J Allergy Clin Immunol Pract. 2022 May;10(5):1325-1333.e5. doi: 10.1016/j.jaip.2021.12.035.Epub 2022 Jan 14.

Brenna LaBere ¹, Maria J Gutierrez ², Hannah Wright ³, Elizabeth Garabedian ⁴, Hans D Ochs ⁵, Ramsay L Fuleihan ⁶, Elizabeth Secord ⁷, Rebecca Marsh ⁸, Kathleen E Sullivan ⁹, Charlotte Cunningham-Rundles ¹⁰, Luigi D Notarangelo ¹¹, Karin Chen ¹²

Author information

¹Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah; Division of Immunology, Boston Children's Hospital, Boston, Mass.

²Division of Pediatric Allergy and Immunology, Johns Hopkins University, Baltimore, Md.

³United States Immunodeficiency Network, Towson, Md.

⁴National Institutes of Health, National Human Genome Research Institute, Bethesda, Md.

⁵Division of Immunology, Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Wash.

⁶Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, Columbia University Irving Medical Center, New York-Presbyterian and Morgan Stanley Children's Hospital, New York, NY.

⁷Division of Allergy and Immunology, Wayne Pediatrics, Wayne State University School of Medicine, Detroit, Mich.

⁸Department of Pediatrics, University of Cincinnati, and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

⁹Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine at University of Pennsylvania, Philadelphia, Pa.

¹⁰Division of Allergy and Immunology, Department of Medicine, the Icahn School of Medicine at Mount Sinai, New York, NY.

¹¹Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.

¹²Division of Allergy and Immunology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah; Division of Immunology, Department of Pediatrics, University of Washington and Seattle Children's Research Institute, Seattle, Wash. Electronic address: Karin.Chen@SeattleChildrens.org.

Abstract

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity caused by defects in the phagocytic nicotinamide adenine dinucleotide phosphate oxidase complex, leading to increased susceptibility to infection and inflammatory autoimmune diseases. Up to 50% of patients have gastrointestinal (GI) involvement and meet diagnostic criteria for inflammatory bowel disease (CGD-IBD).

Objective: We analyzed patients with CGD from the US Immunodeficiency Network (USIDNET) registry to determine whether IBD changes the presentation, treatment, and outcomes of patients with CGD.

Methods: A retrospective evaluation of CGD cases from the USIDNET registry was completed. CGD-IBD was defined as the presence of any major physician-reported inflammatory, noninfectious GI disease manifestation. Demographic information, conditions, infections, antimicrobial therapies, immunomodulator use, and hematopoietic stem cell transplantation data were analyzed.

Results: Of 194 patients with a diagnosis of CGD, 96 met criteria for IBD and 98 were categorized in the non-IBD group. Patients with CGD-IBD had an increased rate of infection compared with the non-IBD group (0.66 vs 0.36 infections/patient/year). Enteric organism infections were more common in patients with IBD. Immunomodulators were used at a significantly higher percentage in patients with IBD compared with patients without IBD (80% vs 56%, P < .001). Of the entire CGD cohort, 17 patients died (8.8%), with no significant difference between patients with IBD and patients without IBD (P = 1.00).

Conclusion: Infectious events, enteric organism infections, and use of immunomodulatory drugs were higher in patients with IBD than patients without IBD; however, mortality was not increased. Patients with CGD and concurrent IBD are at increased risk for disease complications, supporting the importance of early recognition, diagnosis, and treatment.