Systemic Lupus Erythematosus
Disease Details
Family Health Simplified
- Description
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which the immune system attacks the body's own tissues, causing widespread inflammation and tissue damage.
- Type
- Systemic Lupus Erythematosus (SLE) is an autoimmune disease. It is not directly inherited in a Mendelian pattern but is believed to be influenced by multiple genetic factors. The genetic transmission is complex and polygenic, meaning it involves multiple genes, and it may also be influenced by environmental factors. Family history can increase the risk, but it does not guarantee that the disease will occur.
- Signs And Symptoms
- SLE is one of several diseases known as "the great imitator" because it often mimics or is mistaken for other illnesses. SLE is a classical item in differential diagnosis, because SLE symptoms vary widely and come and go unpredictably. Diagnosis can thus be elusive, with some people having unexplained symptoms of SLE for years before a definitive diagnosis is reached.Common initial and chronic complaints include fever, malaise, joint pains, muscle pains, and fatigue. Because these symptoms are so often seen in association with other diseases, these signs and symptoms are not part of the diagnostic criteria for SLE. When occurring in conjunction with other signs and symptoms, however, they are considered suggestive.While SLE can occur in both males and females, it is found far more often in women, and the symptoms associated with each sex are different. Females tend to have a greater number of relapses, a low white blood cell count, more arthritis, Raynaud syndrome, and psychiatric symptoms. Males tend to have more seizures, kidney disease, serositis (inflammation of tissues lining the lungs and heart), skin problems, and peripheral neuropathy.
- Prognosis
- No cure is available for SLE but there are many treatments for the disease.In the 1950s, most people diagnosed with SLE lived fewer than five years. Today, over 90% now survive for more than ten years, and many live relatively symptom-free. 80–90% can expect to live a normal lifespan. Mortality rates are however elevated compared to people without SLE.Prognosis is typically worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within five years, is due to organ failure or overwhelming infections, both of which can be altered by early diagnosis and treatment. The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, the leading cause of death for people with SLE. To reduce the potential for cardiovascular issues, high blood pressure and high cholesterol should be prevented or treated aggressively. Steroids should be used at the lowest dose for the shortest possible period, and other drugs that can reduce symptoms should be used whenever possible.
- Onset
- Systemic lupus erythematosus (SLE) typically has an onset in individuals between the ages of 15 and 45. However, it can occur at any age. The onset is often marked by a range of non-specific symptoms such as fatigue, fever, and joint pain, which can make it difficult to diagnose early. Symptoms can vary widely from person to person.
- Prevalence
- The prevalence of systemic lupus erythematosus (SLE) varies widely depending on the population and geographic region. In the United States, it is estimated to affect approximately 20 to 150 per 100,000 people. SLE is more common in women, particularly those of childbearing age, and has higher prevalence rates among individuals of African, Asian, and Hispanic descent compared to Caucasians.
- Epidemiology
- The global rates of SLE are approximately 20–70 per 100,000 people. In females, the rate is highest between 45 and 64 years of age. The lowest overall rate exists in Iceland and Japan. The highest rates exist in the US and France. However, there is not sufficient evidence to conclude why SLE is less common in some countries compared to others; it could be the environmental variability in these countries. For example, different countries receive different levels of sunlight, and exposure to UV rays affects dermatological symptoms of SLE.Certain studies hypothesize that a genetic connection exists between race and lupus which affects disease prevalence. If this is true, the racial composition of countries affects disease and will cause the incidence in a country to change as the racial makeup changes. To understand if this is true, countries with largely homogenous and racially stable populations should be studied to better understand incidence. Rates of disease in the developing world are unclear.The rate of SLE varies between countries, ethnicity, and sex, and changes over time. In the United States, one estimate of the rate of SLE is 53 per 100,000; another estimate places the total affected population at 322,000 to over 1 million (98 to over 305 per 100,000). In Northern Europe the rate is about 40 per 100,000 people. SLE occurs more frequently and with greater severity among those of non-European descent. That rate has been found to be as high as 159 per 100,000 among those of Afro-Caribbean descent. Childhood-onset systemic lupus erythematosus generally presents between the ages of 3 and 15 and is four times more common in girls.While the onset and persistence of SLE can show disparities between genders, socioeconomic status also plays a major role. Women with SLE and of lower socioeconomic status have been shown to have higher depression scores, higher body mass index, and more restricted access to medical care than women of higher socioeconomic statuses with the illness. People with SLE had more self-reported anxiety and depression scores if they were from a lower socioeconomic status.
- Intractability
- Systemic lupus erythematosus (SLE) is generally considered intractable because it is a chronic autoimmune disease that currently has no cure. Management focuses on controlling symptoms and preventing flares through medication and lifestyle changes. Treatment typically includes immunosuppressive drugs, anti-inflammatory medications, and symptom-specific therapies. Although remission is possible, ongoing treatment is usually necessary to manage the disease effectively.
- Disease Severity
- Systemic lupus erythematosus (SLE) is an autoimmune disease with varying degrees of severity. It can range from mild to severe, with symptoms affecting multiple organ systems. Mild forms may involve skin rashes and joint pain, while more severe cases can lead to complications such as kidney damage, cardiovascular issues, and neurological problems. The severity of SLE often fluctuates, with periods of exacerbation (flares) and remission. Regular monitoring and treatment are essential to manage the disease effectively and prevent severe complications.
- Healthcare Professionals
- Disease Ontology ID - DOID:9074
- Pathophysiology
- SLE is triggered by environmental factors that are unknown. In SLE, the body's immune system produces antibodies against self-protein, particularly against proteins in the cell nucleus. These antibody attacks are the immediate cause of SLE.SLE is a chronic inflammatory disease believed to be a type III hypersensitivity response with potential type II involvement. Reticulate and stellate acral pigmentation should be considered a possible manifestation of SLE and high titers of anti-cardiolipin antibodies, or a consequence of therapy.People with SLE have intense polyclonal B-cell activation, with a population shift towards immature B cells. Memory B cells with increased CD27+/IgD—are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BLyS), also known as B-cell activating factor (BAFF), interleukin 6, interleukin 17, interleukin 18, type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process and are potential therapeutic targets.SLE is associated with low C3 levels in the complement system.
- Carrier Status
- Systemic Lupus Erythematosus (SLE) is an autoimmune disease rather than a condition directly associated with carrier status, like some genetic diseases are. SLE occurs when the body's immune system attacks its own tissues and organs, causing widespread inflammation and tissue damage. It is influenced by a combination of genetic, environmental, and possibly hormonal factors, but there isn't a simple "carrier" status for it.
- Mechanism
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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the immune system attacking the body's own tissues and organs. Here are the key points about its mechanisms and molecular mechanisms:
**Mechanism:**
1. **Immune Dysregulation**: SLE involves the production of autoantibodies against nuclear and cytoplasmic antigens. These antibodies form immune complexes that can deposit in various tissues, causing inflammation and tissue damage.
2. **Multi-System Involvement**: SLE can affect multiple organ systems, including the skin, joints, kidneys, brain, and heart.
**Molecular Mechanisms:**
1. **Genetic Factors**: Multiple genes contribute to susceptibility, including those involved in immune regulation, like HLA-DR2 and HLA-DR3.
2. **Epigenetic Changes**: DNA methylation, histone modification, and non-coding RNAs are also implicated in the pathogenesis.
3. **Autoantibody Production**: B cells produce autoantibodies such as anti-nuclear antibodies (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies.
4. **Cytokine Dysregulation**: There is an overproduction of pro-inflammatory cytokines, like interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6).
5. **Toll-like Receptors (TLRs)**: TLRs on immune cells recognize self-nucleic acids, leading to their activation and an increased immune response.
6. **Defective Clearance of Apoptotic Cells**: Impaired removal of dying cells can result in the release of nuclear antigens, which then become targets for the immune system.
7. **Complement System**: Alterations in the complement system may facilitate the formation of immune complexes and contribute to inflammation.
These mechanisms contribute to the chronic and systemic nature of the inflammation seen in SLE. - Treatment
- There is no cure for Lupus. The treatment of SLE involves preventing flares and reducing their severity and duration when they occur.Treatment can include corticosteroids and anti-malarial drugs. Certain types of lupus nephritis such as diffuse proliferative glomerulonephritis require intermittent cytotoxic drugs. These drugs include cyclophosphamide and mycophenolate. Cyclophosphamide increases the risk of developing infections, pancreas problems, high blood sugar, and high blood pressure.Hydroxychloroquine was approved by the FDA for lupus in 1955. Some drugs approved for other diseases are used for SLE 'off-label'. In November 2010, an FDA advisory panel recommended approving belimumab (Benlysta) as a treatment for the pain and flare-ups common in lupus. The drug was approved by the FDA in March 2011.In terms of healthcare utilization and costs, one study found that "patients from the US with SLE, especially individuals with moderate or severe disease, utilize significant healthcare resources and incur high medical costs."
- Compassionate Use Treatment
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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of treatments, including some that fall under compassionate use, off-label, or experimental categories.
1. **Compassionate Use Treatment**: Compassionate use refers to the use of investigational drugs outside of clinical trials for patients with serious or life-threatening conditions when no viable alternatives exist. These treatments are typically still under investigation and not yet approved by regulatory authorities. For SLE, biologics targeting specific immune pathways, such as new monoclonal antibodies, can fall into this category when traditional treatments fail.
2. **Off-label Treatments**: Off-label use involves prescribing approved medications for conditions outside their official indications. Common off-label treatments for SLE include:
- **Rituximab**: Although primarily approved for certain cancers and autoimmune diseases like rheumatoid arthritis, it is sometimes used off-label for SLE due to its effectiveness in depleting B-cells.
- **Belimumab**: While approved for SLE, it can be used off-label for specific manifestations of the disease not originally indicated in the approval.
- **Mycophenolate Mofetil**: Often used off-label for lupus nephritis, a serious kidney inflammation caused by SLE.
- **Thalidomide**: Used in some severe cases of cutaneous lupus that are resistant to other therapies.
3. **Experimental Treatments**: These are treatments still being evaluated in clinical trials. Some examples include:
- **Anifrolumab**: A monoclonal antibody targeting type I interferon receptors, which may modulate immune activity in SLE.
- **Low-dose IL-2**: Investigated for its potential to restore regulatory T-cell function and balance the immune system.
- **Stem Cell Therapy**: Hematopoietic stem cell transplantation is being explored for its potential to reboot the immune system and induce long-term remission.
These treatments are typically considered when conventional therapies do not provide sufficient control of the disease or cause significant side effects. - Lifestyle Recommendations
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Lifestyle recommendations for individuals with systemic lupus erythematosus (SLE) include:
1. **Healthy Diet**: A balanced diet rich in fruits, vegetables, whole grains, and lean proteins can help manage symptoms. Limit intake of processed foods, excessive salt, and sugars.
2. **Regular Exercise**: Engaging in regular, low-impact physical activities, such as walking, swimming, or yoga, can improve overall health and help manage stress and fatigue.
3. **Sun Protection**: Many people with SLE are sensitive to ultraviolet (UV) light. Wearing sun-protective clothing, using broad-spectrum sunscreen, and avoiding direct sunlight during peak hours can help prevent flare-ups.
4. **Stress Management**: Techniques such as meditation, deep-breathing exercises, and mindfulness can help manage stress, which may trigger symptoms.
5. **Adequate Sleep**: Ensuring adequate, restful sleep is crucial for managing fatigue and overall well-being.
6. **Smoking Cessation**: Avoid tobacco use as it can exacerbate symptoms and increase the risk of cardiovascular complications.
7. **Regular Medical Check-ups**: Maintaining regular appointments with healthcare providers to monitor the disease and adjust treatments as necessary is vital.
8. **Medication Adherence**: Taking prescribed medications consistently and as directed is essential for managing SLE effectively.
These lifestyle modifications can help manage symptoms, improve quality of life, and reduce the frequency of disease flare-ups. - Medication
- Due to the variety of symptoms and organ system involvement with SLE, its severity in an individual must be assessed to successfully treat SLE. Mild or remittent disease may, sometimes, be safely left untreated. If required, nonsteroidal anti-inflammatory drugs and antimalarials may be used. Medications such as prednisone, mycophenolic acid and tacrolimus have been used in the past.
- Repurposable Drugs
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Repurposable drugs for systemic lupus erythematosus (SLE) include:
1. **Hydroxychloroquine** - Originally used for malaria and rheumatoid arthritis.
2. **Methotrexate** - Used in cancer and rheumatoid arthritis treatment.
3. **Azathioprine** - An immunosuppressant often used for organ transplant patients and certain autoimmune conditions.
4. **Mycophenolate mofetil** - Primarily used for organ transplants, it is also effective in SLE.
5. **Rituximab** - Initially used for certain types of cancer and rheumatoid arthritis.
These drugs help manage SLE symptoms and suppress immune system activity. - Metabolites
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Systemic lupus erythematosus (SLE) is an autoimmune disease with a variety of clinical manifestations. Metabolites associated with SLE can provide insights into disease activity and progression. Some of these metabolites include:
1. **Cytokines and Chemokines**: Elevated levels of cytokines (e.g., IL-6, IL-10) and chemokines (e.g., CXCL10) may indicate inflammation and immune activation.
2. **Complement Components**: Reduced levels of C3 and C4 complement proteins can reflect disease activity, as these proteins are consumed during an autoimmune response.
3. **Homocysteine**: Elevated homocysteine levels have been observed in some patients with SLE and can be associated with an increased risk of cardiovascular disease.
4. **Autoantibodies**: Various autoantibodies, such as anti-dsDNA and anti-Smith, are crucial biomarkers for diagnosis and disease monitoring.
Targeted metabolomics and lipidomics can identify other specific metabolites and help in understanding the complex biochemical changes occurring in SLE. - Nutraceuticals
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For systemic lupus erythematosus (SLE), there is ongoing research into the use of nutraceuticals, which are food-derived products that have potential health benefits. Some nutraceuticals investigated for SLE include:
1. **Omega-3 Fatty Acids:** Found in fish oil, omega-3s have anti-inflammatory properties that may help reduce SLE symptoms.
2. **Vitamin D:** Low levels of vitamin D are common in SLE patients, and supplementation might help manage the disease.
3. **Antioxidants:** Vitamins E and C are antioxidants that can help combat oxidative stress, which is thought to contribute to SLE progression.
4. **Turmeric (Curcumin):** Curcumin has anti-inflammatory and antioxidant effects and is being studied for its potential benefits in SLE.
It is important to consult a healthcare provider before starting any nutraceutical regimen, as their effectiveness and safety can vary depending on individual health conditions. - Peptides
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For systemic lupus erythematosus (SLE), peptides can have significant roles, primarily in developing new therapeutic approaches and potential diagnostic tools. Peptide-based strategies might include designing self-antigen peptides to modulate the immune response or using peptides to identify and target specific biomarkers associated with SLE. These approaches aim to reduce disease activity and improve patient outcomes by targeting underlying immune dysregulation specific to SLE.
Nanotechnology (nan) is another promising field in SLE research and treatment. Nanoparticles can be engineered to deliver drugs precisely to affected areas, potentially reducing side effects and increasing treatment efficacy. Nanomaterials can also be used for better diagnostic imaging and monitoring disease progression. Overall, both peptides and nanotechnology offer innovative avenues to enhance the management and understanding of SLE.