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Pediatric Chronic Granulomatous Disease Follow-up

  • Author: Lawrence C Wolfe, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
 
Updated: Nov 17, 2014
 

Complications

Large deletions in the region of the CYBB gene are known to delete adjacent genes, such as XK, the gene that controls the expression of the Kell blood group antigen.

Patients with chronic granulomatous disease (CGD) who have this gene deletion can become sensitized to Kell antigens after RBC transfusion, leading to hemolytic complications after subsequent transfusions.

For this reason, carefully examine the Kell-antigen status in patients with chronic granulomatous disease who require a blood transfusion.

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Prognosis

The prognosis for patients with chronic granulomatous disease has improved over the last 2 decades. Although no formal studies of the natural history of this disease have been conducted, the current median survival duration for a patient with chronic granulomatous disease is estimated to be about 20-25 years, with a mortality rate of 2-3% per year. The highest mortality rate is in early childhood. The usual cause of death is infection. However, chronic granulomatous disease has significant clinical heterogeneity in the severity of disease in affected patients.

Although in general patients with the X-linked form of the disease (X-CGD) have more severe disease and patients with the p47-deficient autosomal recessive form have milder disease, many patients are exceptions to this rule. Patients with identical genetic defects can have different clinical presentations, making definition of prognosis for individual patients difficult.

A French retrospective study showed no significant difference in the frequency or severity of infections in patients with either X-linked or autosomally inherited chronic granulomatous disease.[20] Of 11 patients in whom chronic granulomatous disease was diagnosed after adolescence, 8 had X-CGD. However, all 8 patients had small but detectable quantities of cytochrome b 558.

A case report describes a previously healthy 67-year-old man with X-CGD who developed P cepacia sepsis. He had a CYBB gene mutation consisting of a single base substitution that resulted in a quantitatively normal but dysfunctional cytochrome b. His neutrophils exhibited markedly deficient phox activity.

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Contributor Information and Disclosures
Author

Lawrence C Wolfe, MD Associate Chief for Hematology and Safety, Division of Pediatric Hematology-Oncology, Cohen Children's Medical Center

Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, Eastern Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Elisa Keefe, MD Fellow, Department of Pediatric Hematology and Oncology, Cohen Children’s Medical Center and Feinstein Institute for Medical Research, Northshore Long Island Jewish Health System

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Naynesh R Kamani, MD, and Kevin J Curran, MD, to the original writing and development of this article.

References
  1. von Rosenvinge EC, O'Donnell TG, Holland SM, Heller T. Chronic granulomatous disease. Inflamm Bowel Dis. 2009 Mar 25. [Medline].

  2. Ko SH, Rhim JW, Shin KS, Hahn YS, Lee SY, Kim JG. Genetic analysis of CYBB gene in 26 korean families with X-linked chronic granulomatous disease. Immunol Invest. 2014. 43(6):585-94. [Medline].

  3. Ben-Ari J, Wolach O, Gavrieli R, Wolach B. Infections associated with chronic granulomatous disease: linking genetics to phenotypic expression. Expert Rev Anti Infect Ther. 2012 Aug. 10(8):881-94. [Medline].

  4. Vining M, Sharma N, Guill M. Atypical presentation of chronic granulomatous disease with Burkholderia cepacia. BMJ Case Rep. 2014 Aug 6. 2014:[Medline].

  5. Roos D, Kuhns DB, Maddalena A, et al. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010 Apr 15. 44(4):291-9. [Medline].

  6. Marciano BE, Rosenzweig SD, Kleiner DE, et al. Gastrointestinal involvement in chronic granulomatous disease. Pediatrics. 2004 Aug. 114(2):462-8. [Medline].

  7. Xu H, Tian W, Li SJ, Zhang LY, Liu W, Zhao Y, et al. Clinical and molecular features of 38 children with chronic granulomatous disease in mainland china. J Clin Immunol. 2014 Aug. 34(6):633-41. [Medline].

  8. Jones LB, McGrogan P, Flood TJ, Gennery AR, Morton L, Thrasher A. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008 May. 152(2):211-8. [Medline].

  9. Cole T, McKendrick F, Titman P, Cant AJ, Pearce MS, Cale CM, et al. Health Related Quality of Life and Emotional Health in Children with Chronic Granulomatous Disease: A Comparison of Those Managed Conservatively with Those That Have Undergone Haematopoietic Stem Cell Transplant. J Clin Immunol. 2012 Aug 12. [Medline].

  10. Ahlin A, Fasth A. Chronic granulomatous disease - conventional treatment vs. hematopoietic stem cell transplantation: an update. Curr Opin Hematol. 2014 Nov 12. [Medline].

  11. Shigemura T, Nakazawa Y, Hirabayashi K, Kobayashi N, Sakashita K, Agematsu K, et al. Dramatic Improvement in the Multifocal Positron Emission Tomography Findings of a Young Adult with Chronic Granulomatous Disease Following Allogeneic Hematopoietic Stem Cell Transplantation. J Clin Immunol. 2014 Nov 4. [Medline].

  12. Mouy R, Veber F, Blanche S, et al. Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease. J Pediatr. 1994 Dec. 125(6 Pt 1):998-1003. [Medline].

  13. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1. 46(3):327-60. [Medline].

  14. Sfaihi L, Maaloul I, Fourati H, Stasia MJ, Mnif Z, Hachicha M. Resistant Invasive Aspergillosis in an Autosomal Recessive Chronic Granulomatous Disease. Fetal Pediatr Pathol. 2012 Sep 24. [Medline].

  15. Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003 Jun 12. 348(24):2416-22. [Medline].

  16. International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. The International Chronic Granulomatous Disease Cooperative Study Group. N Engl J Med. 1991 Feb 21. 324(8):509-16. [Medline].

  17. Marciano BE, Wesley R, De Carlo ES, et al. Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis. 2004 Sep 1. 39(5):692-9. [Medline].

  18. Miki M, Ono A, Awaya A, et al. Successful bone marrow transplantation in chronic granulomatous disease. Pediatr Int. 2009 Dec. 51(6):838-41. [Medline].

  19. Seger RA. Modern management of chronic granulomatous disease. Br J Haematol. 2008 Feb. 140(3):255-66. [Medline].

  20. Liese JG, Jendrossek V, Jansson A, et al. Chronic granulomatous disease in adults. Lancet. 1996 Jan 27. 347(8996):220-3. [Medline].

  21. Barton LL, Moussa SL, Villar RG, Hulett RL. Gastrointestinal complications of chronic granulomatous disease: case report and literature review. Clin Pediatr (Phila). 1998 Apr. 37(4):231-6. [Medline].

  22. Berendes H, Bridges RA, Good RA. A fatal granulomatosus of childhood: the clinical study of a new syndrome. Minn Med. 1957 May. 40(5):309-12. [Medline].

  23. Bjorgvinsdottir H, Ding C, Pech N, et al. Retroviral-mediated gene transfer of gp91phox into bone marrow cells rescues defect in host defense against Aspergillus fumigatus in murine X-linked chronic granulomatous disease. Blood. 1997 Jan 1. 89(1):41-8. [Medline].

  24. Carson MJ, Chadwick DL, Brubaker CA, et al. Thirteen boys with progressive septic granulomatosis. Pediatrics. 1965 Mar. 35:405-12. [Medline].

  25. Danziger RN, Goren AT, Becker J, et al. Outpatient management with oral corticosteroid therapy for obstructive conditions in chronic granulomatous disease. J Pediatr. 1993 Feb. 122(2):303-5. [Medline].

  26. Del Giudice I, Iori AP, Mengarelli A, et al. Allogeneic stem cell transplant from HLA-identical sibling for chronic granulomatous disease and review of the literature. Ann Hematol. 2003 Mar. 82(3):189-92. [Medline].

  27. Dohil M, Prendiville JS, Crawford RI, Speert DP. Cutaneous manifestations of chronic granulomatous disease. A report of four cases and review of the literature. J Am Acad Dermatol. 1997 Jun. 36(6 Pt 1):899-907. [Medline].

  28. Gallin JI, Malech HL. Update on chronic granulomatous diseases of childhood. Immunotherapy and potential for gene therapy [clinical conference]. JAMA. 1990 Mar 16. 263(11):1533-7. [Medline].

  29. Goebel WS, Mark LA, Billings SD, et al. Gene correction reduces cutaneous inflammation and granuloma formation in murine X-linked chronic granulomatous disease. J Invest Dermatol. 2005 Oct. 125(4):705-10. [Medline].

  30. Gorlach A, Lee PL, Roesler J, et al. A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease. J Clin Invest. 1997 Oct 15. 100(8):1907-18. [Medline].

  31. Heyworth PG, Cross AR, Curnutte JT. Chronic granulomatous disease. Curr Opin Immunol. 2003 Oct. 15(5):578-84. [Medline].

  32. Ishibashi F, Nunoi H, Endo F, et al. Statistical and mutational analysis of chronic granulomatous disease in Japan with special reference to gp91-phox and p22-phox deficiency. Hum Genet. 2000 May. 106(5):473-81. [Medline].

  33. Jirapongsananuruk O, Malech HL, Kuhns DB, et al. Diagnostic paradigm for evaluation of male patients with chronic granulomatous disease, based on the dihydrorhodamine 123 assay. J Allergy Clin Immunol. 2003 Feb. 111(2):374-9. [Medline].

  34. Johnston RB. Clinical aspects of chronic granulomatous disease. Curr Opin Hematol. 2001 Jan. 8(1):17-22. [Medline].

  35. Kamani N, August CS, Campbell DE, et al. Marrow transplantation in chronic granulomatous disease: an update, with 6-year follow-up. J Pediatr. 1988 Oct. 113(4):697-700. [Medline].

  36. Kume A, Dinauer MC. Gene therapy for chronic granulomatous disease. J Lab Clin Med. 2000 Feb. 135(2):122-8. [Medline].

  37. Landing BH, Shirkey HS. A syndrome of recurrent infection and infiltration of viscera by pigmented lipid histiocytes. Pediatrics. 1957 Sep. 20(3):431-8. [Medline].

  38. Leung T, Chik K, Li C, Yuen P. Bone marrow transplantation for chronic granulomatous disease: long- term follow-up and review of literature. Bone Marrow Transplant. 1999 Sep. 24(5):567-70. [Medline].

  39. Malech HL. Progress in gene therapy for chronic granulomatous disease. J Infect Dis. 1999 Mar. 179 Suppl 2:S318-25. [Medline].

  40. Malech HL, Nauseef WM. Primary inherited defects in neutrophil function: etiology and treatment. Semin Hematol. 1997 Oct. 34(4):279-90. [Medline].

  41. Margolis DM, Melnick DA, Alling DW, Gallin JI. Trimethoprim-sulfamethoxazole prophylaxis in the management of chronic granulomatous disease. J Infect Dis. 1990 Sep. 162(3):723-6. [Medline].

  42. Meischl C, Roos D. The molecular basis of chronic granulomatous disease. Springer Semin Immunopathol. 1998. 19(4):417-34. [Medline].

  43. Mouy R, Fischer A, Vilmer E, et al. Incidence, severity, and prevention of infections in chronic granulomatous disease. J Pediatr. 1989 Apr. 114(4 Pt 1):555-60. [Medline].

  44. Nakhleh RE, Glock M, Snover DC. Hepatic pathology of chronic granulomatous disease of childhood. Arch Pathol Lab Med. 1992 Jan. 116(1):71-5. [Medline].

  45. Ochs HD, Igo RP. The NBT slide test: a simple screening method for detecting chronic granulomatous disease and female carriers. J Pediatr. 1973 Jul. 83(1):77-82. [Medline].

  46. Rae J, Newburger PE, Dinauer MC, et al. X-Linked chronic granulomatous disease: mutations in the CYBB gene encoding the gp91-phox component of respiratory-burst oxidase. Am J Hum Genet. 1998 Jun. 62(6):1320-31. [Medline].

  47. Rosen GM, Pou S, Ramos CL, et al. Free radicals and phagocytic cells. FASEB J. 1995 Feb. 9(2):200-9. [Medline].

  48. Schapiro BL, Newburger PE, Klempner MS, Dinauer MC. Chronic granulomatous disease presenting in a 69-year-old man. N Engl J Med. 1991 Dec 19. 325(25):1786-90. [Medline].

  49. Segal BH, DeCarlo ES, Kwon-Chung KJ, et al. Aspergillus nidulans infection in chronic granulomatous disease. Medicine (Baltimore). 1998 Sep. 77(5):345-54. [Medline].

  50. Segal BH, Leto TL, Gallin JI, et al. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). 2000 May. 79(3):170-200. [Medline].

  51. Thrasher AJ, Keep NH, Wientjes F, Segal AW. Chronic granulomatous disease. Biochim Biophys Acta. 1994 Oct 21. 1227(1-2):1-24. [Medline].

  52. Vowells SJ, Fleisher TA, Sekhsaria S, et al. Genotype-dependent variability in flow cytometric evaluation of reduced nicotinamide adenine dinucleotide phosphate oxidase function in patients with chronic granulomatous disease. J Pediatr. 1996 Jan. 128(1):104-7. [Medline].

  53. Weening RS, Kabel P, Pijman P, Roos D. Continuous therapy with sulfamethoxazole-trimethoprim in patients with chronic granulomatous disease. J Pediatr. 1983 Jul. 103(1):127-30. [Medline].

  54. Weening RS, Leitz GJ, Seger RA. Recombinant human interferon-gamma in patients with chronic granulomatous disease--European follow up study. Eur J Pediatr. 1995 Apr. 154(4):295-8. [Medline].

  55. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000 May. 79(3):155-69. [Medline].

  56. Yang KD, Hill HR. Neutrophil function disorders: pathophysiology, prevention, and therapy. J Pediatr. 1991 Sep. 119(3):343-54. [Medline].

 
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Scanning electron micrograph of Aspergillus species.
 
 
 
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