Systemic Lupus Erythematosus (SLE)
What is SLE?
Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. It is an autoimmune disease that occurs when your body's immune system attacks your own tissues and organs. Inflammation caused by lupus can affect many different body organs and systems: joints, skin, kidneys, blood cells, brain, heart and lungs. SLE can be difficult to diagnose as its signs and symptoms often resembles other medical conditions.
People with SLE have episodes of exacerbations and remissions. Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening. More than 90% of cases of SLE occur in women, frequently starting at childbearing age.The prevalence of SLE in Africa and Asia is believed to be much lower than in Western nations; however, in industrialized Western countries, people of African and Asian descent are two to four times more likely to develop SLE than are people of European descent.
Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. It is an autoimmune disease that occurs when your body's immune system attacks your own tissues and organs. Inflammation caused by lupus can affect many different body organs and systems: joints, skin, kidneys, blood cells, brain, heart and lungs. SLE can be difficult to diagnose as its signs and symptoms often resembles other medical conditions.
People with SLE have episodes of exacerbations and remissions. Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening. More than 90% of cases of SLE occur in women, frequently starting at childbearing age.The prevalence of SLE in Africa and Asia is believed to be much lower than in Western nations; however, in industrialized Western countries, people of African and Asian descent are two to four times more likely to develop SLE than are people of European descent.
Causes of SLE
Although the specific cause of SLE is unknown, multiple genetic predispositions and gene-environment interactions have been identified.Some potential causes/triggers include:
Although the specific cause of SLE is unknown, multiple genetic predispositions and gene-environment interactions have been identified.Some potential causes/triggers include:
- Genetics: Most of the genes associated with SLE are involved in immune system function. At least 35 genes are known to increase the risk of SLE
- Inheritance: tend to run in families
- Sunlight. Exposure to the sun may bring on lupus skin lesions or trigger an internal response in susceptible people.
- Infections: can initiate lupus or cause a relapse in some people.
- Early life risk factors: Low birth weight, pre term birth (>1 month early) and childhood exposures to agricultural pesticides
- Silica dust and cigarette smoking: increase the risk of developing SLE
- Estrogen use in postmenopausal women: increase the risk of developing SLE
- Medications.Some blood pressure medications, anti-seizure medications and antibiotics may trigger SLE. People who have drug-induced lupus usually get better when they stop taking the medication.
- Race: Lupus is more common in African-Americans, Hispanics and Asian-Americans
Symptoms of SLE
No two cases of lupus are identical and the symptoms depends on which organ or system is affected. Signs and symptoms may come on suddenly or develop slowly, may be mild or severe, and may be temporary or permanent.
The classic presentation of a triad of fever, joint pain, and rash in a woman of childbearing age should prompt investigation into the diagnosis of SLE. However, patients may present with any of the following types of manifestations:
No two cases of lupus are identical and the symptoms depends on which organ or system is affected. Signs and symptoms may come on suddenly or develop slowly, may be mild or severe, and may be temporary or permanent.
The classic presentation of a triad of fever, joint pain, and rash in a woman of childbearing age should prompt investigation into the diagnosis of SLE. However, patients may present with any of the following types of manifestations:
- Constitutional: Fatigue, fever, arthralgia, loss of appetite and weight loss
- Musculoskeletal: Joint pain, stiffness, weakness and swelling. In contrast to rheumatoid arthritis, SLE arthritis or arthralgia may be asymmetrical, with pain that is disproportionate to swelling. Joint erosions and deformities are rare. There is an increased prevalence of avascular necrosis (AVN) in the SLE patients.
- Dermatologic: malar rash, photosensitivity, and discoid lupus. Malar rash is flat red rash across the cheeks and bridge of the nose sparing nasolabial folds. Discoid lesions often also develop in sun-exposed areas but are plaquelike in character, with follicular plugging and scarring.
- Raynaud's Phenomenon: Fingers and toes that turn white or blue when exposed to cold or during stressful periods. But it can occur in other autoimmune diseases too.
- Renal: approximately 50% of patients with SLE develop clinically evident renal disease. Acute or chronic renal failure may cause symptoms related to uremia and fluid overload. Acute nephritic disease may manifest as hypertension and hematuria. Nephrotic syndrome may cause edema, weight gain, or hyperlipidemia.
- Neuropsychiatric: The inflammation characteristic of SLE can also damage the nervous system and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke;headaches; visual problems; confusion and cognitive impairment. Anxiety and depression are also common.
- Pulmonary complications: including pleurisy, pleural effusion, pneumonitis, pulmonary hypertension, and interstitial lung disease. The chronic steroids prescribed to patients also place them at increased risk for atypical infections.
- Gastrointestinal: symptoms secondary to SLE are less common than adverse effects of medication or nonspecific complaints. Infectious causes (bacterial, viral eg CMV maybe because of immunosuppression drugs. Use of NSAIDS for pain relief can cause peptic ulcers.
- Cardiac : Pericarditis (inflammation of the sac-like membrane around the heart) is the most common cardiac feature of SLE, manifesting as positional chest pain that is often relieved when the patient leans forward. Myocarditis may occur in SLE with heart failure symptoms. Pulmonary hypertension may present with indolent chest pain or shortness of breath. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis).
- Hematologic: multiple cytopenias such as leukopenia, lymphopenia, anemia or thrombocytopenia may suggest SLE. It can also cause inflammation of the blood vessels (vasculitis).
- Alopecia (hair loss)
- Ulcerations: open sores in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.
Complications of SLE
Having lupus also increases your risk of:
Having lupus also increases your risk of:
- Infection. People with lupus are more susceptible to infection because both the disease and its treatments namely steroids can weaken the immune system.
- Cancer. Having lupus appears to increase your risk of cancer; however the risk is small.
- Avascular necrosis: Blood supply to a bone diminishes, leading to tiny breaks in the bone and eventually to the bone's collapse.
- Pregnancy complications. Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.
Diagnosis using American College of Rheumatology (ACR) criteria for the diagnosis of systemic lupus erythematosus (SLE).
SLE can be diagnosed if any 4 or more of the following 11 criteria are present, serially or simultaneously, during any interval of observation:
1. Malar rash
2. Discoid rash
3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight
4. Oral ulcers: Oral or nasopharyngeal ulceration, usually painless
5. Arthritis: Non-erosive arthritis involving =2 peripheral joints, characterized by tenderness, swelling, or effusion
6. Serositis
(A) Pleuritis: Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion
or
(B) Pericarditis: Documented by ECG or rub or evidence of pericardial effusion
7. Renal disorder
(A) Persistent proteinuria >0.5 g/day or >3+ if quantitation not performed
or
(B) Cellular casts: May be red blood cell, hemoglobin, granular, tubular, or mixed
8. Neurologic disorder
(A) Seizures: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
or
(B) Psychosis: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
9. Hematologic disorder
(A) Hemolytic anemia: With reticulocytosis
or
(B) Leukopenia: < 4000/mm3 total on =2 occasions
or
(C) Lymphopenia: < 1500/mm3 on =2 occasions
or
(D) Thrombocytopenia: < 100,000/mm3in the absence of offending drugs
10. Immunologic disorder
(A) Anti-DNA: Antibody to native DNA in abnormal titer
or
(B) Anti-Sm: Presence of antibody to Smith (Sm) nuclear antigen
or
(C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for =6 months and confirmed by Treponema pallidumimmobilization or fluorescent treponemal antibody absorption tests
11. Antinuclear antibody (ANA)
An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome
SLE can be diagnosed if any 4 or more of the following 11 criteria are present, serially or simultaneously, during any interval of observation:
1. Malar rash
2. Discoid rash
3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight
4. Oral ulcers: Oral or nasopharyngeal ulceration, usually painless
5. Arthritis: Non-erosive arthritis involving =2 peripheral joints, characterized by tenderness, swelling, or effusion
6. Serositis
(A) Pleuritis: Convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion
or
(B) Pericarditis: Documented by ECG or rub or evidence of pericardial effusion
7. Renal disorder
(A) Persistent proteinuria >0.5 g/day or >3+ if quantitation not performed
or
(B) Cellular casts: May be red blood cell, hemoglobin, granular, tubular, or mixed
8. Neurologic disorder
(A) Seizures: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
or
(B) Psychosis: In the absence of offending drugs or known metabolic derangements (eg, uremia, ketoacidosis, electrolyte imbalance)
9. Hematologic disorder
(A) Hemolytic anemia: With reticulocytosis
or
(B) Leukopenia: < 4000/mm3 total on =2 occasions
or
(C) Lymphopenia: < 1500/mm3 on =2 occasions
or
(D) Thrombocytopenia: < 100,000/mm3in the absence of offending drugs
10. Immunologic disorder
(A) Anti-DNA: Antibody to native DNA in abnormal titer
or
(B) Anti-Sm: Presence of antibody to Smith (Sm) nuclear antigen
or
(C) Positive finding of antiphospholipid antibodies based on (1) an abnormal serum level of IgG or IgM anticardiolipin antibodies, (2) a positive test result for lupus anticoagulant using a standard method, or (3) a false-positive serologic test for syphilis known to be positive for =6 months and confirmed by Treponema pallidumimmobilization or fluorescent treponemal antibody absorption tests
11. Antinuclear antibody (ANA)
An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome
Diagnostic tests
Diagnosis of SLE may be difficult as the symptoms may resemble other conditions. The specialist will conduct a series of blood, urine tests to determine markers in the diagnostic criteria above, looking for other organs' damage and imaging tests.
Blood and urine tests :
Imaging tests:
Biopsy
A biopsy is when pieces of tissue are taken from the body to be checked under a microscope. This is done to look for signs of lupus damaging organs like skin and kidneys.
Diagnosis of SLE may be difficult as the symptoms may resemble other conditions. The specialist will conduct a series of blood, urine tests to determine markers in the diagnostic criteria above, looking for other organs' damage and imaging tests.
Blood and urine tests :
- Full blood count: This test checks for low counts of red blood cells, white blood cells, and platelets which may occur in lupus too.
- Erythrocyte sedimentation rate. This blood test determines the rate at which red blood cells settle to the bottom of a tube in an hour. When swelling and inflammation are present, the blood’s proteins clump together and become heavier than normal. They fall and settle faster at the bottom of the test tube. The faster the blood cells fall, the more severe the inflammation. The sedimentation rate isn't specific for any one disease.
- C-reactive protein (CRP). This is protein that is shows up when inflammation is found in the body. ESR and CRP show similar amounts of inflammation. But it is non specific to lupus.
- Kidney and liver assessment. To assess the function of kidneys and liver as Lupus can affect these organs.
- Urinalysis. An examination of a sample of your urine may show an increased protein level or red blood cells in the urine, which may occur if lupus has affected your kidneys.
- Antinuclear antibody (ANA) test. A positive test for the presence of these antibodies indicates a stimulated immune system. While most people with lupus have a positive ANA test, most people with a positive ANA do not have lupus. If you test positive for ANA, your doctor may advise more-specific antibody testing.
- Other antibody tests: Anti-DNA, Anti-Sm and anti-cardiolipin antibodies
- Complement test. This test is done to measure the level of complement. This is a group of proteins in the blood that help destroy foreign substances. Low levels of complement in the blood are often linked with lupus.
Imaging tests:
- Chest X-ray. An image of your chest may reveal abnormal shadows that suggest fluid or inflammation in your lungs in patients with complications of lung diseases.
- Echocardiogram. This test uses sound waves to produce images of your heart. It can check for any complications of the heart.
Biopsy
A biopsy is when pieces of tissue are taken from the body to be checked under a microscope. This is done to look for signs of lupus damaging organs like skin and kidneys.
Treatment of SLE
There is no cure for lupus, but it is treated such that medications are given to treat symptoms and delay progression of end organ damage. You will need to consult a rheumatologist who specializes in lupus, arthritis, and other related diseases. As multiple organs may be involved, a multi-disciplinary specialists will be required to get together and manage the condition.
Medications prescribed for SLE patients include:
There is no cure for lupus, but it is treated such that medications are given to treat symptoms and delay progression of end organ damage. You will need to consult a rheumatologist who specializes in lupus, arthritis, and other related diseases. As multiple organs may be involved, a multi-disciplinary specialists will be required to get together and manage the condition.
Medications prescribed for SLE patients include:
- Nonsteroidal anti-inflammatory drugs (NSAIDs): such as naproxen sodium and ibuprofen may be used to treat pain, swelling and fever associated with lupus.Side effects of NSAIDs include stomach ulcers, kidney impairment and an increased risk of heart problems.
- Antimalarial drugs: such as hydroxychloroquine (Plaquenil), affect the immune system and can help decrease the risk of lupus flares.It can treat fatigue, rashes, joint pain,mouth sores and help prevent blood clots. Side effects can include stomach upset and, very rarely, damage to the retina of the eye. Regular eye exams are recommended when taking these medications.
- Corticosteroids: Prednisone and other types of corticosteroids can counter the inflammation of lupus. High doses of steroids such as methylprednisolone are often used to control serious disease that involves the kidneys and brain. Side effects include weight gain, easy bruising, osteoporosis, high blood pressure, diabetes and increased risk of infection. The risk of side effects increases with higher doses and longer term therapy.
- Immunosuppressants: Drugs that suppress the immune system may be helpful in serious cases of lupus. Drugs include azathioprine, mycophenolate mofetil and methotrexate. Potential side effects may include an increased risk of infection, liver damage, decreased fertility and an increased risk of cancer.
- Biologics: Eg belimumab is administered intravenously. It also reduces lupus symptoms in some people. Side effects include nausea, diarrhea and infections. Rarely, it worsens depression
- Intravenous immune globulin: is used for immunosuppression in serious SLE flares.
- Rituximab can be beneficial in cases of resistant lupus. Side effects include allergic reaction to the intravenous infusion and infections.
- Vitamin D supplementation: As SLE patients often has Vitamin D deficiency, supplements will help decrease disease activity and improve fatigue.