eMedicine Specialties > Pediatrics: General Medicine > Hematology

Chronic Granulomatous Disease: Follow-up

Author: Lawrence C Wolfe, MD, Professor, Department of Pediatrics, Tufts University School of Medicine; Chief of Transfusion Service, Chief, Division of Pediatric Hematology/Oncology, New England Medical Center, Floating Hospital for Infants and Children
Contributor Information and Disclosures

Updated: Apr 13, 2009

Follow-up

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.

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.10 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.

Miscellaneous

Medicolegal Pitfalls

  • Failure to consider chronic granulomatous disease (CGD) in patients with frequent infections with catalase-positive organisms may lead to poor patient outcomes.
 
Acknowledgments

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.



More on Chronic Granulomatous Disease

Overview: Chronic Granulomatous Disease
Differential Diagnoses & Workup: Chronic Granulomatous Disease
Treatment & Medication: Chronic Granulomatous Disease
Follow-up: Chronic Granulomatous Disease
Multimedia: Chronic Granulomatous Disease
References
[ CLOSE WINDOW ]

References

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

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

  3. 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. May 2008;152(2):211-8. [Medline].

  4. 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. Dec 1994;125(6 Pt 1):998-1003. [Medline].

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

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

  7. 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. Feb 21 1991;324(8):509-16. [Medline].

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

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

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

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

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

  13. 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. Jan 1 1997;89(1):41-8. [Medline].

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

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

  16. 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. Mar 2003;82(3):189-92. [Medline].

  17. 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. Jun 1997;36(6 Pt 1):899-907. [Medline].

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

  19. 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. Oct 2005;125(4):705-10. [Medline].

  20. 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. Oct 15 1997;100(8):1907-18. [Medline].

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

  22. 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. May 2000;106(5):473-81. [Medline].

  23. 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. Feb 2003;111(2):374-9. [Medline].

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

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

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

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

  28. 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. Sep 1999;24(5):567-70. [Medline].

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

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

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

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

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

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

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

  36. 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. Jun 1998;62(6):1320-31. [Medline].

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

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

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

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

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

  42. 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. Jan 1996;128(1):104-7. [Medline].

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

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

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

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

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

chronic granulomatous disease, fatal granulomatosis of childhood, chronic granulomatous disease of childhood, progressive septic granulomatosis, CGD, X-linked CGD, X-CGD, X91 CGD, A22 CGD, A47 CGD, A67 CGD,  hypergammaglobulinemia, hepatosplenomegaly, lymphadenopathy, Pseudomonas aeruginosa, Burkholderia cepacia, treatment, diagnosis, osteomyelitis, septicemia, dysphagia, nausea, vomiting, abdominal pain, obstruction, granulomatous colitis, Crohnlike inflammatory bowel disease, IBD, GI obstruction, hypoalbuminemia, discoid lupus erythematosus, photosensitivity, Raynaud phenomenon, aphthous ulcers

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Lawrence C Wolfe, MD, Professor, Department of Pediatrics, Tufts University School of Medicine; Chief of Transfusion Service, Chief, Division of Pediatric Hematology/Oncology, New England Medical Center, Floating Hospital for Infants and Children
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, and Eastern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MB, BS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MB, BS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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; Assistant Clinical Professor, Department of Pediatrics, Creighton University; 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 Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.