Systemic lupus erythematosus

Systemic lupus erythematosus is a systemic autoimmune disease of unknown etiology, which is based on a genetically determined impairment of immune regulation that determines the formation of organonesspecific antibodies to cell nucleogen antigens with the development of immune inflammation in the tissues of many organs.

Systemic lupus erythematosus (SLE, disseminated lupus erythematosus) is a chronic multisystem inflammatory disease, possibly of an autoimmune nature, affecting mainly young women. Most often, the disease manifests itself as arthralgia and arthritis, skin lesions, mainly of the face, pleurisy or pericarditis, renal and central nervous system damage, cytopenia. Diagnosis is determined by the presence of clinical manifestations and the results of serological studies. Severe course of the active phase of the disease requires the appointment of glucocorticoids, often - hydroxychloroquine, in some cases - immunosuppressants.

70-90% of cases of systemic lupus erythematosus are noted in women (mainly in reproductive age), more often in representatives of the Negroid than the Caucasoid race. However, systemic lupus erythematosus can be diagnosed at any age, even in newborns. Worldwide, there is an increase in the incidence of systemic lupus erythematosus, and in some countries the prevalence of systemic lupus erythematosus rivals that of RA. Systemic lupus erythematosus may be due to the action of yet unknown triggering factors triggering autoimmune reactions in genetically predisposed individuals. Some medicines (in particular, hydralazine and procainamide) can cause lupus-like syndrome.

ICD Code 10

• M32.1. Systemic lupus erythematosus.

Epidemiology

Epidemiology of systemic lupus erythematosus

Systemic lupus erythematosus is the most common disease in the group of systemic connective tissue diseases. The prevalence of systemic lupus erythematosus in children aged 1 to 9 years is 1.0-6.2 cases, and at the age of 10-19 years - 4.4-31.1 cases per 100 000 children, and the incidence - in an average of 0.4-0.9 cases per 100 000 children per year.

Systemic lupus erythematosus rarely affects pre-school children; the incidence of morbidity is noted from the age of 8-9 years, the highest rates are recorded at the age of 14-18. Systemic lupus erythematosus is mainly affected by girls, the ratio of sick girls and boys under the age of 15 averages 4.5: 1.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]

Symptoms of the systemic lupus erythematosus

Symptoms of systemic lupus erythematosus

Symptoms of systemic lupus erythematosus can vary widely. The development of the disease can have a sudden nature, accompanied by a fever, or proceed subacute, for months or years with episodes of arthralgia and malaise. Initial manifestations of the disease can also be vascular headaches, epilepsy or psychosis, but in general systemic lupus erythematosus can manifest by the defeat of any organ. Characteristic wave-like flow with periodic exacerbations.

Articular manifestations ranging from intermittent arthralgia to acute polyarthritis are observed in 90% of patients and often precede other manifestations for several years. Most lupus polyarthritis is non-destructive and non-deforming. Nevertheless, with a prolonged course of the disease, deformations can develop (for example, lesions of the metacarpophalangeal and interphalangeal joints can lead to ulnar deviation or "swan neck" deformation without the erosion of bone and cartilage, which is called Jaco's arthritis).

Skin lesions include erythema in the form of a "butterfly" in the area of the cheek bones (not towering or towering above the surface of the skin), usually not affecting nasolabial folds. The absence of papules and pustules makes it possible to differentiate erythema from rosacea. It is also possible to develop other erythematous, dense, maculopapular skin lesions on the face and neck, in the region of the upper half of the thorax and elbows. Often bullae and ulcers are formed, although recurrent ulceration is more common on the mucous membranes (in particular, in the central regions of the hard palate, near the transition to the soft palate, cheeks, gums and anterior septum). With systemic lupus erythematosus, generalized or focal alopecia is often noted. Panniculitis can lead to the development of subcutaneous nodules. Vascular lesions are migratory erythema of hands and fingers, peri-angular erythema, necrosis of nail plates, urticaria, palpable purpura. Petechia can develop again against thrombocytopenia. In 40% of patients, photosensitivity takes place.

From the side of the cardiovascular and bronchopulmonary systems there are recurrent pleurisies, accompanied by pleural effusion or without it. Pneumonitis is rare, while at the same time there is often a minimal violation of pulmonary function. In rare cases, massive pulmonary hemorrhage develops, leading to the death of patients in 50% of cases. Other complications include pulmonary embolism, pulmonary hypertension, pneumofibrosis. Serious, but rare complications are coronary artery vasculitis and Liebman-Sachs endocarditis. Accelerated development of atherosclerosis leads to an increase in the frequency of its associated complications and mortality. In newborns, congenital heart blockages can develop.

Often there is generalized lymphadenopathy, especially in children, young patients and representatives of the Negroid race. Splenomegaly is recorded in 10% of patients. Possible development of fibrosis of the spleen.

As a result of involvement in the pathological process of various parts of the central or peripheral nervous system or the development of meningitis, neurological disorders may appear. Among them - mild changes in cognitive functions, headache, personality changes, ischemic strokes, subarachnoid hemorrhages, convulsions, psychoses, aseptic meningitis, peripheral neuropathy, transverse myelitis and cerebellar disorders.

Renal damage can develop at any stage of the disease and be the only manifestation of systemic lupus erythematosus. The course of it can vary from benign and asymptomatic to rapidly progressive and fatal. Renal damage is possible as a focal, usually benign glomerulitis to diffuse potentially fatal proliferative glomerulonephritis. Most often it is accompanied by proteinuria, changes in microscopy of urine sediment containing leached red blood cells and leukocytes, arterial hypertension and edema.

With systemic lupus erythematosus, the incidence of miscarriages increases early and late. Nevertheless, a safe resolution of pregnancy is possible, especially after a remission of 6 to 12 months.

Hematologic manifestations of systemic lupus erythematosus include anemia (often autoimmune hemolytic), leukopenia (including lymphopenia with a decrease in the number of lymphocytes to <1500 cells / μl), thrombocytopenia (sometimes life-threatening autoimmune thrombocytopenia). Recurrent arterial and venous thromboses, thrombocytopenia and high probability of obstetrical pathology occur in the development of antiphospholipid syndrome, which is characterized by the detection of antiphospholipid antibodies. Thrombosis is probably the cause of many complications of systemic lupus erythematosus, including obstetric pathology.

Manifestations from the gastrointestinal tract develop both as a result of vasculitis of the intestine, and as a result of disturbances in its peristalsis. Possible development of pancreatitis (caused either directly by systemic lupus erythematosus, or by treatment with glucocorticoids or azathioprine). Clinical manifestations of this condition include abdominal pain due to serositis, nausea, vomiting, signs characteristic of intestinal perforation and obstructive bowel obstruction. With systemic lupus erythematosus, the parenchyma of the liver is often affected.

Symptoms of systemic lupus erythematosus

Forms

Types of systemic lupus erythematosus

Discoid lupus erythematosus (DCV)

Discoid lupus erythematosus, sometimes called the cutaneous form of lupus, is a skin lesion that occurs both with systemic manifestations and without it. Skin lesions begin with the appearance of erythematous plaques that progress to atrophic cicatricial changes. These changes are noted in open areas of the skin that are exposed to light, including face, head, ears. In the absence of treatment, skin lesions result in the development of atrophy and scarring and can be common, leading to the development of scarring alopecia. Sometimes the main manifestation of the disease can be lesions of mucous membranes, especially the oral cavity.

Patients with typical discoid skin lesions should be examined for systemic lupus erythematosus. Antibodies to the double chain of DNA in patients with DKV are almost always not determined. A biopsy of the edges of the skin lesions does not allow the differentiation of DKV from systemic lupus erythematosus, although it helps to exclude other diseases (eg, lymphoma or sarcoidosis).

Early treatment can prevent the development of atrophy. To do this, it is necessary to minimize the exposure of solar or ultraviolet light (for example, by wearing outdoor clothing that protects the sun from the sun). Local glucocorticoid ointments (especially for dry skin) or creams (less fatty than ointments) applied 3-4 times per day (for example, triamcinolone acetonide 0.1% or 0.5%; fluocinolone 0.025% or 0.2%; flurandrenolide 0.05%, betamethasone valerate 0.1%, and especially betamethasone dipropionate 0.05%) usually contribute to the involution of small skin lesions. However, their excessive use on the face (where they can cause skin atrophy) should be avoided. Resistant rashes can be covered with a dressing treated with flurandrenolide. As an alternative therapy, intradermal injections of triamcinolone acetonide suspension 0.1% (<0.1 ml per point) can be used, but this treatment often leads to the development of secondary skin atrophy. Antimalarials (eg, hydroxychloroquine 200 mg orally 1-2 times per day) may be useful. In cases that are resistant to therapy, a long-term (for several months to several years) combination therapy (for example, hydroxychloroquine 200 mg / day and quinacrine 50-100 mg orally once a day) may be required.

[15], [16], [17], [18], [19], [20], [21]

Subacute cutaneous lupus erythematosus

In this version of systemic lupus erythematosus, the pronounced recurrent skin lesions are the first place. Ring-shaped or papular-squamous eruptions can be noted on the face, hands, trunk. Lesions are usually photosensitive and can lead to hypopigmentation of the skin and, in rare cases, to the development of atrophic scars. Often there are manifestations of arthritis and increased fatigue, however, the damage to the nervous system and kidneys does not occur. Depending on the fact of detection of antinuclear antibodies, all patients are divided into ANA-positive and ANA-negative. Most patients have antibodies to the Ro antigen (SSA). Children whose mothers have antibodies to the Ro-antigen can suffer from congenital subacute cutaneous lupus erythematosus or congenital heart block. Treatment of this condition is similar to that of SLE.

Diagnostics of the systemic lupus erythematosus

Diagnosis of systemic lupus erythematosus

Systemic lupus erythematosus should be suspected, especially in young women, if there are symptoms associated with it. In the early stages of systemic lupus erythematosus, it may resemble other connective tissue diseases (or other pathologies), including RA, if the joint syndrome predominates. Systemic lupus erythematosus can resemble a mixed connective tissue disease, systemic scleroderma, rheumatoid polyarthritis, polymyositis or dermatomyositis. Infections that develop as a result of immunosuppressive therapy can also mimic manifestations of systemic lupus erythematosus.

Conducting laboratory tests allows differentiating systemic lupus erythematosus from other connective tissue diseases; this requires the determination of the antiserum antibody titer, the counting of white blood cells, the performance of a general urinalysis, the evaluation of renal and hepatic functions. Diagnosis of systemic lupus erythematosus is very likely if the patient has 4 or more criteria in any period of the disease, but is not excluded when only fewer than 4 criteria are found. If the diagnosis is suspected, but not proven, additional studies should be performed on the presence of autoantibodies. In addition, the verification of dia

[22], [23], [24], [25], [26], [27], [28], [29], [30]

Criteria for diagnosis of systemic lupus erythematosus ¹

For the diagnosis of systemic lupus erythematosus, a minimum of 4 of the following signs

1. Rashes on the face in the form of "butterfly wings"
2. Discoid rashes
3. Photosensitivity
4. Ulceration of the oral cavity
5. Arthritis
6. Serosites
7. Renal damage
8. Leukopenia (<4000 μl), lymphopenia (<1500 μl), hemolytic anemia or thrombocytopenia (<100,000 μl)
9. Neurological disorders
10. Detection of antibodies to DNA, Sm-antigen, false positive reaction of Wasserman
11. Increased antinuclear antibody titre

¹ These 11 criteria are proposed by the American College of Rheumatology and are often used for diagnostic purposes. Although the patient's minimum of 4 criteria is not completely specific for the diagnosis of systemic lupus erythematosus, they help to recognize the manifestations of the disease.

For the diagnosis of systemic lupus erythematosus may require repeated studies in months and even years. The best test for the diagnosis of systemic lupus erythematosus is the immunofluorescence determination of antinuclear antibodies; a positive result (usually high titers,> 1:80) is determined in more than 98% of patients. Nevertheless, this test can be false-positive in patients with RA, other connective tissue diseases, malignant tumors and even in 1% of healthy individuals. Such drugs as hydralazine, procainamide, beta-blockers, antagonists of tumor necrosis factor-alpha (TNF-a) can cause the development of lupus-like syndromes and lead to false positive laboratory results; but in this case, with the abolition of these drugs, seroconversion is noted. When antinuclear antibodies are detected, a study should be made of autoantibodies to the DNA double helix, high titres of which are specific for systemic lupus erythematosus.

Other studies for the presence of antinuclear and anti-cytoplasmic antibodies [eg, Ro (SSA), La (SSB), Sm, RNP, Jo-1] should be carried out in cases where the diagnosis of systemic lupus erythematosus remains unclear. Ro antigen is predominantly in the cytoplasm; Anti-Ro antibodies are sometimes found in patients who do not demonstrate the production of antinuclear autoantibodies suffering from chronic cutaneous lupus erythematosus. They are also characteristic of lupus in newborns and children with congenital heart block. Anti-Sm are highly specific for systemic lupus erythematosus, but, like autoantibodies to the double helix DNA, are characterized by low sensitivity.

Leukopenia is a frequent manifestation of the disease, in its active phase, the development of lymphopenia is possible. Hemolytic anemia can also be observed. Thrombocytopenia in systemic lupus erythematosus is difficult, and sometimes impossible to differentiate from idiopathic thrombocytopenic purpura, except for patients with antinuclear antibodies. In 5-10% of patients with systemic lupus erythematosus, false positive serological responses to syphilis are noted. It is believed that this is due to lupus anticoagulant and prolongation of prothrombin time. Therefore, the pathological values of one or more of these indicators indicate the presence of antiphospholipid antibodies (for example, antibodies to cardiolipin) that can be detected by an enzyme immunoassay. The detection of antibodies to beta ₂ -glycoprotein I is probably more informative. The presence of antiphospholipid antibodies allows predicting the development of arterial and venous thromboses, thrombocytopenia and, in pregnancy, spontaneous abortion and intrauterine fetal death.

Other studies help evaluate the nature of the course of the disease and the need for specific therapy. Concentration of complement components (C3, C4) in serum often decreases in the active phase of the disease, and in particular in patients with active nephritis. The increase in ESR always indicates an active phase of the disease. In contrast, the determination of the concentration of C-reactive protein is not necessary: it can be extremely low in systemic lupus erythematosus, even with an ESR value of more than 100 mm / h.

Evaluation of involvement in the kidney process begins with a general analysis of urine. Erythrocytes and hyaline cylinders suggest the presence of active jade. Urine tests should be performed periodically, at intervals of approximately 6 months, even in the remission phase of the disease. Nevertheless, the results of urinalysis, even with repeated analyzes, can be normal, despite kidney damage, verified by a histological examination of the biopsy material. Conducting a kidney biopsy is usually not required for the diagnosis of systemic lupus erythematosus, but helps assess their condition (eg, acute inflammation or post-inflammatory sclerosis) and choose adequate therapy. In patients with chronic renal failure and severe glomerulosclerosis, the advisability of conducting aggressive immunosuppressive therapy is questionable.

Diagnosis of systemic lupus erythematosus

[31], [32], [33], [34], [35], [36], [37]

Treatment of the systemic lupus erythematosus

Treatment of systemic lupus erythematosus

In order to facilitate understanding of the principles of treatment, the course of systemic lupus erythematosus can be classified as a mild (eg, fever, arthritis, pleurisy, pericarditis, headache, rash) and severe (eg, hemolytic anemia, thrombocytopenic purpura, massive pleural and pericardial lesions, severe renal dysfunction, acute vasculitis of the extremities or gastrointestinal tract, CNS damage).

Easy and remittent disease course

Drug treatment is not required at all, or there is a need for a minimum of therapy ¹. Arthralgia is usually well controlled by NSAIDs. Aspirin (in a dose of 80 to 325 mg once a day) is indicated in patients with a tendency to thrombosis, in which anticardiolipin antibodies are detected, but previously there was no thrombosis; it should be remembered that high doses of aspirin in systemic lupus erythematosus can be hepatotoxic. Antimalarial drugs can be useful when skin and joint manifestations predominate. In such cases, hydroxychloroquine (orally 200 mg 1-2 times a day) or a combination of chloroquine (orally 250 mg once a day) and quinacrine (orally 50-100 mg once a day) is used in such cases. It should be remembered that hydroxychloroquine has a toxic effect on the retina of the eye, which requires an ophthalmic examination every 6 months.

[38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48]

Heavy current

Glucocorticoids are a first line therapy. Combination of prednisone with immunosuppressants is recommended for CNS damage, vasculitis, especially internal organs, active lupus-nephritis. Prednisolone is usually administered orally in a dose of 40-60 mg once a day, but the dose depends on the severity of manifestations of systemic lupus erythematosus. Tablet azathioprine (in doses from 1 to 2.5 mg / kg once a day) or tablet cyclophosphamide (CF in doses from 1 to 4 mg / kg once a day) can be used as immunosuppressants.

The scheme of pulse therapy with cyclophosphamide in combination with intravenous injection of mesna

The patient should be under constant supervision for the tolerability of the treatment during the entire procedure

1. Dissolve in 50 ml of saline 10 mg of ondansetron and 10 mg of dexamethasone and inject intravenously drip for 10-30 minutes.
2. Dissolve 250 ml of saline 250 mg mesna and enter the resulting solution intravenously drip for 1 hour.
3. Dissolve in 250 ml of physiological solution of cyclophosphamide at a dose of 8 to 20 mg / kg, enter the resulting solution intravenously drip for 1 hour. The next infusion of mesna is carried out after 2 hours.
4. Dissolve 250 ml of saline 250 mg mesna, enter the resulting solution intravenously drip for 1 hour. In parallel, using another intravenous access, inject 500 ml of physiological saline drip.
5. The next morning, patients should take ondansetron (inside at a dose of 8 mg).

When CNS and other critical conditions are affected, the initial therapy is intravenous drip (for 1 hour) administration of methylprednisolone at a dose of 1 g for three consecutive days, after which intravenous cyclophosphamide is administered as described above. As an alternative to cyclophosphamide in renal lesions, mycophenolate mofetil may be used (orally at doses of 500 to 1000 mg 1-2 times per day). Intravenous administration of immunoglobulin G (IgG) at a dose of 400 mg / kg for 5 consecutive days is performed with refractory thrombocytopenia. For the treatment of refractory systemic lupus erythematosus, the methods of stem cell transplantation after preliminary intravenous cyclophosphamide administration at a dose of 2 g / m 2 are currently being studied. With terminal renal failure, kidney transplantation is performed.

Improvement of the condition in severe systemic lupus erythematosus occurs within 4-12 weeks and may not be evident until the dose of glucocorticoids is reduced. Thrombosis and embolism of the vessels of the brain, lungs and placenta require a short-term appointment of heparin and long-term (sometimes lifelong) therapy with warfarin until reaching an MHO of 3.

Suppressive Therapy

In most patients, the risk of exacerbations may be reduced without prolonged use of high doses of glucocorticoids. In the chronic course of the disease, low doses of glucocorticoids or other anti-inflammatory drugs (for example, antimalarial or low doses of immunosuppressants) are required. In the appointment of treatment should focus on the main manifestations of the disease, as well as the antibody titer to the double strand of DNA and the concentration of complement. Patients who receive glucocorticoids for a long time should prescribe calcium, vitamin D and bisphosphonate preparations.

Local complications and concomitant pathology

Long-term therapy with anticoagulants is indicated for patients who have antiphospholipid antibodies and recurrent thromboses.

When antiphospholipid antibodies are found in a pregnant woman, thrombotic complications are prevented by the appointment of glucocorticoids (prednisolone at a dose of <30 mg once a day), small doses of aspirin or anticoagulant therapy with heparin. The most effective preventive therapy is subcutaneous administration of heparin in combination with aspirin during the II and III trimesters of pregnancy or in the form of monotherapy.

How is systemic lupus erythematosus treated?

Prevention

Prevention of systemic lupus erythematosus

Primary prophylaxis is not developed, since the etiology of systemic lupus erythematosus is not definitively established. In order to prevent exacerbations of the disease, insolation and the use of ultraviolet irradiation (UV) should be avoided: use sunscreen; wear clothes that cover the skin as much as possible, headgear with fields; refuse to travel to regions with a high level of insolation.

It is necessary to reduce psycho-emotional and physical stress: it is necessary to teach children at home (they can attend school only if they develop persistent clinical and laboratory remission) and limit their communication to reduce the risk of developing infectious diseases.

Vaccination of children is carried out only in the period of complete remission of the disease on an individual schedule. The introduction of gamma globulin can be carried out only in the presence of absolute indications.

Forecast

Prognosis of systemic lupus erythematosus

Systemic lupus erythematosus is usually characterized by a chronic, recurrent and unpredictable course. Remission can last for years. When an adequate control of the primary acute phase of the disease is achieved, even in very severe conditions (for example, with cerebral thrombosis or severe nephritis), a long-term prognosis is usually favorable: a ten-year survival rate in developed countries exceeds 95%. Improved prognosis, in particular, is associated with early diagnosis and more effective therapy. Severe course of the disease requires the appointment of more toxic therapy, which increases the risk of death (in particular, as a result of infections against immunosuppressive therapy, coronary artery disease or osteoporosis with prolonged use of glucocorticoids).