Results published recently in the journal Clinical and Experimental Immunology highlight the possibility of developing symptoms similar to lupus when you are a carrier of X-linked CGD.
Lupus is caused by a fault in the immune system. Symptoms of lupus are very varied but can include a combination of one or more of the following: photo-sensitivity (being very sensitive to the sun) resulting in a skin rash, mouth ulcers, joint pain and excessive fatigue. Professor David Goldblatt, Consultant in Paediatric Immunology, Dr Cathy Cale Consultant in Paediatric Immunology, and Louise Morton, our previous CGD Clinical Nurse Specialist, headed the study. It involved questioning X-linked CGD carrier mothers about their health, specifically with regard to symptoms that could be compatible with having lupus.
In an excellent presentation of the full research results at the Family Get-Together Weekend, in Windsor, Dr Cathy Cale explained “There are several forms of lupus. One type really only affects the skin and is called discoid lupus erythematosus. The most extensive type is referred to as systemic lupus erythematosus or SLE for short and can affect body organs such as joints, kidneys and the nervous system”. Her presentation caught many female carriers of X-linked CGD unaware. Two reactions were “This really opened up my eyes to being a carrier”, “I didn’t know I was at risk of developing of lupus or health-related issues by being a carrier. Dr Cale went on to reassure them. She explained that their experience was that many of the symptoms are very treatable and may involve creams for skin rashes or use of anti-inflammatory medicines. Sometimes these medications may involve steroids. Referral to a specialist dermatologist or rheumatologist may be helpful, particularly if the symptoms severe. She continued “It is really important to tell your doctor that you are a carrier if you have any lupus-like symptoms. We know that some X-linked carriers can present with very mild symptoms whilst others might have more severe problems. Some X-linked carriers have no symptoms of lupus at all”. Many in the audience really wanted to know why there is this link with lupus. Dr Cathy Cale commented “Researchers don’t yet know exactly why lupus symptoms develop in some X-linked CGD carriers and not others. We think that there may be other mechanisms at play, other than carrying the genetic fault. It is going to take a lot more work to understand the complexities of this”.
Find out more about lupus in the question and answer forum below.
Q. What is lupus?
A. There are several forms of lupus. One, is called discoid lupus erythematosus (referred to as DLE) and this is largely confined to the skin. The more extensive form is called systemic lupus erythematosus (SLE) and can affect joints, blood, lungs, kidneys, heart and nervous system.
Q. If you are a carrier of X-linked CGD what symptoms should you look out for?
A. In our published study the most common symptom of lupus was photosensitivity (being very sensitive to the sun; 8 people of 19 studied) resulting in a skin rash. The next most common features were mouth ulcers (8 of 19), joint pain (9 of 19) and excessive fatigue (8 of 19). Six of the group studied reported three or more of these symptoms. Symptoms were so severe in some of the carrier mothers that they had been referred to a rheumatologist.
Q. What is the incidence of lupus in the population?
A. Lupus is not an uncommon condition. Over 30,000 people have lupus in the UK of whom 9 of 10 people affected are female.
Q. Can these lupus related symptoms be treated?
A. Yes - very effective treatments can be given to alleviate the problems. A doctor must prescribe all medicines specifically for treating lupus symptoms. People who have joint pain and skin rashes are often simply treated with creams for skin rash (often containing some steroids) or anti-inflammatory medicines. Some people find that anti-malarial drugs (commonly hydroxychloroquinine) are also effective in treating the symptoms of lupus particularly the feelings of tiredness. People who have more serious complications associated with systemic lupus may be treated with steroid tablets or other drugs that damp down the immune system. You may be referred to a specialist dermatologist or rheumatologist. People on these medications need to be monitored carefully and have regular blood tests and review with the doctor.
Q. Should I tell my doctor if I am a carrier?
A. Absolutely, if you are suffering from any of the symptoms of lupus then it is really important to tell your doctor. As a general rule it is important to give clinicians as much information as possible. The information often holds clues to help doctors reach a decision on the cause of the problem, helping diagnosis and treatment.
Q. I do not have CGD but as a carrier I have been told that some of my phagocytes do not work as they should. Please can you explain why?
A. This is quite complicated and is explained by a process called random X-chromosome inactivation (lyonisation). To start simply, you only need one X chromosome to be active (switched on) in any cell. Men have only one X-chromosome and in X-linked CGD this chromosome will carry the ‘mistake’. Female carriers have two X-chromosomes, one carrying a ‘mistake, the other not. During the development of female cells, in every single cell, one of the two X-chromosomes is randomly inactivated (switched off). This means that, in theory, if you look at the neutrophils of a mother of a male X-linked CGD patient, one would expect that 50% of the cells are normal, and 50% of the cells (in which the X-chromosome with the "mistake" is active) do not work normally. We believe people probably need just more than 10% normal granulocytes to live a normal life. So much for statistics! The random process of X-chromosome inactivation can be much more skewed, just by chance. So, a female carrier could have 6 out of 10 normal cells, and 4 out of 10 cells abnormal ones. Or, alternatively, they could have 1 of 10 normal cells, and 9 of 10 cells not working properly. The proportions do differ from one carrier to another. We found that the proportion of working cells ranged from 1 in 10 cells to 9 of 10 cells in our study.
Q. So, why do researchers think X-linked CGD carriers get lupus?
A. We don’t know exactly but we believe that this due indirectly to the lyonisation process. We know that the neutrophils that carry the genetic mistake in CGD do not appear to die as quickly “normal” cells and these abnormal cells also don’t clear up other dead cells as well as they should. Thus, there are extra dead cells in tissues that could set up an inflammatory response and generate abnormal responses in the body that show up as symptoms of SLE. There are likely to be other modifier factors that also influence how badly someone will be affected.
Q. Does this mean that all X-Linked carriers get lupus?
A. No, some carriers will not develop any of the lupus-like symptoms we have described. Of the 19 carriers in our study 3 had no symptoms of lupus and were considered free from this condition. Two others suffered only from acne.
Q. Was there any relationship between the percentage of phagocytes not working properly in carriers of X-linked CGD and the symptoms of lupus?
A. No there was no clear-cut relationship found on our study, but numbers were small so we need to be cautious in interpreting this data. We believe that other genetic factors may play a role in developing lupus.
Q. In an individual carrier do the number of affected phagocytes remain the same over time or do the levels vary?
A. The phagocyte population turns over very quickly in the body and the numbers of non-functioning cells can vary over time. We don’t yet know if this accounts for the episodes of lupus symptoms in carriers of X-linked CGD.
Q. Is there a blood test I can take to find out if I have lupus?
A. Lupus is caused by a fault in the immune system and is termed an autoimmune disease. 'Auto' means 'self’, so autoimmune literally means that the immune system fights the body itself. Instead of fighting and attacking bacteria and viruses through the production of antibodies, it turns on itself and attacks components of our own cells. These antibodies cause damage to the working of cells and organs. Tests have been developed that detect the presence of lupus auto-antibodies in blood. More than 95% of people with typical, non-CGD related systemic lupus have auto-antibodies in their blood. The proportion is lower in individuals with just skin problems (about half to two thirds), and thus a diagnosis of lupus is not solely dependent on finding these antibodies. However, when we tested the blood of X-linked CGD carriers for lupus auto-antibodies these were either not present (16 of 19 people studied) or they were very difficult to detect (remaining 3 people studied). The conclusion is that in CGD carrier related lupus testing for auto-antibodies is not helpful, and diagnosis and treatment should be based on symptoms alone.
Q. If my daughter shows signs of lupus-like symptoms, should she be tested for carrier status?
A. Overall, young women should decide for themselves if they want to know their carrier status. When there are lupus-like symptoms, a doctor may consider that this may be expected, accepting the possibility that the daughter may be a carrier.
Q. If having lupus is not that uncommon does that mean that some people with lupus could be carriers of CGD?
A. The chances are yes but the incidence is likely to be very low. If the doctor sees a case that does not fit into the classical lupus criteria then more history should be taken and carrier status for CGD should be considered as an option.
Q. Can symptoms of lupus become more prevalent during and after pregnancy?
A. There is not a clear correlation. It can happen that pregnancy can alleviate or make worse problems for many conditions. Studies involving pregnant women who are carriers of CGD will be needed.
Q. My daughter is a carrier and her dad has CGD. Does this mean she will suffer badly from lupus?
A. There is not enough information to judge at present the reasons why some carriers are affected badly and others do not show symptoms of lupus. There may be other background genetic factors that we are not aware of at present that determine how severely someone is affected.
Q. Is there a specific age when lupus-like symptoms will occur in carriers of CGD?
A. Symptoms of lupus can occur in some young children. In others it may or may not come on later in life.
Q. My wife is a carrier but has not yet shown any signs of having lupus as yet. Is it possible that it could develop as she gets older?
A. The answer is we don’t know but I expect not.
Q. I am a carrier of X-CGD and severely affected by lupus. Does that mean that my son with X-CGD will have severe CGD?
A. There is no evidence for a connection of this type at present. We believe that variations in an individual’s genetic make-up determines how severe the CGD symptoms will be. Further research is needed.
Q. My daughter is a carrier who gets very tired when she has mouth ulcers. In order that she recovers more quickly, would it be appropriate for her to take extra rest then?
A. It would be worth trying to see if it makes a difference.
Where can I find other information?
We provide information sheets on Lupus in carriers – please see fact sheet No. 8
Some published articles relating to lupus in CGD
> Cutaneous and other lupus-like symptoms in carriers of X-linked Chronic Granulomatous Disease: incidence and autoimmune serology. C.M Cale, L. Morton and D. Goldblatt. Clinical and Experimental Immunology, 148:79-84.
> Abnormal apoptosis in Chronic Granulomatous Disease and autoantibody production characteristic of lupus. A.N. Sanford, A.R. Suriano, D. Herche, K. Dietzmann and K.E. Sullivan.
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
© 2001-2007 The Chronic Granulomatous Disorder (CGD) Research Trust
Registered Charity No. 1003425 email:cgd@cgdrt.co.uk
The CGD Research Trust is a member of the Association of Medical Research Charities (AMRC), the Genetic Interest Group (GiG) and an associate member of the International Patient Organisation of Primary Immunodeficiencies (IPOPI)
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