Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable range of symptoms and features. Normally the body's immune system prevents infection by attacking cells or proteins that are seen as foreign, often using antibodies that are specifically targeted. There are processes that usually prevent the immune system from creating antibodies that react against the body's own cells, but these processes break down in autoimmune disorders. So instead of attaching to a bacteria or a virus and flagging the invader for attack by the rest of the immune system, these auto-antibodies attach to a person's own tissues, and the immune system sees this as a flag to attack. The result is inflammation – similar to the inflammation in the throat that can be caused by the immune system's attack on the bacteria that causes strep throat – but on a chronic basis, and often affecting vital systems.
Like many autoimmune diseases, SLE affects around eight times more women than men, and is most likely to begin during the childbearing years. In the general population, it has been estimated that between 40-240 per 100,000 women have SLE, with higher rates seen in blacks, and lower rates in men and children. SLE is also more common in residents of the Caribbean. While the exact cause of SLE remains unclear, it is believed to result from a complex interaction of genetic, hormonal, and environmental factors; some of these factors are better understood than others.
There are several closely related disorders that all fall under the broader umbrella of 'lupus.' SLE is named as systemic because it can affect the entire system of the body; the other forms of lupus are generally less severe or chronic in nature, including cutaneous lupus erythematosus (which only affects the skin), neonatal lupus erythematosus (a temporary form of lupus occurring in newborn infants), and drug-induced lupus erythematosus (a temporary reaction to some medications in certain people).
A broad variety of symptoms have been associated with SLE, but most individuals will only develop some of these over the course of the illness. Clinically, SLE patients are often divided between those with and without multisystem involvement, the latter being considered less severe and the former including patients with SLE effects in major organ systems such as the kidneys, lungs, heart, or nervous system. Generally, SLE patients will develop multisystem involvement within the first five years of the disease or not at all. Symptoms in SLE often follow an episodic path - that is, there are periods when the symptoms are much worse (often called exacerbations or 'flare-ups'), and periods when they are significantly better. For some people, symptoms disappear almost completely for a time, and these are referred to as remission periods.
Despite dramatic improvement over the last ten years in treatment, diagnosis, and, most significantly, survival rates, it has been estimated that 50% of patients with SLE still suffer permanent damage in one or more organ systems. Survival rates have undoubtedly improved due to advances in treatment, but part of the change in statistics is probably due to increased recognition of those with milder disease.
Across all people with SLE, the two most common types of symptoms include skin rashes and arthritis.
- Around 80% of people with SLE have related skin rashes at some point, which are often triggered by sunlight exposure; the term photosensitive is used to describe those with SLE who have a significant increase in any symptoms after being in the sun. Two of the most common rashes associated with SLE are the malar rash – red with a butterfly-shaped distribution across the cheeks and bridge of the nose – and the discoid rash – sharply defined crusty or scaly patches which can lead to scarring.
- Arthritis is also common in people with SLE, leading to pain and stiffness in affected joints, but generally without the erosions and nodules seen in rheumatoid arthritis. The most commonly-affected joints in SLE include the knees, ankles, and wrists. People with SLE are also more likely than the general population to develop fibromyalgia, which causes fatigue and widespread muscle pain.
The impact of SLE on the major organs is generally through inflammation, sometimes acute (short-term) and sometimes chronic (long-term).
- The most common type of lung involvement in people with SLE is pleuritis (also called pleurisy), when the membranes that surround the lungs become inflamed. While this causes pain, it does not cause the same kind of breathing difficulties seen in the smaller number of patients who experience different conditions caused by inflammation of the lungs themselves. Acute pneumonitis can develop from a short-term inflammation of the lungs, and is somewhat like pneumonia without an infection. Interstitial lung disease is generally a result of scarring in the lung tissue from long-term inflammation, and can decrease the ability of the lungs to transfer oxygen to the blood.
- Heart involvement is somewhat less common, and the seriousness of the condition depends in part on the level of heart tissue affected - inflammation of the outer layers (pericarditis) is generally less serious than inflammation of the inner layers of the heart.
- Some neurological symptoms are common in people with SLE, including headaches, a 'brain fog' causing confusion and inattention, and peripheral neuropathy. More rarely there are serious neurological problems, including seizures and strokes - in some cases this is due to inflammation in the central nervous system (spine and brain), and in some cases due to antiphospholipid antibodies which can interfere with blood clotting.
- Kidney involvement in SLE usually takes the form of nephritis, which is an inflammation of the kidneys. Doctors will often perform regular urine tests on SLE patients to monitor kidney function, paying especial attention to the levels of protein seen in the urine. Low-level positive tests are common, but doctors will often adopt a 'wait and see' approach in these cases, and proceed to more invasive testing and treatment only when protein levels are consistently high. In decades past, kidney failure was common in SLE patients, but today it can often be prevented with medications. Modern medicine recognises different types of nephritis in SLE, and a kidney biopsy can help doctors decide which treatments will best help a patient.
- Involvement of the gastrointestinal system is not common in individuals with SLE; in fact, gastrointestinal symptoms in this population may be more likely a side-effect of medications than a result of the disease itself. Nevertheless, a subset of those with SLE do experience inflammation of the gastrointestinal track leading to ulcers and diarrhoea, akin to that seen in another autoimmune disease, ulcerative colitis. The liver in those with SLE can also become enlarged, sometimes due to an inflammation of the liver, and sometimes as the result of drainage from the spleen.
Diagnosis of SLE
As SLE is a little different in every patient, it can be difficult to diagnose. However, accurate diagnosis is important, as proper treatment early on in the disease can help prevent damage to organs such as the kidneys and liver. Lupus is often diagnosed by a rheumatologist, a doctor who specialises in arthritis and autoimmune conditions; this is important, as the symptoms of SLE are similar to those of many other conditions, and a rheumatologist may be best equipped to see the differences. When a doctor is examining a patient for possible SLE, he also has to consider possibilities such as rheumatoid arthritis, fibromyalgia, thyroid disease, and infections. Further confusing the matter is the fact that it is possible for patients to have all of these conditions at once!
A diagnostic workup for SLE would usually include:
- A thorough physical examination, including patient and family medical history. SLE is more likely in individuals who have close family members with an autoimmune disorder. And because some symptoms of SLE can come and go over time, doctors have to ask questions about previous symptoms as well as those currently a problem.
- Blood tests - including tests to look at blood cell counts and different auto-antibodies, especially the antinuclear antibody (ANA). The ANA test is positive in more than 95% of patients with SLE, but because it can be positive in healthy people as well, the vast majority of those who are positive for the ANA do not, in fact, have lupus. If the ANA test is positive, or the doctor otherwise suspects SLE, other blood tests will often be ordered, such as the anti-DNA antibody test, which is rarely positive in those without SLE. New diagnostic tests are currently being developed to help detect those patients with SLE who do not test positive to the currently-used tests.
- Tests to rule out other conditions, such as blood work and X-rays to rule out rheumatoid arthritis.
Official Diagnostic Criteria
The American College of Rheumatology has developed diagnostic criteria to help ensure that one doctor's diagnosis of SLE is generally the same as another's. These criteria include some, but not all, of the symptoms often seen in SLE - the included symptoms were chosen largely because they are the least likely to show up in patients who may have related disorders, but do not have systemic lupus. Out of the eleven criteria, four must be observed for a diagnosis to be made.
- Malar rash
- Discoid rash
- Sun sensitivity - worsening of rash or other symptoms after sun exposure
- Ulcers in the mouth or nose
- Inflammatory arthritis
- Serositis - an inflammation of the membranes surrounding the lungs or heart
- Kidney disorder
- Seizures, psychosis, or other severe neurological symptoms without other causes
- Blood abnormalities, including anaemia, low platelet counts, or low white blood cell counts
- Immunologic abnormality, including positive results for any of a number of auto-antibodies, or false positive syphilis tests
- Positive ANA test
Treatment of SLE
Proper treatment of SLE is not a one shot process - it requires long-term monitoring to make sure that the most appropriate treatment is always being used, in a balance between preventing organ damage and other symptoms on one side, and avoiding potentially serious side effects of medications on the other. For those without organ involvement, the most commonly used medications are non-steroidal anti-inflammatory drugs (NSAIDs) and antimalarials. For those with organ involvement, immunosuppressive medications are generally used, which suppress the immune system.
Across all types of SLE, systemic steroid medications such as prednisone are often used to treat 'flare-ups' of symptoms. Different than the anabolic steroids misued by some athletes, systemic steroids like prednisone reduce inflammation but can cause weight gain and moodiness, among other side effects. Long-term use of prednisone can have more serious side-effects, but is sometimes necessary in people with organ involvement.
NSAIDs and Antimalarials
Both over-the-counter and prescription NSAIDs (such as ibuprofen) are used in people with SLE, and can help with pain, fever, the inflammation of lung and heart membranes that occurs in some people. However, those with SLE may be more likely than the general population to experience side-effects from NSAIDs.
Anti-malaria medications, such as hydroxychloroquine, are also used in SLE with significant success; these medications are especially known for helping ease the fatigue experienced by many patients, but can worsen sun sensitivity. Because antimalarials can cause eye problems, patients are usually recommended to have checkups with an ophthalmologist regularly while taking them. Compared to NSAIDs, antimalarials can take several weeks to months to show a significant effect, but side-effects such as nausea can be worst in the first weeks.
Immunosuppressive and Cytotoxic Medications
These medications work to prevent the immunological reactions that lead to serious inflammation, but as a side-effect can decrease the regular functioning of the immune system as well. The three main medications of this type used in SLE are azathioprine (Imuran), cyclophosphamide (Cytoxan), and methotrexate - the same medications are also used to treat some cancers, and to prevent rejection after an organ transplant. Depending on the medication and individual, these treatments can be given as pills, injections, or through an IV.
Due to the potential for significant side-effects, these medications are only used when the safer medications are not sufficient alone. Potentially severe side-effects include an increase in infections, problems with blood-clotting, anaemia and fatigue. Less severe but still annoying side-effects include nausea, vomiting, diarrhoea, hair loss, mouth sores, and rashes.
Some Common Myths about SLE
There are many misconceptions about SLE, including:
- All people with SLE have the malar rash; if you don't have it, you don't really have SLE. Untrue, some people with SLE don't have any skin symptoms at all.
- SLE is a disorder of the 'autoimmunity system' (sic) and this immunological defect causes people to be much more susceptible to infections, like with AIDS. Untrue, and just so you know, 'autoimmunity system' isn't a real term.
- SLE and fibromyalgia are really the same thing. Untrue, although people with SLE are more likely to develop fibromyalgia.
- People with SLE cannot have children. Untrue, all those with certain auto-antibodies are more likely to have miscarriages than most women, and pregnancy in lupus can carry special risks.
- Only women get SLE. Untrue - it may be more likely in women, but it happens in men as well.
- Children cannot get SLE. Untrue, although SLE in children can be slightly different than that in adults.
The Future Looks Bright
Research regarding autoimmune disorders in general, including SLE, has progressed at a fantastic pace over the last decade. Significant advances arrive each year in diagnosis, treatment, and our understanding of the causes of SLE. New immunosuppressive medications are being developed that more tightly target the problem areas rather than suppressing the whole immune system. Other treatments include bone marrow transplants leading to a complete remission of symptoms in severely affected patients who hadn't responded to traditional immunosuppressive medications.
For those interested in more detailed information, an up-to-date and well-respected resource is The Lupus Book by Dr Daniel J Wallace, who is also the current author of the main textbook for physicians about lupus.