Systemic lupus erythematosus (SLE) - causes, pathogenesis, symptoms, diagnosis and treatment. Differential Diagnosis
Discoid lupus erythematosus is manifested by limited foci. It is located on any part of the body, including the oral cavity, the red border of the lips, the trunk, the scalp, feet and hands. But the protruding parts of the face are most often affected: the zygomatic parts of the cheeks, the back of the nose, the forehead and chin. The primary symptom is well-defined erythema, first edematous and then infiltrated. If there are several erythematous areas, then they merge, slightly flake and, with further progression, turn into erythematous-infiltrative plaques covered with tightly seated scales. When the scales are removed, horny spines are clearly distinguished on their lower surface, with which the scales are introduced into the mouth of the follicle or sebaceous gland. These horny spines are called "ladies' heel". Horny spines form at the dilated orifices of the sebaceous glands and hair follicles due to hyperkeratosis. Removal of tightly-fitting scales, which have penetrated into the mouths of the follicles with horny spines, is accompanied by a feeling of soreness (Besnier-Meshchersky sign). After the resolution of inflammation in the center of the focus, cicatricial atrophy is formed. Thus, three pathognomonic symptoms of DLE are added - infiltrative erythema, follicular hyperkeratosis and cicatricial atrophy. On the periphery of discoid plaques, secondary symptoms of DLE are clearly detected - telangiectasia, areas of pigmentation and depigmentation. The most common localization of DLE is the symmetrical areas of the zygomatic parts of the cheeks and the back of the nose, resembling the wings and body of a butterfly in appearance, which is also a characteristic symptom. In the case of localization of foci on the skin of the auricles in the hyperkeratotically changed mouths of the follicles, dot comedones are concentrated, outwardly resembling the surface of a thimble (Khachaturian's symptom). On the scalp, the initial stage of the process in the form of erythematous-scaly foci resembles seborrheic eczema, but differs from it in hyperkeratosis of the follicles and cicatricial atrophy, which ends in persistent alopecia. DKV is considered the most benign form. However, under the influence of ultraviolet radiation, other radiation exposure, irrational treatment, infection and other traumatic factors, it can be transformed into a systemic one. Diagnosis of DKV of the oral mucosa and the red border of the lips with a combination of their lesions with characteristic skin rashes is not difficult. It becomes difficult to diagnose with an isolated lesion of the red border of the lips, in which lupus erythematosus must be differentiated from lichen planus. However, the latter is characterized by a pronounced cyanosis of the lesion, consisting of papules merged together, forming a certain pattern, as well as the absence of atrophy. The absence of erythema, atrophy, and a different nature of hyperkeratosis distinguish leukoplakia from lupus erythematosus. Synthetic antimalarial drugs are used for DKV - delagil, plaquenil, rezoquin, hingamin, administered orally at age dosages 2 times a day for 40 days or 3 times a day in 5-day cycles with 3-day breaks. They have photoprotective properties, prevent the polymerization of DNA and RNA, and suppress the formation of antibodies and immune complexes. At the same time, vitamins of the B complex, which have an anti-inflammatory, photosensitizing effect, as well as vitamins A, C, E, P, which normalize the processes of oxidative phosphorylation and activate the exchange of connective tissue components of the dermis.
41. Tuberculous lupus. Etiology, pathogenesis, clinic, differential diagnosis, principles of treatment.
Tuberculous lupus is a severe form of tuberculous skin lesions.
Epidemiology. Currently, the disease is rare.
Etiology and pathogenesis. The causative agent is Mycobacterium tuberculosis. The disease develops as a result of hematogenous metastasis in the presence of a tuberculous process of another localization. Transition from surrounding structures (facial skin, conjunctiva) is possible.
Clinical signs and symptoms of lupus erythematosus. As a rule, small translucent yellowish-pink tubercles the size of a millet grain are formed in the thickness of the skin. The process gradually spreads to adjacent areas of the skin, it becomes infiltrated, compacted.
In rare cases, torpid tuberculous abscesses of the eyelids are noted.
Laboratory methods for the study of tuberculous lupus:
Microbiological examination of the contents of the fistulous passages;
Statement of specific samples (Mantoux reaction).
Differential diagnosis is carried out with an abscess of the eyelids, chalazion, actinomycosis, sporotrichosis.
General principles for the treatment of lupus erythematosus:
It is necessary to conduct long-term specific therapy:
Isoniazid orally 300 mg 1 r / day, 2 months
Pyrazinamide orally 15-20 mg/kg 1 r/day, 2 months
Rifampicin orally 8-10 mg/kg 1 r/day, 2 months
Loratadine orally 10 mg 1 r / day (adults and children over 12 years old) or 5 mg 1 r / day (children 2-12 years old), 7-10 days
Calcium chloride, 10% r, iv 10 ml 1 r/day, 7-10 days.
Immediately after completion of the first course of treatment, anti-tuberculosis drugs are prescribed according to one of the following schemes:
Isoniazid orally 15 mg/kg/day 3 times a week, 4 months
Rifampicin PO 15 mg/kg/day Q3, 4 mo or Pyrazinamide PO 50-70 mg/kg
3 r / week, 4 months or Metazid inside 500 mg 2 r / day 3 r / week, 4 months
Pyrazinamide orally 50-70 mg / kg 3 r / week, 4 months.
Evaluation of the effectiveness of treatment. The criteria for the effectiveness of treatment are the disappearance of local symptoms, as well as improvement in the function of other organs.
Complications and side effects of the treatment of lupus erythematosus. When using pyrazinamide, rifampicin, less often isoniazid, a pronounced violation of liver function is possible.
Against the background of the use of rifampicin, kidney damage may occur. In addition, the development of allergic reactions is possible.
Irrational use and / or insufficiently complete examination of the patient before the appointment of anti-tuberculosis drugs can lead to damage to the liver and kidneys. Untimely and insufficiently active therapy leads to the appearance of pronounced cicatricial changes in the skin.
Forecast. As a result of the process, gross cicatricial changes of the eyelids are formed.
40. Deep form of lupus erythematosus. Etiology, pathogenesis, clinic, differential diagnosis, principles of treatment.
Lupus erythematosus is an autoimmune disease with a predominant lesion of the connective tissue, caused by gene disorders of the immune system with a loss of immune tolerance to their antigens. A hyperimmune response develops, Abs arise against one's own tissues, immune complexes circulate in the blood, which are deposited in the vessels of the skin and internal organs, and vasculitis occurs. In the tissues - an inflammatory reaction. Cell nuclei are destroyed - ME cells or lupus erythematosus cells appear.
Deep lupus erythematosus of Kaposi-Irgang is manifested by subcutaneous deep dense nodes of stagnant red color, not soldered to the underlying tissues. On the surface of the nodes there are foci of follicular hyperkeratosis and areas of atrophy. Deep lupus erythematosus is accompanied by general symptoms (arthralgia, subfebrile condition, leukopenia, anemia, increased ESR). For treatment, synthetic antimalarial drugs are used - delagil, plaquenil, rezoquin, hingamin, administered orally at age dosages 2 times a day for 40 days or 3 times a day in 5-day cycles with 3-day breaks. They have photoprotective properties, prevent the polymerization of DNA and RNA, and suppress the formation of antibodies and immune complexes. At the same time, vitamins of the B complex, which have an anti-inflammatory, photosensitizing effect, as well as vitamins A, C, E, P, which normalize the processes of oxidative phosphorylation and activate the exchange of connective tissue components of the dermis.
11. 1. Discoid lupus (DLE) occurs with a predominant skin lesion. Elements are localized on the face, neck, scalp. Ultimately, they undergo scarring. With DKV, there are no signs of damage to internal organs, there is no photosensitivity. AHA are not detected or are detected in low titer 11. 2. Drug-induced lupus (B) develops against the background of the use of any drugs (antibiotics, sulfonamides, hydralazine, procainamide). Symptoms of PV are similar to those of SLE, however, fever, serositis, and hematological changes predominate. Skin, kidney, and neurological involvement is rare. Symptoms of EV usually disappear after stopping the drugs.
11. 3. Subacute cutaneous lupus erythematosus - AHA negative lupus. The disease begins with photosensitivity and lupus-like syndromes.
11.4. With other diseases:
11.4.1. Hemolytic anemia
11.4.2 Idiopathic thrombocytopenic purpura
11.4.3 Hemorrhagic vasculitis of Schonlein-Henoch
11.4.4 Primary antiphospholipid syndrome
11.4.5 Systemic vasculitis
11.4.6. Infective endocarditis
11.4.7. Tuberculosis of the lungs and internal organs.
12. Treatment of wells.
Purpose of treatment- achievement of induced remission, which
suggests the absence of any clinical manifestations of SLE (in this case, there may be signs that have arisen as a result of lesions of one or another organ or system during previous exacerbations), the absence of a cytopenic syndrome, AHA and other organ-specific antibodies should not be detected during immunological examination. In case of exacerbation of SLE, treatment should be carried out in a hospital (!)
diet with restriction of salt, liquid, spicy and salty
regimen with restriction of motor activity for 3-4 weeks
drug therapy
NHTVP is used to relieve constitutional and musculoskeletal manifestations of SLE, as well as moderately severe serositis. In patients with SLE, more often than in other patients with the use of NSAIDs, impaired renal function and unusual side effects (hepatitis, aseptic meningitis) develop.
Antimalarial (aminoquinoline) drugs:
effective for skin, joint, constitutional disorders
prevent exacerbation in patients with moderate disease activity
reduce lipid levels and reduce the risk of thrombotic complications.
In the first 3-4 months, the dose of hydroxychloroquine is 400 mg/day (6.5 mg/kg), then 200 mg/day. The most dangerous side effect is retinopathy, so it is necessary 1 time during the treatment | a year to conduct a complete ophthalmological examination.
Short-acting glucocorticosteroids (GCS) are the main drug in the treatment of SLE. The most commonly used are prednisolone and methylprednisolone. The dose of corticosteroids depends on the activity of the disease:
small doses (<10 мг/сут) назначают при низкой активности (в случае неэффективности НПВП и антималярийных ЛС)
High doses (1 mg/kg/day or more) are indicated for high SLE activity. The duration of taking high doses of corticosteroids, depending on the clinical effect, ranges from 4 to 12 weeks. Dose reduction should be carried out gradually under close clinical and laboratory control, and maintenance doses (5-10 mg / day) should be taken for many years.
Pulse therapy (1000 mg methylprednisolone intravenously over at least 30 minutes for three days in a row) is an effective treatment method to achieve rapid control of many manifestations of SLE, and in the future to keep patients at lower doses. However, there are no convincing data on the advantages of pulse therapy over oral administration of high corticosteroids. The mechanism of action of loading doses of methylprednisolone when administered intravenously has not yet been fully disclosed, but the available data indicate a significant immunosuppressive effect of the drug already in the first day. A short course of intravenous administration of methylprednisolone causes a significant and prolonged decrease in the level of IgG in the blood serum due to an increase in catabolism and a decrease in its synthesis. It is believed that loading doses of methylprednisolone stop 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. Blocking the action of lymphotoxins is not excluded. Currently, a category of patients (young age, rapidly progressive lupus nephritis, high immunological activity) has been identified in which this type of therapy should be used at the onset of the disease.
Cytotoxic LS.
The choice of cytotoxic drugs depends on the characteristics of the course, the severity of the disease, the nature and effectiveness of previous therapy. Cyclophosphamide (CF) is the drug of choice for:
proliferative lupus nephritis
Membranous VN
Severe CNS damage not controlled by high doses of corticosteroids
Treatment with CF (intravenous bolus injection of 0.5-1 g/m2 monthly for at least 6 months, and then every 3 months for 2 years) in combination with oral GC and pulse therapy increases the survival of patients with proliferative lupus nephritis .
Azathioprine(1-4 mg/kg/day), methotrexate(15 "mg / week) and cyclosporine A(<5 мг/кг/сут) показаны:
For the treatment of less severe but GCS-resistant manifestations of SLE
As a component of maintenance therapy that allows patients to be managed on lower doses of corticosteroids ("steroid-sparing" effect)
Intensive therapy SLE, i.e. the use of shock doses of corticosteroids and cytostatics to suppress activity was first used in our country 20 years ago and showed high efficiency in severe disease.
The main indications for intensive care:
Active lupus nephritis (especially with nephritic syndrome, hypertension, rapid increase in creatinine)
Acute severe damage to the central nervous system (meningoencephalitis,is, transverse myelitis)
Hematological crisis, severe thrombocytopenia
Ulcerative necrotizing cutaneous vasculitis
Pulmonary vasculitis
High activity of the disease, resistant to previous, previously considered adequate therapy
The most common methods of intensive care:
Classic pulse therapy with methylprednisolone: 1000 mg/day IV drip for 3 consecutive days (3000 mg per course)
In / in the introduction of methylprednisolone in reduced doses (250-300 mg / day) until a total dose of about 3000 mg per course is reached
Monthly IV administration of 1000 mg methylprednisolone for 6-12 months
Combined pulse therapy: intravenous administration of 1000 mg of methylprednisolone for 3 consecutive days and 1000 mg of cyclophosphamide on the 1st or 2nd day (drugs are administered sequentially)
Monthly IV administration of 1000 mg of methylprednisolone and 1000 mg of cyclophosphamide for 12 months
It should be noted that rapidly reducing the daily dose of prednisoneper os immediately after pulse therapy is not recommended. With high disease activity, after pulse therapy, which is usually used in the morning, leave for the evening 1 BUT per os daily dose, since methylprednisolone, administered intravenously in the morning, after 4; + -7 hours in the blood is no longer determined and a withdrawal syndrome may develop.
Intravenous immunoglobulin has been used for more than 15 years for the treatment of SLE, but randomized controlled trials have not been conducted. The effectiveness of the drug in relation to the following manifestations of SLE has been demonstrated: I
Pleurisy
Vasculitis
fevers
thrombocytopenia
Currently, the only absolute indication for IV immunoglobulin in SLE is severe refractory thrombocytopenia, especially if there is a risk of bleeding.
Mycophenolate mofetil. In patients with cyclophosphamide-refractory lupus nephritis, treatment with mycophenolate leads to a decrease or stabilization of serum creatinine and proteinuria, a decrease in SLE activity and corticosteroid doses.
extracorporeal procedures.
Plasmapheresis used to treat the most severe patients with rapidly increasing dysfunction of vital organs in combination with active therapy with cyclophosphamide and corticosteroids. It is effective for:
Cytopenia
cryoglobulinemia
Vasculitis
CNS damage
Thrombotic thrombocytopenic purpura
Efficiency pulse sync, consisting in the induction of an exacerbation of the disease by interrupting treatment (rebound syndrome) followed by three sessions of intensive plasmapheresis in combination with pulse therapy with cyclophosphamide and 1) GCS requires further study.
With the development of chronic renal failure are shown program hemodialysis and kidney transplantation.
Systemic lupus erythematosus (SLE)- a chronic autoimmune disease caused by a malfunction of immune mechanisms with the formation of damaging antibodies to one's own cells and tissues. SLE is characterized by damage to the joints, skin, blood vessels and various organs (kidneys, heart, etc.).
The cause and mechanisms of the development of the disease
The cause of the disease has not been elucidated. It is assumed that the trigger mechanism for the development of the disease are viruses (RNA and retroviruses). In addition, people have a genetic predisposition to SLE. Women get sick 10 times more often, which is associated with the peculiarities of their hormonal system (high concentration of estrogen in the blood). The protective effect of male sex hormones (androgens) with respect to SLE has been proven. Factors that can cause the development of the disease can be a viral, bacterial infection, medications.The basis of the mechanisms of the disease is a violation of the functions 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, on the serous membranes of internal organs (heart, lungs, etc.) causing inflammatory reactions.
Symptoms of the disease
SLE is characterized by a wide range of symptoms. The disease proceeds with exacerbations and remissions. The onset of the disease can be both lightning fast and gradual. General symptoms
- Fatigue
- Weight loss
- Temperature
- Decreased performance
- Fast fatiguability
Damage to the musculoskeletal system
- Arthritis - inflammation of the joints
- Occurs in 90% of cases, non-erosive, non-deforming, joints of the fingers, wrists, knee joints are more 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%)
Mucosal and skin lesions
- Skin lesions at the onset of the disease appear only in 20-25% of patients, in 60-70% of patients they occur later, in 10-15% of the 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. Lesions have the appearance of erythema (reddish plaques with peeling), dilated capillaries along 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) is rare, usually affecting the temporal region. Hair falls out in a limited area.
- Increased skin sensitivity to sunlight (photosensitivity) occurs in 30-60% of patients.
- Mucosal involvement occurs in 25% of cases.
- Redness, decreased pigmentation, malnutrition of the tissues of the lips (cheilitis)
- Small punctate hemorrhages, ulcerative lesions of the oral mucosa
Respiratory damage
Respiratory system lesions in SLE are diagnosed in 65% of cases. Pulmonary pathology can develop both acutely and gradually with various complications. The most common manifestation of damage to the pulmonary system is inflammation of the membrane covering the lungs (pleurisy). It is characterized by pain in the chest, shortness of breath. SLE can also cause the development of lupus pneumonia (lupus pneumonitis), characterized by: shortness of breath, cough with bloody sputum. SLE often affects the vessels of the lungs, leading to pulmonary hypertension. Against the background of SLE, infectious processes in the lungs often develop, and it is also possible to develop a serious condition such as blockage of the pulmonary artery by a thrombus (pulmonary embolism).Damage to the cardiovascular system
SLE can affect all structures of the heart, the outer shell (pericardium), the inner layer (endocardium), directly the heart muscle (myocardium), valves and coronary vessels. The most common is the pericardium (pericarditis).- Pericarditis is an inflammation of the serous membranes that cover the heart muscle.
- Myocarditis is inflammation of the heart muscle.
- The defeat of the valves of the heart, the mitral and aortic valves are more often 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 atherosclerosis. Peripheral vascular disease is manifested by:
- Livedo reticularis (blue spots on the skin creating a grid pattern)
- Lupus panniculitis (subcutaneous nodules, often painful, may ulcerate)
- Thrombosis of the vessels of the extremities and internal organs
Kidney damage
Most often in SLE, the kidneys are affected, in 50% of patients lesions of the renal apparatus are determined. A frequent symptom is the presence of protein in the urine (proteinuria), erythrocytes and cylinders are usually not detected at the onset of the disease. The main manifestations of kidney damage in SLE are: proliferative glomerulonephritis and mebran nephritis, which is manifested by nephrotic syndrome (proteins in the urine more than 3.5 g/day, decreased protein in the blood, edema).Damage to the central nervous system
It is assumed that CNS disorders are caused by damage to the cerebral vessels, as well as the formation of antibodies to neurons, to cells responsible for protecting and nourishing neurons (glial cells), and to immune cells (lymphocytes).The main manifestations of damage to the nervous structures and blood vessels of the brain:
- Headache and migraine, the most common symptoms in SLE
- Irritability, depression - rare
- Psychoses: paranoia or hallucinations
- brain stroke
- Chorea, parkinsonism - rare
- Myelopathy, neuropathy and other disorders of the formation of nerve sheaths (myelin)
- Mononeuritis, polyneuritis, aseptic meningitis
Digestive tract injury
Clinical lesions of the digestive tract are diagnosed in 20% of patients with SLE.- Damage to the esophagus, violation of the act of swallowing, expansion 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 white blood cells. It is caused by a decrease in lymphocytes and granulocytes (neutrophils, eosinophils, basophils).
- Thrombocytopenia is a decrease in platelets in the blood. It occurs in 25% of cases, caused by the formation of antibodies against platelets, as well as antibodies to phospholipids (fats that make up cell membranes).
Diagnosis of SLE
Diagnosis of SLE is based on data from the clinical manifestations of the disease, as well as data from laboratory and instrumental studies. The American College of Rheumatology has developed special criteria by which it is possible to make a diagnosis - systemic lupus erythematosus.Criteria for the diagnosis of systemic lupus erythematosus
The diagnosis of SLE is made if at least 4 out of 11 criteria are present.
| Characteristic: without erosion, peripheral, manifested by pain, swelling, accumulation of insignificant fluid in the joint cavity |
| Red in color, oval, round or annular in shape, plaques with uneven contours on their surface are scales, dilated capillaries nearby, scales are difficult to separate. Untreated lesions leave scars. |
| The oral mucosa or nasopharyngeal mucosa is affected in the form of ulcerations. Usually painless. |
| Increased sensitivity to sunlight. As a result of exposure to sunlight, a rash appears on the skin. |
| Specific rash in the form of a butterfly |
| Permanent loss of protein in the urine 0.5 g/day, excretion of cellular casts |
| Pleurisy is an inflammation of the membranes of the lungs. It is manifested by pain in the chest, aggravated by inhalation. Pericarditis - inflammation of the lining of the heart |
| Convulsions, Psychosis - in the absence of drugs that can provoke them or metabolic disorders (uremia, etc.) |
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| Elevated anti-nuclear antibodies (ANA) |
The degree of disease activity is determined by special SLEDAI indices ( Systemic lupus erythematosus disease activity index). The disease activity index includes 24 parameters and reflects the state of 9 systems and organs, expressed in points that are summarized. Maximum 105 points, which corresponds to very high disease activity.
Disease activity indices bySLEDAI
| Manifestations | Description | Punctuation |
| Pseudo-epileptic seizure(development of convulsions without loss of consciousness) | It is necessary to exclude metabolic disorders, infections, medications that could provoke it. | 8 |
| Psychoses | Violation of the ability to perform actions in the usual mode, impaired perception of reality, hallucinations, decreased associative thinking, disorganized behavior. | 8 |
| Organic changes in the brain | Changes in logical thinking, orientation in space is disturbed, memory, intelligence, concentration, incoherent speech, insomnia or drowsiness are reduced. | 8 |
| Eye disorders | Inflammation of the optic nerve, excluding arterial hypertension. | 8 |
| Damage to the cranial nerves | Damage to the cranial nerves revealed for the first time. | |
| Headache | Severe, persistent, may be migraineous, not responding to narcotic analgesics | 8 |
| Cerebral circulatory disorders | First detected, excluding the consequences of atherosclerosis | 8 |
| Vasculitis-(vascular damage) | Ulcers, gangrene of the extremities, painful knots on the fingers | 8 |
| Arthritis- (inflammation of the joints) | Damage to more than 2 joints with signs of inflammation and swelling. | 4 |
| Myositis- (inflammation of skeletal muscles) | Muscle pain, weakness with confirmation of instrumental studies | 4 |
| Cylinders in the urine | Hyaline, granular, erythrocyte | 4 |
| erythrocytes in urine | More than 5 red blood cells in the field of view, exclude other pathologies | 4 |
| Protein in the urine | More than 150 mg per day | 4 |
| Leukocytes in urine | More than 5 white blood cells in the field of view, excluding infections | 4 |
| Skin lesions | Inflammatory damage | 2 |
| Hair loss | Enlargement of lesions or complete hair loss | 2 |
| Mucosal ulcers | Ulcers on the mucous membranes and on the nose | 2 |
| Pleurisy- (inflammation of the membranes of the lungs) | Chest pain, pleural thickening | 2 |
| Pericarditis-( inflammation of the lining of the heart) | Detected on ECG, echocardiography | 2 |
| Decreased compliment | Decreased C3 or C4 | 2 |
| AntiDNA | Positively | 2 |
| Temperature | More than 38 degrees C, excluding infections | 1 |
| Decrease in blood platelets | Less than 150 10 9 /l, excluding medicines | 1 |
| Decrease in white blood cells | Less than 4.0 10 9 /l, excluding medicines | 1 |
- Light activity: 1-5 points
- Moderate activity: 6-10 points
- High activity: 11-20 points
- Very high activity: more than 20 points
Diagnostic tests used to detect SLE
- ANA- screening test, specific antibodies to cell nuclei are determined, is determined in 95% of patients, does not confirm the diagnosis in the absence of clinical manifestations of systemic lupus erythematosus
- Anti DNA– antibodies to DNA, determined in 50% of patients, the level of these antibodies reflects the activity of the disease
- Anti-sm- specific antibodies to the Smith antigen, which is part of short RNA, are detected in 30-40% of cases
- Anti-SSA or Anti-SSB, antibodies to specific proteins located in the cell nucleus, are present in 55% of patients with systemic lupus erythematosus, are not specific for SLE, and are also detected in other connective tissue diseases
- Anticardiolipin - antibodies to mitochondrial membranes (energy station of cells)
- Antihistones- antibodies against proteins necessary for packaging DNA into chromosomes, characteristic of drug-induced SLE.
- Markers of inflammation
- ESR - increased
- C - reactive protein, elevated
- Compliment level lowered
- C3 and C4 are reduced as a result of excessive formation of immune complexes
- Some people are born with reduced compliment levels, which is a predisposing factor for the development of SLE.
- General blood analysis
- Possible decrease in red blood cells, white blood cells, lymphocytes, platelets
- Analysis of urine
- Protein in the urine (proteinuria)
- Red blood cells in the 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 apparatus
- X-ray of the joints
- X-ray and computed tomography of the chest
- Nuclear magnetic resonance and angiography
- echocardiography
Specific Procedures
- A lumbar puncture can help rule out infectious causes of neurological symptoms.
- A biopsy (analysis of organ tissue) of the kidneys allows you to determine the type of glomerulonephritis and facilitate the choice of treatment tactics.
- A skin biopsy allows you to clarify the diagnosis and exclude similar dermatological diseases.
Treatment of systemic lupus
Despite significant advances in the modern treatment of systemic lupus erythematosus, this task remains very difficult. Treatment aimed at eliminating the main cause of the disease has not been found, just as the cause itself has not been found. Thus, the principle of treatment is aimed at eliminating the mechanisms of the development of the disease, reducing provoking factors and preventing complications. - Eliminate physical and mental stress conditions
- Reduce sun exposure, use sunscreen
- Glucocorticosteroids the most effective drugs in the treatment of SLE.
Dosing regimens:
- Inside:
- Initial dose of prednisolone 0.5 - 1 mg / kg
- Maintenance dose 5-10 mg
- Prednisolone should be taken in the morning, the dose is reduced by 5 mg every 2-3 weeks
- High-dose intravenous methylprednisolone (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
- Cytostatics: cyclophosphamide (cyclophosphamide), azathioprine, methotrexate, are used in the complex treatment of SLE.
- Acute lupus nephritis
- Vasculitis
- Forms resistant to treatment with corticosteroids
- The need to reduce doses of corticosteroids
- High SLE activity
- Progressive or fulminant course of SLE
- Cyclophosphamide with pulse therapy 1000 mg, then every day 200 mg until a total dose of 5000 mg is reached.
- Azathioprine 2-2.5 mg/kg/day
- Methotrexate 7.5-10 mg/week, by mouth
- Anti-inflammatory drugs
- Naklofen, nimesil, aertal, catafast, etc.
- Aminoquinoline drugs
- delagil, plaquenil, etc.
- Biologicals are a promising treatment for SLE
- Anti CD 20 - Rituximab
- Tumor necrosis factor alpha - Remicade, Gumira, Embrel
- Other drugs
- Anticoagulants (heparin, warfarin, etc.)
- Antiplatelet agents (aspirin, clopidogrel, etc.)
- Diuretics (furosemide, hydrochlorothiazide, etc.)
- Calcium and potassium preparations
- Methods of extracorporeal treatment
- Plasmapheresis is a method of blood purification outside the body, in which part of the blood plasma is removed, and with it the antibodies that cause SLE disease.
- 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?
The risk of developing complications of systemic lupus erythematosus directly depends on the course of the disease.Variants of the course of systemic lupus erythematosus:
1.
Acute course- is 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, a change in periods of exacerbations and remissions, a predominance of general symptoms (weakness, weight loss, subfebrile temperature (up to 38 0
C) and others), damage to internal organs and complications occur gradually, not 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 it is possible to distinguish 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 body structures.
2. medicinal lupus erythematosus- unlike the systemic form of lupus erythematosus, a completely reversible process. Drug-induced lupus develops as a result of exposure to certain drugs:
- Medicinal products 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 Doppelhertz, 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 in systemic lupus erythematosus, but blood tests (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 to differentiate from diseases similar in appearance (eczema, psoriasis, skin form of sarcoidosis, and others).
4. neonatal lupus erythematosus occurs in newborn babies 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 autoimmune antibodies are detected during their examination.
Symptoms of neonatal lupus erythematosus the child usually manifests itself before the age of 3 months:
- changes on the skin of the face (often look like a butterfly);
- congenital arrhythmia, which is often determined by ultrasound of the fetus in the II-III trimesters of pregnancy;
- lack of blood cells in the general blood test (decrease in the level of erythrocytes, hemoglobin, leukocytes, platelets);
- detection of autoimmune antibodies specific for SLE.
5. Also, the term "lupus" is used for tuberculosis of the skin of the face - tuberculous lupus. Tuberculosis of the skin is very similar in appearance to the systemic lupus erythematosus butterfly. The diagnosis will help to establish a histological examination of the skin and microscopic and bacteriological examination of the scraping - Mycobacterium tuberculosis (acid-fast bacteria) is detected.
A photo:
this is what tuberculosis of the skin of the face or tuberculous lupus looks like.
Systemic lupus erythematosus and other systemic connective tissue diseases, how to differentiate?
Group of systemic connective tissue diseases:- Systemic lupus erythematosus.
- Idiopathic dermatomyositis (polymyositis, Wagner's disease)- defeat by autoimmune antibodies of smooth and skeletal muscles.
- Systemic scleroderma is a disease in which normal tissue is replaced by connective tissue (which does not carry 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, and so on), 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 |
| The onset of the disease |
|
 A photo: Raynaud's syndrome |
|
| Temperature | Prolonged fever, body temperature above 38-39 0 C. | Prolonged subfebrile condition (up to 38 0 С). | Moderate prolonged fever (up to 39 0 C). |
| Appearance of the patient (at the beginning of the disease and in some of its forms, the appearance of the patient may not be changed in all these diseases) | Skin lesions, mostly of the face, "butterfly" (redness, scales, scars). Rashes can be all over the body and on the mucous membranes. Dry skin, loss of hair, nails. Nails are deformed, striated nail plates. Also, throughout the body there may be hemorrhagic rashes (bruises and petechiae).  | The face can acquire a “mask-like” expression without facial expressions, stretched, the skin is shiny, deep folds appear around the mouth, the skin is motionless, tightly soldered to deep-lying tissues. Often there is a violation of the glands (dry mucous membranes, as in Sjögren's syndrome). Hair and nails fall out. Dark spots on the skin of the extremities and neck against the background of "bronze skin".  | A specific symptom is swelling of the eyelids, their color may be red or purple, on the face and in the décolleté area there is a varied rash with reddening of the skin, scales, hemorrhages, scars. With the progression of the disease, the face acquires a “mask-like appearance”, without facial expressions, stretched, may be skewed, and drooping of the upper eyelid (ptosis) is often detected.  |
| The main symptoms during the period of disease activity |
|
|
|
| Forecast | Chronic course, over time, more and more organs are affected. Without treatment, complications develop that threaten the life of the patient. With adequate and regular treatment, it is possible to achieve a long-term, stable remission. | ||
| Laboratory indicators |
|
|
|
| Principles of treatment | Long-term hormonal therapy (Prednisolone) + cytostatics + symptomatic therapy and other drugs (see article section "Treatment of systemic lupus"). | ||
As you can see, there is not a single analysis that would completely differentiate systemic lupus erythematosus from other systemic diseases, and the symptoms are very similar, especially in the early stages. Experienced rheumatologists often need to evaluate the skin manifestations of the disease to diagnose systemic lupus erythematosus (if present).
Systemic lupus erythematosus in children, what are the features of symptoms and treatment?
Systemic lupus erythematosus is less common in children than in adults. In childhood, rheumatoid arthritis is more often detected from autoimmune diseases. SLE predominantly (in 90% of cases) affects girls. Systemic lupus erythematosus can occur in infants and young children, although rarely, the largest number of cases of this disease occurs during puberty, namely at the age of 11-15 years. Given the peculiarity of immunity, hormonal levels, growth intensity, systemic lupus erythematosus in children proceeds with its own characteristics.
Features of the course of systemic lupus erythematosus in childhood:
- more severe disease , high activity of the autoimmune process;
- chronic course disease in children occurs 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 fulminant course SLE - almost simultaneous damage to 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 eruptions (bruises, hemorrhages on the skin), as a result - the development of a shock state of DIC - disseminated intravascular coagulation;
- systemic lupus erythematosus in children often occurs in the form of vasculitis - inflammation of the 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.
The 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, a sharp loss of body weight.
2.
Skin changes in the form of a "butterfly" in children are relatively rare. But, given the development of a lack of blood platelets, a hemorrhagic rash is more common throughout the body (bruises for no reason, petechiae or pinpoint hemorrhages). Also, one of the characteristic signs of systemic diseases is hair loss, eyelashes, eyebrows, up to complete baldness. The skin becomes marbled, very sensitive to sunlight. There may be various rashes on the skin that are characteristic of allergic dermatitis. In some cases, Raynaud's syndrome develops - a violation of the circulation of the hands. In the oral cavity there may be long-term non-healing sores - stomatitis.
3.
Joint pain- a typical syndrome of active systemic lupus erythematosus, the pain is periodic. Arthritis is accompanied by the accumulation of fluid in the joint cavity. Pain in the joints over time is combined with pain in the muscles and stiffness of movement, starting with the small joints of the fingers.
4.
For kids characterized by the formation of exudative pleurisy(fluid in the pleural cavity), pericarditis (fluid in the pericardium, the lining of the heart), ascites and other exudative reactions (dropsy).
5.
Heart failure in children, it usually manifests as myocarditis (inflammation of the heart muscle).
6.
Kidney damage or nephritis much more often develops in childhood than in adults. Such nephritis relatively quickly leads to the development of acute renal failure (requiring intensive care and hemodialysis).
7.
Lung injury is rare in children.
8.
In the early period of the disease in adolescents, in most cases, there is gastrointestinal tract injury(hepatitis, peritonitis, etc.).
9.
Damage to the central nervous system in children it is characterized by capriciousness, irritability, in severe cases, convulsions 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, after all, timely treatment is the key to success in the transition of an active process into a period of stable remission.
Diagnostic principles systemic lupus erythematosus are the same as in adults, based mainly on immunological studies (detection of autoimmune antibodies).
In the general blood test, in all cases and from the very beginning of the disease, a decrease in the number of all blood cells (erythrocytes, leukocytes, platelets) is determined, blood clotting is impaired.
Treatment of systemic lupus erythematosus in children, as in adults, involves long-term use of glucocorticoids, namely Prednisolone, cytostatics and anti-inflammatory drugs. Systemic lupus erythematosus is a diagnosis that requires urgent hospitalization of the child in a hospital (rheumatology department, with the development of severe complications - in the intensive care unit or intensive care unit).
In a hospital, 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, injections of Heparin are often prescribed.
In the case of timely started and regular treatment, it is possible to achieve stable remission, while children grow and develop according to 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 features of treatment?
As already mentioned, young women often suffer from systemic lupus erythematosus, and for any woman, the issue of motherhood is very important. But SLE and pregnancy is always a big risk for both the mother and the unborn baby. Pregnancy risks 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. When taking cytostatics (Methotrexate, Cyclophosphamide and others), it is absolutely impossible to become pregnant
,
since these drugs will affect germ cells and embryonic cells; pregnancy is possible only not earlier than six months after the abolition of these drugs.
3. Half
cases of pregnancy with SLE ends with the birth of healthy, full-term baby
. At 25%
cases such children are born premature
, a in a quarter of cases
observed miscarriage
.
4. Possible complications of pregnancy in systemic lupus erythematosus,
in most cases associated with damage to the vessels of the placenta:
- fetal death;
- . So, in a third of cases, an aggravation of the course of the disease develops. The risk of such deterioration is maximum in the first weeks of I, or in the III trimester of pregnancy. And in other cases, a temporary retreat of the disease is observed, but for the most part one should expect a strong 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 the onset of systemic lupus erythematosus. Also, pregnancy can provoke the transition of discoid (cutaneous) lupus erythematosus to SLE.
7. Mother with systemic lupus erythematosus can pass genes to her baby that predispose him to develop a systemic autoimmune disease during his lifetime.
8. The child may develop neonatal lupus erythematosus associated with the circulation of maternal autoimmune antibodies in the blood of the baby; this condition is temporary and reversible.- It is necessary to plan a pregnancy under the supervision of qualified doctors , namely a rheumatologist and a gynecologist.
- It is advisable to plan a pregnancy during a period of persistent remission chronic course of SLE.
- In case of acute systemic lupus erythematosus with the development of complications, pregnancy can adversely affect not only health, but also lead to the death of a woman.
- And if, nevertheless, pregnancy occurred during an exacerbation, then the question of its possible preservation is decided by the doctors, together with the patient. After all, exacerbation of SLE requires long-term use of drugs, some of which are absolutely contraindicated during pregnancy.
- Pregnancy is recommended no earlier than 6 months after discontinuation of cytotoxic drugs (Methotrexate and others).
- With lupus lesion of the kidneys and heart there can be no talk of pregnancy, this can lead to a woman's death from kidney and / or heart failure, because it is these organs that are under a huge load when carrying a baby.
1. Essential throughout pregnancy observed by a rheumatologist and an obstetrician-gynecologist , the approach to each patient is only individual.
2. Be sure to follow the rules: do not overwork, do not be nervous, eat normally.
3. Pay close attention to any changes in your health.
4. Delivery outside the maternity hospital is unacceptable , as there is a risk of developing severe complications during and after childbirth.
7. Even at the very beginning of pregnancy, a rheumatologist prescribes or corrects 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 the appointment of cytostatics and other drugs for the treatment of SLE - pulse therapy, since it is the postpartum period that is dangerous for the development of severe exacerbations of the disease.Previously, all women with systemic lupus erythematosus were advised not to become pregnant, and in the event of conception, all were recommended artificial termination of pregnancy (medical abortion). Now, doctors have changed their opinion on this matter, you can’t deprive a woman of motherhood, especially since there are considerable chances to give birth to a normal healthy baby. But everything must be done in order to minimize the risk to mother and baby.
Is lupus erythematosus contagious?
Of course, any person who sees strange rashes on the face thinks: “Maybe it’s contagious?”. Moreover, people with these rashes walk for so long, feel unwell and constantly take some kind of medication. Moreover, earlier doctors also assumed that systemic lupus erythematosus is transmitted sexually, by contact, or even by airborne droplets. But having studied the mechanism of the disease in more detail, scientists 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, that the underlying cause is the presence of certain genes. But still, not all carriers of these genes suffer from systemic autoimmune diseases.
The trigger mechanism 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 radiation).
Only tuberculous lupus can be contagious (tuberculosis of the skin of the face), since a large number of tuberculosis sticks are detected on the skin, while 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, trace elements and biologically active substances.The main characteristic of the SLE diet is a balanced and proper diet.
1. foods containing unsaturated fatty acids (Omega-3):
- sea fish;
- many nuts and seeds;
- vegetable oil in a small amount;
3. juices, fruit drinks;
4. lean poultry meat: chicken, turkey fillet;
5. low-fat dairy , especially dairy products (low-fat cheese, cottage cheese, yogurt);
6. cereals and vegetable fiber (grain bread, buckwheat, oatmeal, wheat germ and many others).1. 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);
- dairy products with high fat content and so on.
Photo: alfalfa grass.
3. Garlic - powerfully stimulates the immune system.
4. Salty, spicy, smoked dishes holding fluid in the body.If, against the background of SLE or taking medications, diseases of the gastrointestinal tract occur, then the patient is recommended frequent fractional meals according to a therapeutic diet - table number 1. All anti-inflammatory drugs are best taken with or immediately after meals.
Treatment of systemic lupus erythematosus at home is possible only after the selection of an individual treatment regimen in a hospital setting and the correction of conditions that threaten the life of the patient. 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 can just lose precious time. Folk remedies can give their effectiveness 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 out of the reach of children. One must be careful with such remedies, any poison is a medicine as long as it is used in small doses.Photo, what do the symptoms of lupus erythematosus look like?
A photo: changes on the skin of the face in the form of a butterfly in SLE.
Photo: skin lesions of 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 striation of the nail plate.
Lupus lesions of the oral mucosa . According to the clinical picture, they are very similar to infectious stomatitis, which do not heal for a long time.
And this is what they might look like early 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, reminiscent of measles rashes, leaves pigment spots that do not go away for a long time.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that occurs in young people (mainly in women) and develops against the background of a genetically determined imperfection of immunoregulatory processes, which leads to uncontrolled production of antibodies to one's own cells and their components and the development of autoimmune and immunocomplex chronic lesions (V.A. Nasonova, 1989). The essence of the disease is immuno-inflammatory lesions of the connective tissue, microvasculature, skin, joints and internal organs, while the leading ones are visceral lesions that determine the course and prognosis of the disease.
The incidence of SLE ranges from 4 to 25 cases per 100,000 population. The disease most often develops in women of childbearing age. During pregnancy and in the postpartum period, the risk of exacerbation increases significantly. Women suffer from SLE 8-10 times more often than men. The peak incidence occurs at the age of 15-25 years. In children, the ratio of sick girls and boys is reduced and is 3:1. Mortality in SLE is 3 times higher than in the general population. In men, the disease is just as severe as in women.
SLE belongs to a genetically determined disease: studies conducted in the population have shown that predisposition to the occurrence of SLE is associated with certain class II histocompatibility (HLA) genes, genetically determined deficiency of certain complement components, as well as with gene polymorphisms of some receptors and tumor necrosis factor α (TNF-α).
Etiology
A specific etiological factor in SLE has not been established, but a number of clinical symptoms (cytopenic syndrome, erythema and enanthema) and certain patterns in the development of the disease make it possible to associate SLE with diseases of viral etiology. Currently, RNA viruses (slow or latent viruses) are of importance. The discovery of familial cases of the disease, the frequent existence of other rheumatic or allergic diseases in families, and various immune disorders suggest the possible significance of a family genetic predisposition.
The manifestation of SLE is facilitated by a number of non-specific factors - insolation, non-specific infection, administration of sera, intake of certain drugs (in particular, peripheral vasodilators from the hydralazine group), as well as stress. SLE can start after childbirth or an abortion. All these data allow us to consider SLE as a multifactorial disease.
Pathogenesis
Due to the impact on the immune system of the virus, and possibly antiviral antibodies, against the background of hereditary predisposition, a dysregulation of the immune response occurs, which leads to hyperreactivity of humoral immunity. In the body of patients, uncontrolled production of antibodies to its various tissues, cells and proteins (including various cell organelles and DNA) occurs. It has been established that autoantibodies are produced in SLE to about forty out of more than two hundred potential antigenic cellular components. Subsequently, the formation of immune complexes and their deposition in various organs and tissues (mainly in the microvasculature) occur. Various defects in immunoregulation are characteristic, accompanied by hyperproduction of cytokines (IL-6, IL-4 and IL-10). Then, processes associated with the elimination of fixed immune complexes develop, which leads to the release of lysosomal enzymes, damage to organs and tissues, and the development of immune inflammation. In the process of inflammation and destruction of the connective tissue, new antigens are released, causing the formation of antibodies and the formation of new immune complexes. Thus, there is a vicious circle that ensures the chronic course of the disease.
Classification
At present, a working classification of clinical variants of the course of SLE has been adopted in our country, taking into account:
The nature of the flow;
The activity of the pathological process;
Clinical and morphological characteristics of damage to organs and systems. The nature of the course of the disease
The acute course is characterized by the rapid development of multiorgan changes (including damage to the kidneys and central nervous system) and high immunological activity.
Subacute course: in the debut of the disease, the main symptoms occur, nonspecific damage to the skin and joints. The disease proceeds in waves, with periodic exacerbations and the development of multiple organ disorders within 2-3 years from the onset of the first symptoms.
The chronic course is characterized by a long-term predominance of one or more signs: recurrent polyarthritis, discoid lupus syndrome, Raynaud's syndrome, Werlhof's syndrome or Sjögren's syndrome. Multiple organ lesions occur by the 5-10th year of the disease.
Phase and degree of activity of the process:
Active (high activity - III, moderate - II, minimal - I);
Inactive (remission).
Clinical and morphological characteristics of lesions:
Skin (symptom of "butterfly", capillaritis, exudative erythema, purpura, discoid lupus, etc.);
Joints (arthralgia, acute, subacute and chronic polyarthritis);
Serous membranes (polyserositis - pleurisy, pericarditis and splenitis);
Heart (myocarditis, endocarditis, mitral valve insufficiency);
Lungs (acute and chronic pneumonitis, pneumosclerosis);
Kidneys (lupus nephritis nephrotic or mixed type, urinary syndrome);
Nervous system (meningoencephalopyradiculoneuritis, polyneuritis).
In the chronic course of the disease, 20-30% of patients develop the so-called antiphospholipid syndrome, represented by a clinical and laboratory symptom complex, including venous and (or) arterial thrombosis, various forms of obstetric pathology, thrombocytopenia and various organ lesions. A characteristic immunological sign is the formation of antibodies that react with phospholipids and phospholipid-binding proteins (more on the antiphospholipid syndrome will be discussed later).
There are also three degrees of activity of the pathological process, which characterizes the severity of potentially reversible immune-inflammatory damage and determines the characteristics of the treatment of each individual patient. Activity should be distinguished from the severity of the disease, which refers to the totality of irreversible changes that are potentially dangerous for the patient.
Clinical picture
The clinical picture of the disease is extremely diverse, which is associated with the multiplicity of lesions of organs and systems, the nature of the course, the phase and degree of activity of the inflammatory process.
On the first stage of diagnostic search receive information on the basis of which it is possible to form an idea:
About the onset of the disease;
The nature of the course of the disease;
The degree of involvement in the pathological process of certain organs and systems;
Previous treatment, its effectiveness and possible complications.
Variants of the onset of the disease can be very diverse. Most often it is represented by a combination of various syndromes. Monosymptomatic onset is usually not typical. In this regard, the assumption of SLE disease arises from the moment such a combination is discovered in a patient. In this case, the diagnostic value of certain syndromes increases.
In the early period of SLE, the most common syndromes are damage to the joints, skin and serous membranes, as well as fever. Thus, the combinations that are most suspicious in relation to SLE will be:
Fever, polyarthritis and trophic skin disorders (in particular, hair loss - alopecia);
Polyarthritis, fever and lesions of the pleura (pleurisy);
Fever, trophic skin disorders and pleural lesions.
The diagnostic significance of these combinations increases significantly if the skin lesion is represented by erythema, but in the initial period of the disease it is recorded only in 25% of cases. Nevertheless, this circumstance does not reduce the diagnostic value of the above combinations.
The oligosymptomatic onset of the disease is not typical, but the debut of SLE was noted with the onset of massive edema due to the development from the very beginning of diffuse glomerulonephritis (lupus nephritis) of nephrotic or mixed type.
Involvement in the pathological process of various organs manifests itself with symptoms of their inflammatory lesions (arthritis, myocarditis, pericarditis, pneumonitis, glomerulonephritis, polyneuritis, etc.).
Information about previous treatment allows you to judge:
About its optimality;
About the severity of the course of the disease and the degree of activity of the process (initial doses of glucocorticoids, the duration of their use, maintenance doses, the inclusion of cytostatics in the treatment complex for severe immune disorders, high activity of lupus nephritis, etc.);
On the complications of glucocorticoid and cytostatic treatment.
At the first stage, certain conclusions can be drawn regarding the diagnosis with a long course of the disease, but in its debut, the diagnosis is established at further stages of the study.
On the second stage of diagnostic search you can get a lot of data indicating damage to organs and the degree of their functional insufficiency.
The defeat of the musculoskeletal system manifests as polyarthritis, resembling RA with a symmetrical lesion of the small joints of the hand (proximal interphalangeal, metacarpophalangeal, radiocarpal) and large joints (less often). With a detailed clinical picture of the disease, the defiguration of the joints due to periarticular edema is determined. During the course of the disease, deformities of small joints develop. Articular changes may be accompanied by muscle damage in the form of diffuse myalgias, and very rarely, true PM with edema and muscle weakness. Sometimes the lesion is represented only by arthralgia.
Damage to the skin is noted as often as the joints. The most typical are erythematous rashes on the face in the area of the zygomatic arches and the back of the nose ("butterfly"). Inflammatory rashes on the nose and cheeks, repeating the outlines of the "butterfly", are represented by various options:
Vascular (vasculitic) "butterfly" - unstable, pulsating, diffuse reddening of the skin with a cyanotic tint in the middle zone of the face,
aggravated by external factors (insolation, wind, cold) or unrest;
. "butterfly" type of centrifugal erythema (skin changes are localized only in the region of the nose).
In addition to the “butterfly”, discoid rashes can be detected - erythematous ascending plaques with keratic disturbance and subsequent development of atrophy of the skin of the face, limbs and trunk. Finally, in some patients, nonspecific exudative erythema is noted on the skin of the extremities and chest, as well as signs of photodermatosis on open parts of the body.
Skin lesions include capillaritis - a small-dotted hemorrhagic rash on the fingertips, nail beds and palms. Skin lesions may be associated with enanthema on the hard palate. Painless ulcerations can be found on the mucous membrane of the mouth or nasopharyngeal region.
The defeat of the serous membranes occurs in 90% of patients (the classic diagnostic triad - dermatitis, arthritis, polyserositis). Especially often, lesions of the pleura and pericardium are found, less often - the peritoneum. Symptoms of pleurisy and pericarditis are described in the previous sections, so only their features in SLE will be listed below:
More often there is dry pleurisy and pericarditis;
With effusion forms, the amount of exudate is small;
The defeat of the serous membranes is short-lived, and is usually diagnosed retrospectively when pleuropericardial adhesions or thickening of the costal, interlobar, and mediastinal pleura are detected on x-ray;
A pronounced tendency to the development of adhesive processes (all kinds of adhesions and obliteration of serous cavities) is noted.
SLE is characterized by damage to the cardiovascular system that occurs at various stages of the course of the disease.
Most often, pericarditis is found that is prone to recurrence. Significantly more often than previously thought, endocardial lesions are noted in the form of warty endocarditis (lupus endocarditis) on the leaflets of the mitral, aortic, or tricuspid valves. With a long course of the process, at the second stage of the search, signs of insufficiency of the corresponding valve can be detected (as a rule, there are no signs of stenosis of the hole).
Focal myocarditis is almost never recorded, but a diffuse lesion, especially in severe cases, is accompanied by certain symptoms (see "Myocarditis").
Vascular damage can manifest Raynaud's syndrome, which is characterized by paroxysmal developing disorders of the arterial blood supply to the hands and (or) feet that occur under the influence of cold or excitement. During an attack, paresthesias are noted; the skin of the fingers becomes pale and (or) cyanotic, the fingers are cold. Predominantly there is a lesion of the II-V fingers of the hands and feet, less often - other distal parts of the body (nose, ears, chin, etc.).
Lung lesions can be due to the underlying disease and secondary infection. The inflammatory process in the lungs (pneumonitis) is acute or lasts for months and manifests with signs of the syndrome of inflammatory infiltration of the lung tissue, similar to those in pneumonia. The peculiarity of the process is the occurrence of an unproductive cough in combination with shortness of breath. Another variant of lung damage is chronic interstitial changes (inflammation of the perivascular, peribronchial and interlobular connective tissue), expressed in the development of slowly progressive dyspnea and lung changes during x-ray examination. There are practically no characteristic physical data, so it is almost impossible to judge such a lesion of the lungs at the second stage of the diagnostic search.
The defeat of the gastrointestinal tract, as a rule, is represented by subjective signs detected at the first stage. Physical examination sometimes reveals vague pain in the epigastric region and at the site of the projection of the pancreas, as well as signs of stomatitis. In some cases, hepatitis develops: an increase and soreness of the liver are noted.
Most often, with SLE, kidney damage occurs (lupus glomerulonephritis or lupus nephritis), the evolution of which depends on the further fate of the patient. Kidney damage in SLE can occur in the form of various options, so the data of the direct examination of the patient can vary widely. With isolated changes in the urinary sediment, no disturbances are found during physical examination. With glomerulonephritis occurring with nephrotic syndrome, massive edema and often AH are determined. During the formation of chronic nephritis with constant hypertension, an increase in the left ventricle and an accent of the II tone in the second intercostal space to the right of the sternum are found.
Autoimmune thrombocytopenia (Werlhof's syndrome) manifests itself with typical rashes in the form of hemorrhagic spots of various sizes on the skin of the inner surface of the extremities, the skin of the chest and abdomen, and also on the mucous membranes. After minor injuries (for example, after tooth extraction), bleeding occurs. Nosebleeds sometimes become profuse and lead to anemia. Skin hemorrhages can have a different color: blue-greenish, brown or yellow. Often, SLE manifests for a long time only with Werlhof's syndrome without other typical clinical symptoms.
Damage to the nervous system is expressed to varying degrees, since almost all its departments are involved in the pathological process. Patients complain of migraine headaches. Sometimes seizures occur. Possible violations of cerebral circulation up to the development of a stroke. When examining a patient, signs of polyneuritis are found with a violation of sensitivity, pain along the nerve trunks, a decrease in tendon reflexes and paresthesias. The organic brain syndrome is characterized by emotional lability, episodes of depression, memory impairment, and dementia.
The defeat of the reticuloendothelial system is represented by an early symptom of the generalization of the process - polyadenopathy (enlargement of all groups of lymph nodes, not reaching a significant degree), as well as, as a rule, a moderate enlargement of the spleen and liver.
Damage to the organ of vision manifests dry keratoconjunctivitis, which is due to pathological changes in the lacrimal glands and a violation of their function. Dry eyes lead to the development of conjunctivitis, corneal erosions or keratitis with visual impairment.
With antiphospholipid syndrome, venous (in the deep veins of the lower extremities with repeated pulmonary embolism) and arterial (in the arteries of the brain, leading to strokes and transient ischemic attacks) thromboses can be detected. Valvular heart disease, intracardiac thrombi mimicking myxoma of the heart, and thrombosis of the coronary arteries with the development of MI are recorded. Skin lesions in antiphospholipid syndrome are diverse, but the most common of them is livedo reticularis. (livedo reticularis).
Thus, after the second stage of the examination, multiple organ lesions are detected, and their degree is very different: from barely clinically noticeable (subclinical) to pronounced, prevailing over the others, which creates the prerequisites for diagnostic errors - the interpretation of these changes as signs of independent diseases (for example, glomerulonephritis myocarditis, arthritis).
The third stage of diagnostic search with SLE is very important, because:
Helps to make a definitive diagnosis;
Demonstrates the severity of immune disorders and the degree of damage to internal organs;
Allows you to determine the degree of activity of the pathological (lupus) process.
At the third stage, the most important is the laboratory blood test. There are two groups of indicators.
Indicators that have a direct diagnostic value (indicate severe immunological disorders):
LE cells (lupus erythematosus cells) are mature neutrophils that phagocytize the nuclear proteins of other blood cells degraded by ANF.
ANF is a heterogeneous population of autoantibodies that react with various components of the cell nucleus and circulate in the blood (in 95% of patients it is found in a titer of 1:32 and above). The absence of ANF in the vast majority of cases is evidence against the diagnosis of SLE.
ANA - antibodies to native (i.e. to the whole molecule) DNA. An increase in their concentration correlates with the activity of the disease and the development of lupus nephritis. They are found in 50-90% of patients.
Antibodies to the Sm-nuclear antigen (anti-Sm) are highly specific for SLE. Antibodies to Ro/La ribonucleoprotein are considered specific for SLE (they are detected by immunofluorescence in 30% of cases, by hemagglutination in 20% of patients).
The “rosette” phenomenon is the altered nuclei (hematoxylin bodies) freely lying in the tissues, surrounded by leukocytes.
Diagnosis of antiphospholipid syndrome in SLE is based on the determination of lupus anticoagulants - specific antibodies to phospholipids, which are detected when determining blood clotting using functional tests (determination of increased thromboplastin time) and antibodies to cardiolipin using enzyme immunoassay. The term "lupus anticoagulant" is not correct, since the main clinical sign of the presence of the above antibodies is thrombosis, not bleeding. These antibodies are also found in the so-called primary antiphospholipid syndrome - an independent disease in which thrombosis, obstetric pathology, thrombocytopenia, livedo reticularis and autoimmune hemolytic anemia occur.
Nonspecific acute phase indicators, which include:
Dysproteinemia with an increased content of α2- and γ-globulins;
CRP detection;
Increasing the concentration of fibrinogen;
ESR increase.
With severe articular lesions in a small titer, RF can be detected - an antibody to the Fc fragment of IgG.
In the study of peripheral blood, leukopenia (1-1.2x109 / l) can be detected with a shift in the leukocyte formula to young forms and myelocytes in combination with lymphopenia (5-10% of lymphocytes). Moderate hypochromic anemia is possible, in some cases hemolytic anemia, accompanied by jaundice, reticulocytosis and a positive Coombs test. Sometimes thrombocytopenia is recorded in combination with Werlhof's syndrome.
Kidney damage is characterized by changes in the urine, which can be classified as follows (I.E. Tareeva, 1983):
Subclinical proteinuria (protein content in the urine 0.5 g / day, often in combination with a small leukocyturia and erythrocyturia);
More pronounced proteinuria, serving as an expression of the nephrotic syndrome that accompanies subacute or active lupus nephritis.
Very high proteinuria (as, for example, with amyloidosis) rarely develops. Note moderate hematuria. Leukocyturia can be a consequence of both a lupus inflammatory process in the kidneys, and the result of the frequent addition of a secondary infectious lesion of the urinary tract.
Puncture biopsy of the kidneys reveals nonspecific mesangiomembranous changes, often with a fibroplastic component. Considered characteristic:
Detection in preparations of altered nuclei freely lying in the renal tissue (hematoxylin bodies);
Capillary glomerular membranes in the form of wire loops;
Deposition on the basement membrane of the glomeruli of fibrin and immune complexes in the form of electron-dense deposits.
According to the WHO classification, the following morphological types of lupus nephritis are distinguished:
Class I - no change.
Class II - mesangial type;
Class III - focal proliferative type;
Class IV - diffuse proliferative type;
Class V - membranous type;
Class VI - chronic glomerulosclerosis.
X-ray examination reveals:
Changes in the joints (with articular syndrome - epiphyseal osteoporosis in the joints of the hands and wrist joints, with chronic arthritis and deformities - narrowing of the joint space with subluxations);
Changes in the lungs during the development of pneumonitis (with a long course of the disease - discoid atelectasis, strengthening and deformation of the pulmonary pattern in combination with a high standing diaphragm);
Changes in the heart with the development of lupus disease or exudative pericarditis.
ECG allows you to detect non-specific changes in the final part of the ventricular complex (wave T and segment ST), similar to those previously described for myocarditis and pericarditis.
CT and MRI of the brain detect pathological changes with damage to the central nervous system.
When conducting a diagnostic search, it is also necessary to determine the degree of activity of the lupus process (Table 7-1).
Table 7-1. Criteria for the activity of the pathological process in systemic lupus erythematosus (Nasonova V.A., 1989)
Ending the table. 7-1
Diagnostics
In cases of the classical course of SLE, the diagnosis is simple and based on the detection of a "butterfly", recurrent polyarthritis and polyserositis, which make up the clinical diagnostic triad, supplemented by the presence of LE cells or ANF in diagnostic titers. Of secondary importance is the young age of patients, the connection with childbirth, abortion, the onset of menstrual function, insolation and infectious diseases. It is much more difficult to establish a diagnosis in other cases, especially if the above classic diagnostic features are absent. In this situation, the diagnostic criteria developed by the American Rheumatological Association (ARA) in 1982 and revised in 1992 (Table 7-2) help.
Table 7-2. Diagnostic criteria for systemic lupus erythematosus (ARA)
The end of the table. 7-2
The diagnosis is certain when four or more criteria are met. If less than four criteria are present, then the diagnosis of SLE is doubtful, and dynamic monitoring of the patient is required. This approach has a clear justification: it warns against prescribing glucocorticoids to such patients, since other diseases (including paraneoplastic syndrome) can occur with the same symptoms, in which their use is contraindicated.
Differential Diagnosis
SLE should be differentiated from a number of diseases. How large is the list of organs and systems involved in the pathological process in SLE, just as extensive is the list of diseases that can be misdiagnosed in a patient. SLE can mimic various pathological conditions to a greater extent. This especially often happens at the onset of the disease, as well as with a dominant lesion of one or two organs (systems). For example, the detection of pleural lesions at the beginning of the disease can be regarded as pleurisy of tuberculous etiology; myocarditis can be interpreted as rheumatic or nonspecific. Especially many mistakes are made if SLE debuts with glomerulonephritis. In such cases, only glomerulonephritis is diagnosed.
SLE most often has to be differentiated from ARF (rheumatism), IE, chronic active hepatitis (CAH), hemorrhagic diathesis (thrombocytopenic purpura), and other diseases from the CTD group.
The need for differential diagnosis with rheumatism occurs, as a rule, in adolescents and young men in the debut of the disease - when arthritis and fever occur. Rheumatic arthritis differs from lupus in greater severity of symptoms, predominant damage to large joints and transience. It should not be given differential diagnostic value to a previous infectious lesion (tonsillitis), since it can serve as a non-specific factor causing the development of clinical signs of SLE. The diagnosis of rheumatism becomes reliable from the moment of occurrence of signs of heart damage (rheumatic heart disease). Subsequent dynamic observation allows to detect the emerging heart disease, while in SLE, if mitral valve insufficiency is formed, it is expressed slightly and is not accompanied by distinct
hemodynamic disturbances. Mitral regurgitation is mild. Unlike SLE, leukocytosis is noted in the acute stage of rheumatism. ANF is not detected.
Differential diagnosis between SLE and RA is difficult in the initial stage of the disease, which is associated with the similarity of the clinical picture: a symmetrical lesion of the small joints of the hand occurs, new joints are involved in the process, and morning stiffness is typical. Differential diagnosis is based on the predominance of the proliferative component in RA in the affected joints, the early development of hypotrophy of the muscles that move the affected joints, and the stability of the articular lesions. Erosions of the articular surfaces in SLE are absent, but are a characteristic sign of RA. A high RF titer is characteristic of RA. With SLE, it is rarely found and in a low titer. The differential diagnosis of SLE and the visceral form of RA is extremely difficult. A refined diagnosis in both cases does not affect the nature of the treatment (prescription of glucocorticoids).
With CAH, systemic disorders can occur in the form of fever, arthritis, pleurisy, skin rashes, and glomerulonephritis. Leukopenia, thrombocytopenia, LE cells, and ANF can be detected. When conducting a differential diagnosis, the following should be considered:
CAH often develops in middle age;
In the anamnesis, patients with CAH have indications of past viral hepatitis;
With CAH, pronounced changes in the structure and function of the liver are detected (cytolytic and cholestatic syndrome, signs of liver failure, hypersplenism, portal hypertension);
With SLE, liver damage does not always occur and proceeds in the form of mild hepatitis (with moderate signs of a cytolytic syndrome);
With CAH, various markers of viral liver damage (antiviral antibodies and viral antigen) are detected.
In primary IE, heart damage (inadequacy of the aortic or mitral valve) quickly occurs, and antibiotic therapy has a clear effect. LE cells, anti-DNA antibodies, and ANF are usually absent. With timely bacteriological examination, the growth of pathogenic microflora is detected.
Thrombocytopenic purpura (either idiopathic or symptomatic) lacks many of the syndromes seen in SLE, typical laboratory findings (LE cells, ANF, anti-DNA antibodies), and fever.
The most difficult differential diagnosis with other diseases from the CTD group. Conditions such as SJS and DM may share many features with SLE. This circumstance exacerbates the possibility of detecting ANF and LE cells in these diseases, albeit in a lower titer. The main differential diagnostic signs are more frequent and pronounced damage to internal organs (especially the kidneys) in SLE, a completely different nature of skin lesions in SJS, and a clear myopathic syndrome in DM. In some cases, a correct diagnosis can only be made for a long time.
dynamic observation of the patient. Sometimes it takes many months and even years (especially in chronic SLE with a minimal degree of activity).
The formulation of a detailed clinical diagnosis of SLE should take into account all the headings given in the working classification of the disease. The diagnosis should reflect:
The nature of the course of the disease (acute, subacute, chronic), and in the case of a chronic course (usually mono- or oligosyndromic), the leading clinical syndrome should be indicated;
Process activity;
Clinical and morphological characteristics of damage to organs and systems indicating the stage of functional failure (for example, with lupus nephritis - the stage of renal failure, with myocarditis - the presence or absence of heart failure, with lung damage - the presence or absence of respiratory failure, etc.);
Indication of ongoing treatment (eg, glucocorticoids);
Complications of treatment (if any).
Treatment
Given the pathogenesis of the disease, complex pathogenetic treatment is recommended for SLE patients. His tasks:
Suppression of immune inflammation and immunocomplex disorders (uncontrolled immune response);
Prevention of complications of immunosuppressive therapy;
Treatment of complications arising in the course of immunosuppressive therapy;
Impact on individual, pronounced syndromes;
Removal of CEC and antibodies from the body.
First of all, it is necessary to exclude psycho-emotional stresses, insolation, actively treat concomitant infectious diseases, eat low-fat foods high in polyunsaturated fatty acids, calcium and vitamin D. Active contraception is necessary during an exacerbation of the disease and against the background of treatment with cytostatic drugs. You should not take contraceptives with a high content of estrogen, as they cause an exacerbation of the disease.
To suppress immune inflammation and immunocomplex disorders in the treatment of SLE, the main immunosuppressors are used: short-acting glucocorticoids, cytostatic drugs and aminoquinoline derivatives. The duration of treatment, the choice of drug, as well as maintenance doses are determined by:
The degree of disease activity;
The nature of the flow (sharpness);
Extensive involvement of internal organs in the pathological process;
Tolerability of glucocorticoids or cytostatics, as well as the existence or absence of complications of immunosuppressive therapy;
The existence of contraindications.
In the initial stages of the disease, with minimal activity of the process and the prevalence of joint damage in the clinical picture, glucocorticoids should be prescribed in small doses (prednisolone at a dose of less than 10 mg / day). Patients should be registered with the dispensary so that when the first signs of an exacerbation of the disease occur, the doctor can promptly prescribe treatment with glucocorticoids in the optimal dose.
In the chronic course of the disease with a predominant skin lesion for many months, chloroquine (at a dose of 0.25 g / day) or hydroxychloroquine can be used.
If there are signs of high activity and generalization of the process with the involvement of internal organs, it is necessary to immediately switch to a more effective immunosuppressive treatment with glucocorticoids: prednisolone is prescribed at a dose of 1 mg / day or more. The duration of high doses ranges from 4 to 12 weeks. Dose reduction should be carried out gradually, under careful clinical and laboratory control. Maintenance doses (5-10 mg/day) should be taken by patients for many years.
Thus, the main treatment for SLE is the use of glucocorticoids. When using them, the following principles should be observed:
Start treatment only when the diagnosis of SLE is confirmed (if suspected, these drugs should not be used);
The dose of glucocorticoids should be sufficient to suppress the activity of the pathological process;
Treatment with an overwhelming dose should be carried out until a pronounced clinical effect is achieved (improvement in general condition, normalization of body temperature, improvement in laboratory parameters, positive dynamics of organ changes);
After achieving the effect, you should gradually switch to maintenance doses;
Mandatory prevention of complications of treatment with glucocorticoids. To prevent the side effects of glucocorticoids, use:
Potassium preparations (orotic acid, potassium chloride, potassium and magnesium aspartate);
Anabolic agents (methandienone at a dose of 5-10 mg);
Diuretics (saluretics);
Antihypertensive drugs (ACE inhibitors);
Antacids.
With the development of severe complications appoint:
Antibiotics (for secondary infection);
Anti-tuberculosis drugs (with the development of tuberculosis, more often - pulmonary localization);
Insulin preparations, diet food (for diabetes mellitus);
Antifungal agents (for candidiasis);
Antiulcer treatment (with the formation of a steroid ulcer).
During treatment with glucocorticoids, there are situations when it is necessary to administer extra-high doses of prednisolone (intravenous drip at a dose of 1000 mg over 30 minutes for three days):
A sharp increase (splash) in the activity of the process (III degree), despite the seemingly optimal treatment;
Resistance to doses that previously achieved a positive effect;
Severe organ changes (nephrotic syndrome, pneumonitis, generalized vasculitis, cerebrovasculitis).
Such pulse therapy stops the formation of immune complexes due to inhibition of the synthesis of antibodies to DNA. A decrease in the concentration of the latter, caused by glucocorticoids, leads to the formation of smaller immune complexes (as a result of dissociation of larger ones).
A significant suppression of the activity of the process after pulse therapy allows further administration of small maintenance doses of glucocorticoids. Pulse therapy is most effective in young patients with a short duration of the disease.
Treatment with glucocorticoids is not always successful, due to:
The need to reduce the dose with the development of complications, despite the fact that such therapy is effective in a particular patient;
Intolerance to glucocorticoids;
Resistance to treatment with glucocorticoids (usually detected early enough).
In such cases (especially with the development of proliferative or membranous lupus nephritis), cytostatics are prescribed: cyclophosphamide (monthly intravenous bolus administration at a dose of 0.5-1 g / m2 for at least 6 months, and then every 3 months for 2 years ) in combination with prednisolone at a dose of 10-30 mg / day. In the future, you can return to treatment with glucocorticoids, since resistance to them usually disappears.
For the treatment of less severe, but resistant to glucocorticoid symptoms of the disease, azathioprine (1-4 mg / kg per day) or methotrexate (15 mg / week) and cyclosporine (at a dose of less than 5 mg / kg per day) are prescribed in combination with low doses of prednisolone (10-30 mg / day).
Criteria for evaluating the effectiveness of the use of cytostatics:
Reduction or disappearance of clinical signs;
The disappearance of steroid resistance;
Persistent decrease in process activity;
Prevention of the progression of lupus nephritis. Complications of cytostatic therapy:
Leukopenia;
Anemia and thrombocytopenia;
Dyspeptic phenomena;
infectious complications.
With a decrease in the number of leukocytes less than 3.0x109 / l, the dose of the drug should be reduced to 1 mg / kg of body weight. With a further increase in leukopenia, the drug is canceled and the dose of prednisolone is increased by 50%.
Extracorporeal methods of treatment - plasmapheresis and hemosorption are widely used. They allow you to remove the CEC from the body, increase the sensitivity of cell receptors to glucocorticoids and reduce intoxication. They are used for generalized vasculitis, severe organ damage (lupus nephritis, pneumonitis, cerebrovasculitis), as well as for severe immune disorders that are difficult to treat with glucocorticoids.
Usually, extracorporeal methods are used in combination with pulse therapy or, if it is ineffective, on its own. It should be noted that extracorporeal methods are not used in cytopenic syndrome.
Patients with a high titer of antiphospholipid antibodies in the blood, but without clinical signs of antiphospholipid syndrome, are prescribed small doses of acetylsalicylic acid (75 mg / day). With confirmed antiphospholipid syndrome, accompanied by clinical signs, sodium heparin and small doses of acetylsalicylic acid are used.
For the treatment of musculoskeletal disorders (arthritis, arthralgia, myalgia) and moderate serositis, the usual doses of NSAIDs can be used.
Forecast
In recent years, due to the use of effective methods of treatment, the prognosis has improved: 10 years after the diagnosis, the survival rate is 80%, and after 20 years - 60%. In 10% of patients, especially with kidney damage (death occurs due to progression of chronic renal failure) or cerebrovasculitis, the prognosis remains unfavorable.
Prevention
Since the etiology of SLE is unknown, primary prevention is not carried out. Nevertheless, a risk group is distinguished, which includes, first of all, relatives of patients, as well as persons suffering from an isolated skin lesion (discoid lupus). They should avoid insolation, hypothermia, should not be vaccinated, receive mud therapy and other balneological procedures.
Differential Diagnosis. The main difficulties are associated with the diversity of symptoms. Most often, the following diseases have to be excluded.
1. Other connective tissue diseases.
2. Bacterial endocarditis. In both diseases, you can observe an increase in body temperature, joint pain and an enlarged spleen. The diagnosis of bacterial endocarditis is confirmed when the pathogen is detected in the blood. True, bacterial endocarditis can also develop in SLE as an infectious complication due to the underlying disease or the use of corticoids and immunosuppressants. Difficulties also arise when trying to differentiate this disease from rheumatic endocarditis.
3. Inflammation of the kidneys. If this is the only symptom, then the diagnosis of glomerulonephritis is often misdiagnosed. Diagnosis is facilitated by immunological data and the results of a histological examination of a biopsy of renal tissue with characteristic microscopic changes.
4. Other diseases. Mistakes are often made in cases where mental disorders or neurological symptoms are in the foreground. The first sign of the disease may be Raynaud's syndrome. A presumptive diagnosis of SLE and other collagenoses is made when symptoms appear after sun exposure. Abdominal manifestations can mimic various diseases, such as gastritis, enteritis, colitis, and sometimes the picture of an "acute abdomen". In many cases, with a severe course of the disease with cachexia, there is a suspicion of the development of tumors, and with hepatosplenomegaly - a lymphoproliferative process.
Diagnostics. There are few characteristic signs that would allow the diagnosis of SLE to be made. These include structures stained with hematoxylineosin, certain morphological changes in the kidneys (wire loop phenomenon) and spleen vessels (bulb peel phenomenon). In general, the picture of the pathology of organs can be diverse, but in an acute course it is sometimes mild.
Common data. a) HE bodies are stained with hematoxylin-eosin. First of all, they are found in the area of necrosis. They probably originate from cell nuclei. According to in vitro staining variants, they differ from LE-cell elements. Histochemical studies in the bodies determine DNA and, as a rule, Ig (mostly together with complement). These structures are most often found in the area of fibrinoid changes: in the renal glomeruli, skin and endocardium, as well as in the serous and synovial membranes, in the lymph nodes and spleen.
B) Fibrinoid is not specific for systemic lupus erythematosus. It is also found in other "collagenoses", as well as at the base of gastric ulcers and the placenta. It is an amorphous eosinophilic mass, despite the apparent homogeneity in histological and histochemical studies, it is quite heterogeneous. According to Miescher et al., fibrinoid in SLE has the following features: it contains the structures of cell nuclei, lg, complement, and, in some cases, fibrinogen (according to immunological analysis). The latter indicates that immune complexes play a significant role in the formation of fibrinoid.
Organ disorders. The most characteristic changes are found in the kidneys and spleen.
kidneys. As a rule, typical granular deposits of immune complexes are found, sometimes linear, which is associated with the production of antibodies to basement membrane antigens. Along with hyaline thrombi, they serve as pathognomonic signs of systemic lupus erythematosus. During an acute attack, and sometimes in a chronic course, they can be detected without clinical signs of kidney damage. At the same time, their localization is mostly limited to the mesangial region. Through elution, it is possible to identify antibodies that react with DNA, nucleoproteins and water-soluble antigens of the cell nucleus, less often with ribonucleoproteins. DNA was identified in the precipitates. In almost 60% of cases, the antigens of the epithelium of the tubules are determined in the immune complexes. The lack of correlation between the presence of circulating immune complexes and changes in the kidneys can be explained by the time factor, primarily by the special significance of locally deposited ICs.
Four forms of morphological changes are observed:
Nephritis with minimal manifestations, i.e. mesangial proliferation (frequency not yet known);
Focal proliferation (25-30%);
Diffuse proliferation (50-60%) with sclerosing variants;
Membranous nephropathy (10-25% of cases of kidney lesions with clinical manifestations).
The first three forms seem to have a continuous flow. ICs first appear in the mesangium and then spread to the endothelium of the capillary wall. Membranous lupus nocturnal nephropathy, like idiopathic nephropathy, is characterized by subepithelial deposition of CI. The pathogenesis of these phenomena is debated. In some cases, it was possible to confirm the transition of proliferative forms to membranous and vice versa. While proliferative changes show high levels and activity of antibodies to DNA, with membranous forms, mostly low titers of non-accumulating antibodies are detected, in 20-50% of cases they are completely absent. Circulating ICs are usually not detected. This indicates the local formation of immune complexes by the binding of circulating antibodies to free antigens. In this case, a special affinity of DNA for collagen (for example, basement membranes) can play a certain role. The most severe form is diffuse proliferative nephritis. It proceeds with severe nephrotic syndrome. Not only the glomeruli are damaged. Increased excretion of L-chains indicates damage to the proximal tubules and often precedes damage to the glomeruli. In the immunomorphological study, Ig is found both in the peritubular spaces and in the cells of the tubules. Such tubulointerstitial changes are found in 19-34% of cases, and especially often with concomitant diffuse proliferative glomerulonephritis. The antigens released during tubular processes can be detected in IR in the analysis of glomeruli. The presence of nephritis should be judged not so much by the titer of ANF, but by a decrease in complement activity.
Spleen and lymph nodes. In the spleen, follicular hyperplasia is mostly found with an increase in the number of plasma cells. The phenomenon of onion peel is especially characteristic: perivascular fibrosis around the central and cystic arteries, consisting of concentrically arranged filaments of collagen and fibroblasts. Among them, Ig and complement are localized. In the lymph nodes, delimited necrosis and cell proliferation are found.
Leather. Common changes in maculopapular and discoid forms are epidermal atrophy and hyperkeratosis, degenerative processes in the basal layer, mononuclear infiltration around vessels and skin appendages, and fibrinoid necrosis of vessels and epidermis. The detection of HE bodies is pathognomonic. On the border between the epidermis and the dermis, deposits of Ig in the form of stripes are often detected, with SLE - in 80-90% of cases (unlike discoid lupus), even in macroscopically unaffected skin. In other connective tissue diseases, with the exception of Sharp's syndrome, they are absent. SZ is deposited much more in altered skin than in intact skin. Detect antibodies to DNA and partly to basement membrane antigens. In 20-50% of cases, properdin or properdin factor B (nonspecific C-activation) is detected. The degree of deposits depends on the duration of the disease (less than 1 year - in the form of spots, then - in the form of stripes). No association with kidney damage has been established. Similar changes are found in spouses, as well as in the closest relatives living together with patients.
Heart. Verrucous endocarditis is typical, which affects not so much the edges of the valves as their surface, tendon threads and parietal endocardium. It is referred to as Liebman-Sachs endocarditis. Nowadays, it is rarely observed, due to such localization, it is often not clinically manifested. Valve defects are relatively rare. Warty structures are formed from fibrin deposits in the upper layers of connective tissue and accumulations of granulo-, lymph- and histiocytes, as well as blood, which gives them a peculiar appearance. In the myocardium, vascular changes with perivascular sclerosis are found.
Vessels. Seals and fibrinoid necrosis of the walls of blood vessels are less typical, but have great pathogenetic significance, as they lead to narrowing of the lumen of the vessels, the formation of blood clots and complete blockage. With the defeat of large vessels, extensive necrosis in the bones and brain with hemiplegia can occur. In the altered areas, Ig, complement and fibrinogen are found.
Thymus. Information about her defeat is contradictory. Lymphatic follicles with germinal centers and plasma cells are often reported; in some cases, vacuolar degeneration of Hassal's bodies is found.
Diagnostic criteria. The American Rheumatological Society has proposed 11 diagnostic criteria. The diagnosis of systemic lupus erythematosus can be established when four or more signs are found simultaneously or sequentially (sensitivity 96%, specificity 96%).
The test for the detection of ANF has a high degree of sensitivity (89%), but moderate specificity compared to the test for the detection of antibodies to native DNA or Sm antigen, soluble macroglobulin. In the absence of ANF, a conclusion is made about the need to determine other types of antibodies that have diagnostic value.
