Chronic granulomatous disorder

A guide for medical professionals

Written by medical professionals for medical professionals

www.cgdsociety.org
 Chronic granulomatous disorder
Incidence and prevalence of CGD
The exact incidence of CGD is unknown. The birth prevalence of CGD
in the United Kingdom and Ireland is approximately 8.5 per million.
Despite antibiotic and antifungal prophylaxis, morbidity remains
significant, with severe infectious complications common. Retrospective
data collected in 2001 estimated a survival rate of 50% at the age of 30
years; however, with advances in earlier diagnosis and better treatments,
survival rates are likely to be improving year by year.

Diagnosis
Chronic granulomatous disorder (CGD) is a rare, inherited The functional diagnosis of CGD is made by the demonstration of the
inability of phagocytes from affected individuals to produce superoxides
disorder of the immune system. The basic defect lies in (see Box 2). If CGD is suspected it is important that referral is made to
phagocytic cells (neutrophils and monocytes) which fail to a specialist centre and diagnostic tests carried out in a laboratory that
is familiar with doing these tests on a regular basis. Genetic testing and
effectively destroy invading bacteria and fungi (see Box 1). counselling of the extended family is recommended. For immigrants,
family testing should be done in the new country and in the country
of origin.
Affected individuals are therefore susceptible to serious,
potentially life-threatening, bacterial and fungal infection Inheritance and types of CGD
but have normal immunity to viruses. They also experience In the Western world the majority of CGD cases are of X-linked inheritance
(see Box 3) but the autosomal form of CGD is more common in the
symptoms associated with chronic inflammation, often Middle East.
granulomatous in nature.
Clinical manifestations
The hallmark of the clinical presentation of CGD is recurrent infections
occurring at epithelial surfaces in direct contact with the environment,
such as the skin, lungs and gut. Diagnosis is based on clinical suspicion
and confirmed by demonstrating the inability of phagocytes from affected
individuals to produce superoxides, by NBT test or flow cytometry
(see Box 2).

Infections at these sites which recur, are difficult to treat or otherwise

unusual should arouse a suspicion of an immune deficiency, including
CGD. Signs and symptoms will be as per normal infections. Infections may
present initially as relatively minor (e.g. a cough or cervical lymphadenitis)
but they may not easily respond to conventional therapy or may progress.
Carriers of X-linked CGD may also experience health problems (see Box 4).

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 1 The biochemical basis of CGD 2 Testing for CGD

Neutrophils from CGD patients fail to exhibit a respiratory burst, the Nitroblue tetrazolium test (NBT):
increase in oxidative metabolism associated with phagocytosis. This is Neutrophils are stimulated with
due to the absence of one of the components of NADPH oxidase, found phorbol myristate acetate and
in phagocytic cells. NADPH oxidase catalyses the formation of superoxide, incubated with the yellow dye
the precursor to the generation of potent oxidant compounds, nitroblue tetrazolium. Normal
by transmembrane passage of electrons from NADPH oxidase to phagocytes reduce this to the dark
molecular oxygen. blue pigment, formazan. Cells are
analysed by microscopy, which
requires an experienced observer.
Diagnosis of CGD by the NBT test
Carrier mothers of the X-linked type
of CGD are identified by a mixed
population of NBT+ve and NBT-ve cells.

Flow cytometric reduction of dihydrorhodamine:

The principles are
the same as the NBT
test, but using a
different dye. X-linked
carrier status can also
be detected.

The NADPH oxidase enzyme

Diagnosis of CGD by flow cytometry

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 3 Types of CGD
Management of CGD
Preventing infection
There are four basic types of CGD, grouped according to which of the four The most commonly described infectious complications are pneumonia,
subunits is affected by genetic mutation. lymphadenitis, subcutaneous abscess, liver abscess, osteomyelitis and
sepsis. The pathogens responsible for the majority of infections in CGD
CGD gene Mode of inheritance Frequency Groups affected
are catalase positive bacteria and various fungi (see Box 5).
gp91phox (CYBB) X-linked 65% Males only
p47phox (NCF-1) Autosomal recessive 25% Both sexes Taking daily antibacterial and antifungal prophylaxis is the single most
p67phox (NCF-2) Autosomal recessive 5% Both sexes important factor in keeping CGD patients well.
p22phox (CYBA) Autosomal recessive 5% Both sexes Whilst these medicines do not provide an absolute guarantee against
infections, they are key to reducing the number and severity of infections
that people with CGD encounter.

4 X-linked CGD carrier health issues

5 Pathogens responsible for infection in CGD
Carriers of X-linked CGD are unlikely to have the condition but are known
to be at risk from developing a number of symptoms which may resemble Bacteria the most commonly implicated bacteria include
lupus (especially the skin features). It is recommended that these CGD Staphylococcus aureus and the gram negative Enterobacteriaceae,
carriers presenting with aphthous ulceration, skin rashes, joint pains, including Salmonella, Klebsiella, Aerobacter and Serratia. Pseudomonas
fatigue and headaches are considered for referral to a rheumatologist (Burkholderia) cepacia, Actinomyces and Nocardia are increasingly being
and/or other relevant specialists for treatment of lupus-like symptoms recognised as important pathogens in CGD. Catalase negative bacteria,
regardless of the results of a test for lupus. In CGD carriers, lupus test such as Streptococci, rarely cause problems in CGD.
results are likely to be negative as supported by published evidence, but
symptoms need to be taken seriously. These catalase positive bacteria break down hydrogen peroxide, which the
hosts immune system uses to fight infection. As a consequence, catalase
negative bacteria, such as Streptococci, rarely cause problems in CGD
The majority of affected individuals are diagnosed before the age of 2 because hydrogen peroxide can accumulate to protect against infection.
years although patients may remain undiagnosed until adult life despite
the early onset of symptoms. Fungi Aspergillus fumigatus is the most common cause of fungal
infection in CGD although reports of infections with other members of the
Common presenting features:
Aspergillus family, such as A. nidulans, and other fungi, such as
Skin abscesses
Perianal abscesses Scedosporium apiospermum and Chrysosporium zonatum, are increasing.
Pneumonia
Liver abscess Fungal infections may be difficult to distinguish from bacterial infections
Osteomyelitis on initial presentation (e.g. a cough) but should always be considered
Septicaemia in this patient group if they do not respond as expected to empirical
Diarrhoea (may be misdiagnosed as Crohns disease) antibiotic therapy.
Lymphadenitis
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 Management of CGD (continued)
The importance of taking daily preventative medication should be
emphasised to patients and families. They are advised to take some
simple precautions in daily life to minimise the risk of infection. These
Anti-bacterial prophylaxis include not working or playing with or around compost, hay, wood chips,
All patients should be commenced on Co-trimoxazole. Although thick grass clippings, other garden waste or firewood that has dry rot or
Stevens-Johnson syndrome has been associated with Co-trimoxazole old fungi on it. This will help avoid inhalation of high levels of fungi, as will
use, it is generally well tolerated in CGD patients and has been shown to staying out of barns, caves, sheds and other dusty or damp areas.
reduce the incidence of severe infection. It has broad activity against the
pathogens encountered in CGD, is lipophilic and is thus concentrated A full list of recommended precautions can be found at the CGD Society
inside cells and does not affect anaerobic gut flora. website www.cgdsociety.org. Advice is aimed at providing a balance
between protective precautions and the need to maintain as normal a life
Recommended doses of Co-trimoxazole
as possible.

Age range Co-trimoxazole prophylaxis Immunisations

(all as a single daily dose) The only routine immunisation that adults and children with CGD
06 months 120mg should not have is BCG as it has been associated with disseminated BCG
6 months5 years 240mg infection. An annual flu vaccine is recommended (over 6 months of age),
612 years 480mg because of the possible secondary bacterial complications of influenza.
over 12 years 960mg
Invasive procedures
Antibiotic cover is recommended for all invasive procedures, including
sigmoid/colonoscopy, upper GI endoscopy, bronchoscopy and liver/
Anti-fungal prophylaxis
lung biopsy. Prophylaxis with Ciprofloxacin (and adding Metronidazole
All patients should be commenced on Itraconazole (5mg/kg daily), as this
if investigation below the diaphragm is involved) should commence
has good activity against Aspergillus species.
prior to procedure and continue for at least 24 hours afterwards. Surgical
procedures may require more prolonged courses/different antibiotic
Reported side effects include raised liver enzymes, peripheral neuropathy
combinations and should be discussed with a specialist centre.
and Stevens-Johnson syndrome, but Itraconazole is generally well
tolerated in CGD patients and studies suggest it is effective in reducing
the incidence of fungal infection. Liver enzymes should be checked prior 6 Significant symptoms of infection in CGD
to commencing treatment and subsequently every 6 months.
A fever of 38C or above Frequent or persistent headaches
Acting on significant symptoms
Warm, tender or swollen areas Loss of appetite
CGD patients can mount a normal immune response to viruses
Hard lumps Weight loss
(e.g. colds and flu) and will continue to have these infections with the
Sores with pus or rashes Pain or difficulty on urinating
same frequency as the general population. It can be difficult for
Persistent diarrhoea Difficulty swallowing food
families to distinguish those infections that are normal from those
Persistent cough or chest pain Vomiting shortly after eating (on a
that are a result of CGD. Families are educated to look out for and
Night sweats more or less consistent basis)
act on significant symptoms (see Box 6).

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 Treatment of acute infection Inflammatory complications
Inflammatory complications of CGD include:
Any febrile illness should be treated promptly with antibiotics, proceeding
to appropriate intravenous therapy where necessary. Whilst this may raise
some concern about inappropriate treatment of viral infections/overuse of
antibiotics, a safety-first approach should always be adopted for patients
chronic lung colitis pericardial
with CGD. Patients with CGD may require longer antibiotic courses, disease effusion
sometimes at higher doses, or in combination, because of their poor host
response. If a poor response is made to initial treatment, advice should be
sought from a specialist centre.

The spectrum of bacteria that cause infection in CGD should always fulminant
be taken into account when considering the choice of antibiotics. Oral gingivitis mulch chorioretinitis
Ciprofloxacin is a useful first line agent because of its spectrum of pneumonitis
activity and capacity to penetrate intracellularly. The benefits of using
Ciprofloxacin in children in this context outweigh the risks of arthropathy.
It is important to note that fulminant mulch pneumonitis is a real
Dosage of Ciprofloxacin for treatment of acute infection
emergency that requires both antimycotics and steroid treatment.

Colitis is probably the most common significant inflammatory

complication of CGD. Histological features include an apparent
Dose (orally): Child: Adult:
paucity of neutrophils, increased eosinophilic infiltrate and pigmented
7.5mg/kg 500mg to 750mg
macrophages. Granulomas may or may not be present. A CGD associated
12 hourly 12 hourly
colitis can be misdiagnosed as Crohns disease where symptoms such as
diarrhoea, weight loss, failure to thrive and perianal disease constitute
the initial findings. Where colitis is suspected, referral should be made
IV antibiotics to a gastroenterologist for endoscopic investigation and biopsy (as
IV Teicoplanin and Ciprofloxacin are a good choice for first line therapy macroscopic appearance can be deceptively normal).
in severe sepsis, with Metronidazole being added if infection below the
diaphragm is suspected. If Staphylococcus is isolated, Flucloxacillin and Long-term follow up of CGD has revealed that with improved survival or
Fucidin (or another antistaphylococcal antibiotic, e.g. Clindamycin and increasing age, symptoms of obstruction in hollow organs, or inflammation
Clarithromycin) may be used. not obviously associated with infection, may become prominent.
Although incompletely understood, this is likely to represent an exuberant
Fungal infections should always be considered in the differential diagnosis inflammatory response to a minor stimulus, e.g. a resolved infection.
of any sepsis syndrome. If a prompt response (within 710 days) to A raised ESR and low Hb can be found even in apparently uninfected
antibacterial therapy is not obtained, consideration should be given to patients and probably reflects ongoing, sub-clinical inflammation. The
commencing empirical antifungal treatment (in discussion with a CRP is rarely raised when the patient is apparently infection free and thus
specialist centre). remains a better marker of sepsis in the acutely ill patient.
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 Inflammatory complications (continued)
Monitoring
5-ASA agents (e.g. Sulphasalazine and Mesalazine) are useful first Clinical
line agents in the treatment of CGD-colitis. Steroids, and other All patients should have an identified local physician/paediatrician and
immunosuppressive agents, such as Azathioprine, may be indicated access to advice from an immunologist/physician familiar with CGD.
where 5-ASA has failed to induce/maintain remission. However, these Regular outpatient review (6 monthly if well) is recommended, shared
agents should be used with caution, and in discussion with a specialist between local/specialist centres.
centre, particularly where there is concurrent infection or history of
fungal infection. Blood tests
Regular (approximately 6 monthly) full blood count and liver function tests
NB: Where 5-ASAs are used in conjunction with Co-trimoxazole, a full are recommended (prophylactic medication may be toxic to bone marrow/
blood count should be monitored monthly for the first 3 months and associated with altered LFTs). A CRP and ESR should also be performed
3 monthly thereafter, due to the potential for blood dyscrasias. routinely and whenever the patient is unwell. A microcytic, hypochromic
anaemia is often detected although it often remains refractory to iron therapy.
Obstruction of hollow organs
Ophthalmology
People with CGD are at risk of getting obstruction of the gut or urinary
Patients and carriers of CGD may have chorioretinal lesions and thus
tract due to granulomatous inflammation. This may manifest as a difficulty
should be assessed at diagnosis. The aetiology of these lesions is unclear
in swallowing (obstruction of the oesophagus), vomiting (gastric outlet
and they do not appear to interfere with vision in the majority of patients.
obstruction), abdominal pain (obstruction of the bowel) or difficulty in
However, it is recommended that those with lesions should be assessed
passing urine (obstruction of the ureter). All of these conditions respond every 12 years to monitor progression. Those without lesions at diagnosis
promptly to steroids but it is essential to rule out an infectious cause should be assessed every 23 years using dilated fundoscopy.
before starting steroid therapy. Steroids should be used with particular
caution, and preferably in discussion with a specialist centre, where there is Dental
known concurrent infection or history of fungal infection. The importance of good dental hygiene and mouth care for people
with CGD should be emphasised. Patients are advised to brush their
teeth twice daily and seek regular dental care. A number of patients do
have problems with persistent gingivitis and mouth ulcers. Antibiotic
prophylaxis should be prescribed for any dental treatment likely to cause
bleeding: Ciprofloxacin (7.5mg/kg for a child, 500mg for an adult, oral
prep.) should be given before the procedure followed by 2 doses, 12 hours
People with CGD are at risk apart, in the 24 hours following the procedure.

of getting obstruction of the Nutrition/growth and development

gut or urinary tract due to Some children with CGD grow and develop more slowly than their peer
group. They may also experience some delay in reaching puberty. The
granulomatous inflammation. causes of growth failure in CGD are not yet fully understood and are likely
to involve a number of different factors. It would appear that a number

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 Monitoring (continued)
Cure of CGD
of CGD children achieve catch-up growth and go on to achieve Haematopoietic stem cell transplantation in CGD
reasonable adult height. However, there are some, particularly those who Whilst lifelong antibacterial and antifungal prophylaxis with Co-trimoxazole
have received prolonged courses of steroids, had repeated infections and Itraconazole has improved short- and medium-term survival,
or major fungal infection, who will demonstrate failure to thrive and and steroids and aminosalicylates may ameliorate colitis and other
growth failure. inflammatory complications, these treatments do not cure the underlying
genetic defect. Haematopoietic stem cell transplantation (HSCT) can cure
Weight and height should therefore be measured and plotted on centile CGD, with resolution of infection and colitis. In those with growth failure,
charts at each clinic visit. Failure to thrive is often associated with poor who have remaining growth potential, HSCT can allow catch-up growth
nutritional intake, increased nutritional requirements due to sub-clinical to previously normal centiles. In the majority of patients, prophylactic
inflammation and colitis symptoms. Children failing to maintain their medication can be discontinued post-HSCT. Survival and cure are
weight will benefit from specialist nutritional advice and support with equivalent with either a matched sibling or well-matched unrelated donor
nutritional supplements (rarely tube feeding) and should therefore be
and reach 8590% in specialist centres designated to transplant patients
referred to a dietician. Referral to gastroenterology and endocrinology
with primary immunodeficiency.
should be considered, in liaison with the specialist centre.
Specific timing of transplantation is difficult to recommend but should
Adult patients may also experience problems maintaining their weight,
be considered early. Given that worse transplant outcomes are seen in
for much the same reasons. Patients often report reduced appetite and
patients with refractory infection or significant inflammation, patients
interest in food. Again, advice from a dietician as to how to increase
calorie intake is of benefit. Infection should be suspected with recent, should be considered for transplantation early after diagnosis, or after
sudden weight loss and consideration given to further referral as the development of specific prognostic symptoms, particularly if a
symptoms indicate, e.g. gastroenterology. well-matched donor is available, so that families can be appropriately
counselled. Whilst transplantation is generally best tolerated in childhood,
Emotional impact of CGD successful outcomes are possible in adults using new transplantation
CGD presents a multitude of challenges for patients and their families. techniques.
These challenges involve managing the physical elements of the
condition, as well as the psychological issues involved in coping with a It is recommended that:
complex condition, whilst, at the same time, trying to maintain a family life. HLA-antigen tissue typing is performed soon after the diagnosis is made,
It is sometimes difficult for families to talk about these emotional issues so that potential donors can be identified.
for a variety of reasons, including stigma, fear of being judged and fear of
managing their own emotions. Transplantation be considered early after diagnosis if an HLA-identical
sibling or well-matched unrelated donor is available families and
It is important that families are given time and encouragement to talk patients should be seen by a specialist with experience of transplanting
about their concerns relating to themselves, their child and other family patients with primary immunodeficiency, who can provide good-quality
members. This enables not only a close therapeutic alliance to be formed up-to-date advice about risks and benefits.
with the family but also enables difficult topics to be brought to the fore in
discussion, and appropriate sources of support to be considered.

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 Cure of CGD (continued)

HSCT be undertaken in centres specifically recognised for the For this reason, many groups in the world are developing newer methods
transplantation of patients with primary immunodeficiency. for the treatment of CGD. One such strategy is gene therapy. The
objective here is to correct the patients own bone marrow using defective
Standard conditioning protocols, as published by the EBMT/ESID viruses to take a functional gene into the stem cells. This will allow the
Inborn Errors Working Party, are followed, and that reduced intensity bone marrow to produce cells, such as neutrophils, that are now able to
conditioning is undertaken in the context of a clinical trial, such as that work properly. Many studies have shown that this actually works in the
initiated by Gngr et al. laboratory and more recently in patients. Even short-term correction of the
CGD defect has led to clearance of life-threatening infections that were
resistant to other means of treatment.
Gene therapy for CGD
The principle behind bone marrow transplantation is that stem cells can However, the technology is relatively new. We now know that the way that
be taken from another individual and grafted into a patient with a blood we introduce genetic medicines into bone marrow cells can be improved
disorder such as CGD, or even cancer, to provide a lifelong source of to make it safer and also more long-lasting and effective. This is true
normally functioning cells. In principle this is straightforward, but there are not only for CGD but also for a wide range of diseases which have been
some significant challenges. The main problem with transplantation from previously difficult to treat. Clinical trials using modern technology for the
another individual is that the tissue match (HLA-compatibility) may not be treatment of patients with CGD will commence in 2012, and based on
perfect. This means that there is a risk of rejection, and also of an immune previous proof-of-principle studies are likely to pave the way to a realistic,
reaction against the recipient of the transplant called graft-versus-host- safe alternative therapy for patients.
disease. The better the match, the less likely this is to occur, but it is still a
significant risk, particularly where patients are ill or have infections at the
time of treatment.

Today there are also drugs that can alleviate the risk, but these can lead
to a long period of immunosuppression, during which time the patient
is quite vulnerable to serious infections. This is compounded by the
fact that a transplant for diseases such as CGD will require significant
chemotherapy to kill off the existing bone marrow stem cells and Even short-term correction
allow the new healthy cells to establish themselves in the bone marrow.
However, transplant is today very successful if a family donor or unrelated
of the CGD defect has led to
bone marrow donor (including cord blood donors) are closely matched. In clearance of life-threatening
the absence of this, risks may be considerable.
infections that were resistant
to other means of treatment.

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 Further reading/information
Prevalence, clinical course and complications of CGD Unrelated donor and HLA-identical sibling haematopoietic stem cell
transplantation cure chronic granulomatous disease with good long-term
Special article: chronic granulomatous disease in the United Kingdom outcome and growth.
and Ireland: a comprehensive national patient-based registry. Soncini E, Slatter MA, Jones LB, Hughes S, Hodges S, Flood TJ, Barge
Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A, D, Spickett GP, Jackson GH, Collin MP, Abinum M, Cant AJ, Gennery AR.
Goldblatt D, Parker L, Cant AJ. British Journal of Haematology, 2009; 145(1): 7383.
Clinical and Experimental Immunology, 2008; 152(2): 21118.
Hematopoietic stem cell transplantation for chronic
Chronic granulomatous disease: the European experience. granulomatous disease.
van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska Seger RA.
E, Corbeel L, Espaol T, Fischer A, Kurenko-Deptuch M, Mouy R, Immunology and Allergy Clinics of North America, 2010; 30(2): 195208.
Petropoulou T, Roesler J, Seger R, Stasia MJ, Valerius NH, Weening RS,
Wolach B, Roos D, Kuijpers TW. Excellent survival after sibling or unrelated donor stem cell
The Public Library of Science One, 2009; 4(4): e5234. transplantation for chronic granulomatous disease.
Martinez CA, Shah S, Shearer WT, Rosenblatt HM, Paul ME, Chinen J,
CGD overview and clinical management of CGD Leung KS, Kennedy-Nasser A, Brenner MK, Heslop HE, Liu H, Wu MF,
Hanson IC, Krance RA.
Modern management of chronic granulomatous disease. Journal of Allergy and Clinical Immunology, 2012; 129(1): 17683.
Seger, RA.
British Journal of Haematology, 2008; 140(3): 25566. http://www.esid.org/bone-marrow-transplantation-updated-ebmt-esid-
guidelines-for-haematopoietic-stem-cell-transplantation-for-pi-350-0
Chronic granulomatous disease: complications and management.
Rosenzweig SD. Gene therapy for CGD
Expert Review of Clinical Immunology, 2009; 5(1): 4553.
Gene therapy of chronic granulomatous disease: the engraftment dilemma.
Chronic granulomatous disease. Grez M, Reichenbach J, Schwble J, Seger R, Dinauer MC, Thrasher AJ.
Holland SM. Molecular Therapy, 2011; 19(1): 2835.
Clinical Reviews in Allergy and Immunology, 2010; 38(1): 3 10.
Gene therapy matures in the clinic.
CGD and haematopoietic stem cell transplantation Seymour L and Thrasher AJ.
Nature Biotechnology, 2012 Jul 10; 30(7): 58893.
Successful low toxicity hematopoietic stem cell transplantation for high-
risk adult chronic granulomatous disease patients.
Gngr T, Halter J, Klink A, Junge S, Stumpe KD, Seger R, Schanz U.
Transplantation, 2005 Jun 15; 79(11): 1596606.

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 Further reading/information (continued)

CGD carrier issues Overlap, common features, and essential differences in pediatric
granulomatous inflammatory bowel disease.
Abnormal apoptosis in chronic granulomatous disease and autoantibody Damen GM, Krieken JH, Hoppenreijs E, van Os E, Tolboom JJ, Warris A,
production characteristic of lupus. Yntema JB, Nieuwenhuis E, Escher JC.
Sanford AN, Suriano AR, Herche D, Dietzmann K, Sullivan KE. Journal of Pediatric Gastroenterology and Nutrition,
Rheumatology, 2006; 45(2): 17881. 2010 Dec; 51(6): 6907. Review.

Cutaneous and other lupus-like symptoms in carriers of X-linked chronic Inflammatory bowel complications in CGD
granulomatous disease: incidence and autoimmune serology.
Cale CM, Morton L, Goldblatt D. Gastrointestinal involvement in chronic granulomatous disease.
Clinical and Experimental Immunology, 2007; 148(1): 7984. Marciano BE, Rosenzweig SD, Kleiner DE, Anderson VL, Darnell DN,
Anaya-OBrien S, Hilligoss DM, Malech HL, Gallin JI, Holland SM.
Aspergillosis and CGD Paediatrics, 2004; 114(2): 4628.

Invasive aspergillosis in chronic granulomatous disease. Ophthalmology

Segal BH, Romani LR.
Medical Mycology, 2009; 47 (Supplement 1), S282S290. Chorioretinal lesions in patients and carriers of chronic
granulomatous disease.
Epidemiology and outcome of invasive fungal diseases in patients with Goldblatt D, Butcher J, Thrasher AJ, Russell-Eggitt I.
chronic granulomatous disease: a multicenter study in France. Journal of Pediatrics,1999; 134(6): 7803.
Beaute J, Obenga G, Le Mignot L, Mahlaoui N, Bougnoux ME, Mouy R,
Gougerot-Pocidalo MA, Barlogis V, Suarez F, Lanternier F, Hermine O, Chorioretinal lesions in patients with chronic granulomatous disease.
Lecuit M, Blanche S, Fischer A, Lortholary O; the French PID Study Group Kim SJ, Kim JG, Yu YS.
CEREDIH. Retina, 2003; 23(3): 3605.
Pediatric Infectious Disease Journal, 2011; 30(1): 5762.
Oral pathology in CGD
Differential diagnosis of CGD in patients presenting
with inflammatory bowel disease The NADPH oxidase NOX2 plays a role in periodontal pathologies.
Giannopoulou C, Krause KH, Mller F.
Inflammatory bowel disease in CGD reproduces the clinicopathological Seminars in Immunopathology, 2008; 30(3): 2738.
features of Crohns disease.
Marks DJ, Miyagi K, Rahman FZ, Novelli M, Bloom SL, Segal AW.
American Journal of Gastroenterology, 2009; 104(1): 11724.

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 Further reading/information (continued)

Specialist centres for CGD in the UK Acknowledgements

PAEDIATRIC CARE The CGD Society is grateful to Dr Andrew Gennery, Professor

Adrian Thrasher and Dr Nigel North for their respective sections on
1. Great North Childrens Hospital, haematopoietic stem cell transplantation, gene therapy and the
Newcastle upon Tyne, United Kingdom emotional impact of CGD.
Consultant: Dr Andrew Gennery
Institute of Cellular Medicine This guide is approved by the CGD Society Medical Advisory Panel
Paediatric Immunology Department (August 2012).
Great North Childrens Hospital
Queen Victoria Road 2012 The CGD Society
Newcastle upon Tyne NE1 4LP
Telephone: +44 (0)191 282 5234
Fax: +44 (0)191 273 0183

2. Great Ormond Street Hospital for Children,

London, United Kingdom
Consultants: Professor David Goldblatt and Dr Catherine Cale
Clinical Immunology Department
Great Ormond Street Hospital
Great Ormond Street
LondonWC1N 3JH
Telephone: +44 (0)20 7829 8834

ADULT CARE

The Royal Free London Hospital,

London, United Kingdom
Consultant: Dr Ronnie Chee
Clinical Immunology Department
The Royal Free London Hospital
Pond Street
London NW3 2QG
Telephone: +44 (0)20 7830 2141 or +44 (0)20 7794 0500 and ask
for extension 35979

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For further information, please visit www.cgdsociety.org

The Chronic Granulomatous Disorder Society is a charitable company limited by guarantee and registered in England
(registered charity number 1143049 and registered company number 07607593).
The registered address is 199A Victoria Street, London SW1E 5NE.