Abstract
Chronic granulomatous disease (CGD) is an inborn error of immunity caused by a defect in one of the components of the NADPH oxidase complex, which is responsible for generating reactive oxygen species (ROS) during the respiratory burst in phagocytes. The absence of ROS produced by NADPH oxidase in neutrophils and in macrophages leads to greater susceptibility to certain bacterial and fungal infections, and also to inflammatory manifestations due to a deregulated inflammatory response, which suggests that the ability to adequately regulate inflammatory signaling depends on ROS produced by NADPH oxidase. The disease course in patients with X-linked CGD is more severe, with recurrent invasive infections; in contrast, patients with non-classic CGD do not present invasive bacterial or fungal infections, but have more prominent inflammatory manifestations. The most frequent gastrointestinal manifestations are stomatitis, gingivitis, chronic diarrhea, liver abscesses that are similar to inflammatory bowel disease (IBD), and granulomas that can cause obstruction or stenosis in the esophagus, stomach or intestine. It has been observed that the deficiency of p40phox and ROS (non-classic CGD) are associated with greater susceptibility to colitis and the development of severe inflammation; therefore, it is presented that these proteins participate in the resolution of inflammation. In general, the inflammatory findings in CGD, including gastrointestinal manifestations, are seldom described. In international cohorts, manifestations that are similar to IBD are reported in up to 58% of patients with CGD; however, in the only Mexican cohort, its finding is described in only 4 out of 93 patients (4.3%). In this review, we summarize the gastrointestinal clinical findings of CGD, including infectious and inflammatory manifestations, emphasizing on the latter.
References
Arnold DE, Heimall JR. A review of chronic granulomatous disease. Adv Ther. 2017;34(12):2543-2557. DOI: 10.1007/s12325-017-0636-2
Gennery A. Recent advances in understanding and treating chronic granulomatous disease. F1000Res. 2017;6:1427. DOI: 10.12688/f1000research.11789.1
Song E, Jaishankar GB, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10. DOI: 10.1186/1476-7961-9-10
Dinauer MC. Inflammatory consequences of inherited disorders affecting neutrophil function. Blood. 2019;133(20):2130-2139. DOI: 10.1182/blood-2018-11-844563
Dahlgren C, Karlsson A, Bylund J. intracellular neutrophil oxidants: from laboratory curiosity to clinical reality. J Immunol. 2019;202(11):3127-3134. DOI: 10.4049/jimmunol.1900235
Conway KL, Goel G, Sokol H, Manocha M, Mizoguchi E, Terhorst C, et al. p40phox expression regulates neutrophil recruitment and function during the resolution phase of intestinal inflammation. J Immunol. 2012;189(7):3631-3640. DOI: 10.4049/jimmunol.1103746
Felmy B, Songhet P, Slack EM, Muller AJ, Kremer M, Van Maele L, et al. NADPH oxidase deficient mice develop colitis and bacteremia upon infection with normally avirulent, TTSS-1- and TTSS-2-deficient Salmonella Typhimurium. PLoS One. 2013;8(10):e77204. DOI: 10.1371/journal.pone.0077204
Aviello G, Singh AK, O'Neill S, Conroy E, Gallagher W, D'Agostino G, et al. Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects. Mucosal Immunology. 2019;12(6):1316-26. Disponible en: https://www.nature.com/articles/s41385-019-0205-x
van de Geer A, Nieto-Patlan A, Kuhns DB, Tool AT, Arias AA, Bouaziz M, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. 2018;128(9):3957-3975. DOI: 10.1172/JCI97116
Goldblatt D. Recent advances in chronic granulomatous disease. J Infect. 2014;69(Suppl 1):S32-S35. DOI: 10.1016/j.jinf.2014.07.013
Leiding JW, Holland SM. Chronic granulomatous disease. En: GeneReviews [Internet]. EE. UU.: University of Washington; c2020.
Gao LW, Yin QQ, Tong YJ, Gui JG, Liu XY, Feng XL, et al. Clinical and genetic characteristics of Chinese pediatric patients with chronic granulomatous disease. Pediatr Allergy Immunol. 2019;30(3):378-386. DOI: 10.1111/pai.13033
Raptaki M, Varela I, Spanou K, Tzanoudaki M, Tantou S, Liatsis M, et al. Chronic granulomatous disease: a 25-year patient registry based on a multistep diagnostic procedure, from the referral center for primary immunodeficiencies in Greece. J Clin Immunol. 2013;33(8):1302-1309. DOI: 10.1007/s10875-013-9940-z
Fattahi F, Badalzadeh M, Sedighipour L, Movahedi M, Fazlollahi MR, Mansouri SD, et al. Inheritance pattern and clinical aspects of 93 Iranian patients with chronic granulomatous disease. J Clin Immunol. 2011;31(5):792-801. DOI: 10.1007/s10875-011-9567-x
Kutukculer N, Aykut A, Karaca NE, Durmaz A, Aksu G, Genel F, et al. Chronic granulamatous disease: two decades of experience from a paediatric immunology unit in a country with high rate of consangineous marriages. Scand J Immunol. 2019;89(2):e12737. DOI: 10.1111/sji.12737
Wolach B, Gavrieli R, de Boer M, Gottesman G, Ben-Ari J, Rottem M, et al. Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients. Clin Immunol. 2008;129(1):103-114. DOI: 10.1016/j.clim.2008.06.012
Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Berger-Achituv S, Stauber T, et al. Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients. Am J Hematol. 2017;92(1):28-36. DOI: 10.1002/ajh.24573
Wu J, Wang W-F, Zhang Y-D, Chen T-X. Clinical features and genetic analysis of 48 patients with chronic granulomatous disease in a single center study from Shanghai, China (2005-2015): new studies and a literature review. J Immunol Res. 2017;2017:8745254. DOI: 10.1155/2017/8745254
Blancas-Galicia L, Santos-Chavez E, Deswarte C, Mignac Q, Medina-Vera I, Leon-Lara X, et al. Genetic, immunological, and clinical features of the first mexican cohort of patients with chronic granulomatous disease. J Clin Immunol. 2020;40(3):475-493.
Roos D. Chronic granulomatous disease. Br Med Bull. 2016;118(1):50-63. DOI: 10.1093/bmb/ldw009
Venegas-Montoya E, Sorcia-Ramírez G, Scheffler-Mendoza S, Blancas-Galicia L, Bustamante J, Espinosa-Rosales F, et al. Use of corticosteroids as an alternative to surgical treatment for liver abscesses in chronic granulomatous disease. Pediatr Blood Cancer. 2016;63(12):2254-2255. DOI: 10.1002/pbc.26140
Straughan DM, McLoughlin KC, Mullinax JE, Marciano BE, Freeman AF, Anderson VL, et al. The changing paradigm of management of liver abscesses in chronic granulomatous disease. Clin Infect Dis. 2018;66(9):1427-1434. DOI: 10.1093/cid/cix1012
Dunogué B, Pilmis B, Mahlaoui N, Elie C, Coignard-Biehler H, Amazzough K, et al. Chronic granulomatous disease in patients reaching adulthood: a nationwide study in France. Clin Infect Dis. 2017;64(6):767-775. DOI: 10.1093/cid/ciw837
Liese J, Kloos S, Jendrossek V, Petropoulou T, Wintergerst U, Notheis G, et al. Long-term follow-up and outcome of 39 patients with chronic granulomatous disease. J Pediatr. 2000;137(5):687-693. DOI: 10.1067/mpd.2000.109112
Zhou Q, Hui X, Ying W, Hou J, Wang W, Liu D, et al. A cohort of 169 chronic granulomatous disease patients exposed to BCG vaccination: a retrospective study from a single center in Shanghai, China (2004-2017). J Clin Immunol. 2018;38(3):260-272. DOI: 10.1007/s10875-018-0486-y
Patiroglu T, Gungor HE, Unal E, Koker Y. The clinical features and genetic mutations of chronic granulomatous disease: results from a reference centre at middle Anatolia. Genet Couns. 2013;24(3):327-335.
Feld JJ, Hussain N, Wright EC, Kleiner DE, Hoofnagle JH, Ahlawat S, et al. Hepatic involvement and portal hypertension predict mortality in chronic granulomatous disease. Gastroenterology. 2008;134(7):1917-1926. DOI: 10.1053/j.gastro.2008.02.081
Winkelstein JA, Marino MC, Johnston RB, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155-169. DOI: 10.1097/00005792-200005000-00003
Tajik S, Badalzadeh M, Fazlollahi MR, Houshmand M, Bazargan N, Movahedi M, et al. Genetic and molecular findings of 38 Iranian patients with chronic granulomatous disease caused by p47-phox defect. Scand J Immunol. 2019;90(1):e12767. DOI: 10.1111/sji.12767
Jakobsen MA, Katzenstein TL, Valerius NH, Roos D, Fisker N, Mogensen TH, et al. Genetical analysis of all Danish patients diagnosed with chronic granulomatous disease. Scand J Immunol. 2012;76(5):505-511. DOI: 10.1007/s00281-008-0128-1
Giannopoulou C, Krause KH, Muller F. The NADPH oxidase NOX2 plays a role in periodontal pathologies. Semin Immunopathol. 2008;30(3):273-278. DOI: 10.1007/s00281-008-0128-1
Pasic S, Minic A, Minic P, Veljkovic D, Lilic D, Slavkovic B, et al. Long-term follow-up and prognosis of chronic granulomatous disease in Yugoslavia: is there a role for early bone marrow transplantation? J Clin Immunol. 2003;23(1):55-61. DOI: 10.1023/a:1021952315651
Rawat A, Vignesh P, Sharma A, Shandilya JK, Sharma M, Suri D, et al. Infection profile in chronic granulomatous disease: a 23-year experience from a tertiary care center in North India. J Clin Immunol. 2017;37(3):319-328. DOI: 10.1007/s10875-017-0382-x
Robles-Marhuenda A, Álvarez-Troncoso J, Rodríguez-Pena R, Busca-Arenzana C, López-Granados E, Arnalich-Fernández F. Chronic granulomatous disease: Single-center Spanish experience. Clin Immunol. 2019;211:108323. DOI: 10.1016/j.clim.2019.108323
van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234. DOI: 10.1371/journal.pone.0005234
Martire B, Rondelli R, Soresina A, Pignata C, Broccoletti T, Finocchi A, et al. Clinical features, long-term follow-up and outcome of a large cohort of patients with chronic granulomatous disease: an Italian multicenter study. Clin Immunol. 2008;126(2):155-164. DOI: 10.1016/j.clim.2007.09.008
Agudelo-Florez P, Prando-Andrade CC, Lopez JA, Costa-Carvalho BT, Quezada A, Espinosa FJ, et al. Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics. Pediatr Blood Cancer. 2006;46(2):243-252. DOI: 10.1002/pbc.20455
Khangura SK, Kamal N, Ho N, Quezado M, Zhao X, Marciano B, et al. Gastrointestinal features of chronic granulomatous disease found during endoscopy. Clin Gastroenterol Hepatol. 2016;14(3):395-402. DOI: 10.1016/j.cgh.2015.10.030
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):211-218. DOI: 10.1111/j.1365-2249.2008.03644.x
Liese JG, Jendrossek V, Jansson A, Petropoulou T, Kloos S, Gahr M, et al. Chronic granulomatous disease in adults. Lancet. 1996;347(8996):220-223. DOI: 10.1016/s0140-6736(96)90403-1
Teimourian S, Rezvani Z, Badalzadeh M, Kannengiesser C, Mansouri D, Movahedi M, et al. Molecular diagnosis of X-linked chronic granulomatous disease in Iran. Int J Hematol. 2008;87(4):398-404. DOI: 10.1007/s12185-008-0060-0
Barese C, Copelli S, Zandomeni R, Oleastro M, Zelazko M, Rivas EM. X-linked chronic granulomatous disease: first report of mutations in patients of Argentina. J Pediatr Hematol Oncol. 2004;26(10):656-660.
de Oliveira-Junior EB, Zurro NB, Prando C, Cabral-Marques O, Pereira PV, Schimke LF, et al. Clinical and genotypic spectrum of chronic granulomatous disease in 71 Latin American patients: first report from the LASID registry. Pediatr Blood Cancer. 2015;62(12):2101-2107. DOI: 10.1002/pbc.25674
Wang S, Wang T, Xiang Q, Xiao M, Cao Y, Xu H, et al. Clinical and molecular features of chronic granulomatous disease in mainland China and a XL-CGD female infant patient after prenatal diagnosis. J Clin Immunol. 2019;39(8):762-775. DOI: 10.1007/s10875-019-00680-x
Henrickson SE, Jongco AM, Thomsen KF, Garabedian EK, Thomsen IP. Noninfectious manifestations and complications of chronic granulomatous disease. J Pediatric Infect Dis Soc. 2018;7(Suppl 1):S18-S24. DOI: 10.1093/jpids/piy014
Arnadottir GA, Norddahl GL, Gudmundsdottir S, Agustsdottir AB, Sigurdsson S, Jensson BO, et al. A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018;9(1):4447. DOI: 10.1038/s41467-018-06964-x
Kobayashi S, Murayama S, Takanashi S, Takahashi K, Miyatsuka S, Fujita T, et al. Clinical features and prognoses of 23 patients with chronic granulomatous disease followed for 21 years by a single hospital in Japan. Eur J Pediatr. 2008;167(12):1389-1394. DOI: 10.1007/s00431-008-0680-7
Angelino G, de Angelis P, Faraci S, Rea F, Romeo EF, Torroni F, et al. Inflammatory bowel disease in chronic granulomatous disease: An emerging problem over a twenty years' experience. Pediatr Allergy Immunol. 2017;28(8):801-809. DOI: 10.1111/pai.12814
Marciano BE, Rosenzweig SD, Kleiner DE, Anderson VL, Darnell DN, Anaya-O'Brien S, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004;114(2):462-468. DOI: 10.1542/peds.114.2.462
Wright M, Chandrakasan S, Okou DT, Yin H, Jurickova I, Denson LA, et al. Early onset granulomatous colitis associated with a mutation in NCF4 resolved with hematopoietic stem cell transplantation. J Pediatr. 2019;210:220-225. DOI: 10.1016/j.jpeds.2019.03.042
Sokol H, Suarez F, Meatchi T, Malamut G, Pocidalo MA, Blanche S, et al. Thalidomide as a treatment for refractory CGD colitis. Am J Gastroenterol. 2009;104(4):1069. DOI: 10.1038/ajg.2009.56
Arlet JB, Aouba A, Suarez F, Blanche S, Valeyre D, Fischer A, et al. Efficiency of hydroxychloroquine in the treatment of granulomatous complications in chronic granulomatous disease. Eur J Gastroenterol Hepatol. 2008;20(2):142-144. DOI: 10.1097/MEG.0b013e328277ef5f
Cannioto Z, Berti I, Martelossi S, Bruno I, Giurici N, Crovella S, et al. IBD and IBD mimicking enterocolitis in children younger than 2 years of age. Eur J Pediatr. 2009;168(2):149-155. DOI: 10.1007/s00431-008-0721-2
Campbell N, Chapdelaine H. Treatment of chronic granulomatous disease-associated fistulising colitis with vedolizumab. J Allergy Clin Immunol Pract. 2017;5(6):1748-1749.
Falcone EL, Holland SM. Gastrointestinal complications in chronic granulomatous disease. Methods Mol Biol. 2019;1982:573-586. DOI: 10.1007/978-1-4939-9424-3_34
Bortoletto P, Lyman K, Camacho A, Fricchione M, Khanolkar A, Katz BZ. Chronic granulomatous disease: a large, single-center US experience. Pediatr Infect Dis J. 2015;34(10):1110-1114. DOI: 10.1097/INF.0000000000000840
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright (c) 2021 Revista Alergia México