Lupus

Lupus is an autoimmune disease that can affect the joints, heart, nervous system, brain, skin, lungs and kidneys. It is a chronic condition. If you have lupus, you experience periods when the condition is active, known as flares, separated by periods of remission when you feel normal.

Lupus occurs when our immune system mistakenly begins to react against elements of the body's own cells as foreign material. Immune cells manufacture antibody molecules that cause damage and inflammation to the targeted tissues and organs.

The causes of lupus are not completely understood. Autoimmune diseases in general still present a challenge to medical science and lupus is no exception. Genetic as well as environmental factors can contribute to the development of lupus in an individual.

Lupus can be difficult to diagnose. The symptoms of lupus are common to other conditions and symptoms often vary between individuals. There is no single definitive test for lupus. As a result, lupus can sometimes take a long time to be diagnosed correctly.

Because it can be difficult to recognise and diagnose, it is also hard to know exactly how common lupus is. Recent estimates are that about five million people worldwide have the disease.

There is currently no cure for lupus. However, the advances that have been made in understanding lupus have transformed it from an often fatal condition to a manageable one. Correct treatment combined with lifestyle adaptations can now allow most people with lupus to lead normal lives.

Signs and symptoms

Because lupus can affect multiple parts of the body, the signs and symptoms can vary widely between cases - as can their severity and time of appearance. The most common signs of lupus include:

• Skin rashes on face, upper arms, chest, wrists, and hands, in particular a distinctive 'butterfly rash' across the cheeks and the bridge of the nose. Rashes are often triggered by exposure to the sun;
• Fatigue;
• Swelling and pain in the joints and muscles and around the eyes;
• Fever;
• Mouth ulcers;
• Swollen lymph nodes;
• Chest pain, particularly when taking deep breaths;
• Hair loss;
• Sensitivity to sunlight;
• Loss of appetite and/or loss of weight, and;
• Memory loss, confusion, headaches, seizures or dizziness.

Some people will experience only one or a few signs, confined to one part of the body (such as the skin). Others will experience signs in multiple parts of the body.

Lupus erythematosus appears as a 'butterfly rash' on the face. 

Causes

The causes of lupus are not well understood. It is clear that genetics plays a large part. For instance, an identical twin of a person with lupus has a one-in-four chance of developing the condition. There is no single gene that causes lupus. Several different genes (more than 40 at last count) affect a person's susceptibility to lupus, as well as determining which part of the body is affected.

It is equally clear that lupus is not just a genetic disease. Lupus appears to be a combination of a genetic disposition triggered by environmental conditions.

The main environmental factors that may trigger lupus are:

• Sunlight;
• Hormonal activity;
• Reaction to certain chemicals and medications;
• Infection with viruses, particularly the common Epstein-Barr virus (EBV);
• Smoking, and;
• Stress.

It should be noted, however, that lupus can sometimes appear even without any particular exposure to any of these triggers.

Types

Lupus can appear in many forms. Because its causes and signs are varied and not well understood, it is often hard to categorise lupus definitively. At present, lupus can be classified into the following types:

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is the most well-known form of lupus and the one most people mean when they say 'lupus'. The condition can affect any part of the body. The course of disease can range from mild to life-threatening. About 15% of the people who have SLE first develop symptoms in their teens. SLE will most often affect the kidneys, joints, skin, heart, lungs, blood vessels, liver and the nervous system.

If you have SLE, you experience periods when the condition is active, known as flares, separated by periods of remission when you feel normal. Treatment of SLE focuses on controlling its symptoms by the use of immunosuppressive medication - drugs that suppress the immune system's activity - and other types of drugs that help alleviate the symptoms.

Discoid lupus erythematosus

A mild form of lupus, discoid lupus erythematosus (DLE) is an inflammation of the skin. It typically appears as round, raised red marks on the skin, particularly on exposed areas of the skin such as the face, ears and scalp. These can thicken and turn crusty with time and create permanent scars. DLE can also cause hair loss and bald patches. DLE can last anywhere from days to years. It may disappear, then recur at a later time. The condition can be successfully treated with medication and by avoiding exposure to sunlight.

It is not clear whether DLE is a distinct condition or a milder form of SLE. In about 5-10% of DLE cases, the condition progresses to other body parts and systems, resulting in SLE.

Discoid lupus erythematosus. 

Drug-induced lupus erythematosus

This form of lupus can be a side effect of certain medications, including drugs for thyroid and heart conditions, high blood pressure, tuberculosis, oral contraceptives, anti-seizure medication, antibiotics and antifungals. The symptoms are like those of SLE - mostly joint and muscle pain and arthritis. Symptoms can start at any time, from a month to 10 years after starting to take the medication, but normally stop when the drug is no longer taken.

Subacute cutaneous lupus erythematosus

This form of lupus is characterised by skin lesions on sun-exposed areas of the body (neck, upper back, shoulders, chest, arms and hands), but rarely on the face and scalp. After they heal, the lesions do not leave scars on the skin, but the skin's colour may remain altered. Subacute cutaneous lupus erythematosus can occur together with other types of lupus and rarely develops into serious SLE. Treatment normally involves medication and avoiding exposure to the sun.

Neonatal lupus erythematosus

This is a rare condition that occurs in infants. The affected babies can be born to mothers with SLE or Sjögren's syndrome (another autoimmune disease, see 'Complications' below), but also to healthy mothers. It is important to note here that most babies born to mothers with SLE will be healthy.

Methods for diagnosis

Lupus diagnosis can be challenging. The symptoms can be so varied and appear at such irregular time frames, with long periods of apparent wellness in between, that even suspecting lupus can often take a long time.

A doctor will typically make an initial lupus diagnosis on the basis of a patient's history and a physical examination. Laboratory tests will help confirm the diagnosis and rule out similar conditions (such as rheumatoid arthritis). After lupus has been diagnosed, tests can be performed regularly to help monitor its progression.

Tests for lupus can include:

• Blood tests - these can check for several types of antibodies that the immune system may generate in people with lupus. The most indicative of these is the antinuclear antibody test (ANA). A different antibody test, called the anticardiolipin antibody test, is often performed on pregnant women when lupus is suspected;
• Skin biopsy - removing a small sample from a skin lesion for detailed examination;
• Full blood count;
• Erythrocyte sedimentation rate (ESR) and C-reactive protein tests, to measure levels of inflammation;
• Blood chemistry tests;
• Chest X-rays to search for suspected lung inflammation, and;
• Echocardiography to check for heart problems.

Types of treatment

Lupus is normally treated with several types of medication. The two main goals of lupus treatment are to reduce inflammation and to prevent the immune system from further damaging the body. Different people can have different responses to the various treatments; a process of trial-and-error is sometimes necessary before the best treatment course is found.

Non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) help reduce inflammation and the symptoms associated with it, such as swelling and muscle aches.

Antimalarial drugs

These drugs, originally used to treat malaria, were found to benefit people with lupus. They help modulate the body's immune response, though it is not clear how they work. Antimalarial drugs, particularly hydroxychloroquine, can help alleviate SLE symptoms, as well as prevent SLE flares from occurring.

Corticosteroids

Corticosteroids are a class of drugs that mimic the body's natural anti-inflammatory hormone, cortisol. They often exhibit quite powerful and fast-acting effects - and side effects, particularly if used long-term. For this reason, they are used only in severe cases of SLE, or to help control flares in the short-term. Doctors try to find the lowest effective dosage and combine corticosteroids with other forms of medication for better effect.

Immunosuppressants

Immunosuppressants are a class of drugs that kill off immune cells or actively inhibit their creation, thus reducing the potency of immune reactions. Like corticosteroids, these are powerful drugs that can also have serious side effects and are used mainly for treatment of severe SLE.

In recent years, a number of new immunosuppressive drugs have been proposed and trialled for treating severe SLE that does not respond to other forms of therapy. Rituximab and belimumab are two that have been approved for use in some countries.

Stem cell transplant

Stem cells are being trialled as transplant therapy for severe and persistent cases of lupus that do not respond to current treatments. This advanced type of therapy is still very much in its first stages and involves considerable expertise and expense.

Potential complications

The more common complications of SLE are:

Kidney disease

Kidney disease, or lupus nephritis, is a chronic inflammation of the kidneys. It is a common, serious and potentially fatal complication of SLE, developing in up to 70% of SLE cases. Both men and women can be affected, with men being more likely to suffer more severe complications. Lupus nephritis is caused by the body's immune system targeting cells in the kidneys, resulting in chronic inflammation. Symptoms, in addition to the ones for SLE mentioned above, include foamy urine, increased blood pressure and swelling in the arms, legs, feet and hands. If treatment is not successful, kidney problems will appear and may lead to kidney failure and the need for dialysis or, in some cases, a kidney transplant.

For people with suspected lupus nephritis, the following tests may be performed:

• Kidney biopsy - removing a small sample of kidney tissue for detailed examination;
• Urinalysis - a chemical analysis of a urine sample, and;
• Blood tests for analysing kidney functions.

Heart disease

Lupus increases the risk of heart disease. Heart and circulation problems are responsible for a large share of deaths from the disease. Heart disease in lupus can take on many forms - it can cause inflammation of the blood vessels (veins and arteries), which may lead to atherosclerosis (a stiffening of the blood vessel walls). In addition, lupus can affect the heart itself, its valves and the membrane surrounding it (the pericardium). There may be other yet unknown factors responsible for the link between lupus and heart disease.

Respiratory disease

About half of SLE patients experience respiratory problems of one type or another, stemming from inflammation of the lungs, the airways, or the tissues surrounding them. The blood vessels leading to and from the lungs can also become inflamed, affecting lung function. People with SLE can experience chest and breathing pain, shortness of breath and a dry cough. If the diaphragm muscle has been damaged by SLE inflammation, it can lead to pain when breathing in.

Infection

People with SLE are more susceptible to infection, particularly by bacteria. This can be attributed to two factors:

• The immunosuppressing medication that is used to treat SLE weakens the immune system's ability to cope with infection, and;
• SLE itself changes the immune system and may reduce its ability to fight infection.

Cancer

People with SLE are not generally at a greater risk of developing cancer. However, there are some types of cancer, particularly leukaemia and lymphoma, which are more common in people with SLE than in the general population. Conversely, some types of cancer are less common in people with SLE than in the general population. The immunosuppressive medication that is used to treat SLE has not been found to increase the risk of cancer.

Nervous system

Central nervous system

When the central nervous system (brain and spinal cord) is affected by lupus, this can lead to a variety of symptoms including headache, dizziness, depression and changes in behaviour.

Lupus fog

People with lupus often complain of difficulties in thinking clearly and processing information, particularly during a lupus flare. Confusion, fatigue, difficulty concentrating and memory loss are commonly reported. This is sometimes referred to collectively as cognitive dysfunction, or colloquially as 'lupus brain fog'. The causes of this syndrome are not quite clear, but appear to be linked to the action of antibodies on brain cells and to changes in blood flow to the brain. These spells come and go, with each individual spell typically lasting only a few minutes. This condition does not get worse over time. It is managed mainly using behavioural therapy.

Peripheral nervous system

The peripheral nervous system (PNS) is responsible for sensation and movement of the body. When lupus disrupts the action of the nerve cells that constitute the PNS, the affected person may experience many symptoms, depending on which nerves are affected. Vision problems, eyelid drooping, ringing in the ears and dizziness are common complaints.

Autonomic nervous system

The autonomic nervous system (ANS) is responsible for regulating the actions of the body's automatic systems that we do not consciously control (the digestive system, heart, bladder, etc.). When lupus disrupts the action of the ANS, it may cause a wide range of symptoms, including (among many others) difficulties in digestion, numbness, nausea and vomiting.

Syndromes associated with systemic lupus erythematosus

There are several conditions that, although they are independent syndromes, can also arise in combination with lupus:

Raynaud's phenomenon

A common syndrome that is caused by a decrease of blood flow to certain areas in the body, Raynaud's phenomenon is caused by an overreaction of the capillaries in the extremities of the body - typically the fingers and toes - to cold temperature. The cold makes these tiny blood vessels contract, preventing blood reaching the body part. The fingers or toes then lose their natural colour and appear white, turning to bluish and finally red.

Sjögren's syndrome

This is a reaction of the immune system against the glands of our body that produce saliva and tears. The immune attack of the glands reduces their ability to operate and produce tears and saliva, which causes a chronic dryness of the mouth and the eyes. People who have Sjögren's syndrome often complain of difficulties in swallowing and a dry cough and are more likely to develop mouth infections and dental problems. Eye dryness can cause itching, blurry or distorted vision and increased sensitivity to light.

Anti-phospholipid syndrome

Also known as Hughes syndrome, this occurs when the immune system manufactures antibodies against proteins in the blood. As a result, blood clots form in the bloodstream. These can cause a large and varied number of problems throughout the body. Hughes syndrome is perhaps most notable for causing a large number of miscarriages and foetal deaths, as the mother's thickened blood cannot pass to the foetus through the placenta. It can normally be treated with blood-thinning medication, such as aspirin.

Treatment side effects

Non-steroidal anti-inflammatory drugs (NSAIDs)

Common side effects of NSAID treatment for lupus include mainly the risk of stomach inflammation and ulcers. Other side effects include kidney problems, headache, confusion and dizziness.

Antimalarial drugs

The common side effects of antimalarial medication for people with lupus mostly include digestive problems and some skin complaints.

Corticosteroids

Long-term corticosteroid treatment for lupus can bring with it significant side effects. These can include:

• Increased risk of infection;
• Diabetes (type 1 or type 2);
• Osteoporosis;
• High blood pressure;
• Increased appetite leading to weight gain;
• Short-term mood changes and restlessness, and;
• Easy bruising.

Immunosuppressants

Possible side effects of immunosuppressive treatment for lupus include:

• An increased risk of infection and of cancer;
• Liver damage;
• Diarrhoea;
• High blood pressure;
• Osteoporosis;
• Nausea, and;
• Hair loss.

Prognosis

There is as yet no cure for lupus. Treatment for lupus has, however, advanced dramatically over the past few decades. The 10-year survival rate for a person diagnosed with lupus in 1955 was only around 50%. In contrast, more than 90% of people diagnosed with lupus today can look forward to a normal life expectancy and a fairly normal life.

Prevention

There is no effective way to prevent lupus from occurring in the first place. A person with lupus can reduce the incidence and severity of lupus flares by making behavioural and lifestyle adjustments. These can include:

• Knowledge and awareness of the condition, its symptoms and progression;
• Regular, ongoing medical monitoring of the condition;
• Avoiding exposure to sunlight by wearing protective clothing such as a hat and long-sleeved shirt (and sunscreen);
• Resting and avoiding potentially fatiguing situations;
• Moderate, regular exercise;
• Avoiding infections, and;
• Quitting smoking.