Geographic Variability and Pathogen-Specific Considerations in the Diagnosis and Management of Chronic Granulomatous Disease

Benjamin T Prince,1 Beth K Thielen,2 Kelli W Williams,3 Erinn S Kellner,4 Danielle E Arnold,5 Wilfredo Cosme-Blanco,6 Margaret T Redmond,1 Nicholas L Hartog,7 Hey J Chong,8 Steven M Holland9 1Division of Allergy and Immunology, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Columbus, OH, USA; 2Division of Pediatric Infectious Diseases and Immunology, University of Minnesota, Minneapolis, MN, USA; 3Department of Pediatrics, Division of Pediatric Pulmonology, Allergy & Immunology, Medical University of South Carolina, Charleston, SC, USA; 4Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 5Division of Allergy and Immunology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 6Department of Allergy and Immunology, Veteran Affairs Caribbean Healthcare System, San Juan, Puerto Rico; 7Department of Allergy and Immunology, Spectrum Health Helen DeVos Children’s Hospital, Michigan State University College of Human Medicine, Grand Rapids, MI, USA; 8Division of Allergy and Immunology, UPMC Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA; 9National Institute of Allergy and Infectious Diseases, Bethesda, Maryland National Institutes of Health, Bethesda, MD, USACorrespondence: Benjamin T PrinceNationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USATel +1 (614) 722-4404Fax +1 (614) 722-4423Email Benjamin.Prince@Nationwidechildrens.orgAbstract: Chronic granulomatous disease (CGD) is a rare but serious primary immunodeficiency with varying prevalence and rates of X-linked and autosomal recessive disease worldwide. Functional defects in the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex predispose patients to a relatively narrow spectrum of bacterial and fungal infections that are sometimes fastidious and often difficult to identify. When evaluating and treating patients with CGD, it is important to consider their native country of birth, climate, and living situation, which may predispose them to types of infections that are atypical to your routine practice. In addition to recurrent and often severe infections, patients with CGD and X-linked female carriers are also susceptible to developing many non-infectious complications including tissue granuloma formation and autoimmunity. The DHR-123 oxidation assay is the gold standard for making the diagnosis and it along with genetic testing can help predict the severity and prognosis in patients with CGD. Disease management focuses on prophylaxis with antibacterial, antifungal, and immunomodulatory medications, prompt identification and treatment of acute infections, and prevention of secondary granulomatous complications. While hematopoietic stem-cell transplantation is the only widely available curative treatment for patients with CGD, recent advances in gene therapy may provide a safer, more direct alternative.Keywords: CGD, primary immunodeficiency diseases, nicotinamide adenine dinucleotide phosphate oxidase complex, DHR-123 oxidation assay