Health and quality of life of XL-CGD Carriers

The research project carried out by Dr Alex Battersby at the Great Northern Children’s Hospital (GNCH), Newcastle into the health of X-linked carriers of CGD (XL-CGD) is now complete.  The study involved evaluating associated health problems, psychological issues, quality of life and the possible underlying cause of fatigue that occurs in some XL-CGD carriers. The results of these studies, which are the most comprehensive to date on carrier issues, are summarised below.

The collaborative research involved GNCH, Great Ormond Street Hospital and Royal Free Hospital, London and involved 80 XL-CGD carriers. The work is currently being analysed and written up for publication in medical journals. Some of the provisional findings were shown at the European Society for Immunodeficiencies (ESID) 16th Biennial Meeting in Prague in November 2014.  The poster relating to fatigue in XL-CGD carriers was awarded a ‘best poster’ award.  You can access the ESID abstracts here. These were published in the Journal of Clinical Immunology, October 2014, Volume 34, Issue 2 Supplement, pp 139-515.

Clinical/Physical Findings

The main focus of the research was to evaluate the presence of physical health problems in XL-CGD carriers. This study found that XL-CGD carriers had similar problems with infection, inflammation and autoimmunity as patients with CGD.

The infections experienced by XL-CGD carriers included recurrent skin abscesses in 14 out of 77 CGD carriers. Inflammation of the lymph glands was also seen frequently. The proportion of functioning neutrophils was not predictive of the presence of infection, with the exception that those with a lower proportion of functioning neutrophils were more likely to suffer recurrent skin abscesses.

Inflammatory complications were also seen in XL-CGD carriers with half of those questioned reporting gastrointestinal problems, particularly abdominal pain and diarrhoea.

Features of autoimmune disease including mouth ulcers, photosensitive skin and pain were commonly seen.

It is not clear from this study why some XL-CGD carriers suffer medical problems, whilst others do not. Further investigations are required to understand this. More work is also needed into how best to manage these problems.

Psychological Health

This study looked at anxiety and depression in XL-CGD carriers using psychological health assessments. We found that there were high anxiety scores in XL-CGD carriers.  The average anxiety score in XL-CGD carriers was higher than the definition of anxiety and 40 out of 61 XL-CGD carriers had at least mild anxiety symptoms. Fewer XL-CGD carriers suffered from significant depression.

These scores were compared with scores in studies of other patient groups. The scores were similar to scores seen in patients with SLE (lupus) who experienced high pain and greater than SLE patients who experienced low pain.  The XL-CGD carriers scored more highly in anxiety, indicating increased anxiety, than parents of children with cystic fibrosis.

The PIP (Pediatric Inventory for Parents) scored the difficulties in caring for a child with a chronic illness and was completed by the XL-CGD carrier mothers. The XL-CGD mothers scored very similarly to published data about parents caring for children with cancer. This suggests that there are inherent difficulties in caring for a child with a chronic illness irrespective of the underlying diagnosis.

Quality of Life

Quality of life was assessed in XL-CGD carriers and was compared with CGD patients and UK population scores. XL-CGD carriers had significantly lower scores in all aspect of quality of life than the normal UK population.

This study also found that in several aspects of quality of life, XL-CGD carriers scored lower than CGD patients.

This was a surprising finding as XL-CGD carriers have not been previously considered to be unwell or have significant problems.

Fatigue

Approximately half of XL-CGD carriers suffered from excessive levels of fatigue. We investigated this further by looking at naturally occurring chemicals associated with inflammation. We found that the XL-CGD carriers had higher levels of a chemical called IL-8, when compared with healthy controls and patients with established autoimmune disease. The IL-8 levels were also compared between the fatigued and non-fatigued groups of XL-CGD carriers. This showed that there were higher levels of IL-8 in those XL-CGD carriers who were fatigued than in those who were not.

The exact significance of these findings is uncertain, as this is an observation rather than due to a direct cause. However, it suggests that there is an underlying cause for the fatigue found in XL-CGD carriers.

Posted 20th March 2015