eMedicine Specialties > Dermatology > Pediatric Diseases

Chronic Granulomatous Disease: Treatment & Medication

Author: Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland
Contributor Information and Disclosures

Updated: May 29, 2009

Treatment

Medical Care

Modern therapy of chronic granulomatous disease (CGD) includes aggressive and prolonged administration of antibiotics and prednisone.21 Antibiotics should be chosen carefully, and therapy should be vigorous. Conventional treatment consists of lifelong anti-infectious prophylaxis with antibiotics such as trimethoprim-sulfamethoxazole (TMP-SMZ), antimycotics such as itraconazole, and/or INF-gamma.

  • Long-term antibiotic therapy may be helpful. All infections should be treated with broad-spectrum systemic antibiotics. Aggressive treatment should be initiated at the first signs of infection. Antibiotics should be carefully chosen, and therapy should be vigorous. Currently, standard therapy is continuous antibiotic treatment with TMP-SMZ.  
    • Continuous antifungal therapy with itraconazole is effective in preventing infection by Aspergillus species.22 Amphotericin B should be added to the therapeutic regimen of chronic granulomatous disease patients with established invasive aspergillosis.
    • INF-gamma therapy subcutaneously appears to be a promising way of improving neutrophil and monocyte function and may prove to be of particular value in the prevention or treatment of deep fungal infections. INF-gamma is now recommended as life-long therapy for infection prophylaxis in persons with chronic granulomatous disease.23,24
  • Granulocyte transfusions from granulocyte colony-stimulating factor– and dexamethasone-stimulated donors could be a choice of treatment in chronic granulomatous disease patients, especially those with disseminated invasive aspergillosis.25
  • Bone marrow transplantation, as a last resort, can be undertaken. This treatment has been partially successful. Transplantations with other than perfectly matched donors are presently discouraged.26,27
  • Noninfectious granulomas may resolve spontaneously, and they rarely require systemic corticosteroid therapy unless vital organs are compromised.
  • Gene therapy for chronic granulomatous disease, due to the disease's monogenic character, may perhaps be possible in the future.28,29,30,31

Surgical Care

Surgical drainage of abscesses and resection (when possible) of granulomas.

Consultations

  • Surgeon: Gastrointestinal manifestations include perineal abscesses; fistulae; and, characteristically, obstructive lesions associated with granulomatous infiltration.
  • Internist: Pyrexia should be carefully investigated to reveal the site of the causative infection and the responsible microorganism. Pulmonary disease (eg, recurrent pneumonia, empyema, lung abscess formation) should be treated.

Medication

Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.


Trimethoprim and sulfamethoxazole (Bactrim, Septra)

Current standard therapy. Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.

Adult

160 mg TMP/800 mg SMZ PO q12h continuous treatment

Pediatric

<2 months: Do not administer
>2 months: Not established

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenic purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; G-6-PD deficiency

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of skin rash or signs of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer leucovorin 5-15 mg/d); caution in folate deficiency (eg, elderly patients, patients who drink excessive amounts of alcohol, those who receive anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Antifungal agents

These agents exert a fungicidal effect by altering the permeability of the fungal cell membrane. Their mechanism of action may also involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.


Itraconazole (Sporanox)

Continuous antifungal therapy is effective in preventing infection by Aspergillus species. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Adult

200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses)

Pediatric

Not established

Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations with high doses; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (eg, lovastatin, simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death; may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hepatic insufficiency

Biologic response modifiers

These agents regulate the immune system by a variety of mechanisms including enhancing activity of macrophages and cytotoxic actions of T lymphocytes.


Interferon gamma - 1b (Actimmune)

Reduces frequency and severity of serious infections associated with chronic granulomatous disease. Interferons are synthesized by eukaryotic cells in response to viruses and a variety of natural and synthetic stimuli. Possesses antiviral, immunomodulatory, and antiproliferative activity. INF-gamma has potent phagocyte-activating effects not seen with other interferon preparations, including generation of toxic oxygen metabolites within phagocytes capable of mediating intracellular killing of microorganisms.

Adult

50 mcg/m2/dose SC 3 times/wk

Pediatric

BSA <0.5 m2: 1.5 mcg/kg/dose SC 3 times/wk
BSA >0.5 m2: 50 mcg/m2/dose SC 3 times/wk

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use caution in patients receiving potentially myelosuppressive drugs

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
References
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References

  1. Segal BH, Romani L, Puccetti P. Chronic granulomatous disease. Cell Mol Life Sci. Feb 2009;66(4):553-8. [Medline].

  2. Hauck F, Heine S, Beier R, Wieczorek K, Müller D, Hahn G. Chronic granulomatous disease (CGD) mimicking neoplasms: a suspected mediastinal teratoma unmasking as thymic granulomas due to X-linked CGD, and 2 related cases. J Pediatr Hematol Oncol. Dec 2008;30(12):877-80. [Medline].

  3. Rae J, Noack D, Heyworth PG, Ellis BA, Curnutte JT, Cross AR. Molecular analysis of 9 new families with chronic granulomatous disease caused by mutations in CYBA, the gene encoding p22(phox). Blood. Aug 1 2000;96(3):1106-12. [Medline].

  4. Jurkowska M, Bernatowska E, Bal J. Genetic and biochemical background of chronic granulomatous disease. Arch Immunol Ther Exp (Warsz). Mar-Apr 2004;52(2):113-20. [Medline].

  5. Jurkowska M, Kurenko-Deptuch M, Bal J, Roos D. The search for a genetic defect in Polish patients with chronic granulomatous disease. Arch Immunol Ther Exp (Warsz). Nov-Dec 2004;52(6):441-6. [Medline].

  6. Stasia MJ, Bordigoni P, Floret D, et al. Characterization of six novel mutations in the CYBB gene leading to different sub-types of X-linked chronic granulomatous disease. Hum Genet. Jan 2005;116(1-2):72-82. [Medline].

  7. Noack D, Rae J, Cross AR, et al. Autosomal recessive chronic granulomatous disease caused by defects in NCF-1, the gene encoding the phagocyte p47-phox: mutations not arising in the NCF-1 pseudogenes. Blood. Jan 1 2001;97(1):305-11. [Medline].

  8. Segal BH, Leto TL, Gallin JI, Malech HL, Holland SM. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine (Baltimore). May 2000;79(3):170-200.

  9. Ahlin A, De Boer M, Roos D, et al. Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. Acta Paediatr. Dec 1995;84(12):1386-94. [Medline].

  10. Oh HB, Park JS, Lee W, Yoo SJ, Yang JH, Oh SY. Molecular analysis of X-linked chronic granulomatous disease in five unrelated Korean patients. J Korean Med Sci. Apr 2004;19(2):218-22. [Medline].

  11. Lun A, Roesler J, Renz H. Unusual late onset of X-linked chronic granulomatous disease in an adult woman after unsuspicious childhood. Clin Chem. May 2002;48(5):780-1. [Medline].

  12. Wolach B, Scharf Y, Gavrieli R, de Boer M, Roos D. Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB. Blood. Jan 1 2005;105(1):61-6. [Medline].

  13. Fijolek J, Wiatr E, Gawryluk D, Bestry I, Bernatowska E, Jablonski W. [Chronic granulomatous disease recognised in 42-years-old patient]. Pneumonol Alergol Pol. 2008;76(1):58-65. [Medline].

  14. Carnide EG, Jacob CA, Castro AM, Pastorino AC. Clinical and laboratory aspects of chronic granulomatous disease in description of eighteen patients. Pediatr Allergy Immunol. Feb 2005;16(1):5-9. [Medline].

  15. Chowdhury MM, Anstey A, Matthews CN. The dermatosis of chronic granulomatous disease. Clin Exp Dermatol. May 2000;25(3):190-4. [Medline].

  16. 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].

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

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

  19. Bylund J, Campsall PA, Ma RC, Conway BA, Speert DP. Burkholderia cenocepacia induces neutrophil necrosis in chronic granulomatous disease. J Immunol. Mar 15 2005;174(6):3562-9. [Medline].

  20. Agudelo-Florez P, Lopez JA, Redher J, et al. The use of reverse transcription-PCR for the diagnosis of X-linked chronic granulomatous disease. Braz J Med Biol Res. May 2004;37(5):625-34. [Medline].

  21. 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. Aug 2006;97(2):257-61. [Medline].

  22. 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].

  23. 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].

  24. Nunoi H, Ishibashi F, Mizukami T, Hidaka F. Clinical evaluation of interferon-gamma treatment to chronic granulomatous disease patients with splice site mutations. Jpn J Infect Dis. Oct 2004;57(5):S25-6. [Medline].

  25. Wang J, Mayer L, Cunningham-Rundles C. Use of GM-CSF in the treatment of colitis associated with chronic granulomatous disease. J Allergy Clin Immunol. May 2005;115(5):1092-4. [Medline].

  26. Horwitz ME, Barrett AJ, Brown MR, et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. Mar 22 2001;344(12):881-8. [Medline].

  27. Seger RA, Gungor T, Belohradsky BH, et al. Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000. Blood. Dec 15 2002;100(13):4344-50. [Medline].

  28. Grez M, Becker S, Saulnier S, et al. Gene therapy of chronic granulomatous disease. Bone Marrow Transplant. May 2000;25 Suppl 2:S99-104. [Medline].

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

  30. Malech HL, Choi U, Brenner S. Progress toward effective gene therapy for chronic granulomatous disease. Jpn J Infect Dis. Oct 2004;57(5):S27-8. [Medline].

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

  32. Assari T. Chronic Granulomatous Disease; fundamental stages in our understanding of CGD. Med Immunol. Sep 21 2006;5:4. [Medline]. [Full Text].

  33. Carruthers JA, Greaves MW. Chronic granulomatous disease. Br J Dermatol. Jul 1976;95 Suppl 14:72-4. [Medline].

  34. Curnutte JT. Chronic granulomatous disease: the solving of a clinical riddle at the molecular level. Clin Immunol Immunopathol. Jun 1993;67(3 Pt 2):S2-15. [Medline].

  35. Curnutte JT. Recent advances in chronic granulomatous disease. Curr Opin Pediatr. 1990;2:907-15.

  36. Goldblatt D, Thrasher AJ. Chronic granulomatous disease. Clin Exp Immunol. Oct 2000;122(1):1-9. [Medline].

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

  38. Holland S, Seger R, Sullivan KE. The chronicles of chronic granulomatous disease. Clin Immunol. Aug 2005;116(2):99-100. [Medline].

  39. Lekstrom-Himes JA, Kuhns DB, Alvord WG, Gallin JI. Inhibition of human neutrophil IL-8 production by hydrogen peroxide and dysregulation in chronic granulomatous disease. J Immunol. Jan 1 2005;174(1):411-7. [Medline].

  40. Ma JS, Chen PY, Fu LS, et al. Chronic granulomatous disease: a case report. J Microbiol Immunol Infect. Jun 2000;33(2):118-22. [Medline].

  41. Mallory SB, Leal-Khouri S. Chronic granulomatous disease. In: An Illustrated Dictionary of Dermatologic Syndromes. London, England: Parthenon; 1994:41.

  42. Rosenzweig SD. Inflammatory manifestations in chronic granulomatous disease (CGD). J Clin Immunol. May 2008;28 Suppl 1:S67-72. [Medline].

  43. Westbroek W, Adams D, Huizing M, et al. Cellular defects in Chediak-Higashi syndrome correlate with the molecular genotype and clinical phenotype. J Invest Dermatol. Nov 2007;127(11):2674-7. [Medline].

  44. 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].

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Further Reading

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Keywords

chronic granulomatous disease, CGD, fatal granulomatosis of childhood, immunodeficiency disorders, X-linked recessive disorder, gp91phox, p22phox, p67phox, Xp21.1, Rac2, impaired phagocytic function, defective cytochrome b function, oxidase absence, oxidase malfunction

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Contributor Information and Disclosures

Author

Roman Janusz Nowicki, MD, PhD, Associate Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland
Roman Janusz Nowicki, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and International Society for Human and Animal Mycology
Disclosure: Nothing to disclose.

Medical Editor

Jacek C Szepietowski, MD, PhD, Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland
Disclosure: Stiefel Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System
William D James, MD is a member of the following medical societies: American Academy of Dermatology and Society for Investigative Dermatology
Disclosure: elsevier Royalty Other; american college of physicians Honoraria Other

 
 
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