SYSTEMIC LUPUS ERYTHEMATOSUS

SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

SLE (Libmnan-Sacks disease) is the classic prototype of the multisystem disease of autoimmune origin, characterized by a bewildering array of autoantibodies, particularly antinuclear antibodies. Acute or insidious in its onset, it is chronic, remitting and relasping, often febrile illness characterized principally by injury to the skin, joints, kidney, and serosal membranes.

·        Likely most autoimmune diseases, SLE is predominantly a disease of women, with frequency of 1 in 700 among women between ages of 20 and 64 and female to-male ratio of 9:1.

·        The cause of SLE remains unknown, but the existence of a seemingly limitless number of antibodies in these patients against self-constituents indicates that the fundamental defect in SLE is a failure of the regulatory mechanisms that sustain self-tolerance. Some authors consider that RNA virus may cause it.

·        Antibodies have been identified against an array of nuclear and cytoplasmic components of the cell that are either organ or species specific. Apart from their value in the diagnosis and management of patients with SLE, these antibodies are of major pathogenetic significance, as, for example, in the immune complex-mediated glomerulonephritis so typical of this disease.

·        Antinuclear antibodies are directed against several nuclear antigens and can be grouped into four categories: (1) antibodies to DNA, (2) antibodies to histones, (3) antibodies to nonhistone proteins bound to RNA, and (4) antibodies to nuclear antigens.

·        SLE appears to be a complex disorder of multifactorial origin resulting from interactions among genetic, hormonal, and environmental factors acting in concert to cause activation of helper T cells and B cells that results in the secretion of several species of autoantibodies. In this complex web, each factor may be necessary but not enough for clinical expression of the disease; the relative importance of various factors may vary from individual to individual.

Morphology

The morphologic changes in SLE are extremely variable, reflecting the variability of the clinical manifestations and the course of the disease in individual patients. It can also be said that none of these morphologic changes is pathognomic. The constellation of clinical, serologic, and morphologic changes is essential for diagnosis.

SLE is characterized by different cellular and tissue changes which can be divided into 5 groups:

1. Acute necrotic and degenerative changes of the connective tissue (all stages of disorganization).
2. Subacute interstitial inflammation of all organs including nervous system with involvement of microcirculation (capillaritis, arteriolitis, vasculitis).
3. Changes of sclerotic character caused by the above changes. This group is characterized by onion-like sclerosis in the spleen.
4. Changes of the immune system. Focal accumulations of leukocytes with marked plasmatization are present in the central and peripheral organs. Macrophagic activity is increased.
5. Nuclear pathology in the cells of all organs and tissues, particularly in the lymph nodes. The shape of the nuclei does not change but they gradually lose DNA and look pale after stain. After the death of the cell, the nucleus disintegrates into granules, i.e. hematoxylin bodies. This phenomen characterizes LSE. Neutrophils and macrophages phagocytize hematoxylin bodies and form so-called “lupus cells”. Their presence in the blood is a significant sign of SLE. Except for the blood, they can be found in the bone marrow, spleen, lymph nodes and the vascular walls.

Visceral manifestations of LSE

The most characteristic lesions result from the deposition of immune complexes and are found in the blood vessels, kidneys, connective tissue, and skin.

·        An acute necrotizing vasculitis involving small arteries and arterioles may be present in any tissue although skin and muscles are most commonly affected. Fibrinoid deposits characterize the vessel walls of arteries. In chronic stages, vessels undergo fibrous thickening with narrowing lumen. In the spleen, these vascular lesions involve the central arteries and are characterized by marked perivascular fibrosis, producing so-called “onion-skin” lesions.

·        Kidney. On light microscopic examination, the kidney appears to be involved in 60 to 70% of cases, but if immunofluorescence and electron microscopy are included in the examination of biopsy material, almost all cases of SLE show some renal abnormality. According to WHO morphologic classification of lupus nephritis, five patterns are recognized:

1.      Normal by light, electron, and immunofluorescent microscopy (class 1), which is quite fare.

2.      Mesangial lupus glomerulonephritis (class 2).

3.      Focal proliferative glomerulonephritis (class 3).

4.      Diffuse prolirefative glomerulonephritis (class 4).

5.      Membranous glomerulonephritis (class 5).

It should be noted, however, that none of these patterns are specific for lupus.

·        Skin. The skin is involved in the majority of patients. Characteristic erythema in the bridge of the nose and cheeks (facial “butterfly”) occurs, but a similar rash may also be seen on the extremities and trunk. Urticaria, bullae, maculopapular lesions, and ulcerations also occur. Exposure to sunlight incites or accentuates the erythema. Histologically, the involved areas show liquefactive degeneration of the basal layer of the epidermis together with edema at the dermal junction. In the dermis, there is variable edema and perivascular mononuclear infiltrates. Vasculitis with fibrinoid necrosis of the vessels may be prominent.

·        Joints. Joint involvement is frequent, the typical lesion being a nonserosive synovitis with little deformity. The latter fact distinguishes this arthritis from that seen in rheumatoid disease. In the acute phases of arthritis in SLE, there is exudation of neutrophils and fibrin into the synovium and a perivascular mononuclear cell infiltrate in the synovial tissue.

·        Serosal cavities. Inflammation of the serosal lining membranes may be acute, subacute, or chronic. During the acute phase, the mesothelial surfaces are sometimes covered with fibrinous exudate. Later they become thickened, opaque, and coated with a shaggy fibrous tissue that may lead to partial or total obliteration of the serosal cavity.

·        Cardiovascular system. Involvement is manifested primarily in the form of pericarditis. Valvular endocarditis may occur, but it is clinically insignificant. In the era before the widespread use of steroids, so-called Libman-Sacks endocarditis was more common. The nonbacterial verrucous endocarditis takes the form of single or multiple irregular 1-to3-mm warty deposits on any valve in the heart, distinctively on either surface of the leaflets. Myocarditis, manifested as nonspecific mononuclear cell infiltration, may also be present but is less common.

·        Spleen. The spleen may be moderately enlarged.

·        Lungs. In lungs the pneumanitis, fibrosing alveolitis and diffuse interstitial fibrosis are found out.

The most common causes of death are renal failure (uremia) and intercurrent infections, followed by diffuse central nervous system disease. Patients treated with steroids and immunosuppressive drugs incur the usual risks associated with such therapy.