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Systemic lupus erythematosus (SLE)

Abundant estimations of prevalence and incidence of SLE are rare because it is relatively expensive to capture all reliable diagnosed cases for epidemiologic studies. The following are some of the available related data:

  • According to publications of Centers for Disease Control and Prevention (CDC) in the USA, a conservative estimate suggests a prevalence of 161,000 with definite SLE and 322,000 with definite or probable SLE. In addition, between the year 2002 and year 2004, the annual incidence was much higher for blacks than whites in both Michigan and Georgia and the annual incidence estimates were much higher for women than men in Michigan, Georgia, and the American Indian/Alaska Native population.
  • According to a study published in Annals of the Rheumatic Diseases (ARD) journal, the incidence of SLE has been declining annually (1.8%), but the prevalence has been increasing in the UK in recent years and the highest incidence and prevalence present in people decent from Black Caribbean ethnicity. In addition, SLE was six times more common in women and the peak age of incidence was 50–59 years.
  • According to results of a study published in Lupus (journal), in Northwestern Spain, survival probability of 10-year and 15-year were 74.9 % and 63.3% in the late-onset SLE group , meanwhile survival probability of 10-year and 15-year were 96.3% and 91.0% in patients with early-onset SLE, and the incidence of late-onset SLE was significantly higher in women than in men.
  • A study published in Saudi Medical Journal has been found that familial SLE is common in Arab children, 7.7% of patients were diagnosed before the age of 5 years, and renal involvement was diagnosed in 80%, while neuropsychiatric manifestations were seen in 30%.
Overview

Lupus is a chronic autoimmune disease that causes inflammation in different tissues of the body. Systemic lupus erythematosus (SLE) is the most common type of lupus. Other types of lupus, include discoid lupus erythematosus (DLE), drug-induced lupus, and neonatal lupus.

The exact causes of SLE are unknown but many researchers attribute SLE to various genetic, environmental, and hormonal factors. Moreover, several risk factors have been associated with SLE including being female, being 15 and 40  of age, being African-Americans, Hispanics and Asians, and having the family history of SLE.

The three most common signs and symptoms of SLE include skin rashes, fatigue, and joint pain. Other signs and symptoms include chest pain, skin lesions, seizures, headaches, and mouth and nose ulcers. SLE can trigger a myriad of immune system activities such as autoantibody production and increased numbers of antibody-producing cells, B cells, and T cells.

To diagnose SLE, a physician may perform a physical examination, ask questions regarding medical history, and may recommend several laboratory tests such as complete blood count, erythrocyte sedimentation rate (ESR) test, kidney and liver function tests, urinalysis, and complement level test. In addition, he/she may recommend certain imaging tests such as chest X-ray and echocardiogram and may suggest kidney or skin biopsy.

Treatment of SLE can involve prescribing medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), hydroxychloroquine, corticosteroids, immunosuppressants, and rituximab. If not treated, SLE can lead to various complications, include lupus nephritis, anemia, inflammation of the blood vessels, and accumulation of fluid around the heart.

SLE cannot be prevented, but its flares-up can be prevented by applying several simple measures and coping methods such as, regular checkup, protection from the sun, adequate rest, healthy diet, physical exercise, and using of certain supplements and herbs (after physician consulting) such as flaxseed contains omega-3 fatty acids and alpha-linolenic acid, calcium and vitamin D supplement, and dehydroepiandrosterone (DHEA). A survival rate of 10 years have been associated with the most of SLE patients, however, a survival rate of 20 years has been reported in many cases as well.

Definition

Systemic lupus erythematosus (SLE) is the most common form of lupus. Lupus is a chronic autoimmune disease that causes inflammation in different tissues of the body. Systemic lupus erythematosus is a systemic condition, which means that it can affect the entire body, and can range from mild to life-threatening. Lupus is also known as "the great imitator" because its symptoms can be confused with symptoms of other diseases.

Subtypes

Systemic lupus erythematosus (SLE) is the most common type of lupus. Other types of lupus include:

  • Discoid lupus erythematosus (DLE): This is a chronic condition affects the skin and causes reddened and round scaly patches in sun-exposed areas such as the face, hands, and may results in pigmentary changes, scarring and hair loss.
  • Drug-induced lupus: This type of lupus is mainly triggered by a reaction to a medication. Medications that commonly responsible for lupus-like symptoms include certain drugs used to treat hypertension and heart problems.
  • Neonatal lupus: This type is a rare acquired autoimmune disorder that is present at birth, and manifested mostly by cutaneous lupus lesions and/or congenital heart block.
Causes

The exact causes of SLE are unknown. However, many investigators believe that genetics and environment probably play a role in causing the disease, factors include:

  • Genetic factors: Investigators have discovered 50 genes thought to play a role in developing the condition. Females are twice as likely to receive one of the mutated genes.
  • Environmental factors: Although the evidence for many of these factors is limited, some investigators believe that certain environmental factors can trigger SLE, including:
  • Stressful or emotional events, such as divorce or death in the family.
  • Sulfonamide products, which make a person more sensitive to the sun, such as Bactrim.
  • Sun-sensitizing tetracycline drugs such as minocycline.
  • Exposure to sunlight (particularly ultraviolet light).
  • Certain infections, such as Epstein-Barr virus.
  • An antibiotic such as penicillin.
  • Smoking cigarettes.
  • Exhaustion.
  • Anything that can cause stress to the body such as surgery.
  • Hormonal factors:  Some investigators think hormones play a part in developing SLE because more women than men have SLE and because many women exhibit more SLE symptoms when estrogen production is high, usually before menstrual periods and/or during pregnancy.
Risk Factors

Anyone can get SLE, However, some factors can increase the risk of developing the disease, include:

  • Gender: SLE is more common in women. Women of childbearing ages (15 to 44 years) are at higher risk of developing the condition.
  • Age: People can develop SLE at any age, but it is more common to be diagnosed between the ages of 15 and 40.
  • Ethnicity: It is more common to find SLE cases among African-Americans, Hispanics, and Asians.
  • Family history: SLE can run in families, relatives of people with lupus have a slight increase in SLE risk.
Pathophysiology

The exact pathogenesis and patho-aetiology of SLE remain unclear.Investigators speculate the involvement of an extremely complicated and multifactorial interaction among several genetic and environmental factors. Defective apoptosis (programmed cell death) was thought to be one disease mechanism for SLE. However, new studies oppose defective apoptosis due to several problems remained unexplained by this model.

When SLE occur, breaking of immune tolerance and inflammation caused by major components assembling of the immune system, can be evidenced by the appearance of autoantibodies that are usually observed long before disease onset. Multiple genetic loci (positions on chromosomes) are involved in determining disease susceptibility. Abnormalities found in the cells and molecules influenced by these genes play a crucial part in providing this genetic evidence.

SLE can trigger a myriad of immune system activities such as autoantibody production, hypergammaglobulinaemia, increased numbers of antibody-producing cells, B cells, T cells, and cells of the monocytic lineage, resulting in polyclonal B cell activation, and immune complex formation. Cytokine patterns may play a significant role in the pathogenesis of lupus as well as endogenous estrogen concentrations that may alter disease activity and prognosis of SLE.

Signs And Symptoms

The signs and symptoms of SLE vary according to which body systems have been affected by the disease. The three most common signs and symptoms include:

  • Skin rashes (both on the face and on the body): These rashes take the shape of a butterfly on the face that covers the cheeks and bridge of the nose, and are reported in about half the people with SLE.
  • Fatigue (extreme tiredness).
  • Joint pain, stiffness, and swelling.

Other signs and symptoms include:

  • Chest pain when taking a deep breath, which results from inflammation of the lining of the heart or lungs.
  • Raynaud's phenomenon, which manifests in cold weather and limits the blood supply to the hands and feet.
  • Skin lesions that triggered/worsen with sun exposure (photosensitivity).
  • Seizures or visual disturbances that result from inflammation of the nervous system.
  • Headaches, confusion, memory loss, trouble thinking, and depression.
  • Anemia ( deficiency in the number or quality of red blood cells).
  • General discomfort, uneasiness, or ill feeling (malaise).
  • Ankle swelling and fluid retention (edema).
  • Abnormal heart rhythms (arrhythmias).
  • Fever with no other cause.
  • Swollen lymph nodes.
  • High blood pressure.
  • Mouth and nose ulcers.
  • Shortness of breath.
  • Poor kidney function.
  • Low blood count.
  • Dry eyes.
  • Hair loss.
Diagnosis

Diagnosis of SLE is challenging because the symptoms can vary greatly from person to person and vulnerable to dramatic change over time. Diagnosis of SLE can involve:

  • Complete physical examination: The health care provider may examine the skin rashes, arthritis, or edema in the ankles, and he/she may do a nervous system exam. In addition, he/she may investigate an abnormal sound called a heart friction rub or pleural friction rub.
  • Medical history: Medical history can provide clues to the disease. The physician should be informed about patient’s symptoms and other problems to help him/her evaluate the situation more accurately. In addition, the physician may ask questions that relate to the medical history of close family members including grandparents, parents, brothers and sisters, aunts, uncles, and cousins.
  • Laboratory tests: Blood and urine tests are usually performed to tell whether the immune system is overactive. These tests include:
  • Complete blood count: This test measures the number of certain components in the blood, such as red blood cells and white blood cells. Anemia, which commonly occurs in lupus, can be investigated by performing this test.
  • Erythrocyte sedimentation rate (ESR) test: This test can tell if any inflammation occurs in the body because SLE results in inflammations in the body.
  • Kidney and liver function tests: Such tests can evaluate kidneys and liver enzymes because SLE can affect these organs.
  • Urinalysis: Analyzing a sample of the urine can tell if there is increasing in protein level or if there are red blood cells in the urine, which may occur if SLE has affected the kidneys.
  • Anti-nuclear antibody test: This test investigates the presence of a certain type of antibody in the blood, which most people with SLE have. However, this is not a specific test for SLE.
  • Anti-DNA test: This test also investigates the presence of a certain type of antibody in the blood. The result often varies according to disease activity and sometimes it affects the treatment plan. Increasing in antibody titre may require more immunosuppression.
  • Complement level test: This test investigates the level of a chemical in the blood that forms part of the immune system. The level of complement in the blood decreases when SLE is more active.
  • Imaging tests: If the physician suspects that SLE is affecting the lungs, heart, or other internal organs, he/she may suggest:
  • Chest X-ray: Fluid accumulations and inflammation in the lungs can be revealed by the presence of abnormal shadows in X-rays image.
  • Echocardiogram: This test produces real-time images of the beating heart by using sound waves. These images can reveal problems with the heart that may be resulted from SLE.
  • Other imaging tests that may be used to check internal organs include magnetic resonance imaging (MRI) scan, computerized tomography (CT) scan, and ultrasound scan.
  • Kidney or skin biopsy: In a biopsy, a minor surgical procedure is performed to remove a tissue and send it to the laboratory to examine it under a microscope. Skin or kidney tissue examined in this way can show signs of an autoimmune disease including SLE.
Treatment

There is no definitive cure for SLE. However, SLE can be controlled and managed by using different medications.The most common used medications to control SLE include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs): These medications can be used in treating pain, swelling, and fever associated with SLE; such medications can include naproxen and ibuprofen.
  • Hydroxychloroquine: This drug have been used to treat malaria, but it is also proved effective in treating some of the symptoms associated with SLE, such as rashes, joint and muscle pain. Side effects can include stomach upset and, very rarely, damage to the retina of the eye.
  • Corticosteroids: Although they can produce long-term side effects, prednisone and other types of corticosteroids can help improve the symptoms of inflammation associated with SLE; their side effects include, thinning of the bones, hypertension, and weight gain.
  • Immunosuppressants: This type of medications can help decrease the damage resulted from attacking healthy body parts by the immune system. Examples include mycophenolate, azathioprine, leflunomide, and cyclophosphamide. Side effects may include, weight gain, loss of appetite, and an increased risk of infection.
  • Rituximab: The using of rituximab is relatively new and it is mostly prescribed for patients with severe SLE that show negative results when using other treatments. Side effects may include flu-like symptoms and dizziness.
  • Belimumab: This medication is mostly prescribed for patients who suffer from severe active SLE disease that does not show improvement when using other therapies.
Complications

SLE is associated with several possible complications, including:

  • Kidney damage and kidney failure.
  • Lupus nephritis: This condition is caused by prolonged inflammation of the kidneys. Symptoms include edema and frequent urination.
  • Anemia and increased risk of bleeding or blood clotting.
  • Vasculitis ( inflammation of the blood vessels).
  • inflammation of the chest cavity lining (pleurisy) and pneumonia.
  • Fluid around the heart (pericarditis), or inflammation of the heart (myocarditis or endocarditis).
  • Severely low blood platelet count (platelets are needed to stop any bleeding).
  • Stroke.
  • Atherosclerosis.
  • Coronary heart disease and heart attack.
  • Pregnancy complications: It is unusual for SLE to affect fertility, but it can lead to several pregnancy complications, such as: 
  • Miscarriage (baby dies before 24 completed weeks of pregnancy).
  • Stillbirth (baby born dead after 24 completed weeks of pregnancy).
  • Premature delivery.
  • Pre-eclampsia (a condition that results in hypertension during pregnancy).
  • Other autoimmune conditions: Additional autoimmune conditions are found in approximately one in three people with SLE. Such conditions may include thyroid disease, Sjogren's syndrome (damage of salivary and tear glands, resulting in a dry mouth and eyes) or Hughes syndrome (increased risk of clots developing in the arteries, leading to strokes and heart attacks).
  • Infection, due to the fact that both the disease and its treatments reduce immunity.
  • Cancer; the risk of cancer increases when having SLE.
  • Bone tissue death (avascular necrosis): This occurs when the blood supply to a bone diminishes, leading to bones collapse.
Prevention

While you cannot prevent SLE, you can help prevent flare-ups by adopting simple measures that offer coping methods with signs and symptoms of SLE. Some measures include:

  • Regular checkup: Instead of only seeing a physician when the symptoms worsen, it is advisable to follow regular checkups program to prevent flares-up and to diagnose early complications.
  • Protection from the sun: It is recommended to wear protective clothing, sunglasses, and sunscreen when in the sun.
  • Adequate rest: Having persistent fatigue is a main concern among SLE patients and it is usually hard to be relieved by rest. It is recommended to get enough sleep at night and plenty of breaks during the day.
  • Immunizations: Stay up-to-date with immunizations and get flu and pneumonia vaccines.
  • Early detection of osteoporosis: Having tests to screen for thinning of the bones (osteoporosis) is highly recommended in many SLE cases.
  • Quit smoking: SLE symptoms tend to be worse among heavy smokers and the chance of developing SLE-related heart and blood vessels problems are higher.
  • Healthy diet: A healthy diet that contains enough fruits, vegetables, and whole grains, is strongly advisable.
  • Support groups and counseling: Such groups can help fight the feeling of loneliness that presents in many cases.
  • Regular physical exercise: Physical exercises are useful to promote general well-being.The effect of such exercises can be manifested in reducing the risk of heart attack, fight depression and recover from a flare. Healthcare providers may suggest certain types of exercise including:
  1. Range-of-motion such as stretching.
  2. Strengthening such as weightlifting.
  3. Aerobic or endurance such as brisk walking or jogging.
  • Pain management: Learning ways to manage pain such as heat packs that used to ease muscle pain is advisable in many cases.
  • Stress management: Having a long-lasting disease such as SLE is stressful. Some approaches that may help cope with stress include:
  1. Involvement in social activities.
  2. Practicing techniques such as meditation, yoga, walking, or listening to music.
  3. Proper management of time and energy.
  • Supplements and herbs: Some supplements and herbs may be considered useful, but discussing the using of certain supplements and herbs with a physician is highly recommended before using any of them. These supplements and herbs may include:
  1. Flaxseed contains omega-3 fatty acids and alpha-linolenic acid
  2. Thunder god vine (Tripterygium wilfordii)
  3. Astragalus (Astragalus membranaceus)
  4. Calcium and vitamin D supplement
  5. Dehydroepiandrosterone (DHEA)
  6. Methylsulfonylmethane (MSM)
  7. Turmeric
  8. Fish oil
  • Avoid certain drugs: Avoiding of high-dose birth control pills, penicillin, and sulfonamides (antibacterial agents) is advisable to prevent the disease.
Prognosis

The prognosis for people with SLE varies from patient to another. Half of the people who go into a calm condition stay in calm condition for decades. The long-term prognosis of SLE patients remains poor mainly due to complications of the disease and/or of its treatment. SLE tends to be more active during the first years after diagnosis and in people under age 40.

The vast majority of people with SLE develop complications. Symptoms tend to get better after menopause in females. A survival rate of 10 years have been associated with the most of SLE patients; however, a survival rate of 20 years has been reported in many cases as well. Poorer prognosis has been reported among patients who develop renal problems such as focal and diffuse proliferative glomerulonephritis.

SLE does not prevent many women from getting pregnant or delivering a healthy baby. Women who get proper treatment and who have no serious heart or kidney complications are more likely to have a better outcome.

Epidemiology

Abundant estimations of prevalence and incidence of SLE are rare because it is relatively expensive to capture all reliable diagnosed cases for epidemiologic studies. The following are some of the available related data:

  • According to publications of Centers for Disease Control and Prevention (CDC) in the USA, a conservative estimate suggests a prevalence of 161,000 with definite SLE and 322,000 with definite or probable SLE. In addition, between the year 2002 and year 2004, the annual incidence was much higher for blacks than whites in both Michigan and Georgia and the annual incidence estimates were much higher for women than men in Michigan, Georgia, and the American Indian/Alaska Native population.
  • According to a study published in Annals of the Rheumatic Diseases (ARD) journal, the incidence of SLE has been declining annually (1.8%), but the prevalence has been increasing in the UK in recent years and the highest incidence and prevalence present in people decent from Black Caribbean ethnicity. In addition, SLE was six times more common in women and the peak age of incidence was 50–59 years.
  • According to results of a study published in Lupus (journal), in Northwestern Spain, survival probability of 10-year and 15-year were 74.9 % and 63.3% in the late-onset SLE group , meanwhile survival probability of 10-year and 15-year were 96.3% and 91.0% in patients with early-onset SLE, and the incidence of late-onset SLE was significantly higher in women than in men.
  • A study published in Saudi Medical Journal has been found that familial SLE is common in Arab children, 7.7% of patients were diagnosed before the age of 5 years, and renal involvement was diagnosed in 80%, while neuropsychiatric manifestations were seen in 30%.
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