SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

BY: SAI MANOGNA (MSIWM014)

1. This is a chronic autoimmune inflammatory disease associated with a wide variety of physical findings and symptoms. 

2. It is characterised by a loss of self-antigens resistance, the development of immune complexes, and an interferon type I activated system. 

3. It is also characterised by nuclear and cytoplasmic antigen antibodies, inflammation of the multisystem, clinical manifestations of proteins, and a relapsing and remitting path. 

4. In females, more than 90% of SLE cases occur, mostly beginning at childbearing age. 

5. The first described genetic link to SLE was the major histocompatibility complex (MHC) on chromosome 6, which contains human lymphocyte antigens (HLA). 

6. In the immune system, protein products of the HLA genes are essential components of cell-to-cell contact. Indeed, HLA genes are more closely related to lupus-associated autoantibodies in some instances than to the illness itself.

Types Of SLE:

The most common and most extreme kind of lupus is SLE. The following are other forms of lupus: 

Cutaneous lupus (skin lupus): This type of lupus occurs in any part of the body, but typically appears when the skin is exposed to sunlight, affecting the skin in the form of a rash or lesion. 

Drug-induced lupus: SLE is similar to drug-induced lupus, but develops as a result of an overreaction to such drugs. Symptoms usually arise 3 to 6 months after the drug is initiated, and they disappear until the medication is discontinued. 

Neonatal lupus: This type of lupus develops when a mother with SLE passively acquires auto-antibodies from a child. Body, liver and blood disorders are healed by six months, but the most severe condition needs a pacemaker and mortality rate of around 20%.

Pathophysiology:

1. It is important to remember that there could be antibodies for several years before the onset of the first signs of SLE. 

2. There is a defect in apoptosis that causes increased cell death and disruption in immune tolerance is one long-standing proposed mechanism for the production of autoantibodies. 

3. During necrosis/apoptosis, the redistribution of cellular antigens contributes to the cell-surface display of plasma and nuclear antigens in the form of nucleosomes. 4. Intolerant lymphocytes subsequently start attacking intracellular antigens that are typically covered. 

5. The faulty clearance of the apoptotic cell debris allows for antigen and complex immune development to persist. 

6. It has long been believed that T cells play a central role in SLE pathogenesis, and T cells from lupus patients display defects in both signalling and effector function. 

7. These T cells secrete fewer interleukin (IL)-2 and, likely due to changes in the CD3 signalling subunits, one signalling defect appears to be associated with an increase in calcium influx. 

8. In T cells with SLE, the following tend to be adversely affected: effector activity such as CD8 cytotoxicity; T-regulatory, B-cell assistance; migration; and adhesion. 

In virtually all individuals with active SLE, serum antinuclear antibodies (ANAs) are detected. In order to diagnose SLE, antibodies to native double-stranded DNA (dsDNA) are relatively specific. It is unknown if there is polyclonal B-cell activation or a response to particular antigens, but much of the pathology include B cells, T cells, and dendritic cells. There is a decline in cytotoxic T cells and suppressor T cells (usually down-regulating immune responses). The polyclonal T-cell cytolytic activity generation is impaired. Helper (CD4 +) T cells have been enhanced. In animal lupus models, a lack of immune tolerance is shown. 

Aetiology: 

Gene-environment interactions and multiple genetic predispositions have been identified, although the specific cause of SLE is unknown. Perhaps the variable clinical manifestations in individuals with SLE are explained by this complicated situation. 

Less obvious are environmental and exposure-related causes of SLE. Possible risk factors in early life include the following: 

i. Low (< 2.5 kg) birthweight 

ii. Preterm birth (approximately one month early) 

iii. Childhood exposure to pesticides from agriculture 

The following are other potential factors: 

i. Smoking silica dust and cigarettes can increase the risk of the development of SLE 

ii. It appears that the use of oestrogen in postmenopausal women increases the risk of developing SLE. 

iii. Photosensitivity is an obvious precipitator of skin disease. Ultraviolet light stimulates keratinocytes, leading not only to the overexpression on their cell surfaces of nuclear ribonucleoproteins (snRNPs) but also to the secretion of cytokines that stimulate increased production of autoantibodies. 

A decreased risk of developing SLE is associated with breastfeeding. 

Although more recent data suggest that pregnancy outcomes are favourable and flares are rare among patients with inactive or stable mild-moderate SLE, pregnancy can be a time when lupus initially presents or flares. 

Vitamin D is involved in innate and acquired immunity, and autoimmunity and the development of rheumatic diseases, including SLE, have been implicated in vitamin D deficiency. 

Symptoms and signs of SLE : 

This chronic inflammatory disease that can affect nearly any organ system, although the skin, joints, kidneys, blood cells, and nervous system are primarily involved. Its course range and presentation from indolent to fulminant are highly variable. 

The clinical manifestations commonly found in childhood-onset SLE than in adults are: 

i. Ulcers / mucocutaneous participation 

ii. Renal involvement, proteinuria, the casting of urinary cells 

iii. Convulsions 

iv. Thrombocytopenia Patients 

v. Anemia 

vi. A fever.

The frequency ofRaynaud pleuritis and sicca are more prevalent in adults than in children and adolescents. In a woman of childbearing age, the classic presentation of a triad of fever, joint pain and rash should prompt investigation into the SLE diagnosis.

SLE diagnosis:

SLE diagnosis is based on a combination of laboratory clinical results and evidence. Diagnostic familiarity allows doctors to identify and subclassify SLE according to the target organ manifestations.

Testing: The following are laboratory studies used in the diagnosis of SLE: 

Assay on creatine kinase 

Creatinine serum

The ratio of Spot Protein / Spot Creatinine 

Urinalysis (microscopy)

Levels of ESR or CRP 

Levels for complement 

Tests for Liver Function 

Tests with Autoantibody 

Studies in imaging 

Patients with suspected SLE may be evaluated using the following imaging studies: 

Radiography at the Joint 

Chest radiography and CT scanning of the chest 

Echocardiogram 

MRI / MRA of the Brain 

MRI of the Cardiac 

Approaches 

Procedures that may be performed with suspected SLE in patients include the following: 

Arthrocentesis 

A puncture on the lumbar 

Biopsy of the renal

Treatment: 

A remedy for SLE does not exist. Therapy aims to relieve symptoms. Depending on the severity of symptoms and areas of the body SLE affects, treatment varies. 

Therapies can include: 

i. Anti-inflammatory joint pain and stiffness drugs, such as these online offerings, are available 

1. Creams of hormones for rashes 
2. To minimise the immune response, corticosteroids.
3. Skin antimalarial medications and joint issues 
4. For more extreme cases, disease-modifying drugs or targeted immune system agents

ii. Immunosuppressive medications (these medicines suppress the immune system). In severe lupus that affects the nervous system, the kidney or other organs, corticosteroids are used.

iii. Mycophenolate, azathioprine, and cyclophosphamide are the most widely used drugs. 

iv. Cyclophosphamide is restricted to a brief course of 3 to 6 months because of its toxicity. In certain instances, rituximab (Rituxan) is used as well. 

v. Blood thinners for clotting problems such as antiphospholipid syndrome, such as warfarin (Coumadin).