stomatitis.

Damage to the serous membranes

Such a lesion is one of the diagnostic criteria, as it occurs in 90% of patients. These include:

1. Pleurisy.
2. Peritonitis (inflammation of the peritoneum).

Damage to the cardiovascular system

1. Lupus.
2. Pericarditis.
3. Libman-Sachs endocarditis.
4. Coronary artery disease and development.
5. Vasculitis.

Raynaud's syndrome

Raynaud's syndrome is manifested by spasm of small vessels, which in patients with lupus can lead to necrosis of the fingertips, severe arterial hypertension, and retinal damage.

Lung damage

1. Pleurisy.
2. Acute lupus pneumonitis.
3. Damage to the connective tissue of the lungs with the formation of multiple foci of necrosis.
4. Pulmonary hypertension.
5. Pulmonary embolism.
6. Bronchitis and.

Kidney damage

1. Urinary syndrome.
2. Nephrotic syndrome.
3. Nephritic syndrome.

Damage to the central nervous system

1. Astheno-vegetative syndrome, which manifests itself as weakness, fatigue, depression, irritability, and sleep disturbances.
2. During the period of relapse, patients complain of decreased sensitivity, paresthesia (“goosebumps”). On examination, a decrease in tendon reflexes is noted.
3. In severely ill patients, meningoencephalitis may develop.
4. Emotional lability (weakness).
5. Decreased memory, deterioration of intellectual abilities.
6. Psychosis, seizures.

Diagnosis of systemic lupus erythematosus

In order to make a diagnosis of systemic lupus erythematosus, it is necessary to confirm that the patient has at least four criteria from the list.

1. Rashes on the face. Flat or raised erythema localized to the cheeks and cheekbones.
2. Discoid rashes. Erythematous spots, with peeling and hyperkeratosis in the center, leaving behind scars.
3. Photosensitivity. Skin rashes appear as an excessive reaction to ultraviolet radiation.
4. Ulcers in the mouth.
5. Arthritis. Damage to two or more peripheral small joints, pain and inflammation in them.
6. Serositis. Pleurisy, pericarditis, peritonitis or their combinations.
7. Kidney damage. Changes in (appearance of traces of protein, blood), increased blood pressure.
8. Neurological disorders. Convulsions, psychoses, seizures, emotional disturbances.
9. Hematological changes. At least 2 clinical blood tests in a row must show one of the following indicators: leukopenia (decreased number of white blood cells), lymphopenia (decreased number of lymphocytes), thrombocytopenia (decreased number of platelets).
10. Immunological disorders. Positive LE test (high amount of antibodies to DNA), false positive reaction to, medium or high level of rheumatoid factor.
11. Presence of antinuclear antibodies (ANA). Detected by enzyme immunoassay.

What should be considered for differential diagnosis?

Due to the wide variety of symptoms, systemic lupus erythematosus shares many manifestations with other rheumatological diseases. Before making a diagnosis of lupus, it is necessary to exclude:

1. Other diffuse connective tissue diseases (scleroderma, dermatomyositis).
2. Polyarthritis.
3. Rheumatism (acute rheumatic fever).
4. Still's syndrome.
5. Kidney lesions are not of lupus nature.
6. Autoimmune cytopenias (decrease in the number of leukocytes, lymphocytes, platelets in the blood).

Treatment of systemic lupus erythematosus

The main goal of treatment is to suppress the body’s autoimmune reaction, which underlies all symptoms.

Patients are prescribed different types of drugs.

Glucocorticosteroids

Hormones are the drugs of choice for lupus. They are the ones that best relieve inflammation and suppress the immune system. Before glucocorticosteroids were introduced into the treatment regimen, patients lived a maximum of 5 years after diagnosis. Now life expectancy is much longer and depends to a greater extent on the timeliness and adequacy of the prescribed treatment, as well as how carefully the patient follows all the instructions.

The main indicator of the effectiveness of hormonal treatment is long-term remissions with maintenance treatment with small doses of drugs, a decrease in the activity of the process, and stable stabilization of the condition.

The drug of choice for patients with systemic lupus erythematosus is Prednisolone. It is prescribed on average at a dose of up to 50 mg/day, gradually reducing to 15 mg/day.

Unfortunately, there are reasons why hormonal treatment is ineffective: irregularity in taking pills, incorrect dosage, late start of treatment, very serious condition of the patient.

Patients, especially teenagers and young women, may be reluctant to take hormones because of possible side effects, mainly worrying about possible weight gain. In the case of systemic lupus erythematosus, there is really no choice: take it or not take it. As mentioned above, without treatment with hormones, life expectancy is very low, and the quality of this life is very poor. Don't be afraid of hormones. Many patients, especially those with rheumatological diseases, take hormones for decades. And not all of them develop side effects.

Other possible side effects from taking hormones:

1. Steroid erosions and.
2. Increased risk of infection.
3. Increased blood pressure.
4. Increased blood sugar levels.

All these complications also develop quite rarely. The main condition for effective hormonal treatment with minimal risk of side effects is the correct dose, regular use of pills (otherwise withdrawal syndrome is possible) and self-control.

Cytostatics

These drugs are prescribed in combination with when hormones alone are not effective enough or do not work at all. Cytostatics are also aimed at suppressing the immune system. There are indications for the use of these drugs:

1. High activity of lupus with a rapidly progressing course.
2. Involvement of the kidneys in the pathological process (nephrotic and nephritic syndromes).
3. Low effectiveness of isolated hormone therapy.
4. The need to reduce the dose of Prednisolone due to poor tolerability or sudden development of side effects.
5. The need to reduce the maintenance dose of hormones (if it exceeds 15 mg/day).
6. Formation of dependence on hormone therapy.

Most often, patients with lupus are prescribed azathioprine (Imuran) and cyclophosphamide.

Criteria for the effectiveness of treatment with cytostatics:

• Reducing the intensity of symptoms;
• Disappearance of dependence on hormones;
• Reduced disease activity;
• Persistent remission.

Nonsteroidal anti-inflammatory drugs

Prescribed to relieve joint symptoms. Most often, patients take Diclofenac and Indomethacin tablets. Treatment with NSAIDs lasts until body temperature normalizes and joint pain disappears.

Additional treatments

Plasmapheresis. During the procedure, metabolic products and immune complexes that provoke inflammation are removed from the patient's blood.

Prevention of systemic lupus erythematosus

The goal of prevention is to prevent the development of relapses and to maintain the patient in a state of stable remission for a long time. Prevention of lupus is based on an integrated approach:

1. Regular medical examinations and consultations with a rheumatologist.
2. Take medications strictly in the prescribed dose and at the specified intervals.
3. Compliance with the work and rest regime.
4. Get adequate sleep, at least 8 hours a day.
5. A diet with limited salt and sufficient protein.
6. The use of hormone-containing ointments (for example, Advantan) for skin lesions.
7. Use of sunscreens (creams).

How to live with a diagnosis of systemic lupus erythematosus?

Just because you've been diagnosed with lupus doesn't mean your life is over.

Try to defeat the disease, maybe not in the literal sense. Yes, you will probably be limited in some ways. But millions of people with more severe illnesses live bright, full of impressions lives! So you can too.

What do I need to do?

1. Listen to yourself. If you are tired, lie down and rest. You may need to rearrange your daily schedule. But it’s better to take a nap several times a day than to work yourself to the point of exhaustion and increase the risk of relapse.
2. Learn all the signs of when the disease may become acute. Usually these are severe stress, prolonged exposure to the sun, and even the consumption of certain foods. If possible, avoid provoking factors, and life will immediately become a little more fun.
3. Give yourself moderate physical activity. It is best to do Pilates or yoga.
4. Quit smoking and try to avoid secondhand smoke. Smoking does not improve your health at all. And if you remember that smokers more often get colds, bronchitis and pneumonia, overload their kidneys and heart... You shouldn’t risk many years of your life because of a cigarette.
5. Accept your diagnosis, learn everything about the disease, ask your doctor everything you don’t understand and breathe easy. Lupus today is not a death sentence.
6. If necessary, do not hesitate to ask your family and friends to support you.

What can you eat and what should you avoid?

In fact, you need to eat in order to live, and not vice versa. It's also best to eat foods that will help you fight lupus effectively and protect your heart, brain, and kidneys.

What to limit and what to give up

1. Fats. Deep-fried dishes, fast food, dishes with large amounts of butter, vegetable or olive oils. All of them sharply increase the risk of developing complications from the cardiovascular system. Everyone knows that fatty foods provoke cholesterol deposits in blood vessels. Avoid unhealthy fatty foods and protect yourself from a heart attack.
2. Caffeine. Coffee, tea, and some drinks contain large amounts of caffeine, which irritates the gastric mucosa, prevents you from falling asleep, overloading the central nervous system. You will feel much better if you stop drinking cups of coffee. At the same time, the risk of developing erosion will be significantly reduced.
3. Salt. Salt should be limited in any case. But this is especially necessary in order not to overload the kidneys, which may already be affected by lupus, and not to provoke a rise in blood pressure.
4. Alcohol. harmful in itself, and in combination with medications usually prescribed to patients with lupus, it is generally an explosive mixture. Give up alcohol and you will immediately feel the difference.

What you can and should eat

1. Fruits and vegetables. An excellent source of vitamins, minerals and fiber. Try to eat seasonal vegetables and fruits, they are especially healthy and also quite cheap.
2. Foods and supplements high in calcium and vitamin D. They will help prevent diarrhea, which can develop while taking glucocorticosteroids. Consume low-fat or low-fat dairy products, cheeses and milk. By the way, if you take the tablets with milk rather than water, they will irritate the stomach lining less.
3. Whole grain cereals and baked goods. These foods contain a lot of fiber and B vitamins.
4. Protein. Protein is necessary for the body to effectively fight disease. It is better to eat lean, dietary varieties of meat and poultry: veal, turkey, rabbit. The same applies to fish: cod, pollock, lean herring, pink salmon, tuna, squid. In addition, seafood contains a lot of omega-3 unsaturated fatty acids. They are vital for normal brain and heart function.
5. Water. Try to drink at least 8 glasses of clean, still water per day. This will improve your general condition, improve the functioning of the gastrointestinal tract, and help control hunger.

So, systemic lupus erythematosus in our time is not a death sentence. There is no need to give in to despair if you have been diagnosed with this; rather, it is necessary to “pull yourself together”, follow all the recommendations of the attending physician, lead a healthy lifestyle, and then the quality and life expectancy of the patient will increase significantly.

Which doctor should I contact?

Given the variety of clinical manifestations, sometimes it is quite difficult for a sick person to figure out which doctor to see at the onset of the disease. For any changes in your health, it is recommended to consult a therapist. After conducting tests, he will be able to suggest a diagnosis and refer the patient to a rheumatologist. Additionally, consultation with a dermatologist, nephrologist, pulmonologist, neurologist, cardiologist, or immunologist may be required. Since systemic lupus erythematosus is often associated with chronic infections, it will be useful to be examined by an infectious disease specialist. A nutritionist will provide assistance in treatment.

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Drug-induced lupus occurs approximately 10 times less frequently than systemic lupus erythematosus (SCR). Recently, the list of drugs that can cause lupus syndrome has expanded significantly. These include primarily antihypertensives (hydralazine, methyldopa); antiarrhythmic (procainamide); anticonvulsants (diphenin, hydantoin) and other drugs: isoniazid, aminazine, methylthiouracil, oxodoline (chlorthalidone), diuretin, D-penicillamine, sulfonamides, penicillin, tetracycline, oral contraceptives.

We observed severe nephrotic syndrome with the development of multisystem SLE, which required many years of treatment with corticosteroids, after administration of bilitrast to the patient. Therefore, you should carefully collect anamnesis before prescribing treatment.

The mechanism of development of drug-induced lupus may be due to a change in immune status or an allergic reaction. Positive antinuclear factor is detected in drug-induced lupus caused by drugs of the first three groups listed above. The detection rate of antinuclear factor in drug-induced lupus is higher than in true SLE. Hydralazine and procainamide are especially capable of inducing the appearance of antinuclear, antilymphocyte, and antierythrocyte antibodies in the blood. These antibodies themselves are harmless and disappear when you stop taking the drug.

Sometimes they persist in the blood for several months without causing any clinical symptoms. During development. autoimmune process in a small percentage of patients with a genetic predisposition develop lupus syndrome. The clinical picture is dominated by polyserositis and pulmonary symptoms. Skin syndrome, lymphadenopathy, hepatomegaly, and polyarthritis are observed. In the blood - hypergammaglobulinemia, leukopenia, antinuclear factor, LE cells; the test for antibodies to native DNA is usually negative, the complement level is normal.

Antibodies to single-stranded DNA and antibodies to nuclear histone can be detected. The absence of complement-fixing antibodies partly explains the rarity of renal involvement. Although damage to the kidneys and central nervous system is rare, it can develop with prolonged and persistent use of the drugs listed above. Sometimes all disorders disappear soon after discontinuation of the drug that caused the disease, but in some cases it is necessary to prescribe corticosteroids, sometimes for quite a long time. Severe cases of lupus with cardiac tamponade due to pericarditis, requiring treatment for many years, have been described with the use of hydralazine.

Treatment

Despite the fact that systemic lupus erythematosus has been intensively studied over the past 30 years, treatment of patients remains a challenge. Therapeutic agents are mainly aimed at suppressing individual manifestations of the disease, since the etiological factor is still unknown. The development of treatment methods is difficult due to the variability of the course of the disease, the tendency of some of its forms to long-term, spontaneous remissions, and the presence of forms of malignant, rapidly progressive, sometimes fulminant course.

At the onset of the disease, it is sometimes difficult to predict its outcome, and only extensive clinical experience and observation of a significant number of patients make it possible to determine some prognostic signs and choose the right treatment method in order not only to help the patient, but also not to harm him with the so-called aggressive therapy. Unfortunately, All drugs used for SLE have one side effect or another, and the stronger the drug, the greater the danger of such an effect. This further emphasizes the importance of determining the activity of the disease, the severity of the patient’s condition, and damage to vital organs and systems.

The main drugs for the treatment of patients with SLE Corticosteroids, cytostatic immunosuppressants (azathioprine, cyclophosphamide, chlorambucil), as well as 4-aminoquinoline derivatives (plaquenil, delagil) remain. Recently, methods of so-called mechanical blood purification have gained recognition: plasma exchange, lymphpheresis, immunosorption. In our country, hemosorption is more often used - blood filtration through activated carbon. Used as an additional means non-steroidal anti-inflammatory drugs (NSAIDs).

When treating patients with systemic lupus erythematosus, an individual approach to the choice of therapy is necessary (since there are so many variants of the disease that we can talk about the unique course of SLE in each patient and individual response to treatment) and establishing contact with patients, since they need to be treated throughout their lives , determining, after suppressing the acute phase in the hospital, a set of rehabilitation measures, and then a set of measures to prevent exacerbation and progression of the disease.

It is necessary to educate (educate) the patient, convince him of the need for long-term treatment, compliance with the recommended rules of treatment and behavior, and teach him to recognize signs of side effects of medications or exacerbation of the disease as early as possible. With good contact with the patient, complete trust and mutual understanding, many issues of mental hygiene that often arise in patients with SLE, as in all long-term ill people, are resolved.

Corticosteroids

Long-term observations have shown that corticosteroids remain first-line drugs for acute and subacute systemic lupus erythematosus with severe visceral manifestations. However, a large number of complications when using corticosteroids requires a strict justification for their use, which includes not only the reliability of the diagnosis, but also an accurate determination of the nature of the visceral pathology. The absolute indication for the use of corticosteroids is damage to the central nervous system and kidneys.

In case of severe organ pathology, the daily dose of corticosteroids should be at least 1 mg/kg body weight with a very gradual transition to a maintenance dose. Analysis of our data obtained from the treatment of more than 600 patients with SLE with a reliably established diagnosis, observed at the Institute of Rheumatology of the Russian Academy of Medical Sciences from 3 to 20 years, showed that 35% of patients received a daily dose of prednisolone of at least 1 mg/kg. If the dose was less than indicated, combination therapy with cytostatic immunosuppressants was carried out.

Most patients received corticosteroids in maintenance doses continuously for more than 10 years. Patients with lupus nephritis or lupus of the central nervous system received 50-80 mg of prednisolone (or equivalent other corticosteroid drug) daily for 1-2 months with a gradual reduction over the year of this dose to a maintenance dose (10-7.5 mg), which is the majority patients were admitted for 5-20 years.

Our observations showed that in a number of patients with cutaneous-articular syndrome without severe visceral manifestations, it was necessary to add corticosteroids at a dose of 0.5 mg/(kg day) to quinoline drugs and NSAIDs and carry out long-term maintenance treatment (5-10 mg per day) due to persistent spread of the skin process, frequent exacerbation of arthritis, exudative polyserositis, myocarditis, which occurred when trying to cancel even such a maintenance dose as 5 mg of the drug per day.

Although assessment of the effectiveness of corticosteroids for SLE has never been conducted in controlled trials in comparison with placebo, however, all rheumatologists recognize their high effectiveness in severe organ pathology. Thus, L. Wagner and J. Fries in 1978 published data from 200 US rheumatologists and nephrologists who observed 1900 patients with systemic lupus erythematosus. With active nephritis in 90% of patients, the daily dose of corticosteroids was at least 1 mg/kg. For CNS lesions, all patients received corticosteroids at a dose of at least 1 mg/kg per day.

The authors emphasize the need for long-term treatment of seriously ill patients with SLE, a gradual dose reduction, which is consistent with the data of our long-term observation. Thus, the generally accepted tactic is to switch from 60 mg of prednisolone per day to a daily dose of 35 mg for 3 months, and to 15 mg only after another 6 months. Essentially, over the years, the dosage of the drug (both initial and maintenance) was adjusted empirically.

Of course, certain dosage provisions have been established in accordance with the degree of disease activity and certain visceral pathology. Most patients experience improvement with adequate therapy. It is clear that in some cases improvement is observed only with a daily dose of prednisolone 120 mg for several weeks, in other cases - more than 200 mg per day.

In recent years, there have been reports of the effective intravenous use of ultra-high doses methylprednisolone(1000 mg/day) for a short period (3-5 days). Such loading doses of methylprednisolone (pulse therapy) were initially used only for resuscitation and kidney transplant rejection. In 1975, we had to use intravenous loading doses of prednisolone (1500-800 mg per day) for 14 days in a patient with chronic SLE due to an exacerbation of the disease that developed after a cesarean section. The exacerbation was accompanied by adrenal insufficiency and a drop in blood pressure, which was stabilized only with the help of pulse therapy followed by oral administration of the drug 40 mg per day for 1 month.

E. Cathcart et al. were among the first to report pulse therapy in patients with lupus nephritis. in 1976, who used 1000 mg of methylprednisolone intravenously for 3 days in 7 patients and noted an improvement in renal function, a decrease in serum creatinine levels, and a decrease in proteinuria.

Subsequently, reports from a number of authors appeared, mainly concerning the use of pulse therapy for lupus nephritis. According to all authors, ultra-high doses of methylprednisolone administered intravenously for short periods of time rapidly improve renal function in cases of lupus nephritis in cases with recently developed renal failure. Pulse therapy began to be used in other patients with systemic lupus erythematosus without kidney damage, but during periods of crisis, when all previous therapy was ineffective.

To date, the Institute of Rheumatology of the Russian Academy of Medical Sciences has experience with the intravenous use of 6-methylprednisolone in 120 patients with SLE, most of them with active lupus nephritis. Immediate good results were observed in 87% of patients. Analysis of long-term results after 18-60 months showed that remission remained in 70% of patients, of which 28% had complete disappearance of signs of nephritis.

The mechanism of action of loading doses of methylprednisolone during intravenous administration has not yet been fully disclosed, but available data indicate a significant immunosuppressive effect already in the first day. A short course of intravenous administration of methylprednisolone causes a significant and long-term decrease in serum IgG levels due to increased catabolism and decreased synthesis.

It is believed that loading doses of methylprednisolone suspend the formation of immune complexes and cause a change in their mass by interfering with the synthesis of antibodies to DNA, which in turn leads to a redistribution of the deposition of immune complexes and their release from the subendothelial layers of the basement membrane. It is also possible to block the damaging effects of lymphotoxins.

Taking into account the ability of pulse therapy to quickly suspend the autoimmune process for a certain period of time, the provision on the use of this method only during the period when other therapy no longer helps should be reconsidered. Currently, a certain category of patients has been identified (young age, rapidly progressing lupus nephritis, high immunological activity), in whom this type of therapy should be used at the onset of the disease, since with early suppression of disease activity, long-term therapy with large amounts may not be necessary in the future. doses of corticosteroids, fraught with serious complications.

A large number of complications of corticosteroid therapy with long-term use, especially such as spondylopathy and avascular necrosis, forced the search for additional treatment methods, ways to reduce doses and course of treatment with corticosteroids.

Cytostatic immunosuppressants

The most commonly used drugs for SLE are azathioprine, cyclophosphamide (cyclophosphamide) and chlorbutin (chlorambucil, leukeran). Unlike corticosteroids, quite a few controlled trials have been conducted to evaluate the effectiveness of these drugs, but there is no consensus on their effectiveness. Inconsistencies in the evaluation of the effectiveness of these drugs are explained in part by the heterogeneity of the groups of patients included in the trial. In addition, the potential danger of severe complications requires caution when using them.

Nevertheless, long-term observation has made it possible to develop specific indications for the use of these drugs. Indications for their inclusion in the complex treatment of patients with systemic lupus erythematosus are: 1) active lupus nephritis; 2) high overall disease activity and resistance to corticosteroids or the appearance of adverse reactions of these drugs already in the first stages of treatment (especially the phenomena of hypercortisolism in adolescents, developing already with small doses of prednisolone); 3) the need to reduce the maintenance dose of prednisolone if it exceeds 15-20 mg/day.

There are various combination treatment regimens: Azathioprine and cyclophosphamide orally at an average dose of 2-2.5 mg/(kg day), chlorobutine 0.2-0.4 mg/(kg day) in combination with low (25 mg) and medium (40 mg) doses prednisone. In recent years, several cytostatics have been used simultaneously: azathioprine + cyclophosphamide (1 mg/kg per day orally) in combination with low doses of prednisolone; a combination of oral azathioprine with intravenous cyclophosphamide (1000 mg per 1 m 3 of body surface every 3 months). With this combination treatment, a slowdown in the progression of lupus nephritis was noted.

In recent years, methods of only intravenous administration of cyclophosphamide have been proposed (1000 mg per 1 m 3 of body surface once a month in the first six months, then 1000 mg per 1 m 3 of body surface every 3 months for 1.5 years) against a background of low doses of prednisolone.

Comparison of the effectiveness of azathioprine and cyclophosphamide in double-blind controlled trials showed that cyclophosphamide was more effective in reducing proteinuria, reducing changes in urinary sediment, and the synthesis of antibodies to DNA. In our comparative study (double-blind method) of three drugs - azathioprine, cyclophosphamide and chlorambucil - it was noted that chlorambucil is similar in its effect on “renal” parameters to cyclophosphamide. A clear effect of chlorambucil on articular syndrome was also revealed, while azathioprine turned out to be most effective for diffuse skin lesions.

The effectiveness of cytostatics in SLE is confirmed by the fact of suppression of pronounced immunological activity. J. Hayslett et al. (1979) noted a significant decrease in inflammatory phenomena in a kidney biopsy in 7 patients with severe diffuse proliferative nephritis. When combining treatment with corticosteroids and azathioprine, S. K. Soloviev et al. (1981) discovered a change in the composition of deposits in the dermoepidermal junction during a dynamic immunofluorescent study of a skin biopsy: under the influence of cytostatics in patients with active lupus nephritis, the IgG glow disappeared.

The introduction of cytostatics into the treatment complex makes it possible to suppress disease activity with lower doses of corticosteroids in patients with highly active SLE. The survival rate of patients with lupus nephritis has also increased. According to I. E. Tareeva and T. N. Yanushkevich (1985), 10-year survival is observed in 76% of patients with combined treatment and in 58% of patients treated with prednisolone alone.

With individual selection of doses and regular monitoring, the number of adverse reactions and complications can be significantly reduced. Such serious complications as malignant tumors such as reticulosarcomas, lymphomas, leukemia, hemorrhagic cystitis and bladder carcinoma are extremely rare. Of the 200 patients who received cytostatics at the Institute of Rheumatology of the Russian Academy of Medical Sciences and were observed from 5 to 15 years, one patient developed gastric reticulosarcoma, which does not exceed the incidence of tumors in patients with autoimmune diseases not treated with cytostatics.

The Standing Committee of the European League Against Rheumatism, which studied the results of the use of cytostatic immunosuppressants in 1375 patients with various autoimmune diseases, has not yet recorded a higher incidence of malignant neoplasms in them compared to the group in which these drugs were not used. We observed agranulocytosis in two patients. It was controlled by increasing the dose of corticosteroids. Attachment of a secondary infection, including viral ( herpeszoster), was no more common than in the group treated with prednisolone only.

Nevertheless, taking into account the possibility of complications of cytostatic therapy, strict justification for the use of these potent drugs, careful monitoring of patients, and examination of them every week from the moment treatment is prescribed are necessary. Evaluation of long-term results shows that if the treatment method is followed, the number of complications is small, and there is no harmful effect of therapy on the next generation. According to our data, 15 children born to patients with systemic lupus erythematosus treated with cytostatics are healthy (their follow-up period was more than 12 years).

Plasmapheresis, hemosorption

Due to the lack of perfect methods for treating patients with SLE, the search continues for new means to help patients for whom conventional methods do not give a favorable result.

The use of plasmapheresis and hemosorption is based on the possibility of removing biologically active substances from the blood: inflammatory mediators, circulating immune complexes, cryoprecipitins, various antibodies, etc. It is believed that mechanical purification helps to unload the mononuclear cell system for a while, thus stimulating the endogenous phagocytosis of new complexes, which ultimately reduces the degree of organ damage.

It is possible that during hemosorption there is not just binding of serum immunoglobulins, but also a change in their composition, which leads to a decrease in the mass of immune complexes and facilitates the process of their removal from the bloodstream. It is possible that when blood passes through the sorbent, immune complexes change their charge, which explains the pronounced improvement observed in patients with kidney damage even with a constant level of immune complexes in the blood. It is known that only positively charged immune complexes are capable of depositing on the basement membrane of the glomeruli of the kidney.

A generalization of experience in the use of plasmapheresis and hemosorption shows the feasibility of including these methods in the complex treatment of patients with SLE with a torpid course of the disease and resistance to previous therapy. Under the influence of the procedures (3-8 per course of treatment), there is a significant improvement in the general well-being of patients (often not correlating with a decrease in the level of circulating immune complexes and antibodies to DNA), a decrease in signs of disease activity, including nephritis with preservation of kidney function, the disappearance of pronounced skin changes and a distinct acceleration of healing of trophic ulcers of the extremities. Both plasmapheresis and hemosorption are carried out while taking corticosteroids and cytostatics.

Although there is not yet sufficient data obtained from control studies and in determining the survival of patients treated with plasmapheresis or hemosorption, the use of these methods opens up new opportunities for reducing high disease activity and preventing its progression as a result of influencing the immunopathological process.

Among other methods of so-called aggressive therapy used for severe forms of systemic lupus erythematosus, mention should be made of local X-ray irradiation of the supra and subdiaphragmatic lymph nodes (up to 4000 rad per course). This makes it possible to reduce extremely high disease activity, which is not achievable with other treatment methods. This method is under development.

Immunomodulatory drugs- levamisole, frentisole - have not received widespread use in SLE, although there are individual reports of the effect obtained when these drugs are included in therapy with corticosteroids and cytostatics in forms of the disease refractory to conventional treatment methods or when a secondary infection is attached. Most authors report a large number of serious complications in almost 50% of patients treated with levamisole. During more than 20 years of observation of patients with SLE, we used levamisole in isolated cases and always noted serious complications. A controlled trial of levamisole in systemic lupus erythematosus showed no efficacy. Apparently, it is advisable to add levamisole in cases of severe bacterial infection.

Aminoquinoline derivatives and non-steroidal anti-inflammatory drugs serve as the main drugs in the treatment of patients with SLE without severe visceral manifestations and during the period of reducing doses of corticosteroids and cytostatics to maintain remission. Our long-term observation has shown that the risk of developing ophthalmological complications is significantly exaggerated. This is also emphasized by J. Famaey (1982), who notes that complications develop only at a dose significantly higher than the optimal daily dose. At the same time, long-term use of these drugs in the complex treatment of patients with SLE is very effective.

Of the aminoquinoline drugs, delagil (0.25-0.5 g/day) and plaquenil (0.2-0.4 g/day) are usually used. Of the nonsteroidal anti-inflammatory drugs, indomethacin is most often used as an additional drug for persistent arthritis, bursitis, polymyalgia, as well as voltaren and ortofen.

Treatment of patients with SLE with central nervous system involvement

The reason for the decrease in mortality in acute severe lesions of the central nervous system and kidneys was the use of corticosteroids in large doses. Currently, many researchers believe that acute psychoneurological symptoms (transverse myelitis, acute psychosis, severe focal neurological symptoms, statusepilepticus) are an indication for the prescription of corticosteroids in doses of 60-100 mg/day. For indolent cerebral disorders, high doses of corticosteroids (more than 60 mg/day) are hardly advisable. Many authors unanimously note that corticosteroids form the basis of the treatment of patients with neuropsychiatric symptoms.

In cases where neuropsychiatric disorders occur while taking corticosteroids and it is difficult to determine whether they are caused by prednisolone or active systemic lupus erythematosus, increasing the dose of prednisolone is safer than decreasing it. If neuropsychiatric symptoms increase when the dose is increased, the dose can always be reduced. Of the cytostatics, cyclophosphamide is the most effective, especially its intravenous administration in the form of pulse therapy. Often, in acute psychosis, along with prednisolone, it is necessary to use antipsychotics, tranquilizers, and antidepressants to relieve psychosis.

Upon appointment anticonvulsants It is important to remember that anticonvulsants accelerate the metabolism of corticosteroids, which may require increasing the dose of the latter. For chorea, the effectiveness of prednisolone has not been proven; there are cases of its spontaneous relief. Recently, anticoagulants have been used to treat chorea. In the most severe situations associated with damage to the central nervous system, pulse therapy and plasmapheresis are performed.

Massive intravenous therapy with methylprednisolone (500 mt daily for 4 days) is also effective for cerebrovasculitis with initial signs of coma. However, three cases of signs of damage to the nervous system appearing after pulse therapy in patients with a previously intact central nervous system. The cause of this complication may be a sharp water-electrolyte disturbance in the central nervous system, a violation of the permeability of the blood-brain barrier, and the removal of immune complexes through the reticuloendothelial system.

With the improvement of the prognosis of SLE in general against the background of adequate treatment, mortality in cases of central nervous system damage has also decreased. Nevertheless, the development of adequate therapeutic and rehabilitation measures for damage to the central nervous system requires continued research in this area.

Corticosteroids and cytostatics in various regimens and combinations remain the basis for the treatment of lupus nephritis.

Many years of experience of two centers (Institute of Rheumatology of the Russian Academy of Medical Sciences, I.M. Sechenov Moscow Medical Academy) made it possible to develop treatment tactics for patients with lupus nephritis, depending on the activity and clinical form of nephritis.

For rapidly progressing glomerulonephritis, when rapid nephrotic syndrome, high hypertension and renal failure are observed at an early stage of the disease, the following regimens can be selectively used:

1) pulse therapy with methylprednisolone + cyclophosphamide 3-6 times monthly, in between - prednisolone 40 mg per day with a dose reduction by the 6th month to 30-20 mg / day and in the next 6 months - to a maintenance dose of 5-10 mg /day, which should be taken for 2-3 years, and sometimes for life. Maintenance therapy is required when using any of the treatment regimens carried out in a hospital, and usually includes, in addition to corticosteroids and cytostatics, aminoquinoline drugs (1-2 tablets per day of Plaquenil or Delagil), antihypertensives, diuretics, angioprotectors, disaggregants, which should be taken in for 6-12 months (courses are repeated if necessary);

2) prednisolone 50-60 mg/day + cyclophosphamide 100-150 mg/day for 2 months in combination with heparin 5000 units 4 times a day for 3-4 weeks and chimes 600-700 mg per day. Then the daily doses of prednisolone are reduced to 40-30 mg, cyclophosphamide to 100-50 mg and treatment is carried out for another 2-3 months, after which maintenance therapy is prescribed in the doses indicated above (see point 1).

Both treatment regimens should be carried out against the background of plasmapheresis or hemosorption (prescribed once every 2-3 weeks, a total of 6-8 procedures), antihypertensive and diuretic drugs. In case of persistent edema, plasma ultrafiltration can be resorted to; in case of increasing renal failure, 1-2 courses of hemodialysis are advisable.

For nephrotic syndrome, you can choose one of the following three regimens:

1) prednisolone 50-60 mg per day for 6-8 weeks, followed by a dose reduction to 30 mg for 6 months and to 15 mg over the next 6 months;

2) prednisolone 40-50 mg + cyclophosphamide or azathioprine 100-150 mg per day for 8-12 weeks, subsequently the rate of reduction in the dose of prednisolone is the same, and cytostatics continue to be prescribed at 50-100 mg/day for 6-12 months;

3) combined pulse therapy with methylprednisolone and cyclophosphamide or an intermittent regimen: pulse therapy with methylprednisolone - hemosorption or plasmapheresis - pulse therapy with cyclophosphamide followed by treatment with oral prednisolone 40 mg per day for 4-6 weeks and then switching to a maintenance dose for 6 weeks 12 months

Symptomatic therapy remains important.

For active nephritis with severe urinary syndrome (proteinuria 2 g/day, erythrocyturia 20-30 in the field of view, but blood pressure and renal function are not significantly changed), treatment regimens may be as follows:

1) prednisolone 50-60 mg 4-6 weeks + aminoquinoline drugs + symptomatic agents;

2) prednisolone 50 mg + cyclophosphamide 100 mg per day for 8-10 weeks, then the rate of reduction in the doses of these drugs and maintenance therapy are carried out as indicated above;

3) pulse therapy with methylprednisolone, combined with cyclophosphamide, is possible (3-day course of 1000 mg methylprednisolone every day and 1000 mg cyclophosphamide one day), followed by prednisolone 40 mg for 6-8 weeks, then dose reduction for 6 months up to 20 mg/day. Then, for many months, maintenance therapy according to the principles described above.

In general, active therapy for patients with lupus nephritis should be carried out for at least 2-3 months. After the exacerbation subsides, long-term maintenance therapy is prescribed with small doses of prednisolone (at least 2 years after the exacerbation), cytostatics (at least 6 months), aminoquinoline drugs, sometimes methindole, chimes, antihypertensives, and sedatives. All patients with lupus nephritis should undergo regular examinations at least once every 3 months with assessment of clinical and immunological activity, determination of renal function, proteinuria, and urinary sediment.

When treating patients with terminal lupus nephritis and nephrosclerosis, hemodialysis and kidney transplantation are used, which can significantly increase life expectancy. Kidney transplantation is performed in patients with SLE with a developed picture of uremia. The activity of systemic lupus erythematosus usually completely subsides by this time, so fears of an exacerbation of SLE with the development of lupus nephritis in the graft should be considered not entirely justified.

Prospects for treating patients with SLE, undoubtedly, behind biological methods of influence. In this regard, the use of anti-idiotypic monoclonal antibodies offers great opportunities. So far, only the experiment has shown that the repeated use of syngeneic monoclonal IgG antibodies to DNA obtained using the hybridoma technique delayed the development of spontaneous glomerulonephritis in New Zealand mouse hybrids by suppressing the synthesis of particularly damaging IgG antibodies to DNA, which carry a cationic charge and are nephritogenic.

Currently, the question of a dietary regimen for systemic lupus erythematosus has again been raised, since there is evidence of the influence of certain nutrients on the mechanism of inflammation, for example, on the concentration of precursors of inflammatory mediators in cell membranes, an increase or decrease in the response of lymphocytes, the concentration of endorphins and other intimate metabolic factors. mechanisms. The experiment obtained data on an increase in the life expectancy of New Zealand mouse hybrids even with a decrease in the total amount of food in the diet, and even more so with an increase in the content of eicosapentanoic acid, a representative of unsaturated fatty acids, in food to 25%.

A reduced content of linoleic acid in food leads to a decrease in the synthesis of prostaglandins and leukotrienes, which have a pro-inflammatory effect. In turn, with an increase in the content of unsaturated acids in food, the intensity of the processes of inflammation and fibrosis formation decreases. Knowing the effect of a diet with a certain content of fatty acids on various manifestations of the disease in an experiment, one can approach the study of the effect of dietary regimens on the development of pathology in autoimmune diseases in humans.

Therapeutic programs for the main clinical variants of systemic lupus erythematosus are carried out against the background of corticosteroids and cytostatics prescribed orally, symptomatic drugs, including antihypertensive drugs, angioprotectors, disaggregants, etc. Thus, although the problem of treating SLE cannot be considered completely solved, modern methods of therapy make it possible to achieve significant improvement in most patients, maintaining their ability to work and returning them to a normal lifestyle.

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

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 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. Now, after more than 50 years of trying to develop a specific treatment for lupus, a shift has occurred: the US Food and Drug Administration has officially approved Benlysta, a monoclonal antibody that specifically blocks B lymphocytes, as a drug for lupus. stimulating protein (BLyS).

Systemic lupus erythematosus (SLE) is one of the most common autoimmune diseases, which is based on a genetically determined complex disorder of immunoregulatory mechanisms. During the disease, a wide range of autoantibodies to various components of the cell nucleus are formed and immune complexes are formed. Immune inflammation developing in various organs and tissues leads to extensive damage to the microcirculatory bloodstream and systemic disorganization of 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 disconcerting “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 disturbances in the level of proliferation of various clones of B cells, activated by numerous antigens, which can be medications, bacterial or viral DNA, and even mitochondrial membrane phospholipids. The interaction of antigens with leukocytes is associated either with the uptake of antigens by antigen presenting cells (APCs) or with the interaction of antigen with antibody on the surface of the 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, and T-helper cells differentiate excessively and uncontrollably. Various immunoregulatory defects characteristic of SLE are also associated with overproduction of Th2-type cytokines (IL-2, IL-6, IL-4, IL-10 IL-12).

One of the key points in the disruption of immune regulation in SLE is the difficult 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 a ratio of sick women to men of 18:1. Most often, the disease develops in women of reproductive age with an increased risk of exacerbation during pregnancy, in the postpartum period, as well as after sun exposure and vaccination.

SLE often causes disability. In developed countries, on average 3.5 years after diagnosis, 40% of SLE patients completely stop working, mainly due to neurocognitive dysfunction and increased fatigue. Discoid lupus and lupus nephritis most often lead to 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, one can observe different, successive 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 taking anti-inflammatory drugs, the action of which is aimed at suppressing immune complex inflammation, both during exacerbation and during remission. The main drugs for the treatment of SLE are:

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

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

“I know the password, I see a landmark”

In the late 1990s, the biopharmaceutical company Human Genome Sciences (Rockville, Maryland, USA) discovered a molecular pathway that, by “narrowing” it, can to some extent curb the development of SLE. This pathway involves a protein called B-lymphocyte stimulator (or BLyS), a cytokine from the tumor necrosis factor family. It has been found that inhibiting BLyS can somewhat contain the immune system and reduce the number of B-lymphocyte colonies that produce autoantibodies that attack healthy tissue.

The researchers, wanting to specifically block BLyS, relied on a human monoclonal antibody, developed jointly with the English biotechnology company Cambridge Antibody Technology, and 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. This drug became Benlysta - the commercial name of the antibody belimumab, which is already being produced by GlaxoSmithKline. Previously, the FDA had approved hydroxychloroquine, a malaria drug, for the treatment of SLE; this was in 1956.

Figure 2. A person with systemic lupus erythematosus(watercolor 1902 by Mabel Green). The disease got its name back in the Middle Ages, when people thought 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 testing, no lupus drug had ever reached phase III trials - a randomized multicenter trial involving a large population of patients. (For information about the drug development process and clinical trials, see “Drug Design: How New Drugs Are Created in the Modern World.”) The fact is that the “rigorous” clinical testing system, based on the ideology of evidence-based medicine, simply did not allow drugs to pass through. candidates,” which turned out to be simply ineffective or dangerous to the health of patients.

“It was simply impossible 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 City rheumatologist who led the belimumab clinical trial. - "People openly said, 'You'll never succeed.[in clinical studies] “» .

Targeted Therapy

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

In the course of studying BLyS, HGS researchers discovered that the amount of this cytokine increases greatly during inflammation, and especially in patients with lupus. This was a very important clue, although it was clear from the very beginning that the road ahead would not be easy, given the number of clinical trials of drugs 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 severe lifelong burden in others - which probably prompted the writers of House to include lupus in the series in such an exaggerated context.

By the way, there is even a monument to the BLyS cytokine, 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” the protein from her father for sculpting. The sculpture was installed in the American Research Institute Cold Spring Harbor.

The action of drugs that selectively “turn off” certain branches of the immune system at the molecular level must be very precise. For example, in 2008, clinical trials of atacicept failed ( atacicept), inhibiting not only BLyS, but also another related protein. Testing on patients with a severe form of lupus - lupus nephritis - had to be urgently stopped due to an abnormally high number of adverse infections in those taking the drug. A similar situation occurred with the antibody ocrelizumab ( ocrelizumab), blocking the work of B-lymphocytes by a different mechanism.

Next in line

Belimumab is only the first drug that is being tested 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. A bright future is predicted for belimumab itself - from the point of view of the pharmaceutical giants, this means billions in sales, putting the drug on the coveted list of “blockbusters”. By the way, this does not mean a complete cure for the disease for millions of patients - the effectiveness of the drug is not so high (according to