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Pulmonary Manifestations of Congenital Defects of Phagocytes

  • Seyed Amir Mohajerani
  • Marzieh Tavakol
  • Seyed Alireza Mahdaviani
Chapter

Abstract

The phagocytic system is an indispensable part of the immune defense mechanism and innate immune system. Pulmonary manifestations could be either ambiguous or misleading. The most common involved organ in chronic granulomatous deficiency (CGD) is the lung, which manifests with infectious and non-infectious (granuloma and fibrosis) complications. Myeloperoxidase (MPO)-deficient individuals are mostly asymptomatic; however, invasive Candida (IC) may present as candidemia, disseminated infection, and pneumonia. Neutrophil-specific granule deficiency pulmonary manifestations are recurrent pneumonias and lung abscess mostly due to Staphylococcus aureus and Pseudomonas aeruginosa. In leukocyte adhesion deficiency (LAD), involvement of the skin and mucus membranes is a predominant clinical feature and then recurrent pulmonary infections. In RAC-2 deficiency, pulmonary involvement although uncommon includes recurrent sinopulmonary infections, pneumonia, and bronchiectasis. In congenital neutropenia (CN), the child might begin to have fevers associated with respiratory symptoms of pneumonia. ELANE (neutrophil elastase) mutations are the most frequent known cause of congenital neutropenia which is characterized by oropharyngeal inflammation. G6PC3 deficiency and its severe form called Dursun syndrome are characterized by a triad of familial primary pulmonary hypertension (PPH), leukopenia, and atrial septal defects. Cyclic neutropenia is characterized by oscillating numbers of blood neutrophils. Pulmonary manifestations are upper respiratory infections (sinusitis and otitis media), pneumonia, and bronchitis. In Shwachman-Diamond syndrome (SDS), pulmonary manifestations are recurrent bronchopulmonary bacterial, viral, and fungal opportunistic infections and recurrent otitis media. Cohen syndrome is associated with laryngeal dysfunction and laryngomalacia to stenosis and vocal cord paralysis. Poikiloderma often accompanies severe neutropenia and bronchiectasis, lung abscesses, and lung granulomas. In other phagocytic deficiencies, including b-actin, aggressive periodontitis, Papillon-Lefevre syndrome, Barth syndrome, and glycogen storage disease Ib, no pulmonary manifestations have been reported.

Keywords

Chronic granulomatous disease Leukocyte adhesion deficiency Congenital neutropenia Cyclic neutropenia Shwachman-Diamond syndrome Cohen syndrome 

References

  1. 1.
    Rezaei N, Pourpak Z, Aghamohammadi A, Farhoudi A, Movahedi M, Gharagozlou M, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian primary immunodeficiency registry. Am J Reprod Immunol. 2006;56(2):145–51.PubMedCrossRefGoogle Scholar
  2. 2.
    Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114(15):3309–15.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuhns DB, Alvord WG, Heller T, Feld JJ, Pike KM, Marciano BE, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600–10.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Mansouri D, Adimi P, Mirsaedi M, Mansouri N, Tabarsi P, Amiri M, et al. Primary immune deficiencies presenting in adults: seven years of experience from Iran. J Clin Immunol. 2005;25(4):385–91.PubMedCrossRefGoogle Scholar
  6. 6.
    Van den Berg JM, Van Koppen E, Åhlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PLoS One. 2009;4(4):e5234.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Carnide EG, Jacob CA, Castro AM, Pastorino AC. Clinical and laboratory aspects of chronic granulomatous disease in description of eighteen patients. Pediatr Allergy Immunol. 2005;16(1):5–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Mahdaviani SA, Mohajerani SA, Rezaei N, Casanova J-L, Mansouri SD, Velayati AA. Pulmonary manifestations of chronic granulomatous disease. Expert Rev Clin Immunol. 2013;9(2):153–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Johnston RB Jr. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001;8(1):17–22.PubMedCrossRefGoogle Scholar
  10. 10.
    Khanna G, Kao SC, Kirby P, Sato Y. Imaging of chronic granulomatous disease in children. Radiographics. 2005;25(5):1183–95.PubMedCrossRefGoogle Scholar
  11. 11.
    Almyroudis N, Holland S, Segal B. Invasive aspergillosis in primary immunodeficiencies. Med Mycol. 2005;43(sup1):247–59.CrossRefGoogle Scholar
  12. 12.
    Dorman SE, Guide SV, Conville PS, DeCarlo ES, Malech HL, Gallin JI, et al. Nocardia infection in chronic granulomatous disease. Clin Infect Dis. 2002;35(4):390–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Marciano BE, Wesley R, De Carlo ES, Anderson VL, Barnhart LA, Darnell D, et al. Long-term interferon-γ therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004;39(5):692–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Lacy D, Spencer D, Goldstein A, Weller P, Darbyshire P. Chronic granulomatous disease presenting in childhood with Pseudomonas cepacia septicaemia. J Infect. 1993;27(3):301–4.PubMedCrossRefGoogle Scholar
  15. 15.
    Reichenbach J, Lopatin U, Mahlaoui N, Beovic B, Siler U, Zbinden R, et al. Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen. Clin Infect Dis. 2009;49(11):1703–10.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Vinh DC, Shea YR, Sugui JA, Parrilla-Castellar ER, Freeman AF, Campbell JW, et al. Invasive aspergillosis due to Neosartorya udagawae. Clin Infect Dis. 2009;49(1):102–11.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Lee PP, Chan K-W, Jiang L, Chen T, Li C, Lee T-L, et al. Susceptibility to mycobacterial infections in children with X-linked chronic granulomatous disease: a review of 17 patients living in a region endemic for tuberculosis. Pediatr Infect Dis J. 2008;27(3):224–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Bustamante J, Aksu G, Vogt G, De Beaucoudrey L, Genel F, Chapgier A, et al. BCG-osis and tuberculosis in a child with chronic granulomatous disease. J Allergy Clin Immunol. 2007;120(1):32–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Kuijpers T, Lutter R. Inflammation and repeated infections in CGD: two sides of a coin. Cell Mol Life Sci. 2012;69(1):7–15.PubMedCrossRefGoogle Scholar
  20. 20.
    De Ravin SS, Naumann N, Cowen EW, Friend J, Hilligoss D, Marquesen M, et al. Chronic granulomatous disease as a risk factor for autoimmune disease. J Allergy Clin Immunol. 2008;122(6):1097–103.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    Morgenstern DE, Gifford MA, Li LL, Doerschuk CM, Dinauer MC. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J Exp Med. 1997;185(2):207–18.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine. 2000;79(3):170–200.PubMedCrossRefGoogle Scholar
  24. 24.
    Brown KL, Bylund J, MacDonald KL, Song-Zhao GX, Elliott MR, Falsafi R, et al. ROS-deficient monocytes have aberrant gene expression that correlates with inflammatory disorders of chronic granulomatous disease. Clin Immunol. 2008;129(1):90–102.PubMedCrossRefGoogle Scholar
  25. 25.
    Segal BH, Han W, Bushey JJ, Joo M, Bhatti Z, Feminella J, et al. NADPH oxidase limits innate immune responses in the lungs in mice. PLoS One. 2010;5(3):e9631.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Foster CB, Lehrnbecher T, Mol F, Steinberg SM, Venzon DJ, Walsh TJ, et al. Host defense molecule polymorphisms influence the risk for immune-mediated complications in chronic granulomatous disease. J Clin Invest. 1998;102(12):2146–55.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Khalilzadeh S, Bloorsaz MR, Mansouri D, Baghaie N, Hakimi S, Velayati AA. Clinical and radiological aspects of chronic granulomatous disease in children: a case series from Iran. Iran J Allergy Asthma Immunol. 2006;5(2):85–8.PubMedGoogle Scholar
  28. 28.
    Margolis DM, Melnick DA, Ailing DW, Gallin JI. Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease. J Infect Dis. 1990;162(3):723–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Petropoulou T, Liese J, Tintelnot K, Gahr M, Belohradsky B. Long-term treatment of patients with itraconazole for the prevention of Aspergillus infections in patients with chronic granulomatous disease (CGD). Mycoses. 1994;37:64–9.PubMedCrossRefGoogle Scholar
  30. 30.
    Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38(1):3–10.PubMedCrossRefGoogle Scholar
  31. 31.
    Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-±blockade in chronic granulomatous disease—related colitis. Clin Infect Dis. 2010;51(12):1429–34.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Grez M, Reichenbach J, Schwäble J, Seger R, Dinauer MC, Thrasher AJ. Gene therapy of chronic granulomatous disease: the engraftment dilemma. Mol Ther. 2011;19(1):28–35.PubMedCrossRefGoogle Scholar
  33. 33.
    Ott MG, Schmidt M, Schwarzwaelder K, Stein S, Siler U, Koehl U, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12(4):401.PubMedCrossRefGoogle Scholar
  34. 34.
    Yamazaki-Nakashimada MA, Stiehm ER, Pietropaolo-Cienfuegos D, Hernandez-Bautista V, Espinosa-Rosales F. Corticosteroid therapy for refractory infections in chronic granulomatous disease: case reports and review of the literature. Ann Allergy Asthma Immunol. 2006;97(2):257–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Arnhold J, Flemmig J. Human myeloperoxidase in innate and acquired immunity. Arch Biochem Biophys. 2010;500(1):92–106.PubMedCrossRefGoogle Scholar
  36. 36.
    Rezaei N, Aghamohammadi A, Notarangelo LD. Primary immunodeficiency diseases definition, diagnosis, and management. Berlin/Heidelberg: Springer; 2008.CrossRefGoogle Scholar
  37. 37.
    Antachopoulos C. Invasive fungal infections in congenital immunodeficiencies. Clin Microbiol Infect. 2010;16(9):1335–42.PubMedCrossRefGoogle Scholar
  38. 38.
    Lanza F. Clinical manifestation of myeloperoxidase deficiency. J Mol Med. 1998;76(10):676–81.PubMedCrossRefGoogle Scholar
  39. 39.
    Wada T, Akagi T, Muraoka M, Toma T, Kaji K, Agematsu K, et al. A novel in-frame deletion in the leucine zipper domain of C/EBPε leads to neutrophil-specific granule deficiency. J Immunol. 2015;195(1):80–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Malech HL, Hickstein DD. Genetics, biology and clinical management of myeloid cell primary immune deficiencies: chronic granulomatous disease and leukocyte adhesion deficiency. Curr Opin Hematol. 2007;14(1):29–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C. Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet. 2001;28(1):73.PubMedGoogle Scholar
  42. 42.
    Kinashi T, Aker M, Sokolovsky-Eisenberg M, Grabovsky V, Tanaka C, Shamri R, et al. LAD-III, a leukocyte adhesion deficiency syndrome associated with defective Rap1 activation and impaired stabilization of integrin bonds. Blood. 2004;103(3):1033–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Etzioni A, Tonetti M. Leukocyte adhesion deficiency II–from a to almost Z. Immunol Rev. 2000;178(1):138–47.PubMedCrossRefGoogle Scholar
  44. 44.
    Bazregari S, Azizi G, Tavakol M, Asgardoon MH, Kiaee F, Tavakolinia N, et al. Evaluation of infectious and non-infectious complications in patients with primary immunodeficiency. Cent Eur J Immunol. 2017;42(4):336.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Etzioni A. Novel aspects of phagocytic cell disorders. Curr Opin Allergy Clin Immunol. 2001;1(6):535–40.PubMedCrossRefGoogle Scholar
  46. 46.
    Etzioni A, Harlan J, Pollack S, Phillips L, Gershoni-Baruch R, Paulson J. Leukocyte adhesion deficiency (LAD) II: a new adhesion defect due to absence of sialyl Lewis X, the ligand for selectins. Immunodeficiency. 1993;4(1–4):307.PubMedGoogle Scholar
  47. 47.
    Etzioni A, Alon R. Leukocyte adhesion deficiency III: a group of integrin activation defects in hematopoietic lineage cells. Curr Opin Allergy Clin Immunol. 2004;4(6):485–90.PubMedCrossRefGoogle Scholar
  48. 48.
    Frydman M, Etzioni A, Eidlitz-Markus T, Avidor I, Varsano I, Shechter Y, et al. Rambam–Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype. Am J Med Genet. 1992;44(3):297–302.PubMedCrossRefGoogle Scholar
  49. 49.
    Thomas C, Le Deist F, Cavazzana-Calvo M, Benkerrou M, Haddad E, Blanche S, et al. Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. Blood. 1995;86(4):1629–35.PubMedGoogle Scholar
  50. 50.
    Marquardt T, Lühn K, Srikrishna G, Freeze HH, Harms E, Vestweber D. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. 1999;94(12):3976–85.PubMedGoogle Scholar
  51. 51.
    Bogaert DJ, Dullaers M, Lambrecht BN, Vermaelen KY, De Baere E, Haerynck F. Genes associated with common variable immunodeficiency: one diagnosis to rule them all? J Med Genet. 2016;53(9):575–90.PubMedCrossRefGoogle Scholar
  52. 52.
    Alkhairy OK, Rezaei N, Graham RR, Abolhassani H, Borte S, Hultenby K, et al. RAC2 loss-of-function mutation in 2 siblings with characteristics of common variable immunodeficiency. J Allergy Clin Immunol. 2015;135(5):1380–4.e5.PubMedCrossRefGoogle Scholar
  53. 53.
    Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet J Rare Dis. 2011;6(1):26.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K. Severe congenital neutropenias. Nat Rev Dis Prim. 2017;3:17032.PubMedCrossRefGoogle Scholar
  55. 55.
    Donadieu J, Beaupain B, Fenneteau O, Bellanné-Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. Br J Haematol. 2017;179(4):557–74.PubMedCrossRefGoogle Scholar
  56. 56.
    Boxer LA. Severe congenital neutropenia: genetics and pathogenesis. Trans Am Clin Climatol Assoc. 2006;117:13.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Lanini LLS, Prader S, Siler U, Reichenbach J. Modern management of phagocyte defects. Pediatr Allergy Immunol. 2017;28(2):124–34.PubMedCrossRefGoogle Scholar
  58. 58.
    Dale DC. ELANE-related neutropenia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle: University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle All rights reserved; 2011.Google Scholar
  59. 59.
    Okolo ON, Katsanis E, Yun S, Reveles CY, Anwer F. Allogeneic transplant in ELANE and MEFV mutation positive severe cyclic neutropenia: review of prognostic factors for secondary severe events. Case Rep Hematol. 2017;2017:1.CrossRefGoogle Scholar
  60. 60.
    Banka S. G6PC3 deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle: University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.Google Scholar
  61. 61.
    Banka S, Newman WG. A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency caused by G6PC3 mutations. Orphanet J Rare Dis. 2013;8(1):84.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Aydogmus C, Cipe F, Tas M, Akınel A, Öner Ö, Keskindemirci G, et al. HAX-1 deficiency: characteristics of five cases including an asymptomatic patient. Asian Pac J Allergy Immunol. 2016;34(1):73–6.PubMedGoogle Scholar
  63. 63.
    Palmer SE, Stephens K, Dale DC. Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis. Am J Med Genet. 1996;66(4):413–22.PubMedCrossRefGoogle Scholar
  64. 64.
    Dale DC, Liles WC, Garwicz D, Aprikyan AG. Clinical implications of mutations of neutrophil elastase in congenital and cyclic neutropenia. J Pediatr Hematol Oncol. 2001;23(4):208–10.PubMedCrossRefGoogle Scholar
  65. 65.
    Dale DC, Bolyard AA, Aprikyan A. Cyclic neutropenia. Semin Hematol. 2002;39(2):89–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Mansoor MS, Khan MB. A case of cyclic neutropenia in adults. JPMA J Pak Med Assoc. 2012;62(3):289–90.PubMedGoogle Scholar
  67. 67.
    Dale DC, WPt H. Cyclic neutropenia: a clinical review. Blood Rev. 1988;2(3):178–85.PubMedCrossRefGoogle Scholar
  68. 68.
    Rezaei N, Farhoudi A, Pourpak Z, Aghamohammadi A, Ramyar A, Moin M, et al. Clinical and laboratory findings in Iranian children with cyclic neutropenia. Iran J Allergy Asthma Immunol. 2004;3(1):37–40.PubMedGoogle Scholar
  69. 69.
    Burroughs L, Woolfrey A, Shimamura A. Shwachman-Diamond syndrome: a review of the clinical presentation, molecular pathogenesis, diagnosis, and treatment. Hematol Oncol Clin North Am. 2009;23(2):233–48.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Chandler KE, Kidd A, Al-Gazali L, Kolehmainen J, Lehesjoki AE, Black GC, et al. Diagnostic criteria, clinical characteristics, and natural history of Cohen syndrome. J Med Genet. 2003;40(4):233–41.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Wang H, Falk MJ, Wensel C, Traboulsi EI. Cohen syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle: University of Washington, Seattle University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.Google Scholar
  72. 72.
    Wang L, Clericuzio C, Larizza L. Poikiloderma with neutropenia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews((R)). Seattle: University of Washington, Seattle University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Seyed Amir Mohajerani
    • 1
  • Marzieh Tavakol
    • 2
    • 3
  • Seyed Alireza Mahdaviani
    • 4
  1. 1.Tracheal Diseases Research Center (TDRC) National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran
  2. 2.Non-communicable Diseases Research CenterAlborz University of Medical SciencesKarajIran
  3. 3.Department of Allergy and Clinical ImmunologyEmam Ali Hospital, Alborz University of Medical SciencesKarajIran
  4. 4.Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD)Shahid Beheshti University of Medical SciencesTehranIran

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