Professor Mackay was the first to show that the overproduction of BAFF was driving lupus. In a follow up study, elevated levels of BAFF were discovered in patients with a number of autoimmune diseases including lupus, rheumatoid arthritis and Sjögren’s syndrome.(visit the link for the full news article)
She said this was an exciting discovery as it implied that if BAFF production can be blocked, the entire cascade effect that resulted in autoimmune disease could be prevented.
Lupus and men
It is estimated that for every 10 people who have lupus, only one will be male.
It is often said that men with lupus will be more seriously affected than women, but is this true? Recent studies1 have shown that men with lupus have an increased frequency of seizures, immune-mediated anaemia (low haemoglobin), & lupus anticoagulant (which can lead to blood clots). On the other hand men seem to have a lower frequency of Sjogren's Syndrome, which causes dry eyes & dry mouth. Although men are more likely to have these more serious manifestations, they show up the same in both sexes, i.e. if looking at a man & a woman who have seizures, the man won't necessarily have them worse than the woman.
Do men cope differently? It may be harder for a man to cope with having lupus, because it is often thought of as a women's disease, they may wonder if they are 'less of a man' because they have it, which is certainly not the case. They may also have difficulty in discussing the illness with others, & because there aren't as many men with lupus, they may find it hard to find another sufferer to talk with. Men are often thought of as the bread winner, & if they may feel pressure if they aren't able to work because of their illness. But worrying about such things & getting stressed can make the lupus worse, which leads to being stuck in a viscious circle. This can also lead to problems in their relationships.
Hormones are thought to play a big part in lupus, especially the female hormone oestrogen. Both males & females produce the hormones oestrogen & androgen, but in different quantities. However, it has been shown that men with lupus do not produce abnormal levels of oestrogen. Men with lupus have normal fertility, muscles, hair patterns, voices, etc, they are no less 'manly' than any 'normal' male. More research is needed to determine the role of hormones in lupus.
In 1933, Henrik Sjögren (pronounced show-gren) described some symptoms common to a group of patients - dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), & arthritis. In the late 60s, doctors found that many patients with these symptoms had an autoimmune process. Sjögren's syndrome can be part of many autoimmune diseases, including lupus, or may exist by itself (primary Sjögrens). At least 10% of lupus patients have Sjögren's.
The eyes usually gritty & scratchy, & are sometimes very sensitive to light. A dry mouth can make swallowing dry foods difficult, & can cause tooth decay & dental hygiene problems. Other mucous membranes may be dry including the lining of the stomach and vagina. Joint pains can also be present.
Sjögren's patients often have very high levels of autoantibodies, especially the anti-Ro antibody.
Sjögren's can be diagnosed with the Schirmer's test which involves putting a very small strip of blotting paper in each eye, to measure the amount of tears produced. Another test is the Rose Bengal staining test, which stains the cornea to check for pitting or areas of scarring.
Patients who have both lupus & Sjogren's are more likely to have the autoantibodies anti-SSA/Ro & anti-SSB/La.
Sometimes a lip biopsy is necessary to confirm the diagnosis.
The treatment is usually symptomatic. Dry eyes can be treated with artificial tears, dry mouth with artificial saliva, or just chewing gum or drinking fluids. There has been some evidence to show that Plaquenil (hydroxychloroquine) can be helpful.
Antiphospholipid Antibodies / Syndrome
Antiphospholipid syndrome is also known as Hughes' Syndrome (named after the doctor who discovered it - Dr Graham Hughes).
Patients with antiphospholipid antibodies & certain symptoms are usually diagnosed with Antiphospholipid Syndrome. These patients have an increased risk of thrombosis (clotting) in veins & arteries. It can be present in lupus patients & also non-lupus patients.
The main symptoms of the syndrome are-
Testing for the antiphospholipid antibody
The anticardiolipin (ACA) test measures the actual antibody levels. The three classes of anticardiolipin that are usually tested for are - IgG, IgM & Iga.
Another test, the lupus anticoagulant is a more complicated test & is far less reliable.
The drugs commonly used to treat it are aspirin, Warfarin & Heparin, which help to thin the blood. Aspirin is often given in small doses (75mgs-100mgs daily), this makes the platelets less sticky, which helps to prevent a thrombosis.
Warfarin is usually given to patients who have a larger thrombosis. Warfarin cannot be given to patients who are pregnant, so Heparin is normally used in these cases.
In some patients, anticoagulant therapy is life-long.
Mixed Connective Tissue Disease
Mixed Connective Tissue Disease resembles lupus, it has features of lupus, but also of scleroderma.
It is characterised by four main features -
Raynaud's Phenomenon - Fingers suddenly become cold & turn white, blue, & finally red when circulation returns. The Raynaud's Phenomenon in MCTD is more prominent than in lupus, and is reminiscent of scleroderma.
Prominent arthritis - In MCTD, arthritis is more like rheumatoid arthritis with swelling, especially in the fingers and the fingers become "sausage-like". Other joints may also be involved.
The absence (or rarity) of many general features of lupus, such as kidney disease.
A specific blood test - the anti-RNP - must be positive for a diagnosis of MCTD
There may also be inflammation of the muscles (myositis), with muscle weakness & pain.
MCTD is treated with steroids (low-moderate doses), & some patients respond well to Methotrexate.
What is Scleroderma?
Scleroderma is a chronic autoimmune disease that was first described in the 18th century. The term scleroderma means "hard skin," which describes thickening of the skin from increased deposits of collagen.
There are two types of scleroderma. Localized scleroderma affects the skin in limited areas and the musculoskeletal system. Systemic sclerosis causes more widespread skin changes and may be associated with internal organ damage in the lungs, heart and kidneys. It can cause arthritis, slow contractions in the gastrointestinal tract, muscle inflammation, dry eyes and dry mouth. Most people with scleroderma have cold-induced spasms of small blood vessels in their hands or feet, known as Raynaud’s phenomenon, which caused the fingers or toes to turn white or blue and may be painful.
In most cases, the cause of scleroderma is unknown. However, in a small minority of cases, scleroderma or scleroderma-like illnesses are associated with exposure to certain toxins or as a complication of bone marrow transplants. Scleroderma is not contagious and is rarely inherited.
Systemic sclerosis is associated with over-activation of the immune system, which normally functions to protect the body against cancers and invading infections. This causes damage to cells that line small blood vessels, which in turn leads to the over-production of scar tissue.
The main symptoms-
Diagnosis of scleroderma is based on clinical history and physical findings. Diagnosis may be delayed in those without significant skin thickening. Laboratory, X-ray and pulmonary function tests determine the extent and severity of internal organ involvement.
There is no known cure for scleroderma. No treatment has been scientifically proven to alter the overall course of the disease, although d-penicillamine is commonly used for this purpose and may be of some value.
There are a number of effective organ-specific treatments for scleroderma. Raynaud’s phenomenon may be helped by calcium channel blockers. Declining renal function and hypertension are often treated with drugs. Esophageal damage from reflux of stomach contents can be treated with acid-reducing drugs. Antibiotics, special diets and medication can improve absorption of nutrients in people who have abnormalities of their intestines. Musculoskeletal pain may respond to nonsteroidal anti-inflammatory agents. Lung inflammation may be treated with cyclophosphamide.
Physical and occupational therapies are used to minimize joint disability and functional impairment.
The Scleroderma Foundation can be reached at .
From the American College of Rheumatology factsheet
Fibromyalgia is a pain-amplification syndrome characterised by widespread stiffness & aching.
About 20% of lupus patients have fibromyalgia, but it can occur on its own.
Irritable bowel syndrome
Cognitive dysfunction (memory problems)
To be diagnosed with fibromyalgia, one must have tender points in at least 11 of 18 designated points on the body. Changes in steroid doses can aggravate fibromyalgia, & also patients who are taking corticosteroids develop increased sensitivity to pressure applied to their skin. Therefore it is important to differentiate active lupus from fibromyalgia.
Treatment consists of getting restful sleep, pacing yourself, moist heat, gentle massage & gentle exercise. Medications such as NSAIDs, muscle relaxants & tricyclic antidepressants can also be used.
Drug-induced lupus comes on suddenly in a small number of people taking certain drugs. It mimics SLE, causing joint pains, skin rashes , fatigue & other SLE symptoms.
The main drugs implicated in drug-induced lupus are-
Other drugs that may cause drug-induced lupus include Quinidine, anticonvulsants, beta blockers, & minocycline.
Drugs such as Septrin, ibuprofen, sulfa drugs, don't cause drug-induced lupus as such, but they can exacerbate true underlying lupus, & cause lupus flares.
Drug-induced lupus is different from true lupus in that blood tests are different, heart, lung & kidney involvement is rare. Most patients don't fulfill the criteria for SLE. The symptoms stop when the drug is discontinued, although it can sometimes take up to a few weeks for them to disappear completely.
Some conditions resembling or accompanying Systemic Lupus Erythematosus -
Hardening of the skin caused by overproduction of collagen
Fatigue, heaviness or clumsiness in the arms and legs
Symmetrical joint pain. Also an autoimmune disease and sometimes occurs with SLE
Characterized by dry, scaly skin
Mixed connective tissue disorder
Very similar to SLE, but milder
Inflammation and degeneration of muscle tissues
Lesions are pus-filled blisters and do not atrophy
Skin lesions on lips and nose
Affects mucous membranes
Affects mucous membranes
Causes bluish-red skin eruptions on face and upper body, accompanied by swelling
There is currently no single test that can definitely say whether a person has lupus or not. There are three different types of lupus - Discoid(cutaneous) lupus, Systemic lupus & Drug-induced lupus.
Lupus and infections
Patients with lupus are more susceptible to infections because they have altered immune systems, and also because many patients are on treatment (steroids & cytotoxics) that suppresses immune system function, leaving them more prone to infection.
Lupus patients who get infections frequently show worse clinical signs, & require longer treatment than non-lupus patients.
The most common bacterial infections seen in lupus affect the respiratory tract and the urinary tract. Septic arthritis, tuberculosis, salmonella, cold viruses, & shingles are also more common. The most common fungal infection seen in lupus is candida (thrush).
It is important to distinguish between a lupus flare and an infection. Fever and decreased energy are symptoms that are associated with both infections and lupus flares. Any lupus patient who exhibits symptoms that could be an infection or flare should contact her physician. Blood tests such as a white cell count can help to distinguish a flare from an infection.
Patients at high risk of infection should probably take antibiotics before surgical or dental procedures.
Lupus patients should try to minimise their exposure to people who have colds, 'flu, and other infections, although this is easier said than done!
Lupus patients should probably avoid the antibiotics penicillin and septrin (sulfa), as they may exacerbate lupus, and many lupus patients are allergic to them.
It has been previously thought that lupus patients should avoid immunisations because they could exacerbate lupus. However, the vaccine for influenza has now been shown to be safe and effective; the pneumococcal vaccine is also safe, but resultant antibody levels are somewhat lower in patients with SLE. It is not advisable for patients receiving steroids or cytotoxic therapy to have live vaccines, because these drugs cause immune suppression that may promote infection.
Some patients who receive allergy shots (immunotherapy) will have a flare following this treatment. In 1989, the World Health Organisation recommended that patients with autoimmune diseases should not receive allergy shots. Lupus patients should always consult their rheumatologist before receiving immunotherapy.
Genetics in Lupus
In this article, "lupus" will mean systemic lupus erythematosus. The most common symptoms of lupus are fever, rash, and arthritis. Women tend to develop lupus more commonly than men, and people of African descent develop lupus more commonly than people of European descent.
Lupus is only one of many "auto-immune" diseases. "Auto" means that the body has an immune reaction against itself. Rheumatoid arthritis and scleroderma are also auto-immune diseases.
Given that lupus, rheumatoid arthritis, and scleroderma are all auto-immune disorders, how do physicians tell them apart? The answer is surprisingly old-fashioned. In the case of lupus, physicians compare the patient's symptoms and blood tests to a list of 11 criteria that experts agreed on in 1982. If the patient's data match 4 or more of the criteria, a diagnosis of lupus can be made.
Can lupus run in families?
Yes. This was first observed in the 1950s. More recent studies show that the brother or sister of a lupus patient is 25 times more likely to develop lupus than someone in the general population.
When lupus runs in families, is the reason genes or environment?
As in most human disease, the answer appears to be "both." Lupus has strong genetic components. It has environmental components as well.
What genes are involved in lupus?
In 95% of cases, genetic susceptibility to lupus is not caused by a single gene. Multiple genes are involved. Identifying them has been slow because different genes seem to be at work in different ethnic groups.
Because lupus is an auto-immune disease, scientists first studied genes that control the immune system. The HLA family of genes, all located on the short arm of chromosome 6 , are important controllers of the immune system. They are divided into 3 classes:
Less than 5% of patients with lupus owe their genetic susceptibility to a single gene. Many of these genes relate to the body's "complement system." The complement system is part of the immune system.
What environmental factors are involved in lupus?
It has been difficult to pin down the environmental components of lupus. The following factors are the best known:
When lupus runs in families, why don't all family members have it?
It helps to frame this question a little differently.... All members of a family do not have the same height, weight, and face. So, it makes sense that they don't all have the same conditions and diseases -- or the same susceptibility to various diseases.
Here again, it's genetic and environmental differences that explain differences in our appearance and health. Some family members will inherit genes that predispose to lupus, and others will not. Some family members will be exposed to environmental agents that trigger disease, and others will not.
There is no lupus in my family. Does this mean it will never occur in my family?
No. Anyone can develop lupus. About 90% of people with lupus do not have an immediate family member with lupus. But if someone in your family does have lupus, you are at greater risk.
How will discoveries about DNA help people and families with lupus?
Further discoveries about lupus genes will lead to more individualized medicine. Prevention, diagnosis, treatment, and prognosis will be personalized, based largely on the strengths and weaknesses found in a person's genes.
Several medicines have been approved to treat lupus. How does your physician know which is best for you? Part of the answer may be in your genes.
Whenever scientists discover a gene involved in lupus, it's a doorway to designing new treatments. If the gene is over-active, then scientists can look for ways to turn it off or interfere with its activity. If the gene is under-active or broken, then scientists can look for ways to turn it on or increase its activity.
Prevention, diagnosis, andArticle by DNA Sciences
Osteoporosis and Lupus
Many lupus patients take steroids, and one of the major side effects is osteoporosis. This article is based on a talk given to the Lancashire & Cheshire Lupus Group, by Dr Kilmiuk, consultant rheumatologist.
Osteoporosis is a decrease in bone mass, which causes an increased susceptibility to bone fractures. It is most common in postmenopausal women, but patients who are on steroids are at a greater risk at any age.
However steroid treatment in lupus is often lifesaving, and shouldn't be stopped just because there is an increased risk of osteoporosis. There are things that can be done to reduce your risk of getting osteoporosis, which we will look at later.
The definition of osteoporosis is a condition that affects the skeleton, with thinning of the bone, accompanied by an architectural change in bone structure.
The most common sites of fracture in osteoporosis patients are the vertebrae, hip and wrist. Although any bone in the body can be fractured as a result of osteoporosis. In the UK, there are 250,000 fractures to due osteoporosis annually, 50,000 of which are hip fractures. Hip fractures are the ones with the most severe consequences, and are most associated with mortality. If you have one vertebral fracture, there is a 50% risk that you will have another within a year. If you sustain more than one vertebral fracture, curvature of the spine can occur. 20% of those that suffer hip fractures will die due to complications.
Corticosteroids are live-saving drugs, and are used widely for many conditions, including lupus. An estimated 140,000 people in the UK are taking steroids, and have double the risk of a hip or vertebral fracture due to osteoporosis. 80% of those people don't take any preventative treatments. You need to take over 7.5mg of prenisone/prednisolone a day for more than six months before it has an adverse affect on the bones.
Throughout our lives, our bones are alive and have a blood supply, they may stop growing, but they are still living. We replace our whole skeleton every seven years! Cells in the body eat holes in bones, which are usually replaced by new bone.
However, in osteoporosis more bone is eaten away than is replaced, and we are left with a lower bone density. In our early 20s we stop growing, and the skeleton goes through a resting phase. The in our late 30s, we slowly start to lose bone. When we reach the menopause, our oestrogen levels drop, and there is a rapid decline of bone mass. Then, after 10 years, the rate of bone loss evens out and is equal to the level of bone loss in men.
Risk factors for osteoporosis include: being female; being Caucasian; a family history of osteoporosis; smoking; heavy alcohol intake.
So how is osteoporosis diagnosed? X-rays can't measure bone density, so a DEXA machine is used. DEXA machines don't deliver high-dose radiation like x-rays do, and they can measure the bone density. There is no need to scan the whole body, only a small part, as bone density should be the same throughout the body. The most useful areas to scan are the lumbar spine & the hip.
The key to preventing osteoporosis is to enhance the amount of bone we have in the growing period. We can then afford to lose the bone when we reach the menopause. It is better to start preventative measures when we are children, but later is better than never! You should eat a good balanced diet that includes plenty of calcium-rich foods. Dairy produce is the best source of calcium, and skimmed milk contains as much calcium as whole-fat milk. A good vitamin D intake is also needed, as vitamin D helps the body to absorb calcium. Exercise is also very important, bones need constant weight-bearing exercise.
HRT can help, as it replaces oestrogen, which in turn stops the bone loss. After 10 years of taking HRT there is an increased risk of breast cancer, although this is thought to be an acceptable risk compared to the high possibility of a fatal bone fracture. Plant derived oestrogens do exist, but have not been proven to provide enough oestrogen.
The use of HRT in lupus patients is controversial, as oestrogen is thought to play a part in triggering lupus flares. However, all HRT does is replace the natural level of oestrogen in the body that was there prior to the menopause. So you have no more oestrogen in your body than you did before the menopause. There is no scientific evidence to say that HRT makes lupus worse.
A group of drugs called Bisphosphonates can be used to treat osteoporosis & improve bone mass. One such drug is called alendronate.