FAQs on X-linked carrier issues

• Lupus is an autoimmune condition caused by a fault in the body’s immune system. Normally the immune system produces antibodies to help fight infection. When someone has an autoimmune condition, antibodies are made which act against the body’s own tissues, causing inflammation. These are called autoantibodies. When this happens, it causes inflammation in various parts of the body. This can result in symptoms such as skin rashes and joint pain.

• Lupus is not an uncommon condition. Around 1 in 1,000 people in the UK have lupus. Of the people who have lupus, 9 out of 10 are female. Doctors and researchers think that there could be a link between lupus and female genetics or hormones, but they do not know the exact cause of lupus yet.

• In 2017, a study reported on the results of a digital health survey among 81 X-linked CGD carriers in the UK. Specifically, the researchers looked at lupus-like symptoms. X-linked CGD carriers experienced the following symptoms:

  • Mouth ulcers (~7 in 10 people)
  • Photosensitivity (~7 in 10 people)
  • Joint symptoms (~6 in 10 people)
  • Fatigue (~5 in 10 people)
  • Raynaud’s phenomenon (~3 in 10 people)

There are two forms of lupus that X-linked CGD carriers can be diagnosed with. One is called ‘discoid lupus erythematosus’ (DLE, also called ‘discoid lupus’) and largely affects the skin. The other is ‘systemic lupus erythematosus’ (SLE, also called ‘systemic lupus’) and affects joints, the blood, lungs, kidneys, heart and nervous system.

Occasionally, X-linked CGD carriers may experience symptoms of lupus and be diagnosed with either discoid lupus or systemic lupus. However, it is more common for X-linked CGD carriers to experience symptoms that are associated with lupus, without actually receiving a lupus diagnosis. Doctors refer to this as having ‘lupus-like symptoms’. Please refer to the question How do I know if I have lupus? for more information.

General practitioners (GPs) will look at your symptoms and blood tests to make a diagnosis of lupus. The blood tests for lupus look for particular types of antibodies in your body. Antibodies are proteins that your immune system produces to protect you from infections. They fight off ‘harmful invaders’ such as bacteria and other germs. However, sometimes your immune system can mistake parts of your own body for a ‘harmful invader’. When this happens, your immune system will make special types of antibodies called ‘autoantibodies’.  This is what happens in lupus, and these autoantibodies attack your cells and tissues, including your joints and skin.

The most reliable blood test for lupus is an ‘anti-nuclear antibodies’ (ANA) test. The ANA test looks for a specific type of autoantibody called an ‘anti-nuclear antibody’, which causes autoimmune disorders like lupus.

Research by clinicians at Great Ormond Street Hospital and the Great North Children’s Hospital, Newcastle upon Tyne, has shown that X-linked CGD carriers can have lupus-like symptoms, even though their blood tests show either as negative for lupus or only slightly positive. This is because the antibodies that are used to clinically diagnose lupus are not often present in X-linked CGD carriers. This means that blood tests for lupus may not be helpful for X-linked CGD carriers. However, lupus-like symptoms should be managed and taken seriously by medical professionals. Therefore, diagnosis and management should be based on symptoms, regardless of the results of blood tests.

The most common symptoms of lupus in carriers of X-linked CGD are photosensitivity, which means being very sensitive to the sun. A ‘lupus-like’ skin rash often develops over parts of the body which are exposed to the sun, such as on the face, wrists, hands and chest.

The next most common features are mouth ulcers (known as ‘aphthous ulceration’), headaches, and joint problems which typically include pains and swelling. Mouth ulcers are a symptom commonly found in X-linked CGD carriers, and so they are not a defining feature of lupus. However, they can be associated with lupus. Fatigue is also a common symptom of lupus. The feeling of tiredness tends to come and go, and people find that they have good and bad days.

Some people find that in the cold, the skin on their hands can become very white or blue. This is sometimes referred to as ‘Raynaud’s phenomenon’, which is a recognised symptom of lupus.

No, some X-linked CGD carriers have no symptoms of lupus at all. Others can have very mild symptoms, and some X-linked CGD carriers might have more severe problems. However, there is not enough information to fully understand why some X-linked CGD carriers are severely affected by lupus while others do not show any symptoms. Factors other than genetics may play a role in how symptoms show up in X-linked CGD carriers.

The first step is to tell your doctor that you are an X-linked CGD carrier, and that you are experiencing symptoms of lupus. You should also ask your doctor if you could get tested for lupus, to see if you might be diagnosed with discoid lupus or systemic lupus. Whether you get a lupus diagnosis or not, symptoms of lupus should be taken seriously by your doctor. Some symptoms can affect your long-term health by damaging your organs, so your doctor should give you information on how to manage your symptoms. If your symptoms become more serious, you should consider seeing an immunologist, rheumatologist or dermatologist.

When talking to your doctors, it is important to give them as much information as possible about your symptoms and how you feel. The information often holds clues to help doctors reach a decision on the cause of the problem. This will help them to find the right diagnosis and management.

 

Yes. Although there is no cure for symptoms of lupus, there are effective ways in which you can manage your symptoms and alleviate the problems. Only a doctor can prescribe medicines specifically for managing lupus symptoms. People who have joint pain and skin rashes are often managed with creams for skin rashes (many containing steroids) or anti-inflammatory medicines. Some people find that anti-malarial drugs (commonly hydroxychloroquine) are also effective in managed the symptoms of lupus, particularly joint pain which can make you feel tired. People who have more serious symptoms may be managed with steroid tablets or other drugs that help restore a healthier immune system. People on these medications need to be monitored carefully, have regular blood tests and medication reviews with their doctor.

The skin rashes associated with lupus are often very sensitive to the sun. Therefore, it is recommended to wear a high factor sun cream, of Sun Protection Factor (SPF) 50 or greater when you’re outside. It is also recommended to avoid sun-bathing and sitting in direct sunlight or rooms with fluorescent lighting for long periods of time. In the UK, sun cream may be available on prescription for people with lupus or lupus-like symptoms. You can talk to your doctor if you would like to have more information about a sun cream prescription from the NHS.

People who have problems with Raynaud’s phenomenon should keep warm and wear thick gloves and socks or tights. Tiredness tends to come and go, so it’s probably best to take a break and try and get some rest on bad days, and make the most of good days.

To help manage your symptoms, it is also important to try to stay active and eat a healthy, balanced diet which includes vitamin D and calcium. Also, both stress and smoking can make symptoms of lupus worse. Therefore, try to manage stress using relaxation techniques and refrain from smoking.

We don’t know exactly, but researchers think that lupus symptoms in X-linked CGD carriers are a result of a few things, including genetic factors, somebody’s direct surroundings and personal characteristics. There are two specific processes may cause lupus symptoms in X-linked CGD carriers: ‘X-inactivation’ and ‘reduced cell death and cell clearance’. Both are explained below.

X-inactivation

Females are born with two X chromosomes in each cell in the body, including white blood cells. X-linked CGD carriers carry the CGD genetic variant on one of their two X chromosomes, while the other X chromosome is healthy. Before birth, one of the X chromosomes in each cell is silenced (‘inactivated’) at random – this is called X-inactivation, and is a natural process in all females. Thus, it is random as to whether the X chromosome with the CGD variant, or the healthy X chromosome, is inactivated in a cell. As a result, some white blood cells may have an active chromosome with the CGD variant, and others may not. If a white blood cell has an active chromosome with the CGD variant, it may not function properly. Some carriers of X-linked CGD have more white blood cells that do not function properly, and therefore may experience more symptoms. Others may have more white blood cells that are healthy, and therefore experience little to no symptoms.

Reduced cell death and cell clearance

In everyone’s body, cells naturally die and new cells develop. In people with CGD, white blood cells that carry the CGD genetic variant appear to take longer to die than ‘normal’ cells. This can increase the risk of developing lupus in people with CGD. It is also normal and important that dead cells and other debris in the bodies are ‘cleaned up’. CGD-affected cells aren’t as good as ‘normal cells’ at cleaning up dead cells and debris. As a result, there may be extra dead cells in the body’s tissues. These extra dead cells can cause inflammatory and abnormal responses in the body that show up as symptoms of lupus.

No, as yet, no clear-cut relationship has been found in research studies. Also, in these studies the number of participants is often small, so we need to be cautious about interpreting results. Similarly, we don’t know if the numbers of non-functioning cells can vary over time.

Yes, but this is very unlikely. If a doctor sees a case that does not fit into the classical lupus criteria, they would ask more questions. They may take a history of illnesses in the family and consider testing to see whether the person is a carrier for CGD.

There is not a clear answer. Pregnancy can alleviate or worsen symptoms of many conditions. Generally, females with lupus can remain healthy during pregnancy. However, it is important to discuss a potential pregnancy with your doctor. This is because there are some things you will need to consider, such as being on stable medication that is suitable for pregnancy. Also, during pregnancy, some females may experience more lupus flares than females who are not pregnant. However, these lupus flares are generally mild. Your pregnancy should be closely supervised by your doctor or nurse.

Although information on lupus and pregnancy has become more available over recent years, more research involving pregnant females who are X-linked CGD carriers is needed.

Currently, there is not enough information to fully understand why some X-linked CGD carriers are affected badly by lupus while others do not show any symptoms. There are likely to be a lot of factors which determine how severely someone is affected by lupus, but currently not much is known about what these could be..

There is no evidence for a connection of this type at present. We believe that variations in an individual’s genetic make-up determine how severe CGD symptoms will be. Further research is needed.

Symptoms of lupus can occur in some young girls. In others, it may or may not come on later in life. In X-linked CGD carriers, doctors have noticed that some lupus-like symptoms tend to be more significant in older carriers than younger carriers. In particular, joint pain and fatigue are symptoms of lupus that can get more severe as you get older. More research needs to be done to find out if there is a link between age and when symptoms of lupus occur.

It’s hard for us to know but this is unlikely. Some research suggests that females may present symptoms of lupus during puberty and their reproductive years. After the menopause, symptoms of lupus may improve.