Chronic Granulomatous Disease (CGD): Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management
Abstract
Chronic granulomatous disease (CGD) is a relatively rare inborn error of immune system caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex which leads to impaired production of reactive oxygen species (ROS) and ineffective phagocyte function. Genetic defects of any of proteinaceous components of NADPH oxidase complex results in CGD. The most common type of CGD (65-70%) is caused by X-linked mutations in the CYBB gene encoding gp91phox, followed by autosomal recessive mutations in the NCF1, NCF2, CYBA and NCF4 genes encoding p47phox, p67phox, p22phox, and p40phox, respectively. Dihydrorhodamine (DHR) 123 oxidation and nitroblue tetrazolium (NBT) tests are both used for the diagnosis of CGD that should be confirmed by genetic testing. CGD patients generally present with recurrent infections caused by uncommon pathogens like aspergillus, staphylococcus aureus, burkholderia cepacia, serratia marcescens, Aspergillus species and nocardia. They manifest with deep seated abscess formation, genitourinary and gastrointestinal granuloma development, autoimmunity and malignancy. Apart from comprehensive treatment of acute infections, management of CGD is based on reducing bacterial and fungal infections in addition to minimizing the inflammatory symptoms. Antibiotics, anti-fungal and IFN-γ are used for prophylaxis. Allogeneic hematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD. Gene therapy is considered an alternative, novel therapeutic approach in near future.
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6. Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A, et al. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152(2):211-8.
7. Marciano BE, Spalding C, Fitzgerald A, Mann D, Brown T, Osgood S, et al. Common severe infections in chronic granulomatous disease. Clin Infect Dis. 2015;60(8):1176-83.
8. Rider NL, Jameson MB, Creech CB. Chronic Granulomatous Disease: Epidemiology, Pathophysiology, and Genetic Basis of Disease. J Pediatric Infect Dis Soc. 2018;7(suppl_1):S2-S5.
9. Arnold DE, Heimall JR. A Review of Chronic Granulomatous Disease. Adv Ther. 2017;34(12):2543-57.
10. Anjani G, Vignesh P, Joshi V, Shandilya JK, Bhattarai D, Sharma J, et al. Recent advances in chronic granulomatous disease. Genes Dis. 2020;7(1):84-92.
11. Rider N, Jameson M, Creech C. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. J Pediatric Infect Dis Soc. 2018;7(suppl_1):S2-S5.
12. Leiding JW, Holland SM. Chronic granulomatous disease. Stiehm’s Immune Deficiencies: Elsevier; 2020. p. 829-47.
13. Reeves EP, Lu H, Jacobs HL, Messina CG,Bolsover S, Gabella G, et al. Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature. 2002;416(6878):291-7.
14. Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000;79(3):170-200.
15. Yu HH, Yang YH, Chiang BL. Chronic Granulomatous Disease: a Comprehensive Review. Clin Rev Allergy Immunol. 2020:1-13.
16. Hoffman R. Hematology : basic principles and practice. 6th ed. Philadelphia, PA: Saunders/Elsevier; 2013. xxxi, 2343 p. p.
17. Salvator H, Mahlaoui N, Catherinot E, Rivaud E, Pilmis B, Borie R, et al. Pulmonary manifestations in adult patients with chronic granulomatous disease. Eur Respir J. 2015;45(6):1613-23.
18. Falcone EL, Holland SM. Invasive fungal infection in chronic granulomatous disease: insights into pathogenesis and management. Curr Opin Infect Dis. 2012;25(6):658-69.
19. Beaute J, Obenga G, Le Mignot L, Mahlaoui N, Bougnoux ME, Mouy R, et al. Epidemiology and outcome of invasive fungal diseases in patients with chronic granulomatous disease: a multicenter study in France. Pediatr Infect Dis J. 2011;30(1):57-62.
20. Blumental S, Mouy R, Mahlaoui N, Bougnoux ME, Debre M, Beaute J, et al. Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey. Clin Infect Dis. 2011;53(12):e159-69.
21. Desjardins A, Coignard-Biehler H, Mahlaoui N, Frange P, Bougnoux ME, Blanche S, et al. [Chronic granulomatous disease: pathogenesis and therapy of associated fungal infections]. Med Sci (Paris). 2012;28(11):963-9.
22. Siddiqui S, Anderson VL, Hilligoss DM, Abinun M, Kuijpers TW, Masur H, et al. Fulminant mulch pneumonitis: an emergency presentation of chronic granulomatous disease. Clin Infect Dis. 2007;45(6):673-81.
23. Liese J, Kloos S, Jendrossek V, Petropoulou T, Wintergerst U, Notheis G, et al. Longterm follow-up and outcome of 39 patients with chronic granulomatous disease. J Pediatr. 2000;137(5):687-93.
24. Magnani A, Brosselin P, Beaute J, de Vergnes N, Mouy R, Debre M, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655-62 e8.
25. Spagnolo P, Rossi G, Cavazza A, Bonifazi M, Paladini I, Bonella F, et al. Hypersensitivity Pneumonitis: A Comprehensive Review. J Investig Allergol Clin Immunol. 2015;25(4):237- 50; quiz follow 50.
26. Buchvald F, Petersen BL, Damgaard K, Deterding R, Langston C, Fan LL, et al. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis. Pediatr Pulmonol. 2011;46(11):1098-107.
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| Files | ||
| Issue | Vol 3, No 3 (2020) | |
| Section | Review Article | |
| DOI | https://doi.org/10.22034/igj.2020.242713.1045 | |
| Keywords | ||
| Chronic Granulomatous Disease (CGD) Dihydrorhodamine (DHR) test Nitroblue tetra-zolium (NBT) test | ||
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How to Cite
1.
Fayyaz F, Khashayar K, Nirouei M, Tavakol Z, Tavakol M. Chronic Granulomatous Disease (CGD): Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management. Immunol Genet J. 2020;3(3):16-29.
