Lupus

What causes lupus?

SLE is an autoimmune condition, meaning it comes from problems within the immune system. For reasons that are not fully understood, the immune system in people with SLE begins to attack and inflame healthy cells, tissue and organs.

As with other more common autoimmune conditions, such as rheumatoid arthritis, experts believe a combination of genetic and environmental factors may be responsible for triggering SLE in certain people.

Read more about the causes of lupus below.

Who is affected

SLE is an uncommon condition, and around 90% of cases occur in women. It is most common in women of childbearing age (between 15 and 50), though it can affect people of other ages too.

The condition tends to be less common in people of white European origin and more common in those of African, Caribbean or Asian origin.

Causes of lupus

Systemic lupus erythematosus (SLE) is an autoimmune condition, meaning it is caused by problems with the immune system.

The immune system is the body's natural defence against illness and infection. When it detects an infectious agent, such as bacteria or a virus, it sends white blood cells and antibodies to attack it.

In cases of SLE, antibodies released by the immune system end up attacking healthy tissue, cells and organs instead.

It is not clear exactly why this happens, though most experts believe SLE has more than one cause. It has been suggested that a number of genetic factors may make people more susceptible to the condition, and that one or more environmental factors are then needed to trigger SLE in those who are already susceptible.

The possible genetic and environmental factors are discussed in more detail below.

Genetic factors

Brothers and sisters of people with SLE are much more likely to develop the condition than the general population.

Researchers have identified a number of genetic mutations that seem to make people more susceptible to developing SLE. A genetic mutation happens when the normal instructions carried in certain genes become scrambled, so that the body's processes stop working as they should.

Most of the faulty genes involved are linked to regulating certain functions of the immune system, which may help explain why the immune system in people with SLE starts to malfunction.

Environmental factors

A number of environmental factors may be responsible for triggering SLE in people who are vulnerable to it, although the evidence for many of these remains limited.

Possible environmental factors that have been suggested include:

• exposure to sunlight (ultraviolet light)
• hormonal changes that occur during a woman's life, such as during puberty or pregnancy
• certain infections, such as the Epstein-Barr virus (EBV), a common viral infection that usually does not cause any symptoms
• smoking

Lupus, or systemic lupus erythematosus (SLE), can be hard for doctors to diagnose because its symptoms look so much like those of several other, far more common illnesses. Making things harder still, the symptoms do not stay the same from one person to another, and they can also change over time in the same person. There may be stretches when you barely notice anything wrong, followed by flare-ups when symptoms become much more severe.

Because of this, a doctor will only feel confident diagnosing SLE once you have shown several of its typical symptoms, and a number of blood tests will usually need to be done as well.

One of these is the erythrocyte sedimentation rate test, often called ESR, which helps show whether there is inflammation somewhere in your body. This matters for lupus because the condition can cause swelling in many parts of the body, including the joints and internal organs. The test simply measures how quickly red blood cells settle to the bottom of a test tube. The faster they settle, the more likely it is that inflammation levels are high.

Another test looks for anti-nuclear antibodies in the blood. About 95 percent of people with SLE carry this antibody, so its presence is a useful clue. Even so, it is possible to have this antibody without having lupus at all, so this test alone cannot confirm the diagnosis, and further blood tests are needed alongside it.

A related test checks for anti-DNA antibodies. If these are found, it is highly likely that lupus is present, though this antibody shows up in only around 70 percent of people who have the condition, so a negative result does not rule it out. The amount of anti-DNA antibody in the blood tends to rise when lupus is more active, so during a flare-up your result from this test may come back higher than usual.

Doctors may also test your complement level. Complement is a group of chemicals in the blood that form part of the immune system, and measuring it gives a sense of how active your lupus is at that moment, since complement levels tend to fall when the disease is flaring.

Once lupus has been diagnosed, you will usually need to be monitored regularly to keep track of how it is affecting your body. Because SLE can sometimes lead to other problems, such as kidney trouble, this ongoing monitoring allows your doctor to catch any such complications early and treat them promptly if they arise. As part of this, you may be asked to have scans such as an X-ray, an ultrasound, an MRI, or a CT scan, to see whether lupus is affecting any of your internal organs. You can read more elsewhere about the possible complications of lupus.

There is currently no cure for SLE, but a number of medicines can ease many of the symptoms and lower the chances of organ damage.

These medicines include:

• hydroxychloroquine, a medicine that has long been used to treat malaria and also helps with some symptoms of SLE
• corticosteroids, which are anti-inflammatory medicines
• immunosuppressants, a group of medicines that calm down an overactive immune system

With good support from family, friends and healthcare professionals, many people with SLE learn to manage their condition well and continue living full lives.

Read more about treating lupus below.

Treating lupus

There is currently no cure for systemic lupus erythematosus (SLE), but treatments are available that ease symptoms and make daily life easier. In most cases, treatment combines self-care with medicine.

Protecting yourself from the sun

Sunlight can sometimes make symptoms such as skin rashes worse, so it is important to protect your skin when you are outdoors. This means wearing clothes that cover your skin, a wide brimmed hat and sunglasses, and applying a sunscreen with a high SPF to prevent sunburn. That said, some people with lupus are not affected by sunlight and do not need these extra precautions.

Since most people get their vitamin D from direct sunlight on the skin, avoiding the sun can put you at risk of not getting enough of this vitamin. Because of this, you may need to make a special effort to include good sources of vitamin D in your diet to avoid problems such as osteoporosis, or weakened bones, and your doctor may advise you to take vitamin D supplements.

Non steroidal anti-inflammatory drugs (NSAIDs)

Non steroidal anti-inflammatory drugs, or NSAIDs, are common painkillers that also reduce inflammation in the body. If SLE is causing joint or muscle pain, your doctor may suggest an NSAID to ease these symptoms.

Commonly prescribed NSAIDs for SLE include ibuprofen, naproxen and diclofenac.

Some NSAIDs, such as ibuprofen, can be bought without a prescription and may be enough if your joint or muscle pain is mild. For more severe pain, you will need a stronger medicine prescribed by your doctor.

NSAIDs may not suit people who have, or have had, problems with their stomach, kidneys or liver, and they may not be suitable for people with asthma either. Your doctor will help you find the NSAID that is right for you.

Side effects

Taken in high doses or over a long time, NSAIDs can damage the lining of your stomach, which may lead to internal bleeding. If you need to take NSAIDs long term, your doctor will monitor you closely for any problems, and may also prescribe an additional medicine called a proton pump inhibitor, or PPI, to protect your stomach.

Side effects from hydroxychloroquine are uncommon, but can include indigestion, diarrhoea, headaches and rashes. In rare cases it can also cause more serious side effects, including eye damage. If you notice any changes in your vision while taking hydroxychloroquine, contact your doctor or specialist right away. Depending on your situation, your doctor or specialist may also recommend regular eye check ups.

When corticosteroids are prescribed, doctors always use the lowest dose that will work, because high doses or long term use can bring side effects such as:

• thinning of the bones
• thinning of the skin
• weight gain
• high blood pressure, also called hypertension

Corticosteroids are a safe and effective treatment when taken correctly and under the care of your doctor or specialist, who will adjust the dose to how active your condition is, so it is controlled well while keeping side effects to a minimum.

Immunosuppressant medicines are usually only given for severe SLE, since they are powerful and can bring side effects such as:

• loss of appetite
• vomiting
• diarrhoea
• swollen gums
• bruising or bleeding more easily than usual
• headache
• acne
• extra hair growth
• weight gain
• liver damage
• a higher risk of infection, discussed further below

Methotrexate, mycophenolate mofetil and cyclophosphamide can cause birth defects if taken during pregnancy, so it is important to use reliable contraception if you are taking these medicines and are sexually active. If you are hoping to become pregnant, your doctor may switch you to an alternative such as azathioprine.

Let your doctor know if any side effect becomes hard to bear, since your dose may need to be adjusted.

Common side effects of rituximab include flu like symptoms such as chills and a high temperature, dizziness and vomiting. In rare cases, it can cause a more serious allergic type reaction. Since most reactions happen during or soon after treatment, you will be watched closely once your treatment begins.

Common side effects of belimumab include:

• flu like symptoms such as chills and a high temperature
• nausea and diarrhoea
• headache
• difficulty sleeping, or insomnia
• a cough, sore throat and a blocked or runny nose
• joint pain
• a higher risk of infections
• changes in blood pressure

In rare cases, belimumab can also cause a more serious allergic type reaction. As most reactions occur during or shortly after treatment, you will be closely monitored once treatment begins.

Hydroxychloroquine

Hydroxychloroquine has long been used to treat malaria, and it is also effective against some SLE symptoms such as rashes, joint and muscle pain, and fatigue. It usually takes 6 to 12 weeks of taking it before you notice any benefit.

Most specialists recommend that people with SLE stay on hydroxychloroquine long term, as it helps control symptoms, reduces flare ups and helps prevent more serious problems from developing.

Corticosteroids

Corticosteroids reduce inflammation quickly and can work very well for SLE symptoms, but they are usually reserved for more severe cases. If your symptoms are severe or you are going through a flare up, you may be given a larger dose to bring things under control, and as your symptoms settle, the dose can gradually be lowered.

Immunosuppressants

Immunosuppressants work by calming down the immune system, helping to limit the damage it causes when it attacks healthy parts of the body. This can improve SLE symptoms.

Commonly prescribed immunosuppressants include azathioprine, methotrexate, mycophenolate mofetil and cyclophosphamide.

Immunosuppressants are sometimes combined with corticosteroids, since together they can control symptoms more effectively. In some cases, adding an immunosuppressant allows the corticosteroid dose to be reduced.

Infection risk

Taking immunosuppressant medicine can raise your risk of infection. This matters especially for people with SLE, because organ damage from the condition can make infections more dangerous. Because of this, tell your doctor immediately if you notice any signs of infection.

Signs of infection can look similar to an SLE flare up and may include:

• a fever, or high temperature
• a cough or breathlessness
• a burning feeling when passing urine, or blood in the urine
• diarrhoea

It is also wise to avoid close contact with anyone who has an infection, even one you were previously immune to, such as chickenpox or measles, since immunosuppressants can lower that earlier immunity.

Rituximab

Rituximab is a newer medicine used for severe SLE that has not responded to other treatments. It was originally developed to treat certain cancers, such as lymphoma, but has since proved useful for autoimmune conditions including SLE and rheumatoid arthritis.

It works by targeting and destroying cells called B cells, which produce the antibodies responsible for SLE symptoms. It is given directly into a vein over several hours, in a process called an infusion.

Rituximab does not yet have full approval specifically for treating SLE, but your specialist may still consider it appropriate for you. If it is suggested, your doctor should explain that there is still some uncertainty about exactly how effective and safe it is for SLE.

Belimumab

Belimumab is another newer medicine, given to people with active SLE that has not responded to other treatments. It works by blocking growth factors that B cells need to survive, and like rituximab, it is given into a vein over several hours as an infusion. The first 3 doses are given 14 days apart, and after that it is usually given once a month.

Belimumab is approved for treating SLE, and your specialist may consider it a suitable option for you. If it is suggested, your doctor should explain that some uncertainty still remains about exactly how effective and safe it is for SLE.

Complications

A few decades ago, doctors saw SLE as a condition people could not really survive for long, since many patients died from a related complication within just a few years of diagnosis.

Thanks to earlier diagnosis and better treatment options today, the outlook has changed a great deal for the better. Most people who are diagnosed with SLE now go on to live a normal or nearly normal lifespan.

That said, some people with SLE remain at risk of serious, life threatening complications caused by damage to internal organs and tissues, such as a heart attack or stroke. SLE itself, along with some of the medicines used to treat it, can also make you more prone to serious infections.

Here is more detail on the possible complications of lupus.

Complications of lupus

If your SLE symptoms are mild or well controlled, the condition may barely affect your daily life, and you may never experience any complications at all.

For other people, though, SLE can behave more seriously and lead to complications that can threaten life. Some of the main ones are described below.

Kidney problems

About 1 in every 3 people with SLE go on to develop a serious kidney condition called lupus nephritis, caused by long term inflammation in the kidneys.

This usually shows up early in the course of the illness, often within the first five years after diagnosis.

Signs of lupus nephritis can include:

• swelling in the feet (oedema)
• headaches
• dizziness
• blood in the urine
• needing to urinate more often than usual

Lupus nephritis can also raise blood pressure. Left untreated, it can lead to dangerous problems such as a heart attack or stroke.

In many people, lupus nephritis causes no symptoms that can be felt at all, but that does not mean it is harmless. The kidneys can still be quietly taking damage.

Because of this, if you have SLE you will likely need regular blood tests so your doctor can keep a close eye on how your kidneys are doing. When lupus nephritis does develop, it can usually be brought under control with medicines that calm the immune system, such as mycophenolate mofetil or cyclophosphamide.

In a small number of cases, the kidney damage becomes severe enough that dialysis is needed, where a machine takes over many of the kidneys' jobs, or a kidney transplant becomes necessary.

Cardiovascular disease

Cardiovascular disease, or CVD, is a broad term for conditions affecting the heart and blood vessels. It is closely linked to blood clots and to atherosclerosis, where the arteries become hardened and narrowed.

Coronary heart disease, angina (chest pain that happens when the heart is not getting enough blood), heart attack and stroke are all examples of CVD.

People with SLE face a higher risk of developing CVD than the general population, because the condition can cause inflammation and damage in the heart and arteries.

If you have SLE, you can help lower your risk of CVD through healthy lifestyle habits, such as:

• giving up smoking if you currently smoke
• eating a balanced diet that is low in saturated fat, sugar and salt, with at least five servings of fruit and vegetables each day
• keeping to a healthy weight
• staying physically active, aiming for at least 150 minutes, or two and a half hours, each week of exercise strenuous enough to leave you slightly breathless
• cutting back on alcohol

Pregnancy complications

SLE does not usually make it harder to conceive, but it can raise the chances of certain problems during pregnancy, including:

• pre-eclampsia (a condition that causes high blood pressure during pregnancy)
• premature birth
• miscarriage
• stillbirth

Some babies born to mothers with SLE may also be born with heart block, a disruption in the electrical signals that control the heartbeat, along with skin rashes. Together these are known as neonatal lupus syndrome.

If you have SLE and are considering having a baby, it helps a great deal to plan ahead closely with your medical team. The risk of complications is greater if pregnancy happens while your symptoms are particularly active, so doctors will usually advise waiting until your symptoms are better controlled before trying to conceive.

Once you are pregnant, you will need close monitoring from both your specialist and an obstetrician, so that any problems can be caught and managed early.