IN BRIEF

• Lupus is a long-term condition that causes joint pain, skin rashes and tiredness.
• Lupus is caused by your immune system mistakenly attacking healthy parts of your body.
  • It is not fully understood why this happens.
• Although there is no cure, symptoms can improve if treatment starts early.
  • Lupus is better managed if it is found and treated early.
• Consult a medical professional (most likely your GP) if you often get:
  • Main symptoms:
    • Joint and muscle pain
    • Extreme tiredness that will not go away no matter how much you rest
    • Rashes (often over the nose and cheeks)
  • Secondary symptoms (you might also have):
    • Headaches
    • Mouth sores
    • High temperature
    • Hair loss
    • Sensitivity to light (causing rashes on uncovered skin)
• Do’s and Don’ts:
  • Do use high-factor (50+) sunscreen – you can get it on prescription if you have lupus
  • Do learn to pace yourself to avoid getting too tired
  • Do try to stay active even on a bad day
  • Do try relaxation techniques to manage stress – stress can make symptoms worse
  • wear a hat in the sun
  • Do tell your employer/partners about your condition – you might be able to adjust your working pattern
  • Do ask for help from family, friends and health professionals
  • Do eat a healthy, balanced diet, including vitamin D and calcium
  • Do not smoke – stopping smoking is the most important thing to do if you have lupus
  • Do not sit in direct sunlight or spend a lot of time in rooms with fluorescent lights
• Lupus can cause complications in pregnancy.
  • See a medical professional before trying to get pregnant to discuss the risks and so your medicine can be changed if necessary.
• Exercise:
  • Exercise can strengthen parts of your body that may be affected by lupus – the heart, lungs, bones and joints.
  • Exercise helps reduce inflammation by regulating some of the chemicals involved in the inflammation process.

For easier reading this article is broken down into the following sections:

1. Introduction
2. What is Lupus?
3. What can Cause Lupus?
4. Who can be Affected by Lupus?
5. Prevalence and Risk Factors
6. What are the Symptoms?
7. How is Lupus Diagnosed?
8. Differential Diagnosis
9. Treatment
10. What is the Prognosis?
11. Meeting Others with Lupus
12. Research and New Developments
13. Exercise and Lupus
14. Personal Notes
15. Summary
16. References

IN DETAIL

1.0 Introduction

Lupus is a long-term condition that causes joint pain, skin rashes and tiredness. And, although there is no cure, symptoms can improve if treatment starts early.

It is difficult to say how lupus will affect you, because it can vary greatly between people who have it. And, although treatments have improved a lot in recent years, it is still a serious condition and can even be life-threatening in some situations when people’s vital organs are affected. However, most people do not have the serious complications. If you have lupus, you will need regular check-ups with a medical professional(s) to look for any of the serious complications linked with the condition. Further, because of the risk of serious complications, having a healthy diet and lifestyle, and exercising regularly is important.

Lupus is known as ‘the great imitator’ because its symptoms mimic many other illnesses, and symptoms can also be unclear, can come and go, and can change – making diagnosis more problematic.

2.0 What is Lupus?

Lupus is a long-term condition that can cause inflammation in the skin, organs, and in various other places in the body. It is an autoimmune condition in which the immune system, which normally protects us against infection and illness, starts to attack the body’s own tissues instead.

There are four main types of lupus:

• Discoid Lupus:
  • Also known as cutaneous lupus.
  • Only affects the skin, causing rashes.
  • You can get it in one small area on the skin, or it can be widespread.
• Systemic Lupus Erythematosus (SLE):
  • The most common form of lupus.
  • Can affect many parts of the body in several ways.
  • It can range from mild to severe.
  • There is no cure, but early treatment can help to keep symptoms under control.
  • NPSLE: Neuropsychiatric Syndromes Concurrent with SLE.
    • Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system.
    • The American College of Rheumatology defines 19 NPSLE.
    • The diagnosis of NPSLE is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke.
• Drug-Induce Lupus Erythematosus:
  • Usually known as Drug-Induced Lupus.
  • A lupus-like disease caused by certain prescription medication.
• Neonatal Lupus:
  • A rare condition that affects infants of women who have lupus.

3.0 What Can Cause Lupus?

It is unclear why some people get lupus, although it is thought to be the result of a mix of genetic, hormonal and environmental factors. For example, the immune system makes proteins called antibodies that fight infection. In lupus, the body also makes autoantibodies that are similar, but attack the body’s own tissues instead. Scientists are not sure why this happens.

Research suggests that people with an inherited predisposition for lupus may develop the disease when they come into contact with something in the environment that can trigger lupus. The cause of lupus in most cases, however, is unknown.

There are some factors that probably trigger lupus/make symptoms more likely:

• An illness or (viral) infection:
  • Can initiate lupus or cause a relapse in some people.
• Strong sunlight:
  • Exposure to the sun may bring on lupus skin lesions or trigger an internal resposne in susceptible people.
• Childbirth.
• Hormonal changes, such as during puberty and menopause.
  • While men and women both produce oestrogen, its production is much greater in females.
  • Many women have more lupus symptoms before menstrual periods and/or during pregnancy when oestrogen production is high.
  • This may indicate that oestrogen somehow regulates the severity of lupus.
  • However, no causal effect has been proven between oestrogen, or any other hormone, and lupus.
  • And, studies of women with lupus taking oestrogen in either birth control pills or as postmenopausal therapy have shown no increase in significant disease activity.
  • Researchers are now focusing on differences between men and women, beyond hormone levels, which may account for why women are more prone to lupus and other autoimmune diseases.
• Smoking cigarettes.
• Some medications:
  • Known as drug-induced lupus.
  • Can be triggered by certain types of blood pressure medications, antiseizure medications, and antibiotics.
  • Usually gets better when people come off the medication that caused it; rarely, symptoms may persist even after the medication is stopped.
• Genetics:
  • Researchers have now identified more than 50 genes which they associate with lupus (ranging from contribute to not casual).

Lupus is not directly passed on from a parent to their children, but if you have a close relative with lupus then you may be at increased risk of developing it.

Lupus is not contagious, meaning you can not catch it from anyone else.

3.1 Why is it a Problem?

Having lupus also increases your risk of:

• Infection:
  • People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
• Cancer:
  • Having lupus appears to increase your risk of cancer; however, the risk is small.
• Bone tissue death:
  • This occurs when the blood supply to a bone declines, often leading to tiny breaks in the bone and eventually to the bone’s collapse.
• Pregnancy complications:
  • Women with lupus have an increased risk of miscarriage.
  • Lupus increases the risk of high blood pressure during pregnancy and preterm birth.
  • To reduce the risk of these complications, medical professionals often recommend delaying pregnancy until lupus has been under control for at least six months.

3.2 What are the Complications?

Lupsus is a serious condition and can even be life-threatening in some situations when people’s vital organs are affected. You will require regular check-ups with a medical professional to look for any serious complications linked with the condition.

Inflammation caused by lupus can affect many areas of your body, including your:

• Kidneys:
  • Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
• Brain and central nervous system:
  • If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures.
  • Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
• Blood and blood vessels:
  • Lupus may lead to blood problems, including a reduced number of healthy red blood cells (anemia) and an increased risk of bleeding or blood clotting.
  • It can also cause inflammation of the blood vessels.
• Lungs:
  • Having lupus increases your chances of developing an inflammation of the chest cavity lining, which can make breathing painful.
  • Bleeding into lungs and pneumonia also are possible.
• Heart:
  • Lupus can cause inflammation of your heart muscle, your arteries or heart membrane.
  • The risk of cardiovascular disease and heart attacks increases greatly as well.

Approximately 1 in 3 people with lupus also suffer from multiple autoimmune diseases.

3.3 What is the Role of Genetics in Lupus?

Genes do play a role in the predisposition to the development of lupus. There are dozens of known genetic variants linked to lupus, and these genes impact both who gets lupus and how severe it is.

Approximately 20% of people with lupus will have a parent or sibling who already has lupus or may develop lupus. About 5% of the children born to individuals with lupus will develop the illness.

Although lupus can develop in people with no family history of lupus, there are likely to be other autoimmune diseases in some family members. Approximately one in three will have another autoimmune disease in addition to lupus, and almost half will have a relative with lupus.

4.0 Who can be Affected by Lupus?

Lupus is much more common among women than men, and is more common among women of Chinese origin and most common in women of African or Caribbean origin. It tends to be more severe in those of Afro-Caribbean origin.

Rarely, lupus can affect children, but it is unusual before the age of five.

5.0 Prevalence and Risk Factors

5.1 Prevalence

Research estimates that approximately 300,000 to 1.5 million Americans have lupus (around 16,000 new cases per year) and a worldwide prevalence of at least 5 million.

• Discoid Lupus (Cutaneous Lupus):
  • Accounts for approximately 10% of all lupus cases.
• Systemic Lupus Erythematosus (SLE):
  • Accounts for approximately 70% of all cases of lupus.
  • In approximately half of these cases, a major organ or tissue in the body, such as the heart, lungs, kidneys, or brain will be affected.
  • 10 times more common in females than males.
  • Twice as prevalent in black people than white people.
  • Rates (estimates, which vary between sources):
    • Globally: 20-70 per 100,000 people.
    • US: 53, 98 to 305 per 100,000 people.
      • The rate of SLE in the US increased from 1.0 in 1955 to 7.6 in 1974.
      • Whether the increase is due to better diagnosis or an increased frequency of the disease is unknown.
    • Northern Europe: 40 per 100,000 people.
    • Afro-Carribean: (Up to) 159 per 100,000 people.
  • In females, the rate is highest between 45 and 64 years of age.
  • The lowest overall rate exists in Iceland and Japan, with the highest in France and the US.
  • Childhood-onset SLE generally presents between the ages of 3 and 15, and is four times more common in girls.
• Drug-Induced Lupus:
  • Accounts for about 10% of all lupus cases and is caused by high doses of certain medications.
  • The symptoms of drug induced lupus are similar to systemic lupus; however, symptoms usually subside when the medications are discontinued.
• Neonatal Lupus:
  • This is a rare condition in which the mother’s antibodies affect the foetus.
  • At birth, the baby may have a skin rash, liver problems, or low blood cell counts, but these symptoms typically disappear completely after six months with no lasting effects.

5.2 Risk Factors

Factors that may increase your risk of lupus include:

• Your sex:
  • Lupus, like many autoimmune diseases, is more common in women than men (9 out of 10 diagnosed cases).
    • The X chromosome carries immunological related genes, which can mutate and contribute to the onset of SLE.
    • The Y chromosome has no identified mutations associated with autoimmune disease.
  • Lupus strikes mostly women of childbearing age.
  • However, men, children, and teenagers develop lupus, too.
• Age:
  • Although lupus affects people of all ages, it is most often diagnosed between the ages of 15 and 45.
• Race:
  • Lupus is more common in people of African-American, Hispanic/Latino, Asian-American, Native American, Native Hawaiian, and Pacific Island Descent), which may be related to genes they have in common.
• Familial:
  • Approximately 20% of people with lupus will have a parent or sibling who already has lupus or may develop lupus.
  • About 5% of the children born to individuals with lupus will develop the illness.
  • Although lupus can develop in people with no family history of lupus, there are likely to be other autoimmune diseases in some family members.
  • Approximately one in three will have another autoimmune disease in addition to lupus, and almost half will have a (close or distant) relative with lupus.
• Genetics:
  • Researchers have now identified more than 50 genes which they associate with lupus.
  • These genes are more commonly seen in people with lupus than in those without the disease, and while most of these genes have not been shown to directly cause lupus, they are believed to contribute to it.
  • In most cases, genes are not enough. This is especially evident with twins who are raised in the same environment and have the same inherited features yet only one develops lupus.
  • Although, when one of two identical twins has lupus, there is an increased chance that the other twin will also develop the disease (30% chance for identical twins; 5-10% chance for fraternal twins).
  • Lupus can develop in people with no family history of it, but there are likely to be other autoimmune diseases in some family members.
• Environmental:
  • Most researchers today think that an environmental agent, such as a virus or possibly a chemical, randomly encountered by a genetically susceptible individual, acts to trigger the disease.
  • Researchers have not identified a specific environmental agent as yet but the hypothesis remains likely.
  • While the environmental elements that can trigger lupus and cause flares are not fully known, the most commonly cited are ultraviolet light (UVA and UVB); infections (including the effects of the Epstein-Barr virus), and exposure to silica dust in agricultural or industrial settings.
  • Other examples of potential environmental triggers include:
    • Ultraviolet rays from the sun and/or fluorescent light bulbs
    • Sulfa drugs, which make a person more sensitive to the sun, such as: Bactrim® and Septra® (trimethoprim-sulfamethoxazole); sulfisoxazole (Gantrisin®); tolbutamide (Orinase®); sulfasalazine (Azulfidine®); diuretics
    • Sun-sensitising tetracycline drugs such as minocycline (Minocin®)
    • Penicillin or other antibiotic drugs such as: amoxicillin (Amoxil®); ampicillin (Ampicillin Sodium ADD-Vantage®); cloxacillin (Cloxapen®)
    • Infection, colds or viral illnesses
    • Exhaustion
    • Emotional stress, such as divorce, illness, death in the family, or other life complications
    • Anything else that causes stress to the body such as surgery, physical harm, injury, pregnancy, or giving birth

5.3 Pregnancy and Lupus

Most women with lupus should be able to have a baby if they wish to. It is best to discuss your plans with your medical professional before trying to get pregnant so your treatments can be altered if they need to be. You may need to see an obstetrician with a special interest in lupus for further advice.

The following drugs must be stopped before you get pregnant, because they can harm an unborn baby:

• Cyclophosphamide;
• Methotrexate;
• Mycophenolate; and
• Leflunomide.

You might also need to wait for a period of time after coming off any of these drugs before it is safe to get pregnant. If you become pregnant unexpectedly while on one of these drugs, talk to your medical professional as soon as you can. In contrast, steroids, hydroxychloroquine and azathioprine are safe to take during pregnancy. If you can, it is best to try for a baby when your lupus is not active.

A small number of women with very severe lupus may be advised against having a baby as pregnancy can put a strain on the heart, lungs and kidneys. There is an increased risk of pregnancy complications in women whose lupus affects a number of different organs and who find it difficult to control their symptoms without certain medications. There are also restrictions on drugs that you can take if you are breastfeeding; talk to your rheumatology team or GP.

If you have high levels of antiphospholipid antibodies there is an increased risk of miscarriage. However, treatment with aspirin or heparin reduces this risk, and there are now many more successful pregnancies in women who have these antibodies.

There is conflicting evidence about whether pregnancy is likely to cause a flare-up of lupus. If your condition is well controlled at the time you became pregnant, and you do not have kidney disease, then you are unlikely to have any problems. If you do have kidney disease, you may have increased protein in your urine during the later stages of pregnancy. Protein in urine could also be a sign of a condition called pre-eclampsia. This causes pregnant women to have high blood pressure and it is more common than kidney disease. If you have proteins in your blood during pregnancy it can be difficult to work out whether this is due to kidney disease or pre-eclampsia. The medical professional(s) looking after your pregnancy will check for this and consult your rheumatologist if necessary.

In pregnant women who have anti-Ro antibodies there is a small risk that their babies will have neonatal (newborn) lupus syndrome. This means the baby may have a rash or a slow heartbeat. If this happens in one pregnancy, there is a slightly greater risk that it could happen in any further pregnancies. Most babies born to mothers with anti-Ro antibodies will be fine, but it is important to have regular scans of the baby’s heart during the pregnancy.

6.0 What are the Symptoms?

No two cases of lupus are exactly alike. Signs and symptoms may come on suddenly or develop slowly, may be mild or severe, and may be temporary or permanent. Most people with lupus have mild disease characterised by episodes (called flares or flare-ups) when signs and symptoms get worse for a while, then improve or even disappear completely for a time.

With this in mind, there are a variety of main and secondary symptoms, with some people experiencing one or two occasionally whilst others experience several consistently.

The exact signs and symptoms of lupus that you experience will depend on which body systems are affected by the disease (outlined below).

6.1 Main Symptoms

The three most common (or main) symptoms of lupus are:

• Joint pain, stiffness, and swelling.
• Skin rashes:
  • Which may become noticeable after being out in the sun.
  • Butterfly-shaped rash on the face that covers the cheeks and bridge of the nose or rashes elsewhere on the body.
• Extreme tiredness, known as fatigue.

Some people with lupus will only have these symptoms, though they can still have a big impact on daily life.

6.2 Secondary Symptoms

Other general (or secondary) symptoms are:

• Skin lesions that appear or worsen with sun exposure;
• Fingers and toes that turn white or blue when exposed to cold or during stressful periods;
• Shortness of breath;
• Chest pain;
• Dry eyes;
• Headaches, confusion, and/or memory loss;
• Ulcers in the mouth or nose;
• Hair loss;
• Fever;
• Weight loss;
• Swelling of the lymph glands, in the neck, armpits or groin, or under the chin
• Depression; and/or
• Anxiety.

It is important to note that you may not witness any of the ‘main’ symptoms, only ‘secondary’ symptoms. However, the butterfly-shaped rash is an extremely common symptom. It is also important to consider a differential diagnosis (Section 8 below).

6.3 Relapse and Remission

Lupus often flares up (relapses) and symptoms become worse for a few weeks, sometimes longer. Symptoms then settle down (remission). The reason why symptoms flare up or settle down is not known. Some people do not notice any difference and their symptoms are constant.

6.4 Symptoms by Area/Organ

Lupus can affect many different parts of the body, and when internal organs such as the heart, lungs, brain or kidneys are involved it can be much more serious. It is important to have regular check-ups, and to report any new symptoms to your medical professional. Most people will only have one or a few of the possible symptoms, and many people find that the symptoms come and go.

Area/Organ	Outline of Symptoms
Skin and Mouth	1. It is common for a rash to develop over parts of the body that are exposed to the sun, most commonly the face, wrists and hands. A butterfly-shaped rash over the cheeks and the bridge of the nose is common in lupus. 2. Some people notice that their fingers change colour in cold weather, going first very pale, then blue and finally red. This is called Raynaud’s phenomenon (see below) and is caused by narrowing of the blood vessels, which reduces the blood supply to the fingers or toes. It can happen in the cold or in stressful situations. 3. You may develop mouth ulcers. More rarely, ulcers can occur in the nose.
Hair	1. General thinning of the hair is fairly common among people who have lupus. 2. In some cases, there may be patches where the hair does not grow, and this is called alopecia. 3. Rarely alopecia can be more severe and affect large areas of the scalp. 4. This can be distressing, but once a flare-up is brought under control the hair will usually grow back.
Joints	1. Joint pain is common in lupus, especially in the small joints of the hands and feet. The pain often moves from joint to joint. 2. Joint pain, swelling and stiffness can be the main symptoms for some people with lupus. In most cases, lupus is unlikely to cause permanent damage or change the shape of joints. But it can sometimes cause serious joint problems. It is important you inform your medical professional if you have any new joint pain. 3. A small number of people with lupus have joint hypermobility. This is when joints are very flexible. It can lead to problems such as joint pain, poor balance and in rare cases dislocation – when a joint pops out of place. 4. Pain from muscles and joints may be due to a condition called fibromyalgia. This is a widespread pain syndrome and is thought to be caused by an imbalance in the central nervous system that controls and processes pain signals. It is more common among people with lupus. 5. If you have pain in your groin, you should see your medical professional. This could be a sign of a more serious complication called avascular necrosis. This is when there is a loss of blood supply to bone, which can cause bone damage. Steroid treatment can make this more likely.
Kidneys	1. People with lupus can have problems with their kidneys. Kidneys play several important roles, including helping to remove toxins from the blood. Until kidney damage is severe, it has no visible symptoms. It often causes high blood pressure. 2. In most cases if spotted early, kidney problems caused by lupus can be treated successfully. Medication can prevent permanent kidney damage. 3. Kidney function tests will be a part of your regular check-ups if you have lupus. 4. Although fatigue and arthralgia are present in almost all patients with SLE, renal involvement manifests in about 50% of patients.
Blood and Blood Vessels	1. Lupus may also cause anaemia, which is when you have a lack of red blood cells. These cells carry oxygen around the body, and if you do not have enough of them you can get out of breath and tire quickly. If you have these symptoms you should tell your doctor or nurse specialist. 2. People with lupus might also have a low number of platelets, cells that help the blood to clot. If you find that you are bruising easily or notice bleeding from the gums or nose you should let your doctor or nurse specialist know. Lupus can also affect your white blood cells, which are important in fighting infections. 3. Some people with lupus are more at risk of developing blood clots in veins or arteries. This problem is usually caused by antiphospholipid antibodies. These autoantibodies can also affect pregnancy, causing an increased risk of miscarriage. 4. If blood clots occur blood thinning medication will be needed.
Brain and Nervous System	1. People with lupus may experience anxiety or depression. 2. Some people have dizziness, memory loss or confusion. 3. Lupus can cause fits similar to epilepsy, or very rarely, feelings of paranoia.
Neuropsychiatric	1. Neuropsychiatric syndromes can result when SLE affects the central or peripheral nervous system. 2. The American College of Rheumatology defines 19 NPSLE. 3. The diagnosis of NPSLE, is one of the most difficult challenges in medicine, because it can involve so many different patterns of symptoms, some of which may be mistaken for signs of infectious disease or stroke. 4. A common neurological disorder people with SLE have is headache, although the existence of a specific lupus headache and the optimal approach to headache in SLE cases remains controversial. 4. Other common neuropsychiatric manifestations of SLE include cognitive disorder, mood disorder, cerebrovascular disease, seizures, polyneuropathy, anxiety disorder, psychosis, depression, and in some extreme cases, personality disorders. Steroid psychosis can also occur as a result of treating the disease. 5. It can rarely present with intracranial hypertension syndrome, characterised by an elevated intracranial pressure, papilledema, and headache with occasional abducens nerve paresis, absence of a space-occupying lesion or ventricular enlargement, and normal cerebrospinal fluid chemical and haematological constituents. 6. More rare manifestations are acute confusional state, Guillain-Barré syndrome, aseptic meningitis, autonomic disorder, demyelinating syndrome, mononeuropathy (which might manifest as mononeuritis multiplex), movement disorder (more specifically, chorea), myasthenia gravis, myelopathy, cranial neuropathy and plexopathy. 7. Neurological disorders contribute to a significant percentage of morbidity and mortality in people with lupus. 8. As a result, the neural side of lupus is being studied in hopes of reducing morbidity and mortality rates. 9. One aspect of this disease is severe damage to the epithelial cells of the blood-brain barrier. 10. In certain regions, depression affects up to 60% of women with SLE.
Heart and Lungs	1. Lupus can cause high blood pressure, particularly if the kidneys are involved. Steroid tablets, which are often used to treat lupus, can raise blood pressure when used in high doses. 2. Lupus can also make you more likely to have high cholesterol. Having high levels of cholesterol and high blood pressure can increase the risk of heart attack or strokes. 3. You should have your blood pressure and cholesterol checked regularly and treated if necessary. Having a healthy diet, a healthy lifestyle, exercising regularly and avoiding foods high in saturated fat and salt, can reduce your cholesterol and your chances of having a heart attack or stroke. 4. Occasionally lupus directly affects the heart and lungs. More often, it causes inflammation in the lining tissues around the heart, known as pericarditis. It can also cause inflammation in the lining of the lungs, known as pleurisy. Both these conditions cause breathlessness and sharp pains in the chest. 5. Rarely, large amounts of fluid develop in these lining layers, causing severe breathlessness. 6. Lupus may also cause narrowing of the blood vessels. This can lead to an increased risk of angina, when a reduced amount of blood gets to the heart muscle.
Other Organs	1. People with lupus can experience swelling of the lymph glands, which may cause discomfort. If you notice this happening, and especially if you also have high temperatures and are losing weight, talk to your medical professional. 2. Less frequently, lupus can affect the lining tissue of the gut, the gut itself, pancreas, liver or spleen, all of which can cause pain in the stomach. 3. Very rarely, lupus can cause a painful red eye or changes in your eyesight. If you have any symptoms affecting your eyes, it is important to see your medical professional as soon as possible. If left untreated, eye problems caused by lupus can lead to permanent damage to your eyesight. These issues are very treatable. 4. Sometimes people with lupus can have an underactive thyroid. This is when the thyroid glands in the neck do not produce enough hormones. This can lead to problems such as tiredness, weight gain and depression. 5. A condition known as Sjögren’s syndrome, which causes severe dryness of the eyes and mouth, is more common among people with lupus. 6. Less commonly, people with lupus can have the inflammatory type of arthritis called rheumatoid arthritis, or a condition known as myositis, which is inflammation of the muscles.

6.5 What is Raynaud’s Phenomenon?

Raynaud’s phenomenon causes blood to stop flowing properly to the outer parts of the body. This happens mainly when you get cold, and it can also happen because of stressful situations. It most commonly affects fingers and toes, but can sometimes also affect lips, noses, ears and nipples.

The most common thing to happen is for fingers, and slightly less commonly toes, to change colour. Usually they will go white, then blue, sometimes black, and then red. You may not experience all four stages every time. For example, your hands may just go blue then red. These colour changes often happen alongside pain or a tingling feeling.

Going out on a cold day, or even reaching into the freezer to take out some frozen food, can bring on an attack of Raynaud’s. As can emotionally stressful situations. Raynaud’s phenomenon often occurs on its own. This is called primary Raynaud’s phenomenon. Primary Raynaud’s is a fairly common condition. It affects more women than men. Most people with primary Raynaud’s will not go on to develop any further problems.

Raynaud’s can also be linked with other conditions, such as scleroderma (or systemic sclerosis, a long-term condition which causes thick, hard skin – possibly affecting your organs), and less commonly lupus. When this happens, it is called secondary Raynaud’s phenomenon.

Primary Raynaud’s phenomenon usually affects young women and teenage girls. But men, babies, children and older people can also be affected. It sometimes runs in families.

7.0 How is Lupus Diagnosed?

Lupus is not always easy to diagnose because it can be similar to other conditions. As noted above, symptoms include inflammation of different parts of the body such as the lungs, heart, liver, joints and kidneys. Your medical professional will usually perform some blood tests. High levels of a type of antibody, combined with typical symptoms, means lupus is likely. You might be referred for X-rays and scans of your heart, kidney and other organs if your medical professional thinks they might be affected. Once lupus is diagnosed, you will be advised to have regular checks and tests, such as regular blood tests to check for anaemia (a condition in which you lack enough healthy red blood cells to carry adequate oxygen to your body’s tissues) and urine tests to check for kidney problems.

• It can be difficult to make a diagnosis of lupus because it does not affect any two people exactly the same.
• The most distinctive sign of lupus – a facial rash that resembles the wings of a butterfly unfolding across both cheeks – occurs in many but not all cases of lupus.
• The signs and symptoms may change over time.
• There are also many other conditions it resembles, or overlaps with.
• However, the earlier someone is diagnosed with lupus and treatment is started, the better their chances of keeping this condition under control.
• A diagnosis of lupus is made based on symptoms, a physical examination and blood tests.
• There are a number of tests that can help lead to a diagnosis of lupus or rule it out.
• These can then be used to monitor how well treatments are working.

7.1 What are the Diagnostic Criteria?

SLE should be suspected in a patient with symptoms in at least two of the following organ systems:

• Constitutional;
• Musculoskeletal;
• Skin;
• Renal;
• Neuropsychiatric;
• Haematologic;
• Cardiac;
• Pulmonary;
• Gastrointestinal; or
• Reticuloendothelial.

Medical professionals, in the US, can use one of two diagnostic criteria frameworks to assist in diagnosing SLE:

• ACR Criteria:
  • The American College of Rheumatology (ACR) has 11 classification criteria for lupus.
  • If a patient meets at least four criteria, required for diagnosis, lupus can be diagnosed with 95% specificity and 85% sensitivity.
• SLICC Criteria:
  • The Systemic Lupus International Collaborating Clinics (SLICC) has 13 criteria.
  • At least four criteria, including at least one clinical criterion and one immunologic criterion, required for diagnosis, or patient must have had biopsy-confirmed lupus nephritis in the presence of a poisitive ANA or anti-dsDNA result (see below).

Further details on the diagnostic criteria can be found @ the American Academy of Family Physicians (AAFP) website here (Table 2).

Tests undertaken to aid diagnosis may include (LUPUS UK, 2015):

Test(s)	Outline
Anti-Nuclear Antibody (ANA) Test	1. About 95% of people with lupus test strongly positive for ANA. 2. However, the test can sometimes be positive in people who do not have lupus, so it can not confirm the diagnosis. 3. Discussed further below.
Anti-Double-Stranded DNA (anti-dsDNA) Antibody Test	1. About 70% of people with lupus have these antibodies. 2. A positive test means that lupus is highly likely as the test is hardly ever positive in people who do not have lupus. 3. Levels of this antibody can go up as the lupus becomes more active and will go down if treatment is effective. 4. Lupus patients might be expected to be “sero-negative” for anti-dsDNA antibodies early in disease, post-treatment and when in clinical remission. 5. Anti-dsDNA antibodies are also of less use in subacute or discoid lupus.
Anti-Ro Antibody Test	1. If you test positive for this antibody you may be more likely to get skin rashes and suffer from dry eyes or a dry mouth, known as Sjögren’s syndrome. 2. Rarely, this antibody can pass across the placenta during pregnancy – this is the organ that passes food through from a pregnant woman to her unborn baby. 3. If you carry the anti-Ro antibody and decide to have a baby, your pregnancy will be more closely monitored.
Antiphospholipid Antibody Test	1. A positive test for these antibodies may mean an increased risk of miscarriage and developing blood clots. 2. These antibodies can come and go so these tests can be repeated.
Kidney and Liver Function Tests	1. These include blood and urine tests, which are carried out regularly so any problems caused by the lupus or by drug treatment can be picked up and dealt with quickly. 2. A simple urine test can show if there is protein or blood in the urine. 3. This test can help medical professionals recognise a problem in the kidneys at an early stage. 4. Further tests may be carried out if necessary.
Urinalysis	1. An examination of a sample of your urine may show an increased protein level or red blood cells in the urine, which may occur if lupus has affected your kidneys.
Blood Cell Counts	1. Blood cell counts can help to show whether the bone marrow is affected, either by your condition or the drugs. 2. This test measures the number of red blood cells, white blood cells and platelets as well as the amount of haemoglobin (a protein in red blood cells). 3. Results may indicate you have anaemia, which commonly occurs in lupus. 4. A low white blood cell or platelet count may occur in lupus as well.
Erythrocyte Sedimentation Rate	1. This blood test determines the rate at which red blood cells settle to the bottom of a tube in an hour. 2. A faster than normal rate may indicate a systemic disease, such as lupus. 3. The sedimentation rate is not specific for any one disease. 4. It may be elevated if you have lupus, an infection, another inflammatory condition or cancer.
Scans and X-Rays	1. Different types of scans and x-rays can assess how well your heart, lungs, liver and spleen are working. 2. Chest X-ray: a. An image of your chest may reveal abnormal shadows that suggest fluid or inflammation in your lungs. 3. Echocardiogram: a. This test uses sound waves to produce real-time images of your beating heart. b. It can check for problems with your valves and other portions of your heart.
Biopsy	1. Lupus can harm your kidneys in many different ways, and treatments can vary, depending on the type of damage that occurs. 2. In some cases, it is necessary to test a small sample of kidney tissue to determine what the best treatment might be. 3. The sample can be obtained with a needle or through a small incision. 4. Skin biopsy is sometimes performed to confirm a diagnosis of lupus affecting the skin.

7.2 Classification

Lupus can be classified depending on how it affects the body.

Severity	How It Affects Your Body
Mild	Joint and skin problems, and tiredness.
Moderate	Inflammation of other parts of the skin and body, including your lungs, heart, and kidneys.
Severe	Inflammation causing severe damage to the heart, lungs, brain or kidneys can be life threatening.

7.3 How Long Does it Take to Get Diagnosed?

There are many challenges to reaching a lupus diagnosis. Lupus is known as ‘the great imitator’ because its symptoms mimic many other illnesses. Lupus symptoms can also be unclear, can come and go, and can change.

In the US, on average, it takes nearly six years for people with lupus to be diagnosed, from the time they first notice their lupus symptoms. A majority (approximately 6 in 10) report being incorrectly diagnosed, with around half of the incorrectly diagnosed stating they will see four or more different healthcare providers for their lupus symptoms before being accurately diagnosed. Research suggests it takes approximately six months to be accurately diagnosed.

Research also suggests that 6 in 10 Americans have never heard of lupus or know very little about it.

7.4 Why is it Difficult to Diagnose Lupus, Specifically SLE?

Lupus, and specifically SLE, can be difficult to diagnose because many of the symptoms (e.g. fatigue, rash, and joint pain) are non-specific and overlap with those of more common conditions. Furthermore, biomarkers are often negative or normal early in the course of the illness.

The most common presenting symptoms are constitutional, such as fatigue, weight loss, and fever without a focal infection, occurring in up to 90% of patients.
Other common presenting symptoms include arthralgia and myalgia, which occur in up to 95% of patients with SLE.
Less common presenting symptoms include malar rash (31%), photosensitivity (23%), pleuritic chest pain (16%), new-onset Raynaud phenomenon (16%), and mouth sores (12.5%).

7.5 What is an Anti-Nuclear Antibody (ANA) Test?

An anti-nuclear antibody (ANA) test, also known as a fluorescent anitnuclear antibody (FANA) test, is a blood test that looks for antinuclear antibodies in your blood. Antibodies are proteins that your immune system makes to fight foreign substances, such as viruses and bacteria. But an antinuclear antibody attacks your own healthy cells instead. It is called ‘antinuclear’ because it targets the nucleus (centre) of the cells.

It is normal to have a few antinuclear antibodies in your blood, but a large number may be a sign of an autoimmune disorder. If you have an autoimmune disorder, your immune system attacks the cells of your organs and tissues by mistake. These disorders can cause serious health problems. Other names for the ANA test include: antinuclear antibody panel, fluorescent antinuclear antibody, FANA, ANA, and ANA reflexive panel.

• ANAs are a type of antibody called an autoantibody.
• Like other antibodies, they are produced by the immune system.
• While healthy antibodies protect the body from pathogens like viruses and bacteria, autoantibodies cause disease by mistakenly attacking healthy cells and tissues.

Results from an ANA test alone cannot diagnose a specific disease. Your provider will use your ANA test results along with your symptoms, information about your health, physical exam, and other (laboratory) tests to make a diagnosis.

There are several methods to measure ANAs, and three are outlined below.

Type of ANA Test	Outline
Indirect Immunofluorescent ANA (IIF-ANA or IF-ANA) Test	1. The IIF-ANA test is the most widely used method. 2. This test report includes a negative or positive interpretation, ANA levels, and patterns seen in antibodies during the test. 3. The IIF-ANA test report also describes various fluorescent staining patterns produced during testing. 4. Your blood specimen is mixed with a unique fixed tissue matrix called a substrate (HEp-2 cells) which have a strong affinity for and will bind to ANAs if present. 5. A fluorescent dye is attached to another type of antibody (fluorescent-labelled anti-human immunoglobulin) that will attach to ANA. 6. Under a fluorescent microscope, different fluorescent patterns can be observed. 7. While a staining pattern can not diagnose a health condition definitively, some patterns are loosely associated with certain diseases. 8. They also give medical professionals clues about the type of ANA present in your blood and can signal the need for additional testing.
Direct Immunofluroescence Test	1. Direct immunofluorescence against these antibodies are reported as a titre, such that high values (>1:320 – corresponding to a positive signal when more diluted) are more likely to represent true positives than lower titres (1:40). 2. The best substrate are a cell line ‘Hep-2 cells’, which have large nuclei. 3. A positive result should be followed by characterisation of the staining pattern (see above).
Enzyme Immunoassay (EIA)	1. Another method of ANA testing is a solid phase assay, called an enzyme-linked assay or enzyme immunoassay (EIA). 2. Two types of EIA tests are used: a. A basic EIA test: A generic assay for ANA and is reported much like the IIF-ANA as positive or negative. b. The enzyme-linked immunosorbent assay (ELISA): The ELISA test is more specific and will detect single autoantigens such as daDNA, SS-A/Ro, SS-B/La, Scl-70, Sm, and SM/RNP. 3. ELISA tests have become popular because they can be automated and are less observe dependent. a. They usually comprise a ‘soup’ of the more common lupus autoantigens. b. They will miss ANAs targeting less common autoantigens and are more subject to ‘false positive’ results. c. They are often the first test a laboratory performs, but if negative and suspicion for lupus remains, a direct immunofluorescence test should be requested. d. A positive result should result in testing for the individual components in the ‘soup’ and at least one should be positive.

7.6 How is the Test Performed?

Indirect IIF-ANA involves incubating patient serum on a slide covered with a monolayer of cells from a malignant human epithelial cell line. These malignant cells are ideal for the ANA test as they have large nuclei in different stages of the cell cycle. The slides are washed and any remaining antibodies bound to cell nuclei are then visualised using a detection antibody binding human immunoglobulin which has been conjugated to a fluorescent tag. The detection antibody will then be visible using a fluorescence microscope if there is immunoglobulin from the patient serum that has bound to the cells on the slide.

In ELISAs wells are coated with antigens from cell nuclei. Serum is incubated in the wells and antibodies binding to the antigens are then detected using a detection antibody which has been conjugated with an enzyme tag. Antibody levels may be quantified by the amount of colour change of a substrate by the enzyme tag.

7.7 Interpreting Test Results

ANA Test Result	Interpretation
Negative	1. This means that antinuclear antibodies were not found in your blood, and you are less likely to have an autoimmune disorder. 2. However, a negative ANA test does not completely rule out the possibility that you could have an autoimmune disorder. 3. SLE is unlikely in a patient with negative results.
Positive	1. This means that antinuclear antibodies were found in your blood. 2. A positive result does not always indicate that you have an autoimmune disorder, as some healthy patients can test positive. 3. Positive results can also be related to a viral infection, medications, certain cancers, and other health conditions (discussed below).

7.8 How is the Test Reported?

The results of ANA testing are reported in two components:

• The quantity of ANA in the serum (intensity); and, when the ANA is positive
• The pattern of antibody binding to the nucleus (staining pattern).

The quantitation of an ANA is most commonly reported as a titre (discussed below), reflecting the final step in a series of two-fold dilutions at which the ANA remains positive (e.g. 1:1 280 for a strongly positive ANA, or 1:160 for a weaker, borderline positive ANA). An alternative method involves reporting the intensity of fluorescence, in international units per millilitre (IU/mL), at a pre-determined dilution. With this method, a result of >7 IU/mL is generally considered positive.

While ANAs are associated with a number of autoimmune conditions, they are most useful in the diagnosis and classification of rheumatic diseases (see table below).

ANA Pattern	Associated Rheumatic Disease
Homogenous	Systemic lupus erythematosus Mixed connective tissue disease Drug induced lupus Juvenile idiopathic arthritis
Speckled	Systemic lupus erythematosus Sjögren’s syndrome Polymyositis/dermatomyositis Systemic sclerosis/scleroderma
Nucleolar	Diffuse systemic sclerosis/scleroderma Polymyositis
Centomere	Limited systemic sclerosis/scleroderma
Peripheral (Rim)	Systemic lupus erythematosus Systemic sclerosis/scleroderma

7.9 Sensitivity and Specificity

The ANA test is a highly sensitive test with 90-95% of SLE patients being positive for ANA, and its titre is one of the key diagnostic criteria for SLE. However, ANA positivity is not mandatory for a diagnosis of lupus. The test has low specificity, and may be positive in healthy patients and those with other connective tissue diseases (so it is best applied to those with a high predicted risk). In selected populations, when ANA titres (see below) are high, sensitivity of this test for lupus can approach 100% sensitivity and about 90% for specificity.

Conditions that may result in a positive result include:

• Systemic lupus erythematosus (SLE).
• Sjögren’s syndrome: A disease that causes dry eyes and mouth.
• Scleroderma: A connective tissue disease.
• Rheumatoid arthritis: This causes joint damage, pain, and swelling.
• Polymyositis: A disease that causes muscle weakness.
• Mixed connective tissue disease: A condition that has symptoms of lupus, scleroderma, and polymyositis.
• Juvenile chronic arthritis: A type of autoimmune arthritis that affects children.
• Dermatomyositis: A rare disease that causes weak muscles and a rash.
• Polyarteritis nodosa: A rare disease that causes the blood vessels to swell up and damage organs.
• Autoimmune hepatitis.

The ANA test result can sometimes also be positive if you have one of these conditions:

• Raynaud’s syndrome: A disease that makes your fingers and toes turn blue and feel cold.
• Thyroid diseases: Hashimoto’s thyroiditis or Grave’s disease.
• Liver diseases: Autoimmune hepatitis or primary biliary cirrhosis.
• Inflammatory bowel disease.
• Lung diseases: Idiopathic pulmonary fibrosis.
• Cancer.
• Viral infections.

As such, a positive ANA will be seen in a range of conditions where it is not diagnostically helpful, and many patients with autoimmune disease will not have a positive result. A pre-existing clinical suspicion of systemic rheumatic disease is critical to enhance the clinical utility of a positive result. In the absence of clinical or laboratory markers supporting a diagnosis of rheumatic disease, a positive result is seldom useful.

With this in mind, having antinuclear antibodies in your blood does not always mean you have a disease, known as a false positive:

• Approximately 3-15%, 20% or 40% (depending on your source) of healthy poeple have a small number (low-intensity) of autoantibodies in their blood.
• Approximately 5% of healthy people have a moderate-intensity of autoantibodies in their blood.
• If a randomly selected population were to be screened with ANA testing, 50 or more healthy people with a positive ANA would be identified for every one patient with SLE.
• Levels tend to increase with age, with as many as one-third of healthy adults over the age of 65 having a positive ANA test result.
• False positives are particularly common in unwell elderly patients.
• People with an infection such as monnuceleosis or tuberculosis may have a false positive.
• Also, certain medicines can cause antinuclear antibodies such as blood pressure or anti-seizure medication.
• ANA’s are also occasionally seen in subacute bacterial endocarditis, pregnancy, HIV, liver disease, malignancy and Type 1 diabetes mellitus.

Although most patients with SLE have positive ANA test results, most patients with positive ANA results do not have SLE. It is very rare, but it is possible to have a negative ANA test and still have lupus (in these instances other antibodies are present).

7.10 Titre Ratios

Results of ANA testing may include a titre which measures the number of antibodies in the blood by setting up various dilutions of the blood with normal saline (such as 1:40, 1:60, 1:80, and 1:160) and observing the presence of fluorescence. However, reference ranges vary from laboratory to laboratory, and a positive ANA can be 1:40, 1:60 or greater. This makes reference ranges for ANA tests controversial, as laboratories may vary in what ratio they interpret as positive for ANAs. You may find it helpful to discuss reference ranges with your medical professional.

Generally, if results show a 1:40 titre or higher:

• More specific tests should be performed, including measurement of anti-double-stranded DNA (anti-dsDNA), anti-Smith, anti-RNP, anticardiolipin, and beta-2 glycoprotein antibodies and lupus anticoagulant; elevated levels of one or more of these biomarkers increase the likelihood of SLE.
• Similarly, low levels of complements C3 and C4 increase the likelihood of SLE.
• Other tests that should be performed at initial evaluation include urinalysis, comprehensive metabolic panel, complete blood count, and direct Coombs test.
• The erythrocyte sedimentation rate and C-reactive protein level are useful to quantify disease activity.

When you present with symptoms associated with an autoimmune disorder, the IIF-ANA test may be initially performed and, if positive, followed up with additional testing that specifically identifies certain autoantibodies present.

• An anti-centromere test diagnoses scleroderma.
• An anti-double-stranded DNA (anti-dsDNA) test diagnoses lupus.
• An anti-histone test diagnoses lupus that was caused by medicine you took.
• An extractable nuclear antigen antibodies (ENA) panel helps your medical professional see which autoimmune disease you have.
• An erythrocyte sedimentation rate (ESR) is a blood test that can show if you have inflammaton in your body (and can be used to monitor an existing condition).
• C-Reactive Protein (CRP) is a protein made by the liver and increases when there is inflammation in the body. There are two tests: standard CRP test and high-sensitivity CRP (hs-CRP; it can find smaller increases in CRP than the standard CRP test). It can help show the risk of getting coronary heart disease.

The presence of certain autoantibodies (like daDNA, SS-A/Ro, SS-B/La, Scl-70, Sm, SM/RNP, and Jo-1) have been associated with specific disorders such as lupus, Sjogren’s, and other autoimmune problems. However, note that a single positive ANA test does not necessarily mean that you have a disease.

7.11 What about Sero-Negativity

The concept of sero-negativity was first introduced by Koller et al. (1976), and cutaneous manifestation – particularly photosensitivity – was the predominant feature in the first few cases of sero-negativity. It is also known as ANA-negative lupus and seronegative SLE.

Sero-negativity in lupus patients may be due to technical failure or entrapment of ANA in circulating immune complexes.

It is generally advised that once you are diagnosed with an autoimmune disorder, repeat ANA testing is not necessary. Further, ANA testing does not diagnose a specific disease, nor is it useful in monitoring your disease or response to treatment (serial measurements are not recommended as some commentators suggest there is poor correlation with disease progression). However, this may not be completely accurate. Bohan (1979) suggests that negative serologic tests do not always exclude SLE, and serial testing at periodic intervals may be indicated. Bohan’s case study followed, from 10 months to 7 years, negative serologic markers (including the ANA, LE cell test, and anti-DNA) which were seen to change from negative to positive, analogous to the seronegative rheumatoid patient who may become seropositive.

A test result may be positive one time and negative the next (and vice versa), and different laboratories may produce different test results.

Lupus-like syndromes are recognised in the absence of positive ANA (other serology such as anti-Ro or La may be positive) and patients with previously sero-positive lupus may not be consistently positive for ANA.

7.12 Questions and Answers during Your Appointment

Before your appointment with a medical professional, you may want to write a list of answers to the following questions:

• When did your symptoms begin? Do they come and go?
• Does anything seem to trigger your symptoms?
• Have your parents or siblings had lupus or other autoimmune disorders?
• What medications and supplements do you take regularly?

You may also want to write down questions to ask your medical professional, including:

• What are the possible causes of my symptoms or condition?
• What tests do you recommend?
• If these tests do not pinpoint the cause of my symptoms, what additional tests might I need?
• Are there any treatments or lifestyle changes that might help my symptoms now?
• Do I need to follow any restrictions while we are seeking a diagnosis?
• Should I see a specialist?
• If you are considering pregnancy, be sure to discuss this with your doctor. Some medications cannot be used if you get pregnant.
• In addition to the questions that you have prepared to ask your medical professional, do not hesitate to ask questions during your appointment at any time that you do not understand something.

Your medical professional is likely to ask you a number of questions. Being ready to answer them may leave time to go over any points you want to spend more time on. Your medical professional may ask:

• Does sun exposure cause you to develop skin rashes?
• Do your fingers become pale, numb or uncomfortable in the cold?
• Do your symptoms include any problems with memory or concentration?
• How much do your symptoms limit your ability to function at school, at work or in personal relationships?
• Have you been diagnosed with any other medical conditions?
• Are you pregnant, or do you plan to become pregnant?

8.0 Differential Diagnosis

With regards differential diagnosis, there are a range of other conditions that should be considered:

• Adult-Onset Still Disease.
• Behcet Syndrome.
• Chronic Fatigue Syndrome.
• Endocarditis.
• Fibromyalgia.
• HIV Infection.
• Inflammatory Bowel Disease.
• Lyme Disease.
• Mixed Connective Tissue Disease.
• Psoriatic Arthritis.
• Reactive Arthritis.
• Rheumatoid Arthritis.
• Sarcoidosis.
• Systemic Sclerosis.

Further details on these conditions can be found @ the American Academy of Family Physicians (AAFP) website here (Table 1).

9.0 Treatment

People with lupus will generally see a rheumatologist (doctors who specialise in the diagnosis and treatment of diseases in the joints and muscles). However, because lupus can cause problems anywhere in the body you may see other types of doctor, including:

• Dermatologist (for your skin);
• Nephrologist (for your kidneys); and/or
• Cardiologist (for your heart).

Lupus is generally treated using:

• Anti-inflammatory medicines like ibuprofen;
• Hydroxychloroquine for fatigue and skin and joint problems; and/or
• Steroid tablets, injections and creams for kidney inflammation and rashes.

Two medicines, rituximab and belimumab, are sometimes used to treat severe lupus. These work on the immune system to reduce the number of antibodies in the blood.

Examples of treatments available are outlined below.

Treatment(s)	Outline
Drugs	1. The drugs used to treat lupus will depend on how serious it is and which parts of your body are affected. 2. Your treatment(s) will probably be changed or adjusted as your symptoms flare up or improve. 3. Many drugs used to treat lupus were originally developed for other conditions but were later found to be useful in lupus.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)	1. These drugs can treat inflammation and pain in your joints. 2. Examples include ibuprofen and naproxen (aka naproxen sodium). 3. NSAIDs can be over-the-counter (OTC) and/or prescription. 4. They are often used for short periods of time. 5. If used over a long term they can cause problems with the kidneys (and so may not be advised for people who have had kidney disease), stomach bleeding, and increased risk of heart problems. 6. Other long-term side effects can include thinning of the lining of the stomach, so they may be prescribed with drugs known as antacids to protect against this. 7. You will not usually be given NSAIDs if you have previously had stomach ulcers.
Steroids	1. Steroids, also known as corticosteroids, can reduce inflammation. 2. There are different types of steroid medication. 3. Steroid creams can be used to treat skin rashes. 4. Tablets, for example prednisolone, can be used for short periods when symptoms are active. 5. They can also be used as a longer-term treatment if symptoms persist, but will often be reduced to the lowest effective dose. 6. Steroid injections into a muscle or vein can help control a flare-up. 7. Sometimes people can have steroid injections into the scalp to treat hair loss – though the hair often grows back on its own when the condition is brought under control. 8. When taking steroid tablets, it is a good idea to carry a steroid alert card, which records your dose and how long you have been taking it. 9. If you become ill, or have an accident and are injured or unconscious, it is important for the steroid to be continued or possibly even increased. 10. Steroid treatment can prevent your body producing enough natural steroids in response to a trauma such as an injury. 11. Because of this it is important not to suddenly stop taking them if you have been on them for a while without speaking to your rheumatologist first. 12. Your medical professional (e.g. doctor, rheumatology nurse specialist or pharmacist) can give you a steroid card.
Antimalarials	1. These drugs can help reduce inflammation. 2. They can help to lower cholesterol and control kidney conditions. 3. The most common example used to treat people with lupus is called hydroxychloroquine. 4. It can be used alone or with steroid creams for skin rashes. 5. It is also useful for fatigue and joint pain. 6. In some cases, hydroxychloroquine can affect the eyes. 7. While this is rare, it can be serious. 8. Therefore, you will need regular eye tests if you are taking this drug – especially if you have been taking it for five years or more.
Disease-Modifying Anti-Rheumatic Drugs (DMARDS)	1. These are drugs that reduce the effects of an overactive immune system. 2. This can stop the immune system having a damaging effect on the body’s own tissues. 3. Examples include: azathioprine; ciclosporin; cyclophosphamide; methotrexate and mycophenolate. 4. They may take several weeks or even up to three months to take effect. 5. Then they might need to be taken over a long period. 6. The dose could be reduced once your condition is under control. 7. They may be used along with steroid tablets and may allow the steroid dose to be reduced. 8. People on DMARDs will need to have regular blood testing to check how effective they are, and what impact they are having on the body.
Biological Therapies (or Biologics)	1. Biological therapies are a newer type of DMARDs. 2. They have a more targeted effect on specific cells within the immune system. 3. Examples include rituximab and belimumab. 4. They can remove or reduce the activity of B-cells. 5. These are a type of white blood cells, and in people with lupus they may produce harmful autoantibodies that attack the body’s own tissues. 6. They can be used to treat people with lupus when older types of DMARDs are not effective or if the lupus is very active. 7. If you are taking a biological therapy, it is a good idea to carry a biological therapy alert card. 8. You can get one from your medical professional (e.g. doctor or rheumatology nurse specialist). 9. If you become unwell, anyone treating you will know you are on a biological therapy and that you are therefore possibly at risk of its side effects, including infections. 10. If there is a significant build-up of fluid in the lining tissues of the heart or lungs, this may need to be drained using a needle and syringe. 11. Rarely, some people with lupus develop kidney failure, which may require dialysis. 12. This is a treatment to remove waste products and excess fluid from the blood when the kidneys stop working. 13. In some cases, people may need a kidney transplant. 14. However, severe kidney damage can usually be prevented by early diagnosis and treatment of lupus.
Other Drugs	1. In clinical trials, voclosporin has been shown to be effective in treating lupus. 2. Other potential drugs to treat lupus are currently being studied, including abatacept (Orencia), anifrolumab and others.

9.1 What about Side Effects?

All drugs have some potential side effects, and you and your medical professional will need to balance the risk of side effects with the need to control your symptoms. Sometimes this may mean taking additional medications to protect against the side effects of others.

Treatments such as calcium, vitamin D tablets, and drugs called bisphonphonates may be given to guard against the bone-thinning condition osteoporosis. This condition can be a risk for people who take steroids at high doses or for long periods. You may be given DMARDs instead of high doses of steroids.

If you have lupus, and especially if you are on a DMARD or biological therapy, you will be more prone to infection. Take care to avoid contact with people with infectious diseases like chickenpox or if they have recently been in hospital. You should discuss your vaccination status with your medical professional (e.g. rheumatologist or GP). You might need to avoid live vaccines.

If you suffer from a severe infection or require antibiotics you may need to stop your DMARD treatment for a short time, and restart them once you have recovered from the infection.

9.2 What about Self-Help and Daily Living?

Drugs are important in controlling lupus, but there is also a lot you can do yourself to help manage your symptoms. Having a healthy diet, exercising regularly and not smoking will help reduce your risk of developing the more serious complications of lupus.

Managing…	Outline
A Flare-Up	1. Lupus is a condition that naturally improves and worsens at different times. 2. Learning how to manage a flare-up of your symptoms helps you to be more in control of your condition. 3. The reasons for a flare-up can vary from person to person, but exposure to sunlight, too little rest time, infections and stress can all play a part. 4. It can be useful to try to spot the things that lead to a flare-up and find ways of managing or avoiding them. 5. Keep in touch with your rheumatology team, especially through your rheumatology nurse specialist and the telephone advice line available in most units.
Fatigue	1. You may find you often experience fatigue, and it can be a big problem. 2. If there is a specific cause, such as anaemia or an underactive thyroid gland, this can be identified by a blood test and treated. 3. Some medications such as hydroxychloroquine can help. 4. Learning to pace yourself – finding the right balance between rest and activity – will help. 5. Exercise improves fitness and stamina and can therefore help in overcoming fatigue, but you will need to start gently and gradually increase the amount you do. 6. Ask to see a physiotherapist for advice about suitable exercises.
Smoking	1. Many of the problems caused by lupus can be made worse by smoking. 2. For example: a. Lupus and smoking can both cause narrowing of the blood vessels, causing circulatory problems and increasing the risk of strokes and heart attacks. b.Lupus can make you more at risk of infections involving your throat, airways or lungs. c. Smoking can cause long-term lung damage which can make these infections more frequent and severe. d. When lupus affects the kidneys it can lead to high blood pressure. e. Smoking can also contribute to high blood pressure, increasing the risk of strokes and worsening kidney disease. 2. While it can be difficult to stop smoking, treatments are available that can help you to stop. 3. Talk to your medical professional or call a smoking helpline to find out the ways they can help. 4. If you do smoke, giving up can be one of the most important things you do to reduce the risk of the more serious complications of lupus.
Exercise	1. There will be times when you may not feel like doing very much and it is important to rest when you need to. 2. However, too much rest will cause the muscles to weaken and may make you feel more tired, so you need to find the right balance between rest and exercise. 3. Walking and swimming are recommended as they can improve fatigue, fitness, strength and stamina without putting too much strain on the joints. 4. Even when you are having a flare-up, a small amount of exercise is helpful, and you should find some gentle exercise that you can do even on a bad day. 5. Exercise, particularly weight-bearing exercise such as walking or jogging, can help to keep bones strong. 6. This can reduce the chances of the bone-thinning condition osteoporosis, that can be more likely if you take steroid tablets.
Diet and Nutrition	1. There is only limited evidence available on the effect of diet in controlling lupus. 2. However, there is some evidence that a diet low in saturated fat and high in omega-3, which is found in oily fish, may be helpful. 3. You can also try taking fish oil supplements, but use fish body oil, not fish liver oil. 4. Too much fish liver oil can cause you to have too much vitamin A, which can have side effects such as liver damage and hair loss. 5. Make sure to get enough vitamin D and calcium. 6. These important nutrients are needed for strong bones. 7. Calcium is in dairy products, such as milk, cheese and yoghurts, as well as some green leafy vegetables. 8. In general, the best source of vitamin D is a healthy and safe amount of sunlight on bare skin. 9. Because it is not possible to get enough vitamin D from sunlight all year round in the UK and because too much sunlight can be unhealthy for people with lupus, you might need to take vitamin D supplements. 10. Be careful of any exclusion diets where large food groups are removed from the diet – you need all the nutrients that a well-balanced diet will provide. 11. Consult a dietitian if you need more specific advice.
Sunlight	1. Too much ultraviolet light from sunlight can cause a red rash across the cheeks and the bridge of the nose, often known as the butterfly rash. 2. It can also sometimes cause problems with internal organs to flare up. 3. Bear this in mind when choosing a holiday destination and discuss with your nurse specialist or dermatologist if in doubt. 4. Keep out of the midday sun and wear a hat. 5. Keep your skin covered or use sun cream of factor 50 or greater – which is available on prescription for people with lupus. 6. You can also buy high-factor sun creams that include a tint and can be used as foundation make-up. 7. Be careful when sitting under sun umbrellas on a paved area as the sunlight will be reflected onto your face.
Raynaud’s Phenomenon	1. If you experience Raynaud’s in your hands or feet, dress suitably for cold weather. 2. Smoking is bad for the circulation and is likely to make symptoms worse. 3. Regular exercise will improve your circulation. 4. There are also drugs that can be prescribed to people with Raynaud’s, to improve circulation to the fingers and toes. 5. Talk to your medical professional about these.
Mental Health	1. Because of the pain, fatigue and disruption to life, lupus can cause anxiety and depression. 2. It is important to talk to someone you trust if you are feeling down or worried. Regular exercise can improve feelings of stress, anxiety and depression.
Work	1. If you have lupus, you may want to seek extra support at work. 2. There might be equipment that your company could provide you with to make you more comfortable and help you do your job better. 3. There may also be flexible working arrangements so you could work from home at least some of the week, or alter your shift patterns to avoid rush hours. 4. The Equality Act 2010 means that employers have a responsibility to remove barriers in the workplace for people with a disability and financial support is available to help them do this through the Access to Work scheme. 5. You may not think the term disability is appropriate for you, especially if your condition is well treated and under control a lot of the time. 6. But it can apply to lupus, meaning you are entitled to additional support to help you in your employment or education. 7. The Equality Act states that someone is disabled if they have a physical or mental impairment that has a substantial and long-term negative effect on their abilities to do normal everyday activities, if they were not taking any medication. 8. It might help to ask yourself, if I was not taking any medication, would I find it difficult to do things such as dress or wash myself, go shopping or go out to work on my own?
Contraception	1. If you have lupus you should talk to your doctor about what form of contraception would be best for you. 2. It can be important to avoid unplanned pregnancies if you have lupus, particularly when your condition is active and affecting your kidneys, if you are on certain drugs, or if you have high blood pressure. 3. You might need to avoid contraceptive pills containing oestrogen as there is a very small risk that they can cause blood clots, known as deep vein thrombosis (DVT). 4. These blood clots can be dangerous if they break off and travel around the body, such as to the lungs. 5. This is more of a risk if you have antiphospholipid antibodies, which means you are already at risk of blood clots. 6. It is best to use contraceptive pills that contain only progesterone or only low-dose oestrogen, or consider barrier methods of contraception, such as condoms. 7. If you are taking steroid treatment, you should avoid using the contraceptive medroxyprogesterone acetate, which has the trade name Depo-Provera. This is given by injection. It increases the risk of developing osteoporosis because it reduces the levels of oestrogen in your body, which is important for bone health. 8. The Mirena coil, which releases progesterone only, is often a recommended option for women with lupus.
Hormone Replacement Therapy (HRT)	1. In the past there has been concern about HRT increasing the risk of flare-ups of lupus. 2. However, recent research has suggested that it is relatively safe to use for short periods if symptoms of the menopause are severe and your lupus is otherwise well controlled. 3. Make sure you speak to your rheumatologist if you are planning to start HRT.
Complementary or Alternative Medicines (CAM)	1. There is no scientific evidence that suggests any form of CAM helps to ease the symptoms of lupus. 2. However, if you have joint pain, acupuncture and massage may help. 3. The pain relief may only last a short time to begin with, but repeated treatments may bring longer-lasting benefits. 4. You may need to visit a private practitioner as the treatment may not be available on the NHS. 5. Generally speaking, complementary and alternative treatments are safe if you want to try them, but you should always discuss their use with your medical professional before starting treatment. 6. There are some risks associated with specific therapies. 7. In many cases, the risks associated with CAM treatments are more to do with the therapist than the therapy. 8. This is why it is important to go to a legally registered therapist, or one who has a set ethical code and is fully insured. 9. If you want to try a CAM treatment, it is important to talk to your medical professional first. 10. Potential CAM treatments include: a. Dehydroepiandrosterone (DHEA): Taking supplements containing this hormone along with conventional treatment may help reduce lupus flares. DHEA may lead to acne in women. b. Fish oil. Fish oil supplements contain omega-3 fatty acids that may be beneficial for people with lupus. Preliminary studies have found some promise, though more study is needed. Side effects of fish oil supplements can include nausea, belching and a fishy taste in the mouth. c. Acupuncture. This therapy uses tiny needles inserted just under the skin. It may help ease the muscle pain associated with lupus.

10.0 What is the Prognosis?

No cure is available for lupus but, as noted above, there are many treatments.

In the 1950s, most people diagnosed with lupus (SLE) lived fewer than five years. Today, over 90% now survive for more than ten years, and many live relatively symptom-free. 80-90% can expect to live a normal lifespan. Mortality rates are, however, elevated compared to people without lupus. Between 2006 and 2016, in the US, the five-year survival rate of patients with SLE improved to more than 90-95% because of more effective recognition and treatment of infectious and renal complications. 70-85% of patients have 10 year survival.

Prognosis is typically worse for men and children than for women; however, if symptoms are present after age 60, the disease tends to run a more benign course. Early mortality, within 5 years, is due to organ failure or overwhelming infections, both of which can be altered by early diagnosis and treatment. The mortality risk is fivefold when compared to the normal population in the late stages, which can be attributed to cardiovascular disease from accelerated atherosclerosis, the leading cause of death for people with SLE.

It is believed that between 10-15% of people with lupus will die prematurely due to complications of lupus. However, due to improved diagnosis and disease management, most people with the disease will go on to live a normal life span.

A Lupus Foundation of America funded study found (in the US) that overall, lupus was among the top 20 leading causes of death in females ages 5-64. Among black and Hispanic women lupus ranked 5th in the 15-24 years, 6th in the 25-34 years, and 8th-9th in the 35-44 years age groups, after excluding the three common external injury causes of death from analysis.

11.0 Meeting Others with Lupus

Lupus is a difficult condition to live with and throws up many challenges, especially during periods of life when you may need more energy.

Meeting others with lupus does not necessarily remove these challenges but it can help you to cope with them by sharing your thoughts and concerns with someone who understands.

You may have access to an education programme through a lupus nurse specialist or you may wish to meet others through patient support groups such as LUPUS UK.

12.0 Research and New Developments

There are a wide range of projects that aim to prevent the onset of lupus, transform its treatment and ultimately find a cure. New therapeutic approaches that target cells and molecules believed to be part of the cause of lupus are being used to help many patients. Further research studies should allow us to find out how these and other drugs can be used to the best effect. Examples of research include:

• A study, being carried out at University College London, is looking into the potential link between a lack of iron in the blood and fatigue in lupus patients. This could lead to the development of new treatments to combat fatigue.
• Research is investigating how messaging molecules influence the response produced by the body to rituximab. This could lead to new treatments.
• A pilot study is investigating if a medication called belimumab can be used to prevent relapses after rituximab therapy. This could eventually provide a new treatment option for lupus patients.
• Research is looking at why vascular disease often develops in people who have lupus. This could lead to the development of new drugs that could reduce the risk of heart attack or stroke in lupus patients.
• Research is helping us to understand how changes in a specific gene contribute to the risk of developing adult lupus, and which genetic factors lead to the development of lupus in children. This could help develop new treatments for children and adults.

13.0 Exercise and Lupus

• Regular exercise has been shown to significantly improve quality of life beyond just improving sleep and energy levels in people with lupus.
• Just like everyone else, where possible, people with lupus need to exercise regularly or engage in some kind of movement.
• It is very important to recognise that lupus affects everybody differently and so not everyone with lupus can do a wide range of exercises, but most people with lupus can take part in some form of activity.
• It is also important to realise that the amount of activity you can manage is likely to fluctuate as your lupus does.
• The level of exercise that is safe for you may change if your lupus symptoms become more active.
• If you have a flare of your lupus symptoms, you may need to reduce or stop your exercise activity to prevent damage to inflamed joints and muscles and to avoid fatigue.
• Although exercise can help to reduce feelings of fatigue, too much exercise could trigger a lupus flare-up.
• You will need to find the right balance and avoid pushing yourself too hard.
• Check with your medical professional to see what level of exercise may be best for you.
• Benefits of regular exercise for those with lupus and in general include:
  • Decreased risk of cardiovascular problems.
  • Help to maintain a healthy body weight.
  • Increased bone density to fight osteoporosis.
  • Improved sleep quality.
  • Improved mood and quality of life.

14.0 Personal Notes

My wife is a medical professional in the UK (general practitioner, GP) and has range of health conditions. She occasionally has a butterfly-rash on her face and some of the other symptoms. However, due to differential diagnosis, it is difficult to definitively state she has lupus.

15.0 Summary

This article is about lupus and includes a description of what lupus is, the main types, and what can cause lupus. It then went on to outline who can be affected by lupus, prevalence and risk factors, as well as the ‘main’ and ‘secondary’ symptoms. Next it discussed how lupus is diagnosed, differential diagnosis, and treatment options. Nearing the end, the article looked at the prognosis for lupus, as well as meeting others with the condition, and finally research and new developments. Finally we discussed at exercise and lupus, including some personal notes, a brief summary of what had been discussed, ending with useful references.

16.0 References

Bohan, A. (1979) Seronegative Systemic Lupus Erythematosus. Journal of Rheumatology. 6(5), pp.534-540. https://pubmed.ncbi.nlm.nih.gov/93147/.

Koller, S.R., Johnston, C.L. Jr, & Moncure, C.W.  (1976) Lupus erythematosus cell preparation-antinuclear factor incongruity. A review of diagnostic tests for systemic lupus erythematosus. American Journal of Clinical Pathology. 66(3), pp.495-505.

LUPUS UK. (2015) Testing for Lupus. Available from World Wide Web: https://www.lupusuk.org.uk/medical/lupus-diagnosis-treatment/introduction-to-lupus/testing-for-lupus/. [Accessed: 09 March, 2023].

O’Sullivan, M., McLean-Tooke, A. & Loh, R.K.S. (2013) Antinuclear Antibody Test. Australian Family Physician. 41(10). https://www.racgp.org.au/afp/2013/october/antinuclear-antibody-test.