Systemic Lupus Erythematosus: Causes, Diagnosis and Treatment

Systemic Lupus Erythematosus (SLE) is a multifactorial disease with an unclear exact cause. However, some genetic, immune, endocrine, and environmental factors play an important role in the pathogenesis of the disease.

What is Systemic Lupus Erythematosus?

Systemic Lupus Erythematosus is an autoimmune disease characterized by the presence of autoantibodies against antigens, affecting multiple systems. The disease has various subtypes with different clinical manifestations in each patient, ranging from mild mucosal symptoms to multi-organ involvement such as skin, kidney, joints, heart, and even severe involvement of the central nervous system. More than 90% of systemic lupus erythematosus cases occur in women and typically begin in childbearing age.

Pathogenesis of systemic lupus erythematosus

The pathogenesis of systemic lupus erythematosus (SLE) is very complex, and is known to involve abnormalities in the immune system. Specifically, the following mechanisms have been identified:

Autoantibodies

The immune system produces antibodies to protect the body against invading microorganisms. Antibodies recognize foreign antigens and trigger immune reactions, leading to inflammation and preventing infection. However, in some cases, these antibodies can become misguided and attack the body’s own proteins, known as autoantibodies.

The following autoantibodies are thought to play a role in the development of SLE:

Antibodies against nuclear components

Anti-nuclear antibodies (ANA): These antibodies target normal proteins present in the cell nucleus. ANA are found in up to 90% of SLE patients, but the test results have low specificity since ANA can also be found in other diseases, such as scleroderma and rheumatoid arthritis. ANA positivity can also be seen in 1-3% of healthy individuals, especially the elderly.

Anti-double-stranded DNA (dsDNA) antibodies have three types:

• Type I: Anti-dsDNA antibodies target double-stranded DNA, and are found in 60-70% of SLE patients. This type of antibody has high specificity.
• Type II: Anti-dsDNA antibodies target both single-stranded and double-stranded DNA.
• Type III: Anti-nucleosome antibodies target single-stranded DNA (n-dsDNA), and are found in 30% of SLE patients.
• Anti-histone antibodies: These antibodies are found in drug-induced lupus.

Anti-nucleoprotein antibodies: These antibodies are detected by the Hargraves cell test.

Antibodies against soluble antigens

Anti-Sm antibodies (named after the patient Smith, the first patient to be identified with these antibodies): These antibodies are found in 30-40% of SLE patients.

Anti-ribonucleoprotein (RNP) antibodies: These antibodies have high sensitivity and specificity. Usually, both Sm and RNP antibodies are present, although they recognize different antigens.

Anti-SSA (Ro) antibodies: These antibodies are also highly specific for the diagnosis of congenital lupus. Up to 30% of SLE patients have these antibodies.

Cell-Targeting Antibodies

Anti-red blood cell antibodies: These antibodies are detected by a positive Coombs test. In cases of Lupus, these antibodies are found in 60% of cases.

Anti-white blood cell antibodies: Tests show a decrease in peripheral white blood cell count, primarily affecting lymphocytes, and to a lesser extent, neutrophils.

Anti-platelet antibodies: These are antibodies that target antigens on the surface of platelets, causing mild to moderate thrombocytopenia and sometimes bleeding.

Anti-phospholipid antibodies: These antibodies are clinically expressed as a false-positive syphilis reaction.

Organ-Specific Antibodies

Anti-ribosome antibodies: When these antibodies appear, patients often have psychiatric symptoms.

Anti-Golgi apparatus antibodies: These antibodies are very rare.

Immune Complexes

Circulating immune complexes: Found in the circulation.

Deposited immune complexes: Found in tissues, subcutaneous organs, and glomerular basement membranes.

The causes of systemic lupus erythematosus (SLE)

Systemic lupus erythematosus is a multifactorial disease with no clearly defined exact causes. However, there are some genetic, immune, endocrine, and environmental factors that play an important role in the pathogenesis of the disease.

Gender and hormones are significant risk factors that influence SLE. Estrogen and prolactin promote the immune response and increase the production of B-cell activating factor and the regulation of lymphocyte activation, PDC complexes. The use of estrogen-containing contraceptives and hormone replacement therapy after menopause may trigger flares of SLE. Moreover, patients with SLE have been found to have higher levels of prolactin than normal.

Some environmental factors have been identified to increase the risk of systemic lupus erythematosus (SLE). Certain drugs are related to inducing lupus-like syndrome and altering self-antigen. Over 100 drugs are associated with lupus, among which Procainamide and Hydralazine have the highest incidence rate. Ultraviolet radiation and sunlight exposure increase cell death cycle and are common factors causing lupus. Some cases of viral infections are also related to the pathogenesis of lupus by mimicking molecules. Anti-Epstein-Barr virus (EBV) antibodies are more frequently found in individuals with SLE.

In addition, other underlying risk factors for lupus include smoking, silica exposure, other viruses, vitamin D deficiency, and L-canavanine-containing herb alfalfa.

How is systemic lupus erythematosus diagnosed?

A person is considered to have systemic lupus erythematosus (SLE) if they meet any 4 of the 11 criteria established by the American College of Rheumatology as follows:

• Butterfly-shaped rash across cheeks and nose (malar rash)
• Raised red patches on skin (discoid rash)
• Skin rash from sunlight exposure (photosensitivity)
• Mouth or nose sores, usually painless
• Non-erosive arthritis involving two or more joints
• Inflammation of the lining around the lungs or heart (pleuritis or pericarditis)
• Kidney disorder such as excess protein in the urine (proteinuria) or cellular casts
• Neurologic disorder such as seizures or psychosis
• Blood disorder such as hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia
• Immunologic disorder such as positive anti-double-stranded DNA, anti-Smith, or anti-phospholipid antibody tests
• Abnormalities in blood clotting tests (coagulation)

Note: A diagnosis of SLE can be made even if the person does not meet the fourth criterion but has a positive anti-nuclear antibody (ANA) test result.

The clinical manifestations of systemic lupus erythematosus are very diverse, and for each patient, there will be the following symptoms:

Physical symptoms: Seen in over 90% of patients, they often have symptoms of fatigue, weight loss, non-life-threatening fever, but affecting the quality of life.

Renal manifestations affect about 30% of patients with systemic lupus erythematosus and are the most dangerous complication, threatening life. This symptom often occurs in the first few years of the disease, patients may have urinary protein leading to glomerulonephritis and chronic renal damage. In the onset stage, patients may have high blood pressure, urinary protein, subcutaneous edema, and increased creatinine. Glomerulonephritis in lupus includes minimal mesangial, proliferative, focal, diffuse, membranous, and sclerotic types. Some patients may also have thrombotic microangiopathy, lupus vasculitis, vasculitis, and arteriosclerosis.

Central and peripheral nervous system manifestations can be seen in patients with systemic lupus erythematosus. The characteristic manifestations of these patients’ central nervous system are difficult-to-treat headaches, generalized or focal seizures. In addition, patients may have symptoms of aseptic meningitis, optic neuritis, and myelitis, motor and cognitive disorders. Peripheral nervous system symptoms such as Guillain-Barré syndrome and Myasthenia gravis, and autonomic nervous disorders can also occur.

Skin and mucous membrane-related symptoms can occur in more than 80% of patients with lupus. Patients may have acute or chronic lupus erythematosus ulcers in the mouth and nose, often without pain.

About 80% to 90% of patients with systemic lupus erythematosus have symptoms related to bone and joint, ranging from mild joint pain to deformity. Lupus arthritis is usually non-erosive, symmetrical, and mainly affects small joints in the hands, knees, and wrists. Jaccoud’s arthropathy leads to non-erosive deformities in the hands, including ulnar deviation and flexion of the finger joints, which can mimic rheumatoid arthritis. Typically, these malformations can be reduced. Avascular necrosis occurs in up to 10% of patients with systemic lupus erythematosus and usually occurs bilaterally and is associated with hip joints. Some of these patients also have symptoms of polymyositis.

More than 50% of lupus patients have anemia, mainly chronic anemia. This anemia may be due to iron deficiency, chronic disease, and hemolytic anemia. Lupus patients may also have low white blood cell and platelet counts, and lymphadenopathy.

Symptoms related to the digestive system in patients with systemic lupus erythematosus (SLE) often include abdominal pain and difficulty with digestion. Patients may also have symptoms such as enlarged liver and spleen, gastroesophageal reflux disease (GERD), mesenteric vasculitis, enteritis, and hepatic vein thrombosis.

Systemic lupus erythematosus can also have cardiovascular symptoms such as pericarditis, myocarditis, endocarditis, or coronary artery disease.

In addition, other symptoms may occur in systemic lupus erythematosus, such as macular inflammation, retinal vasculitis, optic neuritis, pleurisy, scleroderma, increased eye pressure, and hearing loss.

It is important to distinguish systemic lupus erythematosus from other conditions such as acute rheumatoid arthritis, other inflammatory joint diseases, hematologic disorders, kidney diseases, and other organs.

The method of treating systemic lupus erythematosus

The goal of treating systemic lupus erythematosus is to prevent organ damage and achieve remission. First, the severity of the disease must be assessed, then treatment should involve attack, consolidation, and maintenance. During the treatment process, the potential side effects and therapeutic effects of the medication must be considered.

Specific medications for treating systemic lupus erythematosus

For patients with lupus who have mild joint pain, fever, and inflammation but no major organ damage, non-steroidal anti-inflammatory drugs can be used. However, they should not be used for lupus patients with kidney inflammation.

Patients with systemic lupus erythematosus who have skin rash, light sensitivity, and symptoms in the joints can take hydroxychloroquine at a daily dose of 200mg. These patients need to have their eyes examined once a year.

When systemic lupus erythematosus affects the nervous system and blood system, leading to life-threatening situations or failure to respond to conservative treatment, systemic glucocorticoids should be used. Patients should take a daily dose of 1 to 2mg/kg, and the dose of prednisolone should be reduced by 10% every 7 to 10 days once the disease is under control. Patients with severe kidney damage, nervous system damage, or low platelet counts can be treated with intravenous methylprednisolone at a dose of 500mg every 12 hours for 3 to 5 days, followed by oral corticosteroids with a similar dose reduction schedule.

For patients with life-threatening systemic lupus erythematosus, immunosuppressive drugs may be used, including those for acute glomerulonephritis, severe nervous system damage, low platelet counts, and refractory lupus. These drugs can be used alone or in combination with each other, or with corticosteroids, including cyclophosphamide combined with mesna, dapsone, azathioprine, mycophenolate mofetil, or methotrexate.

In addition, patients with systemic lupus erythematosus may be treated with leflunomide, bormone, thalidomide, intravenous immunoglobulin, etc.

Treatment of systemic lupus erythematosus without drugs

Systemic lupus erythematosus can be treated without medication in patients with mild symptoms. In this case, patients should rest, avoid direct sunlight, and take precautions against infections. Lupus patients need to be regularly monitored according to their doctor’s instructions.

On the other hand, if a lupus patient has severe kidney damage, they may require treatment with blood filtration or kidney transplantation.

To prevent flare-ups, patients with systemic lupus erythematosus should avoid triggers such as ultraviolet light, sunlight, and smoking.

Additionally, the patient’s diet should be adjusted depending on their individual condition, particularly to maintain a balanced diet. However, if a patient has high blood lipid levels, they may need a low-fat diet, or if they have low vitamin D levels, they may need to supplement with vitamin D.

Furthermore, exercise is crucial for lupus patients to prevent muscle loss, bone demineralization, and fatigue.

These are the basic information about the causes, symptoms, and treatment of systemic lupus erythematosus, which we hope will be useful to our readers.