Lupus and Carriers of X-linked CGD
There is increasing evidence that some carriers of X-linked CGD develop symptoms of the condition lupus. This webpage provides some information on symptoms of lupus in X-linked CGD carriers. It helps explain what lupus and lupus-like symptoms are and how they can affect X-linked CGD carriers. It also explains what to look out for and how symptoms can be managed.
We also want to make sure that medical professionals are aware of health problems that X-linked CGD carrier-related have, such as lupus and lupus-like symptoms, so that they take them seriously and address them quickly and appropriately. That's why we’ve also produced an information document for GPs, which you can download and give to your general practitioner (GP) when you suspect you may have lupus or lupus-like symptoms.
How do I know I am carrier of X-linked CGD?
Testing for X-linked CGD
X-linked CGD carriers are almost always female. Carriers may have male relatives who are affected by X-linked CGD, which is the most common form of CGD. You can get a simple blood test to determine whether you are an X-linked CGD carrier. The blood test could be the nitroblue tetrazolium (NBT) test, dihydrorhodamine (DHR) test or a genetic test. If you would like to get a blood test, you should discuss this with your doctor. Your doctor can do the blood test and will help you understand the results.
The NBT and DHR tests check if your white blood cells are producing a protein called ‘NADPH oxidase’. NADPH oxidase normally makes it possible for white blood cells to fight infections. However, in CGD, NADPH oxidase does not work properly. The DHR test is generally more accurate than the NBT test. This is because the NBT test result can sometimes look normal in X-linked CGD carriers when it should not be.
A genetic test (which is also a blood test) will look to see if your cells have the faulty gene of X-linked CGD. Your doctor may choose to do a genetic test for one or more of the following reasons:
- If they know that a member of your family is affected by CGD.
- If they want to confirm whether you are an X-linked CGD carrier.
- If they want to rule out other diseases (this is called a ‘differential diagnosis’).
Symptoms of CGD in X-linked CGD Carriers
In general, X-linked CGD carriers are healthy. However, in some cases, carriers can experience symptoms of CGD. The CGD Society Carrier Survey highlighted the symptoms that 35 X-linked CGD carriers experienced:
- 85% had mouth ulcers.
- 88% were affected by skin problems.
- 68% experienced abnormal fatigue.
- 45% had recurring headaches.
Many carriers who responded had different combinations of symptoms. In some cases, the symptoms were severe and debilitating. The survey also highlighted that symptoms tend to be more significant in older carriers than younger carriers.
Occasionally, X-linked CGD carriers also experience symptoms similar to a condition called lupus. Doctors may refer to these as ‘lupus-like’ symptoms. Other carriers may have lupus itself.
Lupus and Lupus like symptoms
What is lupus and how can it affect X-linked CGD carriers?
Lupus is an autoimmune condition, caused by a fault in the body's immune system. This means that the immune system attacks the body’s own healthy tissues, in much the same way as it would attack germs. When this happens, it causes inflammation in various parts of the body. This can result in symptoms such as skin rashes and joint pain.
There are two forms of lupus:
- discoid lupus erythematosus (also called discoid lupus) which is largely confined to the skin.
- systemic lupus erythematosus (also called systemic lupus) which affects the joints, heart, blood, lungs and kidneys.
It is possible for X-linked CGD carriers to be diagnosed with discoid lupus or systemic lupus. However, it is also possible for carriers to experience lupus-like symptoms and not be diagnosed with either form of lupus. These lupus-like symptoms should be taken as seriously as discoid lupus or systemic lupus.
For many people, lupus-like symptoms are no more than a nuisance. However for other people, lupus-like symptoms can be more troublesome. People who experience lupus-like symptoms may benefit from medications that are used to manage symptoms in discoid lupus or systemic lupus, even if they are not diagnosed with either of these.
Systemic lupus can be an unpredictable condition, which should be carefully monitored by an immunologist or a rheumatologist (often in a special lupus clinic).
What are the symptoms of lupus?
The most common symptoms of lupus are skin rashes which are very sensitive to the sun (sometimes referred to as ‘photosensitive rashes’), fatigue and joint pains. Other symptoms can also include headaches, mouth ulcers and temporary changes in the colour of your fingers and toes when you are cold, anxious or stressed (this is known as ‘Raynaud’s phenomenon’). Mouth ulcers are a symptom commonly found in X-linked CGD carriers and are therefore not a defining feature of lupus, however, can be associated with lupus. For people with systemic lupus, more severe symptoms may include inflammation of internal organs such as the lungs, heart, nervous system and kidneys.
Although mild symptoms seem to be relatively common in X-linked CGD carriers, the more severe symptoms (like the ones you may read about in the classical descriptions of lupus) are not.
What are lupus-like symptoms?
There are a number of X-linked CGD carriers who have symptoms of lupus, but they do not actually test positive for lupus. Doctors therefore refer to these symptoms as lupus-like symptoms. Lupus-like symptoms mainly include skin rashes that are sensitive to the sun, joint pains and swelling, and fatigue. Some people also experience Raynaud's phenomenon.
A study from 2017 reported on 81 X-linked CGD carriers in the UK. The study specifically focussed on gastrointestinal symptoms (symptoms associated with your stomach or gut, such as diarrhoea) and symptoms associated with systemic lupus. Of the 81 X-linked CGD carriers, many had symptoms often seen in lupus, which is summarised in Figure 1.
Figure 1. Symptoms of lupus occurring in participants of the 2017 study of 81 X-linked CGD carriers in the UK
Blood test results were available for 51 of the X-linked CGD carriers in this study. Out of these people, only 8 carriers (less than 2 in 10) had positive blood tests for lupus. This showed that, despite having symptoms of lupus, the majority of people did not test positive for lupus.
What should I do if I think I have lupus or lupus-like symptoms?
If you are an X-linked CGD carrier and think you may have lupus or lupus-like symptoms, you should discuss these with your GP. Your GP will then recommend that you have screening tests (such as X-rays and scans of your heart, kidney and other organs).
Symptoms of lupus need to be taken seriously, whether you are diagnosed with lupus or not. If your symptoms bother you or interfere with your daily life, your GP should refer you to an immunologist (a doctor that specialises in immune system conditions). It is important that the doctor understands that there is a known link between lupus-like symptoms and being a carrier of X-linked CGD. Other doctors, such as rheumatologists (a doctor that specialises in inflammatory conditions) or dermatologists (a doctor that specialises in skin conditions), may also offer specialist input.
Download our information sheet for GPs about the link between being an X-linked CGD carrier and lupus-like symptoms. We recommend that you give this information sheet to your GP if you think that you may be experiencing symptoms of lupus. If you have any concerns, discuss them with your doctor or the CGD clinical nurse specialist.
How do I know if I have lupus?
A GP can diagnose lupus by looking at the symptoms that you have and the results of blood tests. 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.
One of the most common blood tests for lupus is called an ‘anti-nuclear antibodies’ (ANA) test. This test looks for anti-nuclear antibodies, which are a specific type of autoantibody. However, the ANA test and other blood tests can show as negative in some people who do actually have lupus (especially discoid lupus). This seems to be particularly true for X-linked CGD carriers. This is because the antibodies that are used to clinically diagnose lupus are not often present in X-linked CGD carriers. These blood tests for lupus will also show as negative in X-linked CGD carriers who experience lupus-like symptoms. In Table 1, you can see an overview of how an X-linked CGD carrier might be affected by lupus, how they might be diagnosed and how often each of the possible scenarios happens.
The conclusion is that these types of autoantibody tests for lupus are not particularly helpful in X-linked CGD carriers. Instead, diagnosis and management of lupus should be based on the symptoms which X-linked CGD carriers experience.
Table 1: Overview of how lupus can affect X-linked CGD carriers and the possible outcomes of diagnosis
Managing lupus and lupus like symptoms
While there is no cure for lupus or the symptoms of lupus, there are effective ways in which you can manage your symptoms. The management approach will depend on the types of symptoms you experience. Therefore, the medications given can be slightly different for every person.
People who have skin rashes and joint pain are usually given creams (often containing steroids) or anti-inflammatory medicines like ibuprofen. Skin rashes associated with lupus are often very sensitive to the sun. It’s best to avoid sunbathing and you should wear a high factor sun cream (SPF 50 or higher) when outside. Also, try to avoid sitting in direct sunlight or rooms with fluorescent lighting for long periods of time. In the UK, sun cream may be available to people with lupus or lupus-like symptoms on prescription from a doctor. You can talk to your doctor if you would like to have more information about a sun cream prescription from the NHS.
Some people find that anti-malarial drugs (commonly hydroxychloroquine) are also effective in managing the symptoms of lupus, particularly joint pain which can make you feel tired. A doctor must prescribe these specifically for you. The fatigue tends to come and go, so it’s best to try and get some rest when you are not feeling good and make the most of days when you are.
People who have problems with Raynaud's phenomenon should keep warm and wear thick gloves and socks or tights.
To help manage your lupus symptoms, it is also important to try to stay active and eat a healthy, balanced diet which includes vitamin D and calcium. Also try to manage stress using relaxation techniques and refrain from smoking, as both stress and smoking can make symptoms of lupus worse.
People who experience more severe symptoms of lupus may also be given immunosuppressants, which alleviate symptoms by calming your body’s immune system. Steroid tablets and injections can also help manage symptoms of lupus as they reduce inflammation. When these medicines are prescribed, your doctor will want to review your health regularly through blood tests and regular check-ups.
More information
Read our FAQs concerning Lupus and other carrier issues
Read some of the published research about x-linked carrier issues
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