Lupus erythematosus and lupus nephritis

Systemic lupus erythematosus is the most common disease from the group of diffuse connective tissue diseases, developing on the basis of genetic imperfection of the immune system and characterized by the production of a wide range of autoantibodies to components of the cell nucleus and cytoplasm, a violation of the cellular link of immunity, leading to the development of immune complex inflammation.

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Epidemiology

The prevalence of systemic lupus erythematosus in European countries is 40 per 100,000 population, and the incidence is 5-7 cases per 100,000 population, and these figures depend on race, age and gender. More than 70% of patients become ill at the age of 14-40 years, the peak incidence is at 14-25 years. Systemic lupus erythematosus develops in women of childbearing age 7-9 times more often than in men.

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Causes Lupus erythematosus and lupus nephritis.

The cause of systemic lupus erythematosus is unknown and is currently considered a multigenic disease, as a number of factors (genetic, sexual, environmental) have been identified that play a role in the development of immune disorders that underlie the disease.

• The importance of genetic factors is confirmed by the racial characteristics of the disease, the high frequency of development of the pathology in individuals with certain haplotypes of the HLA system, its high prevalence among relatives of patients, as well as in individuals with a deficiency of early components of the complement system (especially the C2 component).
• The role of sex hormones in the etiology is evidenced by the significant predominance of women among patients with systemic lupus erythematosus, which is associated with the ability of estrogens to suppress immune tolerance and the clearance of circulating immune complexes by mononuclear phagocytes. The importance of hyperestrogenemia is emphasized by the high frequency of the onset and exacerbation of systemic lupus erythematosus during pregnancy and after childbirth, as well as the recent increase in the incidence of women in the postmenopausal period taking hormone replacement therapy with drugs containing estrogens.
• Among environmental factors, the greatest importance is given to ultraviolet radiation (onset or exacerbation of the disease after insolation). The reason for this is unclear, but it is assumed that skin damage caused by exposure to this radiation increases the expression of autoantigens and, therefore, the immune response.
• Other exogenous factors that often cause the development of the disease include drugs (hydralazine, isoniazid, methyldopa) and infections (including viral ones).

Lupus nephritis is a typical immune complex nephritis, the development mechanism of which reflects the pathogenesis of systemic lupus erythematosus as a whole. In systemic lupus erythematosus, polyclonal activation of B cells occurs, which can be caused by both a primary genetic defect and a dysfunction of T lymphocytes and a decrease in the ratio of CD4 ⁺ - and CD8 ⁺ -cells. Pronounced activation of B lymphocytes is accompanied by the production of a wide range of autoantibodies (primarily to nuclear and cytoplasmic proteins) with subsequent formation of immune complexes.

Of greatest importance in the pathogenesis of lupus nephritis are antibodies to double-stranded (native) DNA, which correlate with the activity of nephritis and are found in both circulating and fixed immune complexes in the glomeruli of the kidneys.

The production of antibodies to DNA that is not present in free form outside the cells (in combination with histones it forms nucleosomes within the complex structure of nuclear chromatin) and, thus, is inaccessible to the immune system, becomes possible due to the loss of immune tolerance to one's own antigen. This phenomenon, in turn, is associated with a disruption of the apoptosis process - the physiological removal of old and damaged cells. Disrupted apoptosis leads to the appearance of free nucleosomes, which, as a result of defective phagocytosis, along with other components of the nuclei of dead cells, enter the extracellular environment and stimulate the immune system to produce autoantibodies (primarily antibodies to nucleosomes, some of which are antibodies to DNA).

In addition to antibodies to DNA, a number of autoantibodies to various cellular structures are distinguished, the role of which in the pathogenesis of systemic lupus erythematosus is not equal. Some of them have high specificity and pathogenicity. In particular, anti-Sm antibodies are pathognomonic for systemic lupus erythematosus in general and are believed to serve as an early preclinical marker of the disease, and anti-Ro and anti-Clq antibodies are associated with severe kidney damage. The presence of antiphospholipid antibodies is associated with the development of antiphospholipid syndrome in systemic lupus erythematosus (see "Kidney damage in antiphospholipid syndrome").

Deposits of immune complexes in the renal glomeruli are formed as a result of local formation or deposition of circulating immune complexes. The formation of deposits is influenced by the size, charge, avidity of immune complexes, the ability of the mesangium to eliminate them, and local intrarenal hemodynamic factors. The number and localization of immune deposits and the severity of the inflammatory response in the glomeruli are of certain importance. By causing activation of the complement system, immune complexes promote migration of monocytes and lymphocytes into the glomeruli, which secrete cytokines and other inflammatory mediators that activate the coagulation cascade, cellular proliferation, and accumulation of the extracellular matrix.

In addition to immune complexes, other pathogenetic factors play a role in the progression of lupus nephritis: endothelial damage by antiphospholipid antibodies with subsequent disruption of prostacyclin production and platelet activation, which leads to microthrombosis of glomerular capillaries, arterial hypertension (the severity of which is due to the activity of lupus nephritis) and hyperlipidemia in the presence of nephrotic syndrome. These factors contribute to further damage to the glomeruli.

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Symptoms Lupus erythematosus and lupus nephritis.

The symptoms of lupus nephritis are polymorphic and consist of a combination of various signs, some of which are specific to systemic lupus erythematosus.

• Increased body temperature (from subfebrile to high fever).
• Skin lesions: the most common are erythema of the face in the form of a “butterfly”, discoid rashes, however, erythematous rashes in other locations are possible, as well as rarer types of skin lesions (urticarial, hemorrhagic, papulonecrotic rashes, reticular or dendritic livedo with ulceration).
• Joint damage is most often represented by polyarthralgia and arthritis of the small joints of the hands, rarely accompanied by joint deformation.
• Polyserositis (pleurisy, pericarditis ).
• Peripheral vasculitis: capillary disease of the fingertips, less often of the palms and soles, cheilitis (vasculitis around the red border of the lips), enanthem of the oral mucosa.
• Lung damage: fibrosing alveolitis, discoid atelectasis, high position of the diaphragm, leading to the development of restrictive respiratory failure.

Complications and consequences

The pathological process involves the skin, joints, serous membranes, lungs, heart, but the greatest danger to the life of patients is damage to the central nervous system and kidneys. Clinically, kidney damage (lupus nephritis) is detected in 50-70% of patients.

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Diagnostics Lupus erythematosus and lupus nephritis.

With a comprehensive clinical picture of systemic lupus erythematosus, the diagnosis of lupus nephritis is practically not difficult.

The diagnosis is established in the presence of any 4 or more of the 11 diagnostic criteria of the American Society of Rheumatology (1997).

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Treatment Lupus erythematosus and lupus nephritis.

Treatment of lupus erythematosus and lupus nephritis depends on the activity of the disease, clinical and morphological variant of nephritis. Kidney biopsy is necessary to determine the characteristics of morphological changes in order to select adequate therapy, as well as to assess the prognosis of the disease. The therapy should correspond to the activity of the disease: the higher the activity and the more severe the clinical and morphological signs of the disease, the earlier active therapy should be prescribed. Significant advances in the treatment of lupus nephritis have been achieved over the past 20 years due to the development of complex therapeutic regimens, including mainly two groups of drugs.

Forecast

In recent decades, immunosuppressive therapy has had the greatest impact on the course and prognosis of systemic lupus erythematosus and lupus nephritis in particular. The use of glucocorticoids first, and then cytostatic drugs, led to an increase in the 5-year survival rate of patients with systemic lupus erythematosus in general from 49 to 92% (1960-1995), patients with lupus nephritis - from 44 to 82%, including in the most severe, class IV - from 17 to 82%.

The main factors of unfavorable renal prognosis in patients with Yulchanochny nephritis are elevated blood creatinine levels at the onset of the disease and arterial hypertension. Additional prognostic factors include long duration of nephritis, delayed immunosuppressive therapy, high proteinuria or nephrotic syndrome, thrombocytopenia, hypocomplementemia, low hematocrit, onset of systemic lupus erythematosus in childhood or at the age over 55, as well as Negroid race, smoking, male gender, and low social status. The response to immunosuppressive therapy, determined after one year by proteinuria levels and creatinine concentration in the blood, serves as a convenient indicator in assessing the long-term renal prognosis.

The causes of death in patients with lupus nephritis include renal failure, as well as infections, including sepsis, vascular diseases (coronary heart disease, cerebrovascular complications), thromboembolic complications, partly associated with antiphospholipid syndrome.

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