Chronic Granulomatous Disease (CGD)
Chronic granulomatous disease (CGD) is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly, the superoxide radical) used to kill certain ingested pathogens. This leads to the formation of granulomata in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year. A granuloma is a ball-like collection of immune cells which forms when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as other materials such as keratin, suture fragments and vegetable particles. A granuloma is a special type of inflammatory reaction that can occur in a wide variety of diseases, both infectious and non-infectious. The adjective “granulomatous” refers to diseases or inflammatory reactions that are characterized by granulomas. This condition was first described in 1957.
Most cases of chronic granulomatous disease are transmitted as a mutation on the X chromosome and are thus called an “X-linked trait.” A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD.
Classically, patients with chronic granulomatous disease will suffer from recurrent bouts of infection due to the decreased capacity of their immune system to fight off disease-causing organisms. The recurrent infections they acquire are specific and are, in decreasing order of frequency:
- abscesses of the skin, tissues, and organs
- suppurative arthritis
- superficial skin infections such as cellulitis or impetigo
Most people with CGD are diagnosed in childhood, usually before age 5. Early diagnosis is important since these people can be placed on antibiotics to ward off infections before they occur.
Microscopic image of the fungus, Aspergillus fumigatus, an organism that commonly causes disease in people with chronic granulomatous disease.People with CGD are sometimes infected with organisms that usually do not cause disease in people with normal immune systems such as Staphylococcus aureus, Klebsiella, Pseudomonas cepacia, Nocardia, Aspergillus fumigatus, and Candida species.
Management of chronic granulomatous disease revolves around two goals: (1) diagnose the disease early so that antibiotics can be given to keep an infection from occurring, and (2) educate the patient about his or her condition so that prompt treatment can be given if an infection occurs. Interferon is approved by the FDA for the prevention of infection in CGD. It has been shown to prevent infections in CGD patients by 70% and to reduce their severity. This therapy has been standard treatment for CGD for several years. Gene therapy is currently being studied as a possible treatment for chronic granulomatous disease. CGD is well-suited for gene therapy since it is caused by a mutation in single gene which only affects one body system (the hematopoietic system). Viruses have been used to deliver a normal gp91 gene to rats with a mutation in this gene, and subsequently the phagocytes in these rats were able to produce oxygen radicals.
The prognosis of chronic granulomatous disease is guarded, with long-term outcomes closely tied to early diagnosis and early therapeutic intervention. With increasing treatment options for CGD the life-span for these patients is expected to increase.