National Consensus Guideline on Diagnosis and Management of Chronic Granulomatous Disease
Abstract
Currently, a national consensus or guideline for diagnosing and managing patients suspected of having chronic granulomatous disease (CGD) is lacking. This consensus is written based on a combination of scientific literature and comments from the expert panel of Iranian immunologists. A group of clinical immunologists reviewed the current consensus, presented their comments at a meeting titled “First Meeting on the Diagnosis of Inborn Errors of Immunity (IEI) by IEI Experts” and agreed on this consensus. This consensus guideline provides recommendations on the diagnosis, antimicrobial prophylaxis, management of clinical manifestations, administration of interferon gamma (IFN-γ) and hematopoietic stem cell transplantation (HSCT) for patients with CGD.
2. Kak, Raza, Tiwari. Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases. Biomolecular concepts. 2018;9(1):64-79.
3. Fischer. Gene therapy for inborn errors of immunity: past, present and future. Nature Reviews Immunology. 2023;23(6):397-408.
4. Bousfiha, Moundir, Tangye, Picard, Jeddane, Al-Herz, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. Journal of clinical immunology. 2022;42(7):1508-20.
5. Schwenkenbecher, Neyazi, Donnerstag, Ringshausen, Jacobs, Stoll, et al. Chronic granulomatous disease first diagnosed in adulthood presenting with spinal cord infection. Frontiers in immunology. 2018;9:1258.
6. Song, Jaishankar, Saleh, Jithpratuck, Sahni, Krishnaswamy. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clinical and Molecular Allergy. 2011;9:1-14.
7. Lin, Lee, Wang, Yang, Lau, Lee, et al. Clinical features and outcomes of patients with chronic granulomatous disease in Taiwan. Journal of Microbiology, Immunology and Infection. 2023;56(1):130-8.
8. Blancas-Galicia, Santos-Chávez, Deswarte, Mignac, Medina-Vera, León-Lara, et al. Genetic, immunological, and clinical features of the first Mexican cohort of patients with chronic granulomatous disease. Journal of clinical immunology. 2020;40:475-93.
9. Nunoi, Nakamura, Nishimura, Matsukura. Recent topics and advanced therapies in chronic granulomatous disease. Human cell. 2023;36(2):515-27.
10. Dinauer. Neutrophil defects and diagnosis disorders of neutrophil function: an overview. Neutrophil: Methods and Protocols. 2020:11-29.
11. Zerbe, Holland. Functional neutrophil disorders: Chronic granulomatous disease and beyond. Immunological Reviews. 2024;322(1):71-80.
12. Chiu, Leung, Chan, Yeung, Wong, Mao, et al. Phenomic analysis of chronic granulomatous disease reveals more severe integumentary infections in X-linked compared with autosomal recessive chronic granulomatous disease. Frontiers in Immunology. 2022;12:803763.
13. Staudacher, von Bernuth. Clinical presentation, diagnosis, and treatment of chronic granulomatous disease. Frontiers in Pediatrics. 2024;12:1384550.
14. Rider, Jameson, Creech. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. Journal of the Pediatric Infectious Diseases Society. 2018;7(suppl_1):S2-S5.
15. Yu, Yang, Chiang. Chronic granulomatous disease: a comprehensive review. Clinical reviews in allergy & immunology. 2021;61(2):101-13.
16. Henriet, Verweij, Holland, Warris. Invasive fungal infections in patients with chronic granulomatous disease. Hot Topics in Infection and Immunity in Children IX. 2013:27-55.
17. Bennett, Maglione, Wright, Zerbe. Infectious complications in patients with chronic granulomatous disease. Journal of the Pediatric Infectious Diseases Society. 2018;7(suppl_1):S12-S7.
18. Thomsen, Smith, Holland, Creech. A comprehensive approach to the management of children and adults with chronic granulomatous disease. The Journal of Allergy and Clinical Immunology: In Practice. 2016;4(6):1082-8.
19. Fayyaz, Khashayar, Nirouei, Tavakol, Tavakol. Chronic granulomatous disease (CGD): epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis and management. Immunology and Genetics Journal. 2020:16-29.
20. Staudacher, von Bernuth. Clinical presentation, diagnosis, and treatment of chronic granulomatous disease. Front Pediatr. 2024;12:1384550.
21. van den Berg, van Koppen, Ahlin, Belohradsky, Bernatowska, Corbeel, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.
22. Marciano, Spalding, Fitzgerald, Mann, Brown, Osgood, et al. Common severe infections in chronic granulomatous disease. Clinical Infectious Diseases. 2015;60(8):1176-83.
23. King, Henriet, Warris. Aspergillosis in Chronic Granulomatous Disease. J Fungi (Basel). 2016;2(2).
24. van den Berg, van Koppen, Åhlin, Belohradsky, Bernatowska, Corbeel, et al. Chronic granulomatous disease: the European experience. PloS one. 2009;4(4):e5234.
25. Gallin, Alling, Malech, Wesley, Koziol, Marciano, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. New England Journal of Medicine. 2003;348(24):2416-22.
26. Welzen, Brüggemann, Van Den Berg, Voogt, Gilissen, Pajkrt, et al. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease. The Pediatric infectious disease journal. 2011;30(9):794-7.
27. Cowan, Pakhale, Angel. Mulch pneumonitis in a patient with chronic granulomatous disease. Cmaj. 2022;194(44):E1510.
28. Straughan, McLoughlin, Mullinax, Marciano, Freeman, Anderson, et al. The Changing Paradigm of Management of Liver Abscesses in Chronic Granulomatous Disease. Clin Infect Dis. 2018;66(9):1427-34.
29. Lublin, Bartlett, Danforth, Kauffman, Gallin, Malech, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg. 2002;235(3):383-91.
30. Kobayashi, Murayama, Takanashi, Takahashi, Miyatsuka, Fujita, et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. European journal of pediatrics. 2008;167:1389-94.
31. Bennett, Maglione, Wright, Zerbe. Infectious Complications in Patients With Chronic Granulomatous Disease. J Pediatric Infect Dis Soc. 2018;7(suppl_1):S12-s7.
32. Zwerling, Behr, Verma, Brewer, Menzies, Pai. The BCG World Atlas: a database of global BCG vaccination policies and practices. PLoS medicine. 2011;8(3):e1001012.
33. Conti, Lugo-Reyes, Blancas Galicia, He, Aksu, Borges de Oliveira, et al. Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases. Journal of Allergy and Clinical Immunology. 2016;138(1):241-8.e3.
34. Marciano, Huang, Joshi, Rezaei, Carvalho, Allwood, et al. BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies. Journal of allergy and clinical immunology. 2014;133(4):1134-41.
35. Mohammadpour, Mamishi, Oaji, Pourpak, Parvaneh. Successful treatment of fungal osteomyelitis with voriconazole in a patient with chronic granulomatous disease. Iran J Pediatr. 2010;20(4):487-90.
36. Marks, Miyagi, Rahman, Novelli, Bloom, Segal. Inflammatory bowel disease in CGD reproduces the clinicopathological features of Crohn's disease. Official journal of the American College of Gastroenterology| ACG. 2009;104(1):117-24.
37. Alimchandani, Lai, Aung, Khangura, Kamal, Gallin, et al. Gastrointestinal histopathology in chronic granulomatous disease: a study of 87 patients. The American journal of surgical pathology. 2013;37(9):1365-72.
38. Uzel, Orange, Poliak, Marciano, Heller, Holland. Complications of tumor necrosis factor-±blockade in chronic granulomatous disease—related colitis. Clinical Infectious Diseases. 2010;51(12):1429-34.
39. Conrad, Neven, Mahlaoui, Suarez, Sokol, Ruemmele, et al. Infections in patients with chronic granulomatous disease treated with tumor necrosis factor alpha blockers for inflammatory complications. Journal of Clinical Immunology. 2021;41:185-93.
40. Hahn, Ho, Yockey, Kreuzberg, Daub, Rump, et al. Treatment with anakinra, a recombinant IL-1 receptor antagonist, unlikely to induce lasting remission in patients with CGD colitis. Official journal of the American College of Gastroenterology| ACG. 2015;110(6):938-9.
41. Yu, Yang, Chiang. Chronic Granulomatous Disease: a Comprehensive Review. Clin Rev Allergy Immunol. 2021;61(2):101-13.
42. Good, Quie, Windhorst, Page, Rodey, White, et al. Fatal (chronic) granulomatous disease of childhood: a hereditary defect of leukocyte function. Semin Hematol. 1968;5(3):215-54.
43. Gul, Hazar, Kapaklı, Guner, Nayir, Kutuk, et al. Chronic Granulomatous Disease: A Single-Center Experience in Central Anatolia. Pediatrics & Neonatology. 2024.
44. Lhomme, Peyrard, Babinet, Abou-Chahla, Durieu, Moshous, et al. Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series. J Clin Immunol. 2020;40(5):752-62.
45. Holland. Chronic granulomatous disease. Clinical reviews in allergy & immunology. 2010;38:3-10.
46. Climax, Lenehan, Lambe, Kenny, Caffrey, Darragh. Interaction of antimicrobial agents with human peripheral blood leucocytes: uptake and intracellular localization of certain sulphonamides and trimethoprims. J Antimicrob Chemother. 1986;17(4):489-98.
47. Thomsen, Smith, Holland, Creech. A Comprehensive Approach to the Management of Children and Adults with Chronic Granulomatous Disease. J Allergy Clin Immunol Pract. 2016;4(6):1082-8.
48. Kutluğ, Kökçü Karadağ, Şensoy, Birinci, Köker, Yıldıran. The Efficacy of Long-Term Voriconazole Prophylaxis on Seven Patients with Chronic Granulomatous Disease and Review of the Literature. Journal of Pediatric Infection/Cocuk Enfeksiyon Dergisi. 2021(4).
49. Arnold, Heimall. A Review of Chronic Granulomatous Disease. Adv Ther. 2017;34(12):2543-57.
50. Welzen, Brüggemann, Van Den Berg, Voogt, Gilissen, Pajkrt, et al. A twice daily posaconazole dosing algorithm for children with chronic granulomatous disease. Pediatr Infect Dis J. 2011;30(9):794-7.
51. Ezekowitz, Orkin, Newburger. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease. The Journal of clinical investigation. 1987;80(4):1009-16.
52. Newburger, Ezekowitz. Cellular and molecular effects of recombinant interferon gamma in chronic granulomatous disease. Hematology/Oncology Clinics of North America. 1988;2(2):267-76.
53. Sechler, Malech, White, Gallin. Recombinant human interferon-gamma reconstitutes defective phagocyte function in patients with chronic granulomatous disease of childhood. Proceedings of the National Academy of Sciences. 1988;85(13):4874-8.
54. Marciano, Wesley, De Carlo, Anderson, Barnhart, Darnell, et al. Long-term interferon-γ therapy for patients with chronic granulomatous disease. Clinical infectious diseases. 2004;39(5):692-9.
55. Slack, Thomsen. Prevention of Infectious Complications in Patients With Chronic Granulomatous Disease. J Pediatric Infect Dis Soc. 2018;7(suppl_1):S25-s30.
56. Seger. Modern management of chronic granulomatous disease. British journal of haematology. 2008;140(3):255-66.
57. Slatter, Gennery. Haematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. J Clin Med. 2023;12(18).
58. Alonso García, Bueno Sánchez, Fernández Navarro, Regueiro Garcia, Blanquer Blanquer, Benitez Carabante, et al. Hematopoietic stem cell transplantation in children with chronic granulomatous disease: the Spanish experience. Frontiers in Immunology. 2024;15:1307932.
59. Conrad, Neven, Mahlaoui, Suarez, Sokol, Ruemmele, et al. Infections in Patients with Chronic Granulomatous Disease Treated with Tumor Necrosis Factor Alpha Blockers for Inflammatory Complications. J Clin Immunol. 2021;41(1):185-93.
60. Holland. Chronic granulomatous disease. Hematol Oncol Clin North Am. 2013;27(1):89-99, viii.
61. Roesler, Koch, Pörksen, Von Bernuth, Brenner, Hahn, et al. Benefit assessment of preventive medical check-ups in patients suffering from chronic granulomatous disease (CGD). Journal of Evaluation in Clinical Practice. 2005;11(6):513-21.
62. Shearer, Fleisher, Buckley, Ballas, Ballow, Blaese, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol. 2014;133(4):961-6.
Files | ||
Issue | Vol 8, No 3 (2025) | |
Section | Review Article | |
DOI | https://doi.org/10.18502/igj.v8i3.18170 | |
Keywords | ||
National Consensus Inborn Errors of Immunity Chronic Granulomatous Disease Management IFN-γ HSCT |
Rights and permissions | |
![]() |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |