Systemic Lupus Erythematosus Disease: An Overview of the Clinical Approach to Pathogenesis, Diagnosis, and Treatment

The systemic lupus erythematosus (SLE), commonly known as Lupus, is a rare and complex multisystem autoimmune disease where one’s immune system is overactive, and the body attacks its organ systems. SLE is a historically old disease described already in antiquity; it is an example of a chronic disease with physical, psychological, financial, and social implications for individuals diagnosed. It has inspired medical and basic biological scientists that focus on molecular biology, basic immunology, immunopathology, clinical science, genetics, and epidemiology. The syndrome is real in its existence-although hidden behind obstacles, cumbersome for patients and clinicians, and rebellious for scientists. There is currently no cure for SLE. The goal of treatment is to ease symptoms. This article will review information on the general approach to SLE therapy, focusing on currently approved therapies and novel approaches that might be used in the future.


INTRODUCTION
. Systemic lupus erythematosus can be divided into three periods: the classical period, the neoclassical period, and the modern period. Each period is marked with important discoveries that have allowed a better understanding of this disease 8 . This mini-review will discuss several things related to SLE and its clinical approach, including epidemiology, pathogenesis, diagnosis, and treatment, based on a review of the latest related studies.

EPIDEMIOLOGY
The SLE is seen worldwide and occurs in all racial or ethnic groups, although regional variations in frequency and severity have been reported 9 . An estimated 5 million people worldwide have some form of lupus disease. The 70% of lupus cases diagnosed are SLE, 20% of people with lupus will have a parent or sibling who already has lupus or may develop lupus, and about 5% of the children born to individuals with lupus will develop the illness 10, 11 . Studies have shown that the incidence rate of SLE around the world is about 1 to 10 per 100000 people/years 12 , while the prevalence rates range 3.2 cases per 100000 persons, with the highest prevalence reported in India, and it appears to be increasing as the disease is recognized more readily and survival increases 13, 14 . In the US, people of African, Hispanic, or Asian ancestry as compared to those of other racial or ethnic groups, tend to have an increased prevalence of SLE and greater involvement of vital organs 15-17 . Neonatal lupus erythematosus is a rare condition that affects infants of women who have lupus and is caused by antibodies (Abs) from the mother acting upon the infant in the uterus. At birth, the infant may have a skin rash, liver problems, or low blood cell counts, but these symptoms disappear completely after several months with no lasting effects 20,21 . Cutaneous or discoid lupus erythematosus (CLE) This form of lupus is limited to the skin. Although CLE can cause many types of rashes and lesions (sores), the most common discoid rash is raised, scaly, and red, but not itchy. Areas of rash appear like disks or circles. Another typical e.g., of CLE is a rash over the cheeks and across the bridge of the nose. Hair loss and changes in the pigment, or color, of the skin are also symptoms of CLE 22 . Drug-induced lupus erythematosus (DILE) The symptoms of DILE are similar to those of SLE, but it rarely affects major organs. DILE is a lupuslike disease caused by certain prescription drugs like Hydralazine, Procainamide, Isoniazid, and others 23 . Systemic lupus erythematosus (SLE) Systemic lupus erythematosus is the most common form of lupus-it can be mild or severesome of the more severe complications involving major organ systems. Inflammation of the kidneys can affect the body's ability to filter waste from the blood. Inflammation of the nervous system and the brain's blood vessels can cause high fevers, seizures, behavioral changes, confusion, headaches, and strokes 24 .    Figure 2. Seizures or psychosis occur in the absence of offending drugs or known metabolic derangement (e.g., uremia, ketoacidosis, electrolyte imbalance). Hematologic disorder Hemolytic anemia with reticulocytosis; or leukopenia, 4.0 x 109/L on two or more occasions; or lymphopenia, 1.5 x 109/L on two or more occasions; or thrombocytopenia, 100 x 109/L in the absence of offending drugs. Immunologic disorder Antibody to a double-stranded deoxyribonucleic acid antigen (anti-dsDNA) in abnormal titer; or presence of antibody to Smith nuclear antigen (anti-Sm); or positive finding of antiphospholipid Abs based on an abnormal serum level of Immunoglobulin (Ig) G or Ig M anticardiolipin Abs, a positive test result for lupus anticoagulant using a standard method, or a false positive serologic test for syphilis that is known to be positive for at least six months and is confirmed by negative Treponema pallidum immobilization or fluorescent treponemal antibody absorption test. Antinuclear antibodies An abnormal antinuclear antibodies (ANA) titer by immunofluorescence or an equivalent assay at any time and in the absence of drugs known to be associated with DILE.

Figure 2. Factors involved in the pathogenesis of SLE 37 TREATMENT
There is no cure for SLE at present, but the condition is most often very treatable and usually responds well to some different types of drugs-especially when treatment is started in the early stages of the disease 38 . Most of the drugs described in Table III were initially developed for other diseases but were later found to be helpful in SLE 39 .
There are many levels of severity and complications of SLE that require management. Treatment is dependent on presentation, and options include antimalarials, glucocorticoids, immunosuppressants, and biologics.
NSAIDs may also be used to treat inflammation and pain enlisted 40 .
In addition to these therapies, the current development of treatments for SLE has primarily led to the development of monoclonal antibodies 41 , as presented in Table IV.  Over-the-counter NSAIDs, such as naproxen sodium and ibuprofen may be used to treat pain, swelling, and fever associated with SLE. Stronger NSAIDs are available by prescription.

Antimalarial
Drugs commonly used to treat malaria, such as hydroxychloroquine, affect the immune system, and decrease the risk of SLE flares.

Corticosteroids
Prednisone and other types of corticosteroids can counter the inflammation of SLE. High doses of steroids such as methylprednisolone often used to control serious disease that involves the kidneys and brain.

Immunosuppressants
Drugs that suppress the immune system may be helpful in serious cases of SLE e.g. azathioprine and methotrexate. Biologics Biological agents used in the treatment of SLE include rituximab and belimumab, both monoclonal antibodies. Rituximab targets B cells and is used to treat renal and CNS presentations of SLE. This agent is recognized as an II-or III-line agent for active disease. Belimumab targets the B cellactivating factor B-lymphocyte stimulator. Belimumab is approved for use in active disease in conjunction with standard therapies including glucocorticoids, antimalarials, NSAIDs, mycophenolate mofetil, and azathioprine. Other biologics, such as tumor necrosis factor inhibitors, abatacept, and tocilizumab, are also considered. Other agents Besides the agents listed above, there are other agents used off-label to treat SLE. These include disease-modifying antirheumatic drugs such as methotrexate, leflunomide, and calcineurin inhibitors (tacrolimus and cyclosporine).

CONFLICT OF INTEREST
There are no conflicts of interest.