Systemic Lupus Erythematosus (SLE)

Lupus is a chronic autoimmune disease which can cause inflammation in tissues and organs throughout the body. The full medical name for the condition is Systemic Lupus Erythematosus (SLE) but it is usually referred to simply as 'lupus'.

Unlike many autoimmune conditions which affect a specific organ (e.g. autoimmune thyroiditis), lupus affects many different parts of the body including the skin, joints, heart, lungs, blood, kidneys and brain. This is due to the fact that in lupus the body's immune system attacks proteins present in the nucleus of every cell in the body rather than proteins that are specific to cells of a particular type.

To explain a little further, an autoimmune condition is one in which the body's own immune system becomes "confused" and begins to attack the body itself rather than invading pathogens such as viruses, bacteria, and fungi. Autoimmune conditions are similar to allergic conditions in that the immune system is attacking substances it should not be. In allergic conditions it is harmless foreign substances such as pollen that are targeted where as in autoimmune conditions the patients own body is the target.

The result of the immune system dysfunction in lupus is widespread inflammation and this is considered the primary feature of the disease. In most cases, lupus is a mild disease that only affects a few organs. In some patients however the disease can become life-threatening if critical organs are severely damaged by the inflammatory process. Thankfully, this situation is now very rare as a result of better diagnosis and treatment.

According to the Lupus Foundation of America epidemiological data on lupus suggests that there are over 16,000 new diagnoses of lupus in the US each year. Estimates of the total number of Americans who suffer from lupus range from 270,000 to 1.5 million. Meanwhile Lupus UK state that there are more than 50,000 people with lupus in the United Kingdom. These figures make lupus more common than much more well known diseases such as leukaemia, multiple sclerosis, cystic fibrosis, and cerebral palsy.

Lupus can affect anybody but the distribution is somewhat uneven. The disease is much more common in women, especially those of childbearing age, with ratio of women to men being around 9:1. The disease also appears to be more prevalent in women of African, Asian, Hispanic and Native American origin but the degree to which this is due to genetics or socioeconomic factors is unknown.

Symptoms

Joints and Muscles:

• pain
• swelling
• tenderness
• a feeling of warmth
• fluid collection
• Avascular Necrosis - death of bone due to loss of blood supply which can occur in patients on long-term steroid therapy
• Osteoporosis

Skin:

Skin problems that only occur in lupus:

• chronic cutaneous LE (CCLE), also called discoid LE (DLE)
• subacute cutaneous LE (SCLE)
• acute cutaneous LE (ACLE).

Skin problems that can occur in lupus but may also be a sign of other conditions:

• Mouth/Nose ulcers
• Malar Rash/Butterfly Rash - so called as it forms a butterfly shape over the bridge of the nose and cheeks
• Discoid Rash - thick scarring, can be raised or flat, red, with well-defined borders
• Hairloss
• Hives
• Raynaud's Phenomenon - fingers, feet, tip of the nose & outsides of the ears turn red, white and blue in response to stress or cold
• Purpura - black and blue marks that appear as blotches under the skin resulting from abnormal blood coagulation
• Livedo Reticularis - a disorder in which blood vessels are constricted, or narrowed resulting in mottled discolouring on large areas of the legs and arms

Many of the skin conditions associated with lupus are due to the photosensitivity which occurs in the disease.

Central Nervous System:

• Depression
• Cognitive Dysfunction - poor memory, concentration etc
• Lupus Headache - a migraine-like condition
• Seizures
• CNS Vasculitis - inflammation of blood vessels in brain and CNS
• Psychosis

Blood:

• Anaemia - low red blood cells
• Thrombocytopaenia - low blood platelets
• Leukopaenia - low white blood cells

Organ Complications:

• Pericarditis - inflammation of the sac that surrounds the heart
• Myocarditis - inflammation of the heart muscle
• Endocarditis - inflammation of the inner lining of the heart
• Coronary Artery Problems
• Kidney Problems
• Serositis - inflammation of the delicate tissues covering internal organs
• Pneumonitis - inflammation of the lungs
• Chronic Diffuse Interstitial Lung Disease - chronic lung inflammation
• Pulmonary Embolism - sudden bloackage of artery in the lunga
• High Blood Pressure
• Liver Problems

Gastrointestinal:

• Nausea
• Weight loss
• Abdominal pain
• Diarrhoea

Eyes:

• Conjunctivitis - inflammation of tissues around the eyeball
• Iritis - inflammation of the iris
• Dry Eyes

Other Symptoms:

• Fatigue
• Fever
  

Diagnosis

The diagnosis of lupus is arrived at after consideration of symptoms and medical history, physical examination, and lab test results.

Diagnostic criteria developed by the American Rheumatism Association are in widespread use for the diagnosis of the condition. To make a diagnosis of Lupus the patient must have had at least FOUR of the following 11 manifestations at any time since the onset of the disease:

1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Mucosal ulcers
5. Serositis
6. Arthritis
7. Renal disorders
8. Neurological disorder
9. Blood disorders
10. Immunologic disorder
11. Anti-Nuclear Antibody (ANA blood test)

Lupus is sometimes offered as a dual diagnosis with condtions that share similar signs and symptoms such as Fibromyalgia and Rheumatoid Arthritis.

Diagnosic Tests

There are a number of laboratory tests that can be carried out to help confirm a diagnosis of lupus. The most important of these is the anti-nuclear antibody (ANA) test which can be used as a specific diagnostic marker but other tests can also be useful.

Anti-Nuclear Antibody (ANA) Test
This is a blood test which looks for anti-nuclear antibodies which are antibodies produced by the immune system which attack the cell nucleus. The nucleus is the control centre of every cell where the DNA is stored. It is estimated that 95%-98% of patients with lupus will have a positive ANA test. The presence of anti-nuclear antibodies is not unique to lupus however as they are also present in patients with other diseases such as rheumatoid arthritis, Sjogren's Syndrome, and scleroderma. It is possible however for the ANA test to be a fairly reliable predictor of lupus as the autoantibodies present in the condition attack the nucleus in a specific manner which can be seen when a patient's blood is viewed under a microscope. To confirm a diagnosis of lupus however, doctors usually run further tests and consider a patient's medical history and results of physical examination.

Anti-DNA and Anti-RNA Antibody Tests
These blood tests are used to detect antibodies that specifically target DNA and RNA, the gentic material held in the nucleus of cells.

Anti-Smith Antibody Test
Another blood test which is used to detect antibodies that target another specific protein in the nucleus of cells. The anti-smith antibody is found only in lupus.

Patients who test positive on all of these blood tests are usually considered to have lupus without further confirmation being required.

Causes of Lupus

Much is known about the etiology of lupus since it has been shown to be an autoimmune infmmatory condition and specific antibodies are known to be involved. The issue of what causes lupus to develop however is less clear. The main factors thought to contribute to the onset of the disease are discussed here.

Genetics
Most researchers feel that it is likely that there is a genetic component to lupus. The condition can be considered hereditary in that people who have a family history or lupus itself, other autoimmune condtions, or allergic conditions, seem to be at increased risk of developing the disease. This is not to say that everyone with a family history such as this will develop lupus. Researchers have not discovered a single gene that is linked to lupus but have found groups of genes, particularly on chromosomes 6, 16 and 20, which seem to indicate a person is at greater risk of developing the condition.¹

Environmental Factors
Environmental factors are also thought to play a major role in the development of lupus and the exacerbation of symptoms once the disease is established. Of particular interest to researchers is the role of sunlight since photosensitivity is such a major symptom and sun exposure is thought to be the initial trigger in a substantial number of cases.² The UV radiation from the sun has been demonstrated to photosensitive lupus rash, known as malar rash or the butterfly rash. There is also some evidence that UV radiation is capable of altering the structure of the DNA, leading to the creation of autoantibodies.

Other environmental factors implicated in lupus include stress and exposure to chemical pollutants such as cigarette smoke, traffic pollution, water contaminated with chemicals such as trichloroethylene, and silica dust. One study found that environmental pollution and industrial emissions increased the risk of people developing lupus.³

Some researchers have sought to find a link between infectious agents such as viruses and bacteria but a single pathogen has not been identified thus far. People infected with viruses such as cytomegalovirus and hepatitis B may eventually develop lupus however. Additonally, Epstein-Barr virus (EBV) has classically been linked to triggering the development of lupus.⁴ EBV is a common viral infection that often does not causes symptoms. It is however also implicated in chronic fatigue syndrome (CFS).

Medications
Certain drugs are known to cause a specific type of lupus known as Drug Induced Lupus. Rather than being caused by autoantibodies drug inducled lupus simply mimicks the symptoms of SLE and is the result of side-effects from certain drugs, particularly those that are taken long term. Many drugs (up to 400 )have been known to cause this condition but the main culprits tend to be those used to treat chronic conditions such as coronary heart disease and hypertension (high blood pressure) , thryroid disease, psychiatric/mood disorders, and other inflammatory conditions. There are three drugs in particular that are known to pose a high risk for the development of drug induced lupus and they are procainamide (Pronestyl) which is used to treat heart arrythmias, hydralazine (Apresoline) which is used to treat hypertension, and quinidine (Quinaglute) used in the treatment of heart arrythmias. The symptoms of drug induced lupus disappear once the culprit medication is stopped.

Hormones
The research in this area is presently rather sketchy but nevertheless the involvement of hormones in the onset of lupus cannot be ruled out. Many researchers involved with autoimmune conditions believe that there is a link to hormonal factors. In light of this a handful of studies have been conducted looking for a correlation and some have found that high levels of estrogen (for example during pregnancy) increase the risk for development of lupus. Other researchers have found abnormalities in the way the receptors for estrogen work in lupus patients.⁵ Given this and the fact that substantially more women than men are affected by lupus, estrogen metabolism is considered a risk factor for the disease.

Poor Clearance of Old Cells
Another mechanism that could explain the development of lupus involves impaired clearance of dead and dying cells. When cells come to the end of their lives they are usually removed from the body efficiently through a process called phagocytosis involving immune cells. Two of the most important of these immune cells are monocytes and macrophages, both of which show abnormalities in lupus patients. Furthermore, other components essential for removal of old cells, such as complement factors and glycoproteins, have been found to be deficient, missing entirely, or otherwise functioning abnormally. It has been suggested that autoimmunity may develop as a result of the immune system being exposed for longer periods to nuclear material from dead and dying cells that are not disposed of efficiently.

Treatment of Lupus

Since there is currently no known cure for lupus treatment involves controlling symptoms which tend to wax and wane with periodic acute attacks known as 'flares'. A number of approaches may be taken to control symptoms during flares using both conventional and alternative medicine. If a patient is aware of the signs that a flare is approaching and have a good relationship with their healthcare provider then the worst symptoms can often be avoided by initiating appropriate treatment early. Common treatments for lupus are discussed below.

Conventional Medicine
Doctors prescribe a variety of different medications to treat the symptoms of lupus and these work in a number of different ways. The main classes of drugs used in lupus are:

Non-steroidal anti-inflammatory drugs (NSAIDs) - a class of drugs used to fight pain through their anti-inflammatory action. NSAIDs are typically used in lupus patients who suffer mainly from joint and muscle pain. A well known example of an NSAID is aspirin.

Anti-Malarials - a class of drugs approved for patients with moderately active lupus who have predominant joint and skin symptoms. They may also be of some use in treating the fatigue associated with the disease. Hydroxychloroquine (Plaquenil) is the most commonly used anti-malarial drug for lupus having anti-inflammatory actions, some sun-protective features, and some blood thinning actions to help prevent clotting. This class of drugs may be sufficiently effective in some patients to reduce the need for the use of steroids which have more serious side-effects.

Corticosteroids - are a well-known class of drugs that suppress the immune system in higher dosages and therefore are highly effective at reducing inflammation. These drugs are used in severe cases of lupus where there is the possibility of organ damage and can therefore be life-saving. They have been instrumental in virtually eradicating fatalities from the disease. Unfortunately corticosteroids frequently produce quite severe side-effects so their use is limited to severe cases of the disease or particularly bad flares and safer alternatives such as anti-malarials and NSAIDs are used where possible. Side-effects from steroid use frequently include weight gain, diabetes and osteoporosis. The most widely used corticosteroid drug is prednisolone.

Immunosuppressants - are often used, either alone or in combination with corticosteroids for very active lupus, particularly when kidney or neurologic involvement or acute blood vessel inflammation is present. Like corticosteroids, this class of drugs suppresses the immune system but in this case does so by damaging rapidly growing cells, including those that produce the antibodies responsible for the symptoms of lupus. It has been estimated that around a third of lupus patients takes immunosuppressants during the course of their illness. Also like corticosteroids, immunosuppressants also have various side-effects which range from digestive upset and skin rash to high blood pressure, infertility and anemia. Common immunosuppressants include Mycophenolate mofetil (CellCept) and Cyclosporine (Sandimmune).

Other Drugs - may include powerful prescription painkillers including opiates such as oxycodone (OxyContin), anti-depressants such as Prozac, and anto-coagulants such as Warfarin.

Complementary and Alternative Medicine

There are a number of natural treatment options that may be beneficial to lupus patients either in combination with standard drug therapies or as alternatives. Some of the most well documented include:

Omega-3 Essential Fatty Acids (EFAs) - the ability of these EFAs which include EPA and DHA primarily from fish, and ALA from plant sources such as flaxseeds, to reduce inflammation and effectively treat inflammatory conditions has been well demonstrated. EFAs are used by the body to produce a group of chemicals called eicosanoids. Omega-3 EFAs produce a specific types of eicosanoids that have powerful anti-inflammatory actions. In one preliminary trial, nine lupus patients who had suffered kidney damage as a result of the disease were given increasing amounts of flaxseed over a period of 12 weeks. The researchers found that 30g per day significantly decreased inflammation, improved kidney function, and reduced the development of artherosclerosis.⁶ In a double-blind placebo controlled trial, 20g per day of fish oil combined with a low-fat diet for 12 weeks resulted in improvement in 14 out of 17 lupus patients.⁷

Dehydroepiandrosterone (DHEA) - the most abundant steroid hormone produced in the body. DHEA is thought to have many benefits including helping us deal with stress, maintaining blood sugar balance, and balancing the immune system. It is thought to provide a counter-balance to many of the negative effects of cortisol and other corticosteroids. It is currently being investigated as a treatment for a number of conditions such as depression, diabetes, obesity, and chronic fatigue syndrome. Low blood levels of DHEA have been associated with more severe symptoms in people with lupus.⁸ Initial research studies have found have suggested that dosages of 50 to 200mg per day of DHEA may improve symptoms in people suffring from lupus.9 DHEA at a dosage of 200mg per day was found to improve symptoms and allow a decrease in prednisone use in a double-blind placebo controlled trial of women with mild to moderate lupus. DHEA is available as a dietary supplement without a prescription but many have concerns about its safety, particularly at the high dosages used in the trials discussed here. There is no long-term safety data available on DHEA and reported side-effects include acne, increased facial hair, weight gain, mood swings, headache, oily skin, and menstrual irregularity.¹⁰

Antioxidants - those suffering from lupus have been found to have deficiencies of various antioxidant nutrients and increased oxidative stress as a result. Animal studies have found that supplementation with antioxidants including vitamin C, vitamin E, beta-carotene, and selenium are effective at treating systemic lupus but it is not known whether this holds true in humans.¹¹ Both vitamin E and vitamin A (as beta-carotene) have shown effectiveness in Discoid Lupus Erythematosus (DLE), a mild form of the disease which mainly presents with skin symptoms. Doctors have reported significant positive results from supplementation of 800-2000IU of vitamin E per day in DLE patients.¹² One preliminary study found that all malar rashes cleared up completely in DLE patients given 250,000 IU beta-carotene per day in less than one week.¹³ Studies of antioxidants in systemic lupus are currently lacking.

Dietary Interventions - low calorie diets that are low in fat and the amino acids phenylalanine and tyrosine (found mainly in high protein foods such as meat and dairy products) may be helpful in lupus according to initial research in both animals and humans.¹⁴ Lupus is known to be associated with an increased incidence of allergies and some researchers have found that allergies, including food allergies, are more common in lupus patients than even people with other autoimmune conditions.¹⁵ A number of studies have found particular foods that appear to be a problem for lupus patients including beef¹⁶ and dairy products¹⁷ and patients appear to improve when these foods are removed from the diet. Many doctors recommend that patients undergo allergy testing to identify specific problem foods. Casein, a protein found in milk, is known to have immune-stimulating actions so may also exacerbate the symptoms of lupus through this mechanism.¹⁸ In addition, a diet high in fish, flaxseeds and other sources of omega-3 EFAs may be beneficial for the reasons discussed previously.

Tripterygium wilfordii - is a Chinese herb that has shown promising results in treating lupus. It's thought it may be useful due to its anti-inflammatory and immunosuppressant activities. In one study a group of 18 DLE patients were given 30 to 45g of tripterygium per day for two weeks with most experiecing some level of improvement Improvements in skin rashes were particularly impressive, completely clearing up in eight people and improving by at least 50% in a further ten.¹⁹ In another study patients with systemic lupus were given the same dose of 30-45g per day and after one month 54% reported experiencing relief from symptoms such as joint pain and fatigue.²⁰ It is recommended that anyone wishing to use tripterygium do so under the supervision of an experienced herbalist as side-effects from long-term use include increased risk for osteoporosis. It is also recommended that pregnant women do not use this herb.

UVA1 Phototherapy - rather unexpectedly given that photosensitivity is a major symptom of lupus and sun exposure is known to trigegr and worsen symptoms, it has been found that long-wave ultraviolet radiation (UVA1) has beneficial effects on the disease. First reported in the late eighties after studies on mice researchers have now shown that UVA1 phototherapy using special lamps can indeed relieve the symptoms of lupus in humans.²¹ UVA1 devices are available for the treatment of lupus in many European countries but have not yet been approved in the United States.

References

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