Chronic granulomatous disease (CGD) is caused by genetic deficiency of components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which is necessary for effective phagocyte killing.
Results in recurrent serious bacterial and fungal infections, most commonly with Staphylococcus aureus, Aspergillus species, Nocardia species, Serratia marcescens, and Burkholderia cepacia.
Infections include pneumonia, superficial and deep abscesses, lymphadenitis, and osteomyelitis.
Antibiotic and antifungal prophylaxis and early treatment of infections are imperative.
Hematopoietic stem cell transplantation should be undertaken early if human leukocyte antigen (HLA) genotypically matched donors are available.
Somatic gene therapy is effective at least transiently for restoration of NADPH oxidase activity.
Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by genetic defects in components of the NADPH oxidase complex. NADPH oxidase is responsible for optimal phagocyte killing through production of superoxide and regulation of ionic content within the phagosome. As a result, affected patients suffer recurrent serious bacterial and fungal infections, most commonly with Staphylococcus aureus, Aspergillus species, Nocardia species, Serratia marcescens, and Burkholderia cepacia, as well as abnormal inflammatory responses that result in granuloma formation.
History and exam
Key diagnostic factors
- history of prior infections
- shortness of breath
- perianal pain
- flank pain
- red skin lesion
- abnormal chest examination
- chronic lymphadenopathy
- poor growth
- joint pain
- facial pain
- chorioretinal lesions
- skin scarring
Other diagnostic factors
- abdominal pain
- nausea and vomiting
- bloody urine
- abnormal urinary flow
- family history of discoid lupus
- oral ulcer
- skin rash
- family history of CGD
- age <5 years
- male sex
- abnormally skewed X chromosome inactivation in X-linked carriers
- myeloperoxidase and FCgammaRIIIb polymorphisms
1st investigations to order
- fecal calprotectin
- CT chest
- CT or ultrasound for active infection
- whole body PET scan with F-18 fluorodeoxyglucose (FDG)
- MRI scan
- pulmonary function tests
- nitroblue tetrazolium test (NBT)
- dihydrorhodamine (DHR) 123 test
Investigations to consider
- genetic sequencing for genes encoding NADPH oxidase components
- Western blotting
- flow cytometric analysis of individual NADPH oxidase components
active non-life-threatening infection: on first presentation
active life-threatening infection: on first presentation
following initial empiric treatment
following resolution of acute episode
David Lowe, MA, MB Bchir, PhD, FRCP
Consultant Clinical Immunologist
The Royal Free Hospital
DL has received travel and subsistence costs for consultancy work from CSL Behring and has participated in an advisory board for Merck.
Dr David Lowe would like to gratefully acknowledge Dr Adrian Thrasher, Dr Rebecca A. Marsh, and Dr Jack J. Bleesing, previous contributors to this topic. AT is an author of a number of references cited in this topic. RAM and JJB declare that they have no competing interests. Dr Rebecca A. Marsh and Dr Jack J. Bleesing wish to thank Dan Marmer, Carrie Koenig, and the Cincinnati Children's Hospital Clinical Diagnostic Immunology Lab. They also wish to thank Steven M. Holland, MD, Thomas Fleisher, MD, and Anthony Segal, MD, PhD, for helpful correspondence.
Steven M. Holland, MD
Laboratory of Clinical Infectious Diseases
National Institute of Allergy and Infectious Diseases
SMH declares that he has no competing interests.
Andrew Gennery, MD
Reader in Paediatric Immunology & HSCT
Institute of Cellular Medicine
AG is an author of a reference cited in this topic. AG declares that he has no competing interests.
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