{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:58:17Z","timestamp":1787504297696,"version":"build-2736575974"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Chronic granulomatous disease (CGD) is a rare inborn error of immunity that typically manifests with infectious complications. As the name suggest though, inflammatory complications are also common, often affecting the gastrointestinal, respiratory, urinary tracts and other tissues. These can be seen in all various types of CGD, from X-linked and autosomal recessive to X-linked carriers. The pathogenetic mechanisms underlying these complications are not well understood, but are likely multi-factorial and reflect the body\u2019s attempt to control infections. The different levels of neutrophil residual oxidase activity are thought to contribute to the large phenotypic variations. Immunosuppressive agents have traditionally been used to treat these complications, but their use is hindered by the fact that CGD patients are predisposed to infection. Novel therapeutic agents, like anti-TNFa monoclonal antibodies, anakinra, ustekinumab, and vedolizumab offer promise for the future, while hematopoietic stem cell transplantation should also be considered in these patients.<\/jats:p>","DOI":"10.3390\/jcm13041092","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T03:57:29Z","timestamp":1707969449000},"page":"1092","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inflammatory Complications in Chronic Granulomatous Disease"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6544-8218","authenticated-orcid":false,"given":"Alexandros","family":"Grammatikos","sequence":"first","affiliation":[{"name":"The Bristol Immunology and Allergy Centre, North Bristol NHS Trust, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6218-1324","authenticated-orcid":false,"given":"Andrew R.","family":"Gennery","sequence":"additional","affiliation":[{"name":"Paediatric Stem Cell Transplant Unit, Great North Children\u2019s Hospital, Newcastle upon Tyne NE1 4LP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/bjh.16939","article-title":"Progress in Treating Chronic Granulomatous Disease","volume":"192","author":"Gennery","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1084\/jem.20161382","article-title":"Eros Is a Novel Transmembrane Protein That Controls the Phagocyte Respiratory Burst and Is Essential for Innate Immunity","volume":"214","author":"Thomas","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mackay, I.R., Rose, N.R., Diamond, B., and Davidson, A. (2014). Encyclopedia of Medical Immunology: Autoimmune Diseases, Springer.","DOI":"10.1007\/978-0-387-84828-0"},{"key":"ref_4","unstructured":"BMJ Best Practice (2024, January 10). Chronic Granulomatous Disease\u2014Symptoms, Diagnosis and Treatment. Available online: https:\/\/bestpractice.bmj.com\/topics\/en-gb\/703."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jaci.2014.04.014","article-title":"Inflammatory Manifestations in a Single-Center Cohort of Patients with Chronic Granulomatous Disease","volume":"134","author":"Magnani","year":"2014","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1093\/jpids\/piy014","article-title":"Noninfectious Manifestations and Complications of Chronic Granulomatous Disease","volume":"7","author":"Henrickson","year":"2018","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1056\/NEJMoa1007097","article-title":"Residual NADPH Oxidase and Survival in Chronic Granulomatous Disease","volume":"363","author":"Kuhns","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.jaci.2013.05.039","article-title":"Clinical, Functional, and Genetic Characterization of Chronic Granulomatous Disease in 89 Turkish Patients","volume":"132","author":"Barlan","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"625320","DOI":"10.3389\/fimmu.2021.625320","article-title":"Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients from India","volume":"12","author":"Rawat","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000496181","article-title":"Common Infections and Target Organs Associated with Chronic Granulomatous Disease in Iran","volume":"179","author":"Mortaz","year":"2019","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s10875-011-9567-x","article-title":"Inheritance Pattern and Clinical Aspects of 93 Iranian Patients with Chronic Granulomatous Disease","volume":"31","author":"Fattahi","year":"2011","journal-title":"J. Clin. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Roxo-Junior, P., and Sim\u00e3o, H.M.L. (2014). Chronic Granulomatous Disease: Why an Inflammatory?. Braz. J. Med. Biol. Res., 47.","DOI":"10.1590\/1414-431X20143735"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1542\/peds.114.2.462","article-title":"Gastrointestinal Involvement in Chronic Granulomatous Disease","volume":"114","author":"Marciano","year":"2004","journal-title":"Pediatrics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1097\/00005792-200005000-00003","article-title":"Chronic Granulomatous Disease. Report on a National Registry of 368 Patients","volume":"79","author":"Winkelstein","year":"2000","journal-title":"Medicine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Van den Berg, J.M., van Koppen, E., \u00c5hlin, A., Belohradsky, B.H., Bernatowska, E., Corbeel, L., Espan\u00f1ol, T., Fischer, A., Kurenko-Deptuch, M., and Mouy, R. (2009). Chronic Granulomatous Disease: The European Experience. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005234"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1053\/j.gastro.2008.02.081","article-title":"Hepatic Involvement and Portal Hypertension Predict Mortality in Chronic Granulomatous Disease","volume":"134","author":"Feld","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/hep.21524","article-title":"Hepatic Abnormalities in Patients with Chronic Granulomatous Disease","volume":"45","author":"Hussain","year":"2007","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1183\/09031936.00118414","article-title":"Pulmonary Manifestations in Adult Patients with Chronic Granulomatous Disease","volume":"45","author":"Salvator","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1086\/520985","article-title":"Fulminant Mulch Pneumonitis: An Emergency Presentation of Chronic Granulomatous Disease","volume":"45","author":"Siddiqui","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s10875-013-9899-9","article-title":"Molecular Identification of Bacterial DNA in the Chorioretinal Scars of Chronic Granulomatous Disease","volume":"33","author":"Wang","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/cid\/ciw837","article-title":"Chronic Granulomatous Disease in Patients Reaching Adulthood: A Nationwide Study in France","volume":"64","author":"Pilmis","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/j.jaci.2008.07.050","article-title":"Chronic Granulomatous Disease as a Risk Factor for Autoimmune Disease","volume":"122","author":"Naumann","year":"2008","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","unstructured":"Zhang, K., Astigarraga, I., Bryceson, Y., Lehmberg, K., Machowicz, R., Marsh, R., Sieni, E., Wang, Z., and Nichols, K.E. (2021). Familial Hemophagocytic Lymphohistiocytosis, University of Washington."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1007\/s10875-013-9940-z","article-title":"Chronic Granulomatous Disease: A 25-Year Patient Registry Based on a Multistep Diagnostic Procedure, from the Referral Center for Primary Immunodeficiencies in Greece","volume":"33","author":"Raptaki","year":"2013","journal-title":"J. Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1067\/mpd.2000.109112","article-title":"Long-Term Follow-up and Outcome of 39 Patients with Chronic Granulomatous Disease","volume":"137","author":"Liese","year":"2000","journal-title":"J. Pediatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.clim.2007.09.008","article-title":"Clinical Features, Long-Term Follow-up and Outcome of a Large Cohort of Patients with Chronic Granulomatous Disease: An Italian Multicenter Study","volume":"126","author":"Martire","year":"2008","journal-title":"Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1002\/pbc.25674","article-title":"Clinical and Genotypic Spectrum of Chronic Granulomatous Disease in 71 Latin American Patients: First Report from the LASID Registry","volume":"62","author":"Zurro","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1046\/j.1365-2249.2000.01234.x","article-title":"Follow up of Patients with Chronic Granulomatous Disease Diagnosed since 1990","volume":"120","author":"Cale","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-2249.2008.03644.x","article-title":"Special Article: Chronic Granulomatous Disease in the United Kingdom and Ireland: A Comprehensive National Patient-Based Registry","volume":"152","author":"Jones","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1097\/INF.0000000000000840","article-title":"Chronic Granulomatous Disease: A Large, Single-Center US Experience","volume":"34","author":"Bortoletto","year":"2015","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1365-2249.2007.03321.x","article-title":"Cutaneous and Other Lupus-like Symptoms in Carriers of X-Linked Chronic Granulomatous Disease: Incidence and Autoimmune Serology","volume":"148","author":"Cale","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jaci.2017.04.035","article-title":"X-Linked Carriers of Chronic Granulomatous Disease: Illness, Lyonization, and Stability","volume":"141","author":"Marciano","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.jaci.2017.02.029","article-title":"Inflammatory and Autoimmune Manifestations in X-Linked Carriers of Chronic Granulomatous Disease in the United Kingdom","volume":"140","author":"Battersby","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1110115","DOI":"10.3389\/fped.2023.1110115","article-title":"Granulomatous Inflammation in Inborn Errors of Immunity","volume":"11","author":"Sacco","year":"2023","journal-title":"Front. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/adc.84.2.147","article-title":"Colitis in Chronic Granulomatous Disease","volume":"84","author":"Smith","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s10875-022-01294-6","article-title":"Chronic Granulomatous Disease: An Updated Experience, with Emphasis on Newly Recognized Features","volume":"42","author":"Oikonomopoulou","year":"2022","journal-title":"J. Clin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7570","DOI":"10.1182\/blood-2022-157594","article-title":"Allogeneic Transplantation for High Risk Patients with Chronic Granulomatous Disease (CGD)","volume":"140","author":"Kang","year":"2022","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1476-7961-9-10","article-title":"Chronic Granulomatous Disease: A Review of the Infectious and Inflammatory Complications","volume":"9","author":"Song","year":"2011","journal-title":"Clin. Mol. Allergy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/ajh.24573","article-title":"Chronic Granulomatous Disease: Clinical, Functional, Molecular, and Genetic Studies. The Israeli Experience with 84 Patients","volume":"92","author":"Wolach","year":"2017","journal-title":"Am. J. Hematol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"291147","DOI":"10.3389\/fimmu.2017.01167","article-title":"Very Early-Onset Inflammatory Manifestations of X-Linked Chronic Granulomatous Disease","volume":"8","author":"Labrosse","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s10875-007-9160-5","article-title":"Inflammatory Manifestations in Chronic Granulomatous Disease (CGD)","volume":"28","author":"Rosenzweig","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"ref_42","first-page":"474995","article-title":"High Levels of IL-18 and IFN-\u03b3 in Chronically Inflamed Tissue in Chronic Granulomatous Disease","volume":"10","author":"Valencia","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nature06471","article-title":"Defective Tryptophan Catabolism Underlies Inflammation in Mouse Chronic Granulomatous Disease","volume":"451","author":"Romani","year":"2008","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1097\/MIB.0000000000000966","article-title":"Genetic Risk for Inflammatory Bowel Disease Is a Determinant of Crohn\u2019s Disease Development in Chronic Granulomatous","volume":"22","author":"Huang","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Falcone, E.L., Abusleme, L., Swamydas, M., Lionakis, M.S., Ding, L., Hsu, A.P., Zelazny, A.M., Moutsopoulos, N.M., Kuhns, D.B., and Deming, C. (2016). Colitis Susceptibility in P47(Phox\u2212\/\u2212) Mice Is Mediated by the Microbiome. Microbiome, 4.","DOI":"10.1186\/s40168-016-0159-0"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., Han, Y., Zerbe, C.S., Heller, T., DeRavin, S.S., Kreuzberg, S.A., Marciano, B.E., Siu, Y., Jones, D.R., and Abraham, R.S. (2023). Intestinal Microbiome and Metabolome Signatures in Patients with Chronic Granulomatous Disease. J. Allergy Clin. Immunol., 152.","DOI":"10.1016\/j.jaci.2023.07.022"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/s41385-019-0205-x","article-title":"Colitis Susceptibility in Mice with Reactive Oxygen Species Deficiency Is Mediated by Mucus Barrier and Immune Defense Defects","volume":"12","author":"Aviello","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1073\/pnas.1322831111","article-title":"IL-1 Receptor Blockade Restores Autophagy and Reduces Inflammation in Chronic Granulomatous Disease in Mice and in Humans","volume":"111","author":"Smeekens","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1182\/blood-2008-05-160564","article-title":"Impaired Apoptotic Cell Clearance in CGD Due to Altered Macrophage Programming Is Reversed by Phosphatidylserine-Dependent Production of IL-4","volume":"113","author":"Frasch","year":"2009","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1189\/jlb.1202599","article-title":"Diminished Production of Anti-Inflammatory Mediators during Neutrophil Apoptosis and Macrophage Phagocytosis in Chronic Granulomatous Disease (CGD)","volume":"73","author":"Brown","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1002\/eji.200737348","article-title":"Th17 Development and Autoimmune Arthritis in the Absence of Reactive Oxygen Species","volume":"38","author":"Nygren","year":"2008","journal-title":"Eur. J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1086\/657308","article-title":"Complications of Tumor Necrosis Factor-\u00b1Blockade in Chronic Granulomatous Disease-Related Colitis","volume":"51","author":"Uzel","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"707369","DOI":"10.3389\/fped.2021.707369","article-title":"Candida Glabrata Lymphadenitis Following Infliximab Therapy for Inflammatory Bowel Disease in a Patient with Chronic Granulomatous Disease: Case Report and Literature Review","volume":"9","author":"Lehman","year":"2021","journal-title":"Front. Pediatr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s10875-020-00901-8","article-title":"Infections in Patients with Chronic Granulomatous Disease Treated with Tumor Necrosis Factor Alpha Blockers for Inflammatory Complications","volume":"41","author":"Conrad","year":"2021","journal-title":"J. Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/ajg.2015.135","article-title":"Treatment with Anakinra, a Recombinant IL-1 Receptor Antagonist, Unlikely to Induce Lasting Remission in Patients with CGD Colitis","volume":"110","author":"Hahn","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.cgh.2021.03.039","article-title":"Safety and Efficacy of Ustekinumab in the Inflammatory Bowel Disease of Chronic Granulomatous Disease","volume":"20","author":"Bhattacharya","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_57","first-page":"CD013611","article-title":"Vedolizumab for Induction and Maintenance of Remission in Crohn\u2019s Disease","volume":"2023","author":"Hui","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/gastro\/goaa005","article-title":"The Response to Vedolizumab in Chronic Granulomatous Disease-Related Inflammatory Bowel Disease","volume":"8","author":"Kamal","year":"2020","journal-title":"Gastroenterol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Slatter, M.A., and Gennery, A.R. (2023). Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. J. Clin. Med., 12.","DOI":"10.3390\/jcm12186083"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1182\/blood.2022016074","article-title":"Lentiviral Gene Therapy for X-Linked Chronic Granulomatous Disease Recapitulates Endogenous CYBB Regulation and Expression","volume":"141","author":"Wong","year":"2023","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/B978-0-12-386509-0.00007-7","article-title":"Gene Therapy for Chronic Granulomatous Disease","volume":"507","author":"Kang","year":"2012","journal-title":"Methods Enzymol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/4\/1092\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:59:56Z","timestamp":1760104796000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/4\/1092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":61,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["jcm13041092"],"URL":"https:\/\/doi.org\/10.3390\/jcm13041092","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,15]]}}}