Well forms Lupus erythematosus (disease). Signs of lupus erythematosus. Drug-induced lupus syndrome

A disease that manifests itself in skin lesions is called lupus erythematosus. This term comes from the fact that the damage during the development of the disease is similar to a wolf bite. You can notice the first signs of problems with the immune system and a genetic predisposition to inflammatory processes in internal organs.

The most susceptible group of people are young women and girls aged about 14-20 years. After therapy, a certain lifestyle and regular intake of necessary medications are required.

Causes of the disease

It is impossible to name one reason why a particular person developed lupus erythematosus. Several factors can be identified that provoke the development of a dangerous disease. For example, genetic features, hormonal imbalances and other serious health problems. In addition, there are some reasons that negatively affect the development of the disease.

1. Heredity. If there have been several recorded outbreaks of lupus in the family, then there is a high risk that the disease will return again, even after several generations.
2. According to most scientists, the Epstein-Barr virus can provoke an inflammatory process.
3. A surge in the hormone estrogen, according to other medical professionals, occurs before the first signs of lupus develop and may also be a cause.
4. Allergic reaction to frost.

Most often, this disease appears in women. According to statistics, women suffer from lupus 8 times more often than men. This is explained simply: girls more often spend time in the open sun or in a solarium, achieving a perfect tan. With prolonged exposure to the sun, mutation processes often develop in the body. A similar problem appears due to the estrogen saturation experienced by young girls of childbearing age.

The following reasons may increase the risk of lupus:

• immunodeficiency syndrome;
• the presence of infections in the body;
• skin diseases;
• frequent symptoms of colds and flu;
• bad habits that reduce immunity (smoking, drinking alcohol and drugs);
• disturbances in the functioning of the endocrine system.

There are cases of lupus developing in a mother almost immediately after the birth of a child. This is explained by the weakened immunity of the mother in labor, frequent stress, and non-compliance with the rest regime. Sudden changes in hormonal levels that occur when taking certain drugs negatively affect the functioning of internal organs and affect health.

Symptoms and signs

Discoid lupus erythematosus can be localized in many places in the human body: in the respiratory system, on the mucous membranes and skin, in the circulatory system, etc. The general symptoms of the disease are the same and cannot be ignored. The patient begins to experience weakness, malaise, loss of appetite and chills. During illness, red spots appear on the body, which have clear contours and peel off. In addition, exacerbation of old chronic diseases often occurs, which is why it is sometimes difficult to independently find out the true cause of poor health.

The danger of the disease is that symptoms often disappear a short time after an exacerbation, but this does not mean the disease has subsided. Most often, people mistakenly think that the disease has gone away on its own and there is no need to start treatment. In fact, at this moment, damage to internal tissues and organs occurs. Then the symptoms appear again, but more pronounced, so it is important to recognize the signs in time and begin treatment as soon as possible. Dangerous complications of the disease can be prevented by contacting a medical facility in a timely manner.

Manifestation of the dermatological plan

Skin lesions are easy to recognize: small red spots appear on the cheeks, cheekbones, under the eyes or in the décolleté area, which gradually merge into a large spot. The skin becomes uneven and peels. The spot is located symmetrically on both cheeks, capturing the bridge of the nose, and resembles a butterfly in shape. With prolonged exposure to the sun, dryness and itching appear due to microcracks in the dermis. Subsequently, the skin may heal and leave a large scar. In addition to the appearance of spots on the face and neck, edematous redness with points of hemorrhage are noticeable on the legs and arms, which indicates that the problem is advanced. A pink rash on the head can sometimes cause partial baldness, and on the hands – changes in the nails to serious deformation. In addition to the listed signs, the patient notices itching and swelling of the skin, constantly experiences headaches and mood swings.

Manifestation of orthopedic type

The disease can be identified by pain in the joints, which most often occurs in the arms, knees and legs. The disease causes arthralgia and arthritis, but lupus erythematosus does not cause bone destruction. However, the joints are damaged and cause severe discomfort to the person. Upon examination, it is easy to notice swelling of the inflamed small joints in the area of ​​the fingers and toes.

Hematological signs of the disease

Systemic lupus often causes the development of hematological syndrome, which manifests itself in autoimmune thrombocytopenia, lymphopenia, anemia and leukopenia. These diseases appear not only from lupus, but also after taking the necessary therapy.

Manifestation of heart character

As lupus erythematosus progresses, tissue grows inside the heart muscle. Such tissue does not serve any function, but on the contrary interferes with the normal functioning of the heart, which is why the mitral valve fuses with other parts of the atria. Due to such deviations, irreversible changes can occur: heart attack, coronary heart disease and heart failure.

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Significant factors associated with kidneys

Lupus also provokes the occurrence of diseases of the kidneys and genitourinary system. For example, patients develop nephritis, renal failure and pyelonephritis. Untimely treatment of these diseases is a threat to human life, often resulting in complications and even death.

Manifestation of a neurological nature

Lupus erythematosus affects not only internal organs, but also the central nervous system. The sick person often experiences severe headaches, neuroses and sudden changes in mood, reaching the point of aggression at the slightest provocation. When the nervous system is damaged, seizures, psychosis and stroke often appear. These syndromes often persist for a long time even with therapy.

Tests for lupus erythematosus: what needs to be taken

At the first suspicion of lupus erythematosus, as well as if several symptoms are detected, you should immediately see a doctor. You cannot wait for the patient’s condition to worsen and try to prescribe treatment on your own. This way, a person risks getting not only a dose of unnecessary drugs, but also additional problems with the stomach or liver.

To make an accurate diagnosis, you should take a blood and urine test. Before donating blood, you need to avoid fatty, fried and junk foods 8 hours before the procedure. During the day, it is necessary to completely eliminate alcohol and limit smoking, if possible. You are only allowed to drink clean, still water. When taking blood for markers of lupus erythematosus, indicators of the following diseases are examined:

• lupus (red, cutaneous or drug);
• rheumatism;
• periarteritis;
• thrombocytopenic purpura;
• anemia;
• tuberculosis;
• liver diseases;
• erythroderma;
• leukemia;
• chronic arthritis.

When studying blood samples, they contain high levels of fibrinogen, sialic acids and a high content of lupus cells. This indicator is valid when more than 5 LE cells are detected per 1000 units of leukocytes. After submitting urine for analysis, proteinuria, cylindruria and erythrocyturia can be detected.

Modern methods of diagnosis and treatment

It is almost impossible to diagnose erythematous lupus on your own without waiting for red spots to appear on the skin. The specialist must conduct an examination and prescribe a number of research procedures. After them, the diagnosis is made based on major and minor diagnostic signs. Major signs of the disease include lupus arthritis, butterfly-shaped spots on the face, anemia, the presence of LE cells and DNA antibodies in the blood. Minor symptoms include leukopenia, malgia, lymphadenopathy, the appearance of capillaries on the fingers and fever. To make a diagnosis, the doctor must be guided by a system that was developed in America. Lupus erythematosus is defined by the presence of more than 4 of the 11 main signs of the disease:

• flaky spots on the face;
• rashes on the arms, legs and other parts of the body;
• skin pigmentation when exposed to the sun or when using an ultraviolet lamp;
• the appearance of ulcers on the mucous membranes, which prevent a person from eating, drinking and talking;
• the first symptoms of arthritis or pain in the joints;
• inflammatory processes in the body;
• diseases of the genitourinary system;
• unstable emotional state;
• abnormalities in blood tests;
• increasing the level of antinuclear antibodies;
• immune system disorders.

Of course, one cannot be guided only by general signs, but if several from the list are identified, the person should be sent for a narrowly targeted diagnosis. When examining and interviewing the patient, the doctor finds out what diseases the person has recently suffered and what he did for treatment. The doctor must also be informed about hereditary diseases and abnormalities.

When ulcers appear on the mucous membranes and skin, they should be examined using a Wood's lamp. This research method helps to distinguish lupus from lichen ruber, tuberculous lupus and other skin rashes.

Treatment is selected for each patient individually, based on the person’s condition, severity of the disease, number of symptoms, age and gender. It is possible to carry out therapy with prescribed drugs at home for several months. Hospitalization is necessary in cases where there is a threat to a person’s health and life: suspected pneumonia, stroke, heart attack, fever up to 39 degrees and a sharp deterioration in condition. In any case, treatment should include the following medications or their analogues:

• Hormonal drugs - Prednisolone or Cyclophosphamide during an exacerbation of lupus erythematosus;
• Diclofenac to relieve inflammation in joints;
• Ibuprofen or Paracetamol to lower the temperature and reduce pain.

Ointments, solutions and creams based on hormonal agents will help restore the skin and get rid of itching, flaking or dryness. If you have skin rashes, you should limit your time in the sun. Ultraviolet rays negatively affect the course of the disease, so it is better to use creams to protect against UV rays with an SPF level of at least 30.

To improve immunity, taking vitamins is not enough. It is necessary to use immunostimulants, as well as attend physical procedures that will help relieve attacks of pain.

Almost all sick people are interested in: how long do they live with this disease? Lupus erythematosus is not a death sentence and after treatment you can live for a long time. The main thing is to recognize the disease in time, visit a medical facility and take medications. To prevent the disease from returning, you need to carefully monitor your health and regularly visit your doctor. Nutrition should be balanced, with useful trace elements and minerals. Alcohol and smoking must be completely eliminated, as bad habits greatly affect the immune system. We should not forget about protection from sunlight even in autumn and winter.

Video: all about lupus erythematosus

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Systemic lupus erythematosus (SLE)– a chronic autoimmune disease caused by a disruption of the immune mechanisms with the formation of damaging antibodies to one’s own cells and tissues. SLE is characterized by damage to joints, skin, blood vessels and various organs (kidneys, heart, etc.).

Cause and mechanisms of disease development

The mechanisms of the disease are based on dysfunction of immune cells (T and B lymphocytes), which is accompanied by excessive formation of antibodies to the body’s own cells. As a result of excessive and uncontrolled production of antibodies, specific complexes are formed that circulate throughout the body. Circulating immune complexes (CIC) settle in the skin, kidneys, and on the serous membranes of internal organs (heart, lungs, etc.) causing inflammatory reactions.

Symptoms of the disease

• Fatigue
• Weight loss
• Temperature
• Decreased performance
• Fast fatiguability

Damage to the musculoskeletal system

• Arthritis – inflammation of the joints
  • Occurs in 90% of cases, non-erosive, non-deforming, the joints of the fingers, wrists, and knee joints are most often affected.
• Osteoporosis – decreased bone density
  • As a result of inflammation or treatment with hormonal drugs (corticosteroids).

• Muscle pain (15-64% of cases), muscle inflammation (5-11%), muscle weakness (5-10%)

Damage to mucous membranes and skin

• Skin lesions at the onset of the disease appear in only 20-25% of patients, in 60-70% of patients they appear later, in 10-15% skin manifestations of the disease do not occur at all. Skin changes appear on areas of the body exposed to the sun: face, neck, shoulders. The lesions have the appearance of erythema (reddish plaques with peeling), dilated capillaries at the edges, areas with excess or lack of pigment. On the face, such changes resemble the appearance of a butterfly, as the back of the nose and cheeks are affected.
• Hair loss (alopecia) occurs rarely, usually affecting the temporal areas. Hair falls out in a limited area.
• Increased sensitivity of the skin to sunlight (photosensitization) occurs in 30-60% of patients.
• Damage to the mucous membranes occurs in 25% of cases.
  • Redness, decreased pigmentation, impaired nutrition of lip tissue (cheilitis)
  • Pinpoint hemorrhages, ulcerative lesions of the oral mucosa

Respiratory system damage

Damage to the cardiovascular system

• Pericarditis is an inflammation of the serous membranes covering the heart muscle.

• Myocarditis is inflammation of the heart muscle.

• Damage to the heart valves, most often the mitral and aortic valves are affected.
• Damage to the coronary vessels can lead to myocardial infarction, which can also develop in young patients with SLE.
• Damage to the inner lining of blood vessels (endothelium) increases the risk of developing atherosclerosis. Peripheral vascular damage manifests itself:
  • Livedo reticularis (blue spots on the skin creating a grid pattern)
  • Lupus panniculitis (subcutaneous nodules, often painful, may ulcerate)
  • Thrombosis of blood vessels of the extremities and internal organs

Kidney damage

Damage to the central nervous system

• Headache and migraine, the most common symptoms in SLE
• Irritability, depression – rare
• Psychoses: paranoia or hallucinations
• Brain stroke
• Chorea, parkinsonism – rare
• Myelopathies, neuropathies and other disorders of nerve sheath (myelin) formation
• Mononeuritis, polyneuritis, aseptic meningitis

Damage to the digestive tract

• Damage to the esophagus, impaired swallowing, dilatation of the esophagus occurs in 5% of cases
• Ulcers of the stomach and 12th intestine are caused both by the disease itself and by the side effects of treatment
• Abdominal pain as a manifestation of SLE, and can also be caused by pancreatitis, inflammation of the intestinal vessels, intestinal infarction
• Nausea, abdominal discomfort, indigestion

• Hypochromic normocytic anemia occurs in 50% of patients, the severity depends on the activity of SLE. Hemolytic anemia is rare in SLE.
• Leukopenia is a decrease in leukocytes in the blood. Caused by a decrease in lymphocytes and granulocytes (neutrophils, eosinophils, basophils).
• Thrombocytopenia is a decrease in platelets in the blood. Occurs in 25% of cases, caused by the formation of antibodies against platelets, as well as antibodies to phospholipids (fats that make up cell membranes).

Diagnosis of SLE

Criteria for the diagnosis of systemic lupus erythematosus

The diagnosis of SLE is made if at least 4 out of 11 criteria are present.

Disease activity indices bySLEDAI

• Light activity: 1-5 points
• Moderate activity: 6-10 points
• High activity: 11-20 points
• Very high activity: more than 20 points

Diagnostic tests used to detect SLE

1. ANA- screening test, specific antibodies to cell nuclei are determined, detected in 95% of patients, does not confirm the diagnosis in the absence of clinical manifestations of systemic lupus erythematosus
2. Anti DNA– antibodies to DNA, detected in 50% of patients, the level of these antibodies reflects the activity of the disease
3. Anti-Sm – specific antibodies to the Smith antigen, which is part of short RNAs, are detected in 30-40% of cases
4. Anti –SSA or Anti-SSB, antibodies to specific proteins located in the cell nucleus, are present in 55% of patients with systemic lupus erythematosus, are not specific for SLE, and are also detected in other connective tissue diseases
5. Anticardiolipin - antibodies to mitochondrial membranes (cell energy station)
6. Antihistones– antibodies against proteins necessary for packaging DNA into chromosomes, characteristic of drug-induced SLE.

• Markers of inflammation
  • ESR – increased
  • C – reactive protein, increased

• Compliment level reduced
  • C3 and C4 are reduced as a result of excessive formation of immune complexes
  • Some people have a reduced level of compliment from birth, this is a predisposing factor to the development of SLE.

• General blood analysis
  • Possible decrease in red blood cells, white blood cells, lymphocytes, platelets

• Analysis of urine
  • Protein in urine (proteinuria)
  • Red blood cells in urine (hematuria)
  • Casts in the urine (cylindruria)
  • White blood cells in urine (pyuria)

• Blood chemistry
  • Creatinine – an increase indicates kidney damage
  • ALAT, ASAT – an increase indicates liver damage
  • Creatine kinase – increases with damage to the muscular system

• X-ray of joints

• X-ray and computed tomography of the chest

• Nuclear magnetic resonance and angiography

• Echocardiography

• A spinal tap can rule out infectious causes of neurological symptoms.
• A kidney biopsy (analysis of organ tissue) allows you to determine the type of glomerulonephritis and facilitate the choice of treatment tactics.
• A skin biopsy allows you to clarify the diagnosis and exclude similar dermatological diseases.

Treatment of systemic lupus

• Eliminate physical and mental stress conditions
• Reduce sun exposure and use sunscreen

1. Glucocorticosteroids the most effective drugs in the treatment of SLE.

• Inside:
  • Initial dose of prednisolone 0.5 – 1 mg/kg
  • Maintenance dose 5-10 mg
  • Prednisolone should be taken in the morning, the dose is reduced by 5 mg every 2-3 weeks

• Intravenous administration of methylprednisolone in large doses (pulse therapy)
  • Dose 500-1000 mg/day, for 3-5 days
  • Or 15-20 mg/kg body weight

Indications for pulse therapy: young age, fulminant lupus nephritis, high immunological activity, damage to the nervous system.

• 1000 mg methylprednisolone and 1000 mg cyclophosphamide on the first day

1. Cytostatics: cyclophosphamide (cyclophosphamide), azathioprine, methotrexate, are used in the complex treatment of SLE.

• Acute lupus nephritis
• Vasculitis
• Forms refractory to treatment with corticosteroids
• The need to reduce corticosteroid doses
• High SLE activity
• Progressive or fulminant course of SLE

• Cyclophosphamide during pulse therapy is 1000 mg, then 200 mg every day until a total dose of 5000 mg is reached.
• Azathioprine 2-2.5 mg/kg/day
• Methotrexate 7.5-10 mg/week, orally

1. Anti-inflammatory drugs

• Naklofen, nimesil, airtal, katafast, etc.

1. Aminoquinoline drugs

• delagil, plaquenil, etc.

1. Biological drugs are a promising treatment for SLE

• Anti CD 20 – Rituximab
• Tumor necrosis factor alpha – Remicade, Gumira, Embrel

1. Other drugs

• Anticoagulants (heparin, warfarin, etc.)
• Antiplatelet agents (aspirin, clopidogrel, etc.)
• Diuretics (furosemide, hydrochlorothiazide, etc.)
• Calcium and potassium preparations

1. Extracorporeal treatment methods

• Plasmapheresis is a method of purifying blood outside the body, in which part of the blood plasma is removed, and with it the antibodies that cause the disease SLE.
• Hemosorption is a method of purifying blood outside the body using specific sorbents (ion exchange resins, activated carbon, etc.).

What are the complications and prognosis for life with systemic lupus erythematosus?

Variants of the course of systemic lupus erythematosus:

1. Acute course- characterized by a lightning-fast onset, a rapid course and the rapid simultaneous development of symptoms of damage to many internal organs (lungs, heart, central nervous system, and so on). The acute course of systemic lupus erythematosus, fortunately, is rare, since this option quickly and almost always leads to complications and can cause the death of the patient.
2. Subacute course– characterized by a gradual onset, alternating periods of exacerbations and remissions, a predominance of general symptoms (weakness, weight loss, low-grade fever (up to 38 0

C) and others), damage to internal organs and complications occur gradually, no earlier than 2-4 years after the onset of the disease.
3. Chronic course– the most favorable course of SLE, there is a gradual onset, damage mainly to the skin and joints, longer periods of remission, damage to internal organs and complications occur after decades.

Damage to organs such as the heart, kidneys, lungs, central nervous system, and blood, which are described as symptoms of the disease, in fact, are complications of systemic lupus erythematosus.

But we can highlight complications that lead to irreversible consequences and can lead to the death of the patient:

1. Systemic lupus erythematosus– affects the connective tissue of the skin, joints, kidneys, blood vessels and other structures of the body.

2. Drug-induced lupus erythematosus– unlike the systemic type of lupus erythematosus, a completely reversible process. Drug-induced lupus develops as a result of exposure to certain medications:

• Medicines for the treatment of cardiovascular diseases: phenothiazine groups (Apressin, Aminazine), Hydralazine, Inderal, Metoprolol, Bisoprolol, Propranolol and some others;
• antiarrhythmic drug - Novocainamide;
• sulfonamides: Biseptol and others;
• anti-tuberculosis drug Isoniazid;
• oral contraceptives;
• herbal preparations for the treatment of venous diseases (thrombophlebitis, varicose veins of the lower extremities, and so on): horse chestnut, venotonic Doppelgerz, Detralex and some others.

3. Discoid (or cutaneous) lupus erythematosus may precede the development of systemic lupus erythematosus. With this type of disease, the skin of the face is affected to a greater extent. Changes on the face are similar to those with systemic lupus erythematosus, but blood test parameters (biochemical and immunological) do not have changes characteristic of SLE, and this will be the main criterion for differential diagnosis with other types of lupus erythematosus. To clarify the diagnosis, it is necessary to conduct a histological examination of the skin, which will help differentiate from diseases that are similar in appearance (eczema, psoriasis, cutaneous form of sarcoidosis, and others).

4. Neonatal lupus erythematosus occurs in newborns whose mothers suffer from systemic lupus erythematosus or other systemic autoimmune diseases. At the same time, the mother may not have symptoms of SLE, but when examined, autoimmune antibodies are detected.

Symptoms of neonatal lupus erythematosus In a child, they usually appear before the age of 3 months:

• changes on the skin of the face (often have the appearance of a butterfly);
• congenital arrhythmia, which is often determined by ultrasound of the fetus in the 2nd-3rd trimesters of pregnancy;
• lack of blood cells in a general blood test (decrease in the level of red blood cells, hemoglobin, leukocytes, platelets);
• identification of autoimmune antibodies specific for SLE.

5. The term “lupus” is also used for tuberculosis of the facial skin - tuberculous lupus. Skin tuberculosis is very similar in appearance to systemic lupus erythematosus. The diagnosis can be established by histological examination of the skin and microscopic and bacteriological examination of scrapings - mycobacterium tuberculosis (acid-fast bacteria) is detected.

Photo: This is what tuberculosis of the facial skin or tuberculous lupus looks like.

Systemic lupus erythematosus and other systemic connective tissue diseases, how to differentiate?

• Systemic lupus erythematosus.
• Idiopathic dermatomyositis (polymyositis, Wagner's disease)– damage by autoimmune antibodies to smooth and skeletal muscles.
• Systemic scleroderma is a disease in which normal tissue is replaced by connective tissue (not bearing functional properties), including blood vessels.
• Diffuse fasciitis (eosinophilic)- damage to the fascia - structures that are cases for skeletal muscles, while in the blood of most patients there is an increased number of eosinophils (blood cells responsible for allergies).
• Sjögren's syndrome– damage to various glands (lacrimal, salivary, sweat, etc.), for which this syndrome is also called dry.
• Other systemic diseases.

Differential diagnosis of systemic connective tissue diseases.

Diagnostic criteria	Systemic lupus erythematosus	Systemic scleroderma	Idiopathic dermatomyositis
Onset of the disease	weakness, fatigue; increased body temperature; weight loss; impaired skin sensitivity; periodic joint pain.	weakness, fatigue; increased body temperature; impaired skin sensitivity, burning sensation of the skin and mucous membranes; numbness of the limbs; weight loss; joint pain; Raynaud's syndrome is a severe disruption of blood circulation in the extremities, especially in the hands and feet. Photo: Raynaud's syndrome	severe weakness; increased body temperature; muscle pain; there may be pain in the joints; stiffness of movements in the limbs; compaction of skeletal muscles, their increase in volume due to edema; swelling, blueness of the eyelids; Raynaud's syndrome.
Temperature	Prolonged fever, body temperature above 38-39 0 C.	Prolonged low-grade fever (up to 38 0 C).	Moderate prolonged fever (up to 39 0 C).
Patient's appearance (at the onset of the disease and in some of its forms, the patient’s appearance may not change in all these diseases)	Damage to the skin, mostly the face, “butterfly” (redness, scales, scars). The rash can be all over the body and on the mucous membranes. Dry skin, loss of hair and nails. Nails are deformed, striated nail plates. There may also be hemorrhagic rashes (bruises and petechiae) throughout the body.	The face may acquire a “mask-like” expression without facial expressions, tense, the skin is shiny, deep folds appear around the mouth, the skin is motionless, tightly fused to deep-lying tissues. Often there is a disruption of the glands (dry mucous membranes, as in Sjögren's syndrome). Hair and nails fall out. On the skin of the limbs and neck there are dark spots against the background of “bronze skin”.	A specific symptom is swelling of the eyelids, their color can be red or purple; on the face and décolleté there is a variety of rashes with redness of the skin, scales, hemorrhages, and scars. As the disease progresses, the face acquires a “mask-like appearance”, without facial expressions, tense, may be skewed, and drooping of the upper eyelid (ptosis) is often detected.
Main symptoms during the period of disease activity	skin lesions; photosensitivity - skin sensitivity when exposed to sunlight (like burns); joint pain, stiffness of movement, impaired flexion and extension of fingers; changes in bones; nephritis (swelling, protein in the urine, increased blood pressure, urinary retention and other symptoms); arrhythmias, angina pectoris, heart attack and other cardiac and vascular symptoms; shortness of breath, bloody sputum (pulmonary edema); impaired intestinal motility and other symptoms; damage to the central nervous system.	changes on the skin; Raynaud's syndrome; pain and stiffness in joints; difficulty extending and bending fingers; dystrophic changes in bones, visible on x-rays (especially the phalanges of the fingers, jaw); muscle weakness (muscle atrophy); severe disturbances of the intestinal tract (motility and absorption); heart rhythm disturbances (growth of scar tissue in the heart muscle); shortness of breath (overgrowth of connective tissue in the lungs and pleura) and other symptoms; damage to the peripheral nervous system.	changes on the skin; severe muscle pain, weakness (sometimes the patient is unable to lift a small cup); Raynaud's syndrome; impaired movement, over time the patient becomes completely immobilized; if the respiratory muscles are damaged - shortness of breath, up to complete muscle paralysis and respiratory arrest; if the masticatory and pharyngeal muscles are affected, there is a violation of the act of swallowing; if the heart is damaged - rhythm disturbance, up to cardiac arrest; if the smooth muscles of the intestine are damaged - its paresis; violation of the act of defecation, urination and many other manifestations.
Forecast	Chronic course, over time, more and more organs are affected. Without treatment, complications develop that threaten the patient's life. With adequate and regular treatment, it is possible to achieve long-term, stable remission.
Laboratory indicators	increased gammaglobulins; acceleration of ESR; positive C-reactive protein; decreased level of immune cells of the complementary system (C3, C4); low blood counts; the level of LE cells is significantly increased; positive ANA test; anti-DNA and detection of other autoimmune antibodies.		increased gammaglobulins, as well as myoglobin, fibrinogen, ALT, AST, creatinine - due to the breakdown of muscle tissue; positive test for LE cells; rarely anti-DNA.
Principles of treatment	Long-term hormonal therapy (Prednisolone) + cytostatics + symptomatic therapy and other drugs (see article section "Treatment of systemic lupus").

Systemic lupus erythematosus in children, what are the symptoms and treatment?

Taking into account the peculiarities of immunity, hormonal levels, and the intensity of growth, systemic lupus erythematosus in children occurs with its own characteristics.

Features of the course of systemic lupus erythematosus in childhood:

• more severe course of the disease , high activity of the autoimmune process;
• chronic course the disease occurs in children only in a third of cases;
• more common acute or subacute course diseases with rapid damage to internal organs;
• also isolated only in children acute or lightning-fast course SLE is an almost simultaneous lesion of all organs, including the central nervous system, which can lead to the death of a small patient in the first six months from the onset of the disease;
• frequent development of complications and high mortality;
• the most common complication is bleeding disorder in the form of internal bleeding, hemorrhagic rashes (bruises, hemorrhages on the skin), as a result - the development of a shock state of DIC syndrome - disseminated intravascular coagulation;
• Systemic lupus erythematosus in children often occurs in the form of vasculitis – inflammation of blood vessels, which determines the severity of the process;
• children with SLE are usually malnourished , have a pronounced deficiency of body weight, up to cachexia (extreme degree of dystrophy).

1. Onset of the disease acute, with an increase in body temperature to high numbers (over 38-39 0 C), with pain in the joints and severe weakness, sudden loss of body weight.
2. Skin changes in the form of a “butterfly” are relatively rare in children. But, given the development of a lack of blood platelets, hemorrhagic rashes throughout the body (bruises for no reason, petechiae or pinpoint hemorrhages) are more common. Also, one of the characteristic signs of systemic diseases is hair loss, eyelashes, eyebrows, up to complete baldness. The skin becomes marbled and very sensitive to sunlight. There may be various rashes on the skin, characteristic of allergic dermatitis. In some cases, Raynaud's syndrome develops - a violation of blood circulation in the hands. In the oral cavity there may be ulcers that do not heal for a long time - stomatitis.
3. Joint pain– typical syndrome of active systemic lupus erythematosus, pain is periodic. Arthritis is accompanied by the accumulation of fluid in the joint cavity. Over time, joint pain is combined with muscle pain and stiffness of movement, starting with the small joints of the fingers.
4. For children formation of exudative pleurisy is characteristic(fluid in the pleural cavity), pericarditis (fluid in the pericardium, the lining of the heart), ascites and other exudative reactions (dropsy).
5. Heart damage in children it usually manifests itself as myocarditis (inflammation of the heart muscle).
6. Kidney damage or nephritis It develops much more often in childhood than in adulthood. Such nephritis relatively quickly leads to the development of acute renal failure (requiring intensive care and hemodialysis).
7. Lung damage It is rare in children.
8. In the early period of the disease in adolescents, in most cases there is damage to the gastrointestinal tract(hepatitis, peritonitis and so on).
9. Damage to the central nervous system in children it is characterized by capriciousness, irritability, and in severe cases, seizures may develop.

That is, in children, systemic lupus erythematosus is also characterized by a variety of symptoms. And many of these symptoms are masked under the guise of other pathologies; the diagnosis of systemic lupus erythematosus is not immediately assumed. Unfortunately, timely treatment is the key to success in transitioning the active process into a period of stable remission.

Diagnostic principles systemic lupus erythematosus are the same as for adults, based mainly on immunological studies (detection of autoimmune antibodies).
In a general blood test, in all cases and from the very beginning of the disease, a decrease in the number of all formed blood elements (erythrocytes, leukocytes, platelets) is determined, and blood clotting is impaired.

Treatment of systemic lupus erythematosus in children, as in adults, involves long-term use of glucocorticoids, namely Prednisolone, cytostatics and anti-inflammatory drugs. Systemic lupus erythematosus is a diagnosis that requires urgent hospitalization of the child in a hospital (rheumatology department, if severe complications develop - in the intensive care unit or intensive care unit).
In a hospital setting, a complete examination of the patient is carried out and the necessary therapy is selected. Depending on the presence of complications, symptomatic and intensive therapy is carried out. Given the presence of bleeding disorders in such patients, Heparin injections are often prescribed.
If treatment is started on time and regularly, you can achieve stable remission, while children grow and develop according to their age, including normal puberty. In girls, a normal menstrual cycle is established and pregnancy is possible in the future. In this case forecast favorable for life.

Systemic lupus erythematosus and pregnancy, what are the risks and treatment features?

Risks of pregnancy for a woman with systemic lupus erythematosus:

1. Systemic lupus erythematosus In most cases does not affect the ability to get pregnant , as well as long-term use of Prednisolone.
2. It is strictly forbidden to become pregnant while taking cytostatics (Methotrexate, Cyclophosphamide and others). , since these drugs will affect germ cells and embryonic cells; pregnancy is possible only no earlier than six months after discontinuation of these drugs.
3. Half cases of pregnancy with SLE ends in birth healthy, full-term baby . In 25% cases such babies are born premature , A in a quarter of cases observed miscarriage .
4. Possible complications of pregnancy with systemic lupus erythematosus, in most cases associated with damage to the blood vessels of the placenta:

• fetal death;
• . Thus, in a third of cases, a worsening of the disease develops. The risk of such deterioration is greatest in the first weeks of the first or third trimester of pregnancy. And in other cases, there is a temporary retreat of the disease, but in most cases one should expect a severe exacerbation of systemic lupus erythematosus 1-3 months after birth. No one knows which path the autoimmune process will take.
  6. Pregnancy can be a trigger in the development of systemic lupus erythematosus. Pregnancy can also provoke the transition of discoid (cutaneous) lupus erythematosus to SLE.
  7. A mother with systemic lupus erythematosus can pass the genes on to her baby , predisposing him to develop a systemic autoimmune disease during his life.
  8. The child may develop neonatal lupus erythematosus associated with the circulation of maternal autoimmune antibodies in the baby’s blood; this condition is temporary and reversible.
  • It is necessary to plan a pregnancy under the supervision of qualified doctors , namely a rheumatologist and gynecologist.
  • It is advisable to plan a pregnancy during a period of stable remission chronic course of SLE.
  • In acute cases systemic lupus erythematosus with the development of complications, pregnancy can have a detrimental effect not only on the health, but also lead to the death of the woman.
  • And if, nevertheless, pregnancy occurs during an exacerbation period, then the question of its possible preservation is decided by doctors, together with the patient. After all, exacerbation of SLE requires long-term use of medications, some of which are absolutely contraindicated during pregnancy.
  • It is recommended to become pregnant no earlier than 6 months after discontinuation of cytotoxic drugs (Methotrexate and others).
  • For lupus damage to the kidneys and heart There is no talk of pregnancy; this can lead to the death of a woman from kidney and/or heart failure, because these organs are under enormous stress when carrying a baby.
  Management of pregnancy with systemic lupus erythematosus:

  1. Necessary throughout pregnancy be observed by a rheumatologist and obstetrician-gynecologist , the approach to each patient is individual.
  2. It is necessary to adhere to the following regime: don’t overwork, don’t be nervous, eat normally.
  3. Be attentive to any changes in your health.
  4. Delivery outside the maternity hospital is unacceptable , since there is a risk of developing severe complications during and after childbirth.
  7. Even at the very beginning of pregnancy, the rheumatologist prescribes or adjusts therapy. Prednisolone is the main drug for the treatment of SLE and is not contraindicated during pregnancy. The dose of the drug is selected individually.
  8. Also recommended for pregnant women with SLE taking vitamins, potassium supplements, aspirin (up to the 35th week of pregnancy) and other symptomatic and anti-inflammatory drugs.
  9. Mandatory treatment of late toxicosis and other pathological conditions of pregnancy in a maternity hospital.
  10. After childbirth the rheumatologist increases the dose of hormones; in some cases, it is recommended to stop breastfeeding, as well as prescribe cytostatics and other drugs for the treatment of SLE - pulse therapy, since the postpartum period is dangerous for the development of severe exacerbations of the disease.

  Previously, all women with systemic lupus erythematosus were not recommended to become pregnant, and if they conceived, everyone was recommended to have an induced termination of pregnancy (medical abortion). Now doctors have changed their opinion on this matter; a woman cannot be deprived of motherhood, especially since there is a considerable chance of giving birth to a normal, healthy baby. But everything must be done to minimize the risk for mother and baby.

  Is lupus erythematosus contagious?

  Of course, any person who sees strange rashes on their face thinks: “Could it be contagious?” Moreover, people with these rashes walk for so long, feel unwell and constantly take some kind of medication. Moreover, doctors previously assumed that systemic lupus erythematosus was transmitted sexually, by contact, or even by airborne droplets. But having studied the mechanism of the disease in more detail, scientists have completely dispelled these myths, because this is an autoimmune process.

  The exact cause of the development of systemic lupus erythematosus has not yet been established; there are only theories and assumptions. It all boils down to one thing: the main cause is the presence of certain genes. But still, not all carriers of these genes suffer from systemic autoimmune diseases.

  The trigger for the development of systemic lupus erythematosus can be:

  • various viral infections;
  • bacterial infections (especially beta-hemolytic streptococcus);
  • stress factors;
  • hormonal changes (pregnancy, adolescence);
  • environmental factors (for example, ultraviolet irradiation).
  But infections are not causative agents of the disease, so systemic lupus erythematosus is absolutely not contagious to others.

  Only tuberculous lupus can be contagious (facial skin tuberculosis), since a large number of tuberculosis bacilli are detected on the skin, and the contact route of transmission of the pathogen is isolated.

  Lupus erythematosus, what diet is recommended and are there any methods of treatment with folk remedies?

  As with any disease, nutrition plays an important role in lupus erythematosus. Moreover, with this disease there is almost always a deficiency, or against the background of hormonal therapy - excess body weight, lack of vitamins, microelements and biological active substances.

  The main characteristic of a diet for SLE is a balanced and proper diet.

  1. foods containing unsaturated fatty acids (Omega-3):

  • sea ​​fish;
  • many nuts and seeds;
  • vegetable oil in small quantities;
  2. fruits and vegetables contain more vitamins and microelements, many of which contain natural antioxidants; essential calcium and folic acid are found in large quantities in green vegetables and herbs;
  3. juices, fruit drinks;
  4. lean poultry meat: chicken, turkey fillet;
  5. low-fat dairy , especially fermented milk products (low-fat cheese, cottage cheese, yogurt);
  6. cereals and vegetable fiber (grain bread, buckwheat, oatmeal, wheat germ and many others).

  1. Foods with saturated fatty acids have a bad effect on blood vessels, which can aggravate the course of SLE:

  • animal fats;
  • fried food;
  • fatty meats (red meat);
  • high fat dairy products and so on.
  2. Alfalfa seeds and sprouts (legume crop).
  
  Photo: alfalfa grass.
  3. Garlic – powerfully stimulates the immune system.
  4. Salty, spicy, smoked dishes that retain fluid in the body.

  If diseases of the gastrointestinal tract occur against the background of SLE or taking medications, then the patient is recommended to eat frequent meals according to the therapeutic diet - table No. 1. All anti-inflammatory drugs are best taken with or immediately after meals.

  Treatment of systemic lupus erythematosus at home is possible only after selecting an individual treatment regimen in a hospital setting and correcting conditions that threaten the patient’s life. Heavy drugs used in the treatment of SLE cannot be prescribed on their own; self-medication will not lead to anything good. Hormones, cytostatics, non-steroidal anti-inflammatory drugs and other drugs have their own characteristics and a bunch of adverse reactions, and the dose of these drugs is very individual. The therapy selected by doctors is taken at home, strictly adhering to the recommendations. Omissions and irregularity in taking medications are unacceptable.

  Concerning traditional medicine recipes, then systemic lupus erythematosus does not tolerate experiments. None of these remedies will prevent the autoimmune process; you may simply waste valuable time. Folk remedies can be effective if they are used in combination with traditional methods of treatment, but only after consultation with a rheumatologist.

  Some traditional medicines for the treatment of systemic lupus erythematosus:

  
  
  Precautionary measures! All folk remedies containing poisonous herbs or substances should be kept out of the reach of children. You have to be careful with such drugs; any poison is a medicine as long as it is used in small doses.

  Photos of what the symptoms of lupus erythematosus look like?

  
  Photo: Butterfly-shaped changes on the facial skin in SLE.
  
  Photo: skin lesions on the palms with systemic lupus erythematosus. In addition to skin changes, this patient shows thickening of the joints of the phalanges of the fingers - signs of arthritis.
  
  Dystrophic changes in nails with systemic lupus erythematosus: fragility, discoloration, longitudinal striations of the nail plate.
  
  Lupus lesions of the oral mucosa . The clinical picture is very similar to infectious stomatitis, which does not heal for a long time.
  
  And this is what they might look like first symptoms of discoid or cutaneous lupus erythematosus.
  
  And this is what it might look like neonatal lupus erythematosus, These changes, fortunately, are reversible and in the future the baby will be absolutely healthy.
  
  Skin changes in systemic lupus erythematosus, characteristic of childhood. The rash is hemorrhagic in nature, resembles measles rashes, and leaves pigment spots that do not go away for a long time.
  

Lupus erythematosus (lupus) - affects the vascular system and tissues as a result of autoimmune pathology.

The disease causes irreversible dysfunction of organs and systems. Let's take a closer look at what lupus is and what features it has.

To date, official medicine has not established the causes of lupus erythematosus. Only the presumed causes of occurrence that may contribute to pathological dysfunction have been identified.

Genetic mutations. There is a whole group of genes that determine the likelihood of lupus erythematosus. They are responsible for removing “hostile” cells from the body (apoptosis). When this system fails, harmful cells are retained and healthy cells are damaged by them. Another reason is disorganization in the process of protecting the immune system. In this case, the production of phagocytes becomes too active, and not only “foreign” cells are destroyed, but also healthy ones.

Hereditary predisposition. Medicine knows cases of transmission of lupus erythematosus by inheritance. However, the risk of having a sick child in a family is extremely low, even if the mother is sick.

Age. The risk group includes people from 15 to 45 years old. But there are cases when the disease manifests itself in children or the elderly.

Floor. According to statistics, the number of women suffering from lupus erythematosus is ten times higher than the number of men with the same problem.

Race. Scientists have found that lupus erythematosus most often affects people with dark skin; there are three times more of them than white-skinned people.

External factors. Excessive tanning, directly related to ultraviolet irradiation, can provoke a genetic failure. There is an opinion that people whose professional affiliation is associated with prolonged exposure to the sun, frost, and temperature changes are susceptible to the disease. This includes construction workers, sailors, and agricultural workers.

Systemic lupus erythematosus (SLE) affects several million people worldwide. These are people of all ages, from babies to the elderly. The reasons for the development of the disease are unclear, but many factors contributing to its occurrence have been well studied. There is no cure for lupus yet, but this diagnosis no longer sounds like a death sentence. Let's try to figure out whether Dr. House was right in suspecting this disease in many of his patients, whether there is a genetic predisposition to SLE and whether a certain lifestyle can protect against this disease.

We continue the series on autoimmune diseases - diseases in which the body begins to fight itself, producing autoantibodies and/or autoaggressive clones of lymphocytes. We talk about how the immune system works and why sometimes it starts to “shoot at its own people.” Separate publications will be devoted to some of the most common diseases. To maintain objectivity, we invited Doctor of Biological Sciences, corresponding member to become the curator of the special project. RAS, professor of the Department of Immunology of Moscow State University Dmitry Vladimirovich Kuprash. In addition, each article has its own reviewer, who delves into all the nuances in more detail.

The reviewer of this article was Olga Anatolyevna Georginova, Candidate of Medical Sciences, rheumatologist, assistant at the Department of Internal Medicine, Faculty of Fundamental Medicine, Moscow State University named after M.V. Lomonosov.

Drawing by William Bagg from Wilson's atlas (1855)

Most often, a person comes to the doctor exhausted by febrile fever (temperature above 38.5 °C), and it is this symptom that serves as the reason for him to see a doctor. His joints swell and hurt, his whole body aches, his lymph nodes become enlarged and cause discomfort. The patient complains of rapid fatigue and increasing weakness. Other symptoms reported at the appointment include mouth ulcers, alopecia and gastrointestinal dysfunction. Often the patient suffers from excruciating headaches, depression, and severe fatigue. His condition negatively affects his work performance and social life. Some patients may even experience mood disorders, cognitive impairment, psychosis, movement disorders and myasthenia gravis.

It is not surprising that Josef Smolen from the Vienna General Hospital (Wiener Allgemeine Krankenhaus, AKH) called systemic lupus erythematosus “the most complex disease in the world” at a 2015 congress on the disease.

In order to assess the activity of the disease and the success of treatment, about 10 different indices are used in clinical practice. They can be used to track changes in the severity of symptoms over a period of time. Each disorder is assigned a specific score, and the final score indicates the severity of the disease. The first such methods appeared in the 1980s, and now their reliability has long been confirmed by research and practice. The most popular of them are SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), its modification used in the Safety of Estrogens in Lupus National Assessment (SELENA) study, BILAG (British Isles Lupus Assessment Group Scale), SLICC/ACR damage index (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and ECLAM (European Consensus Lupus Activity Measurement). In Russia, they also use the assessment of SLE activity according to V.A.’s classification. Nasonova.

Main targets of the disease

Some tissues are more affected by attacks from autoreactive antibodies than others. In SLE, the kidneys and cardiovascular system are especially often affected.

Autoimmune processes also disrupt the functioning of blood vessels and the heart. According to the most conservative estimates, every tenth death from SLE is caused by circulatory disorders that develop as a result of systemic inflammation. The risk of ischemic stroke in patients with this disease increases twofold, the risk of intracerebral hemorrhage increases threefold, and the risk of subarachnoid hemorrhage increases almost fourfold. Survival after stroke is also much worse than in the general population.

The totality of manifestations of systemic lupus erythematosus is immense. In some patients, the disease may affect only the skin and joints. In other cases, patients are exhausted by excessive fatigue, increasing weakness throughout the body, prolonged febrile fever and cognitive impairment. This may be accompanied by thrombosis and severe organ damage, such as end-stage renal disease. Because of these different manifestations, SLE is called a disease with a thousand faces.

Family planning

One of the most important risks associated with SLE is the numerous complications during pregnancy. The vast majority of patients are young women of childbearing age, so family planning, pregnancy management and monitoring the condition of the fetus are now of great importance.

Before the development of modern methods of diagnosis and therapy, maternal illness often negatively affected the course of pregnancy: conditions arose that threatened the woman’s life, pregnancy often ended in intrauterine fetal death, premature birth, and preeclampsia. Because of this, for a long time, doctors strongly discouraged women with SLE from having children. In the 1960s, women lost their fetuses 40% of the time. By the 2000s, the number of such cases had more than halved. Today, researchers estimate this figure at 10–25%.

Now doctors advise getting pregnant only during remission of the disease, since the survival of the mother, the success of pregnancy and childbirth depends on the activity of the disease several months before conception and at the very moment of fertilization of the egg. Because of this, doctors consider counseling the patient before and during pregnancy a necessary step.

In rare cases now, a woman finds out that she has SLE while she is already pregnant. Then, if the disease is not very active, pregnancy can proceed favorably with maintenance therapy with steroid or aminoquinoline drugs. If pregnancy, coupled with SLE, begins to threaten health and even life, doctors recommend an abortion or an emergency caesarean section.

About one in 20,000 children develops neonatal lupus- a passively acquired autoimmune disease, known for more than 60 years (case incidence is given for the USA). It is mediated by maternal antinuclear autoantibodies to the Ro/SSA, La/SSB antigens or to the U1-ribonucleoprotein. The presence of SLE in the mother is not at all necessary: ​​only 4 out of 10 women who give birth to children with neonatal lupus have SLE at the time of birth. In all other cases, the above antibodies are simply present in the mothers’ bodies.

The exact mechanism of damage to the baby's tissues is still unknown, and most likely it is more complex than simply the penetration of maternal antibodies through the placental barrier. The prognosis for the newborn's health is usually good, and most symptoms resolve quickly. However, sometimes the consequences of the disease can be very severe.

In some children, skin lesions are noticeable at birth, while in others they develop over several weeks. The disease can affect many body systems: cardiovascular, hepatobiliary, central nervous, and lungs. In the worst case scenario, the child may develop life-threatening congenital heart block.

Economic and social aspects of the disease

A person with SLE suffers not only from the biological and medical manifestations of the disease. A significant portion of the disease burden is social, and this can create a vicious cycle of worsening symptoms.

Thus, regardless of gender and ethnicity, poverty, low levels of education, lack of health insurance, insufficient social support and treatment contribute to the deterioration of the patient’s condition. This, in turn, leads to disability, loss of productivity and a further decline in social status. All this significantly worsens the prognosis of the disease.

One should not discount the fact that treatment for SLE is extremely expensive, and the costs directly depend on the severity of the disease. TO direct expenses include, for example, the costs of inpatient treatment (time spent in hospitals and rehabilitation centers and related procedures), outpatient treatment (treatment with prescribed mandatory and additional medications, doctor visits, laboratory tests and other tests, ambulance calls), surgical operations, transportation to medical facilities and additional medical services. According to 2015 estimates, in the United States, a patient spends an average of $33 thousand per year on all of the above items. If he develops lupus nephritis, then the amount more than doubles - up to $71 thousand.

Indirect costs may even be higher than direct ones, since they include loss of working capacity and disability due to illness. Researchers estimate the amount of such losses at $20 thousand.

Russian situation: “for Russian rheumatology to exist and develop, we need state support”

In Russia, tens of thousands of people suffer from SLE - about 0.1% of the adult population. Traditionally, rheumatologists treat this disease. One of the largest institutions where patients can turn for help is the Research Institute of Rheumatology named after. V.A. Nasonova RAMS, founded in 1958. As the current director of the research institute, academician of the Russian Academy of Medical Sciences, Honored Scientist of the Russian Federation Evgeniy Lvovich Nasonov recalls, at first his mother, Valentina Aleksandrovna Nasonova, who worked in the rheumatology department, came home almost every day in tears, since four out of five patients died from in her hands. Fortunately, this tragic trend has been overcome.

Patients with SLE are also provided with assistance in the rheumatology department of the Clinic of Nephrology, Internal and Occupational Diseases named after E.M. Tareev, Moscow City Rheumatology Center, Children's City Clinical Hospital named after. BEHIND. Bashlyaeva Department of Health (Tushino Children's City Hospital), Scientific Center for Children's Health of the Russian Academy of Medical Sciences, Russian Children's Clinical Hospital and Central Children's Clinical Hospital of the FMBA.

However, even now it is very difficult to suffer from SLE in Russia: the availability of the latest biological drugs for the population leaves much to be desired. The cost of such therapy is about 500–700 thousand rubles per year, and the medication is taken for a long time, and is by no means limited to one year. However, such treatment is not included in the list of vitally important drugs (VED). The standard of care for patients with SLE in Russia is published on the website of the Ministry of Health of the Russian Federation.

Currently, therapy with biological drugs is used at the Research Institute of Rheumatology. First, the patient receives them for 2–3 weeks while he is in the hospital; compulsory medical insurance covers these costs. After discharge, he needs to submit an application at his place of residence for additional drug provision to the regional department of the Ministry of Health, and the final decision is made by the local official. Often his answer is negative: in some regions, patients with SLE are not of interest to the local health department.

At least 95% of patients have autoantibodies, recognizing fragments of the body’s own cells as foreign (!) and therefore posing a danger. It is not surprising that the central figure in the pathogenesis of SLE is considered B cells producing autoantibodies. These cells are the most important part of adaptive immunity, having the ability to present antigens T cells and secreting signaling molecules - cytokines. It is assumed that the development of the disease is triggered by the hyperactivity of B cells and their loss of tolerance to the body's own cells. As a result, they generate a variety of autoantibodies that are directed at nuclear, cytoplasmic and membrane antigens contained in the blood plasma. As a result of the binding of autoantibodies and nuclear material, immune complexes, which are deposited in tissues and are not effectively removed. Many clinical manifestations of lupus are the result of this process and subsequent organ damage. The inflammatory response is exacerbated by the fact that B cells secrete about inflammatory cytokines and present T-lymphocytes not with foreign antigens, but with antigens of their own body.

The pathogenesis of the disease is also associated with two other simultaneous events: with an increased level of apoptosis(programmed cell death) of lymphocytes and with the deterioration of the processing of waste material arising during autophagy. This “littering” of the body leads to an incitement of the immune response towards its own cells.

Recent research shows that autophagy is important for the normal functioning of many immune responses: for example, the maturation and function of immune cells, pathogen recognition, and antigen processing and presentation. There is now more and more evidence that autophagic processes are associated with the occurrence, course and severity of SLE.

It has been shown that in vitro macrophages from SLE patients ingest less cellular debris compared to macrophages from healthy controls. Thus, if disposal is unsuccessful, apoptotic waste “attracts the attention” of the immune system, and pathological activation of immune cells occurs (Fig. 3). It turned out that some types of drugs that are already used for the treatment of SLE or are at the stage of preclinical studies act specifically on autophagy.

In addition to the above features, patients with SLE are characterized by increased expression of type I interferon genes. The products of these genes are a very well-known group of cytokines that play antiviral and immunomodulatory roles in the body. It is possible that an increase in the amount of type I interferons affects the activity of immune cells, which leads to a malfunction of the immune system.

Figure 3. Current ideas about the pathogenesis of SLE. One of the main causes of clinical symptoms of SLE is the deposition in tissues of immune complexes formed by antibodies that have bound fragments of cell nuclear material (DNA, RNA, histones). This process provokes a strong inflammatory response. In addition, with increased apoptosis, NETosis, and decreased efficiency of autophagy, unutilized cell fragments become targets of immune system cells. Immune complexes via receptors FcγRIIa enter plasmacytoid dendritic cells ( pDC), where the nucleic acids of the complexes activate Toll-like receptors ( TLR-7/9) , . Activated in this way, pDC begin the powerful production of type I interferons (including IFN-α). These cytokines, in turn, stimulate the maturation of monocytes ( Mø) to antigen-presenting dendritic cells ( DC) and the production of autoreactive antibodies by B cells, prevent apoptosis of activated T cells. Monocytes, neutrophils and dendritic cells under the influence of type I IFN increase the synthesis of the cytokines BAFF (a stimulator of B cells, promoting their maturation, survival and antibody production) and APRIL (an inducer of cell proliferation). All this leads to an increase in the number of immune complexes and even more powerful activation of pDC - the circle closes. The pathogenesis of SLE also involves abnormal oxygen metabolism, which increases inflammation, cell death and the influx of autoantigens. This is largely the fault of mitochondria: disruption of their work leads to increased formation of reactive oxygen species ( ROS) and nitrogen ( RNI), deterioration of the protective functions of neutrophils and netosis ( NETosis)

Finally, oxidative stress, together with abnormal oxygen metabolism in the cell and disturbances in the functioning of mitochondria, can also contribute to the development of the disease. Due to the increased secretion of pro-inflammatory cytokines, tissue damage and other processes that characterize the course of SLE, an excessive amount of reactive oxygen species(ROS), which further damage surrounding tissues, promote a constant influx of autoantigens and specific suicide of neutrophils - netozu(NETosis). This process ends with the formation neutrophil extracellular traps(NETs) designed to trap pathogens. Unfortunately, in the case of SLE, they play against the host: these network-like structures are composed predominantly of major lupus autoantigens. Interaction with the latter antibodies makes it difficult to cleanse the body of these traps and enhances the production of autoantibodies. This creates a vicious circle: increasing tissue damage as the disease progresses entails an increase in the amount of ROS, which destroys tissue even more, enhances the formation of immune complexes, stimulates the synthesis of interferon... The pathogenetic mechanisms of SLE are presented in more detail in Figures 3 and 4.

Figure 4. The role of programmed neutrophil death - NETosis - in the pathogenesis of SLE. Immune cells typically do not encounter most of the body's own antigens because potential self-antigens are found within cells and are not presented to lymphocytes. After autophagic death, the remains of dead cells are quickly disposed of. However, in some cases, for example, with an excess of reactive oxygen and nitrogen species ( ROS And RNI), the immune system encounters autoantigens “nose to nose”, which provokes the development of SLE. For example, under the influence of ROS, polymorphonuclear neutrophils ( PMN) are exposed netozu, and a “network” is formed from the remains of the cell. net), containing nucleic acids and proteins. This network becomes the source of autoantigens. As a result, plasmacytoid dendritic cells are activated ( pDC), releasing IFN-α and provoking an autoimmune attack. Other symbols: REDOX(reduction-oxidation reaction) - imbalance of redox reactions; ER- endoplasmic reticulum; DC- dendritic cells; B- B cells; T- T cells; Nox2- NADPH oxidase 2; mtDNA- mitochondrial DNA; black up and down arrows- amplification and suppression, respectively. To see the picture in full size, click on it.

Who is guilty?

Although the pathogenesis of systemic lupus erythematosus is more or less clear, scientists find it difficult to name its key cause and therefore consider a combination of various factors that increase the risk of developing this disease.

In our century, scientists turn their attention primarily to hereditary predisposition to the disease. SLE did not escape this either - which is not surprising, because the incidence varies greatly by gender and ethnicity. Women suffer from this disease approximately 6–10 times more often than men. Their incidence peaks at 15–40 years of age, that is, during childbearing age. Prevalence, course of disease and mortality are associated with ethnicity. For example, a butterfly rash is typical in white patients. In African Americans and Afro-Caribbeans, the disease is much more severe than in Caucasians; relapses of the disease and inflammatory disorders of the kidneys are more common among them. Discoid lupus is also more common in dark-skinned people.

These facts indicate that genetic predisposition may play an important role in the etiology of SLE.

To clarify this, the researchers used a method genome-wide association search, or GWAS, which allows thousands of genetic variants to be correlated with phenotypes—in this case, disease manifestations. Thanks to this technology, it was possible to identify more than 60 susceptibility loci for systemic lupus erythematosus. They can be roughly divided into several groups. One such group of loci is associated with the innate immune response. These are, for example, the pathways of NF-kB signaling, DNA degradation, apoptosis, phagocytosis, and utilization of cellular debris. It also includes variants responsible for the function and signaling of neutrophils and monocytes. Another group includes genetic variants involved in the work of the adaptive part of the immune system, that is, associated with the function and signaling networks of B and T cells. In addition, there are loci that do not fall into these two groups. Interestingly, many risk loci are common to SLE and other autoimmune diseases (Fig. 5).

Genetic data could be used to determine the risk of developing SLE, its diagnosis or treatment. This would be extremely useful in practice, since due to the specifics of the disease, it is not always possible to identify it from the patient’s first complaints and clinical manifestations. Selecting treatment also takes some time, because patients respond to therapy differently, depending on the characteristics of their genome. So far, however, genetic tests are not used in clinical practice. An ideal model for assessing disease susceptibility would take into account not only specific gene variants, but also genetic interactions, levels of cytokines, serological markers, and many other data. In addition, it should, if possible, take into account epigenetic features - after all, according to research, they make a huge contribution to the development of SLE.

Unlike the genome, epi the genome is relatively easily modified under the influence external factors. Some believe that without them, SLE may not develop. The most obvious is ultraviolet radiation, as patients often experience redness and rashes on their skin after exposure to sunlight.

The development of the disease, apparently, can provoke viral infection. It is possible that in this case autoimmune reactions arise due to molecular mimicry of viruses- the phenomenon of similarity of viral antigens with the body’s own molecules. If this hypothesis is correct, then the Epstein-Barr virus becomes the focus of research. However, in most cases, scientists find it difficult to name the specific culprits. It is believed that autoimmune reactions are not provoked by specific viruses, but through general mechanisms to combat this type of pathogen. For example, the activation pathway of type I interferons is common in the response to viral invasion and in the pathogenesis of SLE.

Factors such as smoking and drinking alcohol, however, their influence is ambiguous. It is likely that smoking can increase the risk of developing the disease, exacerbating it and increasing organ damage. Alcohol, according to some data, reduces the risk of developing SLE, but the evidence is quite contradictory, and it is better not to use this method of protection against the disease.

There is not always a clear answer regarding the influence occupational risk factors. If contact with silicon dioxide, according to a number of studies, provokes the development of SLE, then there is no exact answer about exposure to metals, industrial chemicals, solvents, pesticides and hair dyes. Finally, as mentioned above, lupus can be triggered by medication use: Common triggers include chlorpromazine, hydralazine, isoniazid, and procainamide.

Treatment: past, present and future

As already mentioned, it is not yet possible to cure “the most difficult disease in the world.” The development of a drug is hampered by the multifaceted pathogenesis of the disease, which involves different parts of the immune system. However, with competent individual selection of maintenance therapy, deep remission can be achieved, and the patient will be able to live with lupus erythematosus simply as with a chronic disease.

Treatment for various changes in the patient’s condition can be adjusted by a doctor, or rather, by doctors. The fact is that in the treatment of lupus, the coordinated work of a multidisciplinary group of medical professionals is extremely important: a family doctor in the West, a rheumatologist, a clinical immunologist, a psychologist, and often a nephrologist, hematologist, dermatologist, neurologist. In Russia, a patient with SLE first of all goes to a rheumatologist, and depending on the damage to systems and organs, he may require additional consultation with a cardiologist, nephrologist, dermatologist, neurologist and psychiatrist.

The pathogenesis of the disease is very complex and confusing, so many targeted drugs are currently in development, while others have shown their failure at the trial stage. Therefore, in clinical practice, nonspecific drugs are still most widely used.

Standard treatment includes several types of medications. First of all, they write out immunosuppressants- to suppress excessive activity of the immune system. The most commonly used of them are cytostatic drugs methotrexate, azathioprine, mycophenolate mofetil And cyclophosphamide. In fact, these are the same drugs that are used for cancer chemotherapy and act primarily on actively dividing cells (in the case of the immune system, on clones of activated lymphocytes). It is clear that such therapy has many dangerous side effects.

During the acute phase of the disease, patients usually take corticosteroids- nonspecific anti-inflammatory drugs that help calm the most violent storms of autoimmune reactions. They have been used in the treatment of SLE since the 1950s. Then they moved the treatment of this autoimmune disease to a qualitatively new level, and still remain the basis of therapy for lack of an alternative, although many side effects are also associated with their use. Most often, doctors prescribe prednisolone And methylprednisolone.

For exacerbation of SLE, it has also been used since 1976. pulse therapy: the patient receives pulsed high doses of methylprednisolone and cyclophosphamide. Of course, over 40 years of use, the regimen of such therapy has changed greatly, but is still considered the gold standard in the treatment of lupus. However, it has many severe side effects, which is why it is not recommended for some patient groups, such as people with poorly controlled hypertension and systemic infections. In particular, the patient may develop metabolic disorders and behavior changes.

When remission is achieved, it is usually prescribed antimalarial drugs, which have been successfully used for a long time to treat patients with lesions of the musculoskeletal system and skin. Action hydroxychloroquine, one of the best known substances of this group, for example, is explained by the fact that it inhibits the production of IFN-α. Its use provides long-term reduction in disease activity, reduces damage to organs and tissues, and improves pregnancy outcomes. In addition, the drug reduces the risk of thrombosis - and this is extremely important given the complications that arise in the cardiovascular system. Thus, the use of antimalarial drugs is recommended for all patients with SLE. However, there is also a fly in the ointment. In rare cases, retinopathy develops in response to this therapy, and patients with severe renal or hepatic impairment are at risk for hydroxychloroquine-associated toxicity.

Used in the treatment of lupus and newer ones, targeted drugs(Fig. 5). The most advanced developments target B cells: the antibodies rituximab and belimumab.

Figure 5. Biological drugs in the treatment of SLE. Apoptotic and/or necrotic cell debris accumulate in the human body, for example, due to viral infection and exposure to ultraviolet radiation. This "garbage" can be taken up by dendritic cells ( DC), whose main function is the presentation of antigens to T and B cells. The latter acquire the ability to respond to autoantigens presented to them by DCs. This is how the autoimmune reaction begins, the synthesis of autoantibodies starts. Many biological drugs are currently being studied - drugs that affect the regulation of the body's immune components. The innate immune system is targeted anifrolumab(anti-IFN-α receptor antibody), sifalimumab And Rontalizumab(antibodies to IFN-α), infliximab And etanercept(antibodies to tumor necrosis factor, TNF-α), sirukumab(anti-IL-6) and tocilizumab(anti-IL-6 receptor). Abatacept (cm. text), belatacept, AMG-557 And IDEC-131 block costimulatory molecules of T cells. Fostamatinib And R333- splenic tyrosine kinase inhibitors ( SYK). Various B cell transmembrane proteins are targeted rituximab And ofatumumab(antibodies to CD20), epratuzumab(anti-CD22) and blinatumomab(anti-CD19), which also blocks plasma cell receptors ( PC). Belimumab (cm. text) blocks the soluble form BAFF, tabalumab and blisibimod are soluble and membrane-bound molecules BAFF, A

Another potential target of anti-lupus therapy is type I interferons, which were already discussed above. Some antibodies to IFN-α have already shown promising results in patients with SLE. Now the next, third, phase of their testing is being planned.

Also, among the drugs whose effectiveness in SLE is currently being studied, it should be mentioned abatacept. It blocks costimulatory interactions between T and B cells, thereby restoring immunological tolerance.

Finally, various anti-cytokine drugs are being developed and tested, e.g. etanercept And infliximab- specific antibodies to tumor necrosis factor, TNF-α.

Conclusion

Systemic lupus erythematosus remains a daunting challenge for the patient, a challenge for the physician, and an underexplored area for the scientist. However, we should not limit ourselves to the medical side of the issue. This disease provides a huge field for social innovation, since the patient needs not only medical care, but also various types of support, including psychological. Thus, improving the methods of providing information, specialized mobile applications, platforms with accessible information significantly improve the quality of life of people with SLE.

They help a lot in this matter patient organizations- public associations of people suffering from some disease and their relatives. For example, the Lupus Foundation of America is very famous. The activities of this organization are aimed at improving the quality of life of people diagnosed with SLE through special programs, research, education, support and assistance. Its primary goals include reducing time to diagnosis, providing patients with safe and effective treatment, and increasing access to treatment and care. In addition, the organization emphasizes the importance of educating health care personnel, communicating concerns to government officials, and raising social awareness regarding systemic lupus erythematosus.

The global burden of SLE: prevalence, health disparities and socioeconomic impact. Nat Rev Rheumatol. 12 , 605-620;

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!

Lupus erythematosus and systemic lupus erythematosus are different names for the same disease

The term "systemic lupus erythematosus" is a corruption of the common name for "systemic lupus erythematosus."

Doctors and scientists prefer the fuller term systemic lupus erythematosus to refer to the systemic autoimmune disease because the reduced form lupus erythematosus can be misleading. This preference is due to the fact that the name “lupus erythematosus” is traditionally used to refer to tuberculosis of the skin, which is manifested by the formation of red-brown tubercles on the skin. Therefore, the use of the term “lupus erythematosus” to designate a systemic autoimmune disease requires clarification that we are not talking about skin tuberculosis.

When describing an autoimmune disease, in the following text we will use the terms “systemic lupus erythematosus” and simply “lupus erythematosus” to refer to it. In this case, it is necessary to remember that lupus erythematosus refers to a systemic autoimmune pathology, and not skin tuberculosis.

Autoimmune lupus erythematosus

Lupus erythematosus - what is this disease?

Connective tissue is important for all organs, as it is where blood vessels pass. After all, the vessels do not pass directly between the cells of organs, but in special small “cases,” as it were, formed precisely by connective tissue. Such layers of connective tissue pass between areas of various organs, dividing them into small lobes. Moreover, each such lobule receives a supply of oxygen and nutrients from those blood vessels that pass along its perimeter in “cases” of connective tissue. Therefore, damage to connective tissue leads to disruption of the blood supply to areas of various organs, as well as to disruption of the integrity of the blood vessels in them.

In relation to lupus erythematosus, it is obvious that damage by antibodies to connective tissue leads to hemorrhages and destruction of the tissue structure of various organs, which causes a variety of clinical symptoms.

Lupus erythematosus affects women more often, and according to various sources, the ratio of sick men and women is 1:9 or 1:11. This means that for every man with systemic lupus erythematosus, there are 9–11 women who also suffer from this pathology. In addition, it is known that lupus is more common among representatives of the Negroid race than among Caucasians and Mongoloids. People of all ages, including children, fall ill with systemic lupus erythematosus, but most often the pathology first appears between the ages of 15 and 45. Children under 15 years of age and adults over 45 years of age develop lupus extremely rarely.

There are also known cases neonatal lupus erythematosus, when a newborn child is born with this pathology. In such cases, the child becomes ill with lupus while still in the womb of the mother, who herself suffers from this disease. However, the presence of such cases of transmission of the disease from mother to fetus does not mean that women suffering from lupus erythematosus will necessarily give birth to sick children. On the contrary, usually women suffering from lupus carry and give birth to normal, healthy children, since this disease is not infectious and cannot be transmitted through the placenta. And cases of births of children with lupus erythematosus by mothers also suffering from this pathology indicate that the predisposition to the disease is due to genetic factors. And therefore, if a baby receives such a predisposition, then he, while still in the womb of a mother suffering from lupus, becomes ill and is born with a pathology.

The causes of systemic lupus erythematosus have not yet been reliably established. Doctors and scientists suggest that the disease is polyetiological, that is, it is caused not by any one cause, but by a combination of several factors acting on the human body in the same period of time. Moreover, probable causative factors can provoke the development of lupus erythematosus only in people who have a genetic predisposition to the disease. In other words, systemic lupus erythematosus develops only in the presence of a genetic predisposition and under the simultaneous influence of several provoking factors. Among the most likely factors that can provoke the development of systemic lupus erythematosus in people with a genetic predisposition to the disease, doctors identify stress, long-term viral infections (for example, herpetic infection, infection caused by the Epstein-Barr virus, etc.), periods of hormonal changes in the body, prolonged exposure to ultraviolet radiation, taking certain medications (sulfonamides, antiepileptic drugs, antibiotics, drugs for the treatment of malignant tumors, etc.).

Although chronic infections may contribute to the development of lupus, the disease is not contagious and does not relate to tumor. Systemic lupus erythematosus cannot be contracted from another person; it can only develop individually if there is a genetic predisposition.

Systemic lupus erythematosus occurs in the form of a chronic inflammatory process that can affect almost all organs and only some individual tissues of the body. Most often, lupus erythematosus occurs as a systemic disease or in an isolated cutaneous form. In the systemic form of lupus, almost all organs are affected, but the joints, lungs, kidneys, heart and brain are most affected. Cutaneous lupus erythematosus usually affects the skin and joints.

Due to the fact that the chronic inflammatory process leads to damage to the structure of various organs, the clinical symptoms of lupus erythematosus are very diverse. However Any form or variety of lupus erythematosus is characterized by the following general symptoms:

• Pain and swelling of the joints (especially large ones);
• Prolonged unexplained increase in body temperature;
• Rashes on the skin (on the face, on the neck, on the torso);
• Chest pain that occurs when taking a deep breath or exhalation;
• Sharp and severe paleness or blue discoloration of the skin of the toes and hands in the cold or during a stressful situation (Raynaud's syndrome);
• Swelling of the legs and area around the eyes;
• Enlarged and painful lymph nodes;
• Sensitivity to solar radiation.

For lupus characterized by the presence of not all symptoms at once, but their gradual appearance over time. That is, at the beginning of the disease, a person develops only some symptoms, and then, as lupus progresses and more and more organs are affected, new clinical signs appear. Thus, some symptoms may appear years after the disease develops.

Women suffering from lupus erythematosus can have a normal sex life. Moreover, depending on your goals and plans, you can either use contraceptives or, on the contrary, try to get pregnant. If a woman wants to carry a pregnancy to term and give birth to a child, then she should register as early as possible, since with lupus erythematosus there is an increased risk of miscarriage and premature birth. But in general, pregnancy with lupus erythematosus proceeds quite normally, although with a high risk of complications, and in the vast majority of cases, women give birth to healthy children.

Currently systemic lupus erythematosus cannot be completely cured. Therefore, the main goal of disease therapy that doctors set for themselves is to suppress the active inflammatory process, achieve stable remission and prevent severe relapses. A wide range of medications are used for this. Depending on which organ is most affected, various medications are selected for the treatment of lupus erythematosus.

The main drugs for the treatment of systemic lupus erythematosus are glucocorticoid hormones (for example, Prednisolone, Methylprednisolone and Dexamethasone), which effectively suppress the inflammatory process in various organs and tissues, thereby minimizing the degree of their damage. If the disease has led to damage to the kidneys and central nervous system, or the functioning of many organs and systems is impaired at once, then in combination with glucocorticoids, immunosuppressants are used to treat lupus - drugs that suppress the activity of the immune system (for example, Azathioprine, Cyclophosphamide and Methotrexate).

In addition, sometimes in the treatment of lupus erythematosus, in addition to glucocorticoids, antimalarial drugs (Plaquenil, Aralen, Delagil, Atabrine) are used, which also effectively suppress the inflammatory process and maintain remission, preventing exacerbations. The mechanism of the positive effect of antimalarial drugs in lupus is unknown, but in practice it has been clearly established that these drugs are effective.

If a person with lupus develops secondary infections, he or she is given immunoglobulin. If there is severe pain and swelling of the joints, then, in addition to the main treatment, it is necessary to take drugs from the NSAID group (Indomethacin, Diclofenac, Ibuprofen, Nimesulide, etc.).

A person suffering from systemic lupus erythematosus must remember that this disease is lifelong, it cannot be cured completely, as a result of which you will have to constantly take any medications in order to maintain a state of remission, prevent relapses and be able to lead a normal life.

Causes of lupus erythematosus

Thus, doctors and scientists came to the conclusion that lupus develops only in people who have a genetic predisposition to the disease. Thus, the main causative factor is conventionally considered to be the genetic characteristics of a person, since without a predisposition, lupus erythematosus never develops.

However, in order for lupus erythematosus to develop, genetic predisposition alone is not enough; additional long-term exposure to certain factors that can trigger the pathological process is also necessary.

That is, it is obvious that there are a number of provoking factors that lead to the development of lupus in people who have a genetic predisposition to it. It is these factors that can be conditionally attributed to the causes of systemic lupus erythematosus.

Currently, doctors and scientists consider the following to be the triggering factors for lupus erythematosus:

• The presence of chronic viral infections (herpetic infection, infection caused by the Epstein-Barr virus);
• Frequent bacterial infections;
• Stress;
• The period of hormonal changes in the body (puberty, pregnancy, childbirth, menopause);
• Exposure to high-intensity ultraviolet radiation or for a long time (sun rays can both provoke a primary episode of lupus erythematosus and lead to an exacerbation during remission, since under the influence of ultraviolet radiation it is possible to start the process of producing antibodies to skin cells);
• Exposure of the skin to low temperatures (frost) and wind;
• Taking certain medications (antibiotics, sulfonamides, antiepileptic drugs and drugs for the treatment of malignant tumors).

Medicines that are one of the causative factors of lupus can cause both the disease itself and the so-called lupus syndrome. At the same time, in practice, it is lupus syndrome that is most often recorded, which in its clinical manifestations is similar to lupus erythematosus, but is not a disease, and goes away after discontinuation of the drug that caused it. But in rare cases, medications can also provoke the development of lupus erythematosus in people who have a genetic predisposition to this disease. Moreover, the list of drugs that can provoke lupus syndrome and lupus itself is exactly the same. Thus, among the medications used in modern medical practice, the following can lead to the development of systemic lupus erythematosus or lupus syndrome:

• Amiodarone;
• Atorvastatin;
• Bupropion;
• Valproic acid;
• Voriconazole;
• Gemfibrozil;
• Hydantoin;
• Hydralazine;
• Hydrochlorothiazide;
• Glyburide;
• Griseofulvin;
• Guinidine;
• Diltiazem;