See how a mutation in any of the 5 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase component genes can lead to life-threatening bacterial and fungal infections.
Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency disorder where the immune system does not work properly. This primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) results from impaired killing of fungi and bacteria, which can lead to severe and recurrent infections.1,2
CGD can be inherited in 2 ways:
X-linked CGD is passed down from the carrier mother and is the most common form of CGD. It primarily affects male children, and symptoms usually appear early in childhood.1,3
Autosomal recessive CGD presents later in life, which can delay diagnosis. Serious infections* may be less frequent.1 Autosomal recessive CGD is passed down by 2 carrier parents and can affect both male and female children.
X-linked carriers can experience various symptoms and may be at risk for serious infections. Up to 23% of carriers may experience CGD-related, lupus-like symptoms including4-8:
Knowing what to look for can aid in the diagnosis of CGD. Suspect CGD in a patient with:
Infections caused by bacteria and fungi can occur from many places. They live in places like gardens (in mulch), playgrounds (in woodchips), and in lakes and ponds. People with CGD can still enjoy outdoor activities, but they should be cautioned to stay away from these places. Patients with CGD should also avoid the following:
Early diagnosis and prophylactic treatment is beneficial for patients with CGD because they are more susceptible to and have a higher incidence of serious infections.1,7* Serious infections can be life threatening and result in long hospital stays.
To help protect patients with CGD against serious infections, the triple therapy regimen of ACTIMMUNE® (Interferon gamma-1b), antibiotic therapy, and antifungal therapy is recommended by the9-11:
The recommended treatment paradigm consists of an antibacterial, an antifungal, and immunomodulatory therapy with ACTIMMUNE® (Interferon gamma-1b).1,7,12,13 ACTIMMUNE® (Interferon gamma-1b) is the only FDA-approved biologic therapy indicated for reducing the frequency and severity of serious infections* associated with CGD.14,15
With the development of preventative therapies and the early recognition of infectious complications, 90% of children with CGD now survive into adulthood. This remains, however, largely dependent on several factors, including time of diagnosis, access to care, expertise of caregiver, adherence to therapy, and lifestyle modifications.7,12
*Serious infection is defined as a clinical event requiring hospitalization and intravenous antibiotics.
References: 1. Leiding JW, Holland SM. Chronic granulomatous disease. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews Washington, Seattle; 1993-2016. 2. Winkelstein JA, Marino MC, Johnston RB Jr, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine. 2000;79(3):155-169. 3. Rider NL, Jameson MB, Creech CB. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. J Pediatric Infect Dis Soc. 2018;7(suppl 1):S2-S5. 4. Battersby AC, Bruggins H, Pearce MS, et al. Inflammatory and autoimmune manifestations in X-linked carriers of chronic granulomatous disease in the United Kingdom. J Allergy Clin Immunol. 2017;140(2):628-630.e6. 5. Marciano BE, Zerbe CS, Falcone EL, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365-371. 6. Magnani A, Brosselin P, Beauté J, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655-662.e8. 7. Holland SM. Chronic granulomatous disease. Hematol Oncol Clin North Am. 2013;27(1):89-99. 8. 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):10-24. 9. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeﬁciency. J Allergy Clin Immunol. 2015;136(5):1186-1205.e1-e78. 10. Leiding JW, Malech HL, Holland SM. Chronic granulomatous disease. Clinical Focus on Primary Immunodeﬁciencies. 2013;15:1-9. 11. Mendelian susceptibility to mycobacterial disease. In: Buckley RH, ed. Immune Deficiency Foundation Diagnostic & Clinical Care Guidelines for Primary Immunodeficiency Diseases. 3rd ed. Immune Deficiency Foundation; 2015:25. 12. Thomsen IP, Smith MA, Holland SM, et al. A comprehensive approach to the management of children and adults with chronic granulomatous disease. J Allergy Clin Immunol Pract. 2016;4(6):1082-1088. 13. Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348(24):2416-2422. 14. ACTIMMUNE® (Interferon gamma-1b) [prescribing information] Horizon. 15. The International Chronic Granulomatous Disease Cooperative Study Group. A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med. 1991;324(8):509-516.
ACTIMMUNE® (Interferon gamma-1b) is indicated:
ACTIMMUNE® (Interferon gamma-1b) is indicated: