Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable range of symptoms and features. SLE tends to preferentially affect women, being most likely to occur during the childbearing years. In a general population, it has been estimated that around 40 per 100,000 women have SLE, with higher rates seen in blacks.
The exact cause of SLE remains unclear, it results from a complex interaction of environmental, hormonal and genetic (inherited) factors.
Some of the genetic and environmental factors are better understood than others.
Normally the body's immune system prevents infection.
In SLE, the immune system's mechanisms for preventing it 'attacking' self tissues fails, and self-reactive antibodies are produced.
These antibodies are not directed against infective organisms such as bacteria but instead 'attack' the bodies own tissues, so that the immune system 'attacks' the body as if it were an invading microorganism or unmatched transplant. Most of the damage in SLE is caused by inflammation, brought about by these abnormal immune responses to the bodies own tissues.
Not all persons with SLE will demonstrate all symptoms, mild cases may present with skin involvement or arthritic symptoms, whilst in more severe disease, (approximately half of patients), multi-system involvement is manifested through nephritis, central nervous system involvement, vasculitis, pulmonary hypertension, interstitial lung disease, stroke and several other conditions. A typical patient (should one exist) with SLE is a young woman in her childbearing years who presents with intermittent fatigue, joint pain and swelling, skin rashes, low white blood cell count, and chest pains due to pleuritis.
Skin involvement is the most conspicuous feature of SLE, being affected in 80% of cases at some point during the diseases course. About 20% of skin lesions are triggered by exposure to sunlight, termed photosensitive. A typical skin lesion is a red (termed Erythematosus) Rash, with a butterfly distribution on the cheeks
of the face and across the bridge of the nose.
The rash may also consist of flat discoloured areas of the skin (termed macules), with small raised bumps termed papules.
Arthritis is a common feature, causing stiffness, pain, and tenderness, typically affecting the wrists, small joints of the hands, knees, or ankles.
The lungs may be involved in disease in up to two-thirds of patients. Recurrent inflammation of the pleural membranes which surround the lungs (pleurisy) and pleural effusions (fluid around the lungs) are the commonest manifestations.
Cardiac involvement in SLE may include inflammation of different types of heart tissue, some of which are more serious than others.
Neurological symptoms may include headaches, 'brain fog' (confusion and/or concentration problems), and problems with sensations in the peripheral nerves (peripheral neuropathy).
More rarely serious neurological problems such as seizures or strokes may occur. These can be caused by inflammation in the blood vessels of the central nervous system (CNS vasculitis), or by antiphospholipid antibodies carried by some individuals with SLE.
Gastrointestinal symptoms are usually not a major presenting feature of the disease. Gastrointestinal symptoms of SLE include nausea, vomiting, anorexia and diarrhoea. Ulceration and other features are rarer still.
Liver and spleen involvement in SLE usually takes the form of excessive enlargement of the organs caused by inflammation. Chronic active hepatitis is not a feature of SLE, because it can resemble SLE it must be differentiated from SLE.
Lupus nephritis or lupus glomerulonephritis is the medical term for inflammation in the kidney occurring in SLE. About a third of patients
with lupus will develop nephritis which is an important and potentially serious symptom that requires medical evaluation and treatment. Many patients often have low-level positive tests , doctors usually don't call for biopsy or anything in such cases, but monitor patients with regular urine
testing, only intervening with further tests when patients consistently and repeatedly have positive urine tests. in the minority of patients with consistent
evidence of kidney disease specific treatment is required to prevent loss of kidney function.
The course of disease is highly characteristic, taking an episodic course of exacerbations and complete remissions (that may last for long periods of time).
Periods of disease exacerbation cause acute disease flares, which tend to resemble previous episodes of acute disease. However the clinical course
of SLE shows great variability, and in some individual's disease may take a chronic course.
Within the first few years of disease, SLE generally falls into a pattern which will generally continue; therefore if severe complications of disease have
not developed by this point, they are unlikely to do so.
SLE preferentially affects females, with a female to male ratio of around 8:1.
A person's racial background influences their likelihood of having SLE, with black people having an increased occurrence of SLE as compared to white people living in the USA. SLE is also more common in residents of the Caribbean.
SLE is estimated to occur in around 40 per 100,000 females.
It has been estimated that cases of SLE have more than tripled over the last four decades, although this may in part be due to increased diagnosis of
Disease can onset at any age, with an average age of between 37 and 50 for white females.
The highly variable nature of SLE makes diagnosis difficult at best, yet a rapid and accurate diagnosis is essential to allow for close monitoring of the disease, and appropriate treatment to prevent the effects of damage to organs such as the liver and kidneys. There is no single test which is able to diagnose SLE.
The diseases pattern of exacerbations and remissions complicates diagnosis, so not only can patients present to the physician with a large range of different
symptoms, but these symptoms may not always be present at any given time in a single patient.
The diverse range of symptoms, and the often non-specific nature of these symptoms (E.G., malaise), may mimic other conditions, because of which SLE often
takes two or more years to be correctly diagnosed, frequently following examination by several physicians.
SLE can be mistaken for such conditions as;
Chronic fatigue syndrome
And many others besides.
A physical examination, serilogical tests and consultation with specialists (if required), should be conducted to provide a swift, accurate diagnosis.
An extensive patient history may be useful in cases not initially identifiable as SLE, symptoms other than those present at the time of consultation can be revealed which may further define the diagnosis.
Among serologic tests, the anti nuclear antibody (ANA), rheumatoid factor (RF) are the most commonly performed to help establish diagnosis,
although this depends largely on which symptoms are initially presented to the physician.
The ANA test is positive in more than 95% of patients with SLE since nearly all of them express antibodies to components of the cell nucleus. Although the ANA is sensitive for SLE, it has low specificity, the test produces both false positive and negative results, most especially false positive test results in individuals who do not have SLE. False positive results can be produced by many other pathologic conditions, including scleroderma, rheumatoid
arthritis, thyroid disease, Sjogren's syndrome, liver disease, hepatitis, infectious mononucleosis, and subacute bacterial endocarditis. A positive result
may also be commonly found in the elderly or during pregnancy, and in many individuals taking any of about 70 different prescription drugs.
The RF test is used to test for rheumatoid factor, and is used to eliminate rheumatoid arthritis as a possible diagnosis.
More specific tests like the anti-DNA antibody test, will normally be performed after testing for anti nuclear antibodies (the ANA test), and testing for rheumatoid factor(the RF test).
SLE: American College of Rheumatology classification criteria
The American College of Rheumatology has developed criteria that provide a standardized system for the classification of SLE (below). Although developed primarily for use in research settings, the classification system can be used as a guide in the diagnostic process, helping clinicians differentiate patients with SLE from those with other connective tissue diseases. However, some manifestations of SLE, such as vasculitis or stroke, are not part of the criteria, and many clinicians believe that these should be incorporated.
At least 4 of these 11 criteria must be present for the
diagnosis of systemic lupus erythematosus to be made, malar rash, arthritis, renal disorder, and abnormal ANA are the most predictive of the disease.
Arthritis with inflammation
Serositis (pleuritis or pericarditis)
Renal disorder, or cellular casts)
Hematologic disorder: leukopenia
Thrombocytopenia, or hemolytic anemia
Neurologic disorder (seizures or psychosis without other causes)
Abnormal antinuclear antibody (ANA) titer
Despite dramatic improvement over the last 10 years in treatment, diagnosis, and most significantly survival rates, it has been estimated that 50% of patients
with SLE still incur permanent damage in one or more organ systems. Survival rates have undoubtedly improved due to advances in treatment, but part of
the increase is probably due to better diagnosis, particularly of patients with milder SLE who are those least likely to suffer the most severe complications
The treatment of SLE should be a multidisciplinary process, reflecting the multitude of variations present within patient populations and in a single patient
during the diseases life-time, constant reappraisal of disease progression, alongside monitoring of treatment, is therefore necessary, as a case that initially
presents with arthritic and skin involvement, may develop to more severe disease, with heart, kidney or central nervous system involvement, which may require
an entirely different treatment regime.
The most commonly prescribed agents in the treatment of milder manifestations of SLE are nonsteroidal anti inflammatory drugs (NSAIDs) and antimalarials.
Non-steroidal anti-inflammatory drugs
NSAIDs are useful for analgesia, fever reduction, and treatment of serositis in SLE.
Persons with SLE experience more NSAID associated side effects (GI, neurological, dermatologic and renal) than healthy people. These medications can cause
renal dysfunction, which in patients with SLE can be mistaken for lupus nephritis.
Drugs such as hydroxychloroquine sulphate and chloroquine phosphate may be used to treat SLE, though only the former is FDA approved for this use. In patients
with non-organ threatening SLE, antimalarials can reduce not only arthritis but also serositis, skin rash, and constitutional symptoms
such as fatigue and fever.
Though generally safe at recommended levels, antimalarial drugs can produce toxicity that may rarely lead to eye abnormalities. Because of this a check-up
every six months (whilst on anti malarial treatments) with an ophthalmologist is recommended.
Cytotoxic drug therapy
Cytotoxic drugs are powerful medicines, that can be used to treat organ involvement in SLE. They operate by affecting the growth and action of some immune cells which cause the joint pain, swelling, warmth, and damage in diseases like SLE and autoimmune forms of arthritis where inflammation is the main cause of organ damage.
Cytotoxic drugs work gradually, it may be several weeks or even months after treatment has commenced before the effect of the drugs is noticed.
The three main cytotoxic drugs used to treat SLE are
Azathioprine (Brand name; Imuran)
Cyclophosphamide (Brand name; Cytoxan)
Methotrexate (Brand name; Rheumatrex)
Cytotoxic drugs are typically given in pill form, but cyclophosphamide is often given by IV injection, and in many areas methotrexate is routinely digiven by injection.
Cytotoxic drugs may cause a range of different side effects, which tend to vary between different people.
At the most severe, side effects may include;
Suppression of white blood cells, leading to more infections than normal.
Platelets can be affected, interfering with the normal blood clotting process, leading to increased tendency for bruising and bleeding.
Red blood cells can be affected, leading to anaemia (extreme tiredness and fatigue), due to a lowering of oxygen carrying capabilities of the red blood cells.
Other, less severe side effects, may include
Loss of appetite
Nausea or stomach pain
Sores or ulcers in the mouth
Missed menstrual periods
Some common myths about SLE
All people with SLE have the malar rash; if you don't have it, you don't really have SLE- Untrue
SLE is a disorder of the "autoimmunity system" (sic) and this immunological defect causes people to be much more susceptible to infections, like with
SLE and fibromyalgia are really the same thing- Untrue
People with SLE cannot have children- Untrue
Only women get SLE- Untrue
Children cannot get SLE- Untrue
Future and conclusions
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. For example, recent research has found
* a new diagnostic test that captures many of the SLE patients who test negative on commonly used tests such as that for the double-stranded DNA antibody
In treatments improvements are occuring rapidly, improved immunosuppressive agents, that target specific immunological proteins rather than suppressing the entire immune system, significantly reduce side effects, as the treatment becomes more targeted to the affected proteins tissues and organs. 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.
A greater understanding of the ways genetic and environmental causes may interact to cause SLE is progressively developing, this greater understanding may lay the path for future as yet unconsidered treatments for SLE based on the cause of SLE on an individual basis
Positive anti double stranded DNA antibodies or anti Sm antibody test, or positive finding of antiphospholipid antibodies based on;
(1) an abnormal serum lipid 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 at least 6 months and confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test.
Hochberg MC, for the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology: Updating the American College of Rheumatology Revised Criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.