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About
Primary Immune Deficiency IDF PATIENT/FAMILY HANDBOOK | CHAPTER VI Chronic Granulomatous Disease
DEFINITION: Chronic Granulomatous Disease (CGD) is a genetically determined (inherited) disease characterized by an inability of the body's phagocytic cells to kill certain microorganisms. As a result of this defect in phagocytic cell killing, patients with CGD have an increased susceptibility to infections caused by certain bacteria and fungi. The term “phagocytic cell” is a general term used to describe any white blood cell in the body that can “phagocytose”, or ingest, microorganisms. In general, there are two main categories of phagocytic cells, or phagocytes; 1) polymorphonuclear leukocytes (also called neutrophils or granulocytes) and 2) mononuclear phagocytes (also called monocytes when in the blood and macrophages when in tissues). Very complex interactions are necessary for normal function of phagocytic cells. First, the phagocyte must be able to migrate to the site of microbial invasion, whether that is under the skin, under a mucous membrane, or in an internal organ such as the lung or liver. Then the phagocyte must be able to ingest the microorganism, whether bacteria or fungus, and bring it into the interior of the phagocyte. After ingestion, a series of complex interactions, including metabolic and mechanical changes, must occur within the phagocyte in order for it to kill the bacteria or fungus. Although phagocytic cells from patients with CGD can move normally and ingest microorganisms normally, they are unable to kill certain bacteria and fungi because of abnormal metabolism within the cell. Hydrogen peroxide and other oxygen-containing compounds are produced during phagocytosis in normal phagocytes. These oxygen-containing compounds are needed to kill certain bacteria and fungi once these microorganisms are inside the phagocytic cells. The phagocytic cells of patients with CGD are unable to process oxygen properly and create the oxygen-containing compounds needed for killing. As a result, these patients lack an important mechanism to kill certain bacteria. Some bacterial species, such as the pneumococcus and streptococcus, produce oxygen-containing compounds such as hydrogen peroxide. When these bacteria are ingested by the phagocytic cells of patients with CGD, the bacterium contributes its own hydrogen peroxide to the defective phagocytic cell. As a result, the defect is overcome, and the phagocytic cell can kill these organisms using the hydrogen peroxide contributed by the bacteria itself. Thus, patients with CGD do not have an increased susceptibility to infection with these organisms. They are only susceptible to organisms, such as staphylococci and fungi, which cannot produce hydrogen peroxide and other oxygen-containing compounds. These microbes cannot supply the missing chemical needed by the phagocytic cell for normal killing. Patients with CGD have normal antibody production, normal T-cell function, and a normal complement system; in short, the rest of their immune system is normal. CLINICAL PRESENTATION: Children with Chronic Granulomatous Disease (CGD) are usually healthy at birth. However, sometime in their first few months or years of life, they develop recurrent infections, infections that are difficult to treat, or infections that are caused by unusual organisms such as fungi. The infections may involve any organ system or tissue of the body, but the skin, lungs, lymph nodes, liver, or bones are the usual sites of infection. Infected lesions may have prolonged drainage, delayed healing and residual scarring. Pneumonia is a recurrent and common problem in patients with CGD. Many of the lung infections are chronic. In some instances, patients develop lung abscesses. Abscesses of other organs, such as the liver and spleen, can also occur. Infections of the lymph nodes are also relatively common and may affect the lymph nodes of the neck, axilla or groin. Osteomyelitis (bone infections) frequently involves the small bones of the hands and feet. Although osteomyelitis requires prolonged therapy, complete healing and return of function usually occurs. Some infections may result in the formation of localized, swollen collections of infected tissue. In some instances, these swellings may cause obstruction of the intestine or urinary tract. They often contain microscopic collections of cells called granulomas. In fact, it is the granuloma formation that was the basis for the name of the disease. DIAGNOSIS: The diagnosis of Chronic Granulomatous Disease (CGD) is usually first suspected because of serious infections. Abscesses of the lung, the liver, the region around the anus and the small bones of hand and feet are often the first clues to the diagnosis. In addition, infections caused by an unusual microbial species such as Serratia, Nocardia, Burkholderia and Aspergillus may provide a valuable clue to the diagnosis. The diagnosis of CGD is made by analyzing the metabolic function and killing capacity of the patient's phagocytic cells. Blood from CGD patients is obtained and the phagocytes are isolated. A number of tests are performed to test the metabolic machinery of the cell and determine if the patient's cells can metabolize oxygen correctly and produce hydrogen peroxide and other oxygen-containing compounds. Confirmation of a diagnosis of CGD may be done by measuring the ability of the phagocytes to kill staphylococci or other bacteria. These tests are usually done in specialized laboratories. INHERITANCE PATTERN: Chronic Granulomatous Disease (CGD) is a genetically determined disease and therefore can be inherited or passed on in families. There are two patterns for transmission. One form of the disease is inherited in a sex-linked (or X-linked) recessive manner; i.e. it is carried on one of the sex chromosomes or “X” chromosome (see chapter on Inheritance). Other forms of the disease are inherited in an autosomal recessive fashion; they are carried on chromosomes other than the “X” chromosome. A complete discussion of the manner of inheritance of either Xlinked recessive or autosomal recessive disorders is beyond the scope of this chapter. The chapter in this Handbook on Inheritance covers both these patterns of inheritance in detail. It is important to understand the type of inheritance so families can understand why a child has been affected, the risk that subsequent children may be affected, and the implications for other members of the family. TREATMENT: A mainstay of therapy is the early diagnosis of infection and prompt, aggressive use of appropriate antibiotics. Initial therapy with antibiotics aimed at the most likely offending organisms may be necessary while waiting for results of cultures. A careful search for the cause of infection is important so that sensitivity of the microorganism to antibiotics can be determined. Intravenous antibiotics are usually necessary for treating serious infections in CGD patients and clinical improvement may not be obvious for a number of days in spite of treatment with the appropriate antibiotics. Granulocyte transfusions may also be helpful for some CGD patients when aggressive antibiotic therapy fails and the infection is life-threatening. Patients with CGD have such frequent infections, especially as young children, that continuous oral antibiotics (prophylaxis) are often recommended. CGD patients who receive prophylactic antibiotics may have infection — free periods and prolonged intervals between serious infections. The most frequently recommended agent for prophylaxis is a combination of trimethoprim and sulfamethoxasole. A natural product of the immune system, gamma interferon, is also used to treat patients with CGD in order to boost their immune system. Patients with CGD who are treated with gamma interferon may have fewer infections and when infections do occur they may be less serious (see chapter on Specific Medical Therapy). Many physicians suggest that swimming should be confined to wellchlorinated pools since fresh water lakes and salt water swimming may expose patients to organisms which are not virulent (or infectious) for normal swimmers but may be infectious for CGD patients. Aspergillus is present in many samples of marijuana, so CGD patients should be discouraged from smoking “pot.” Patients should also avoid dusty conditions, especially spoiled or moldy grass and hay and compost. Since early treatment of infections is very important, patients are urged to consult their physicians about even minor infections. EXPECTATIONS: The quality of life for many patients with Chronic Granulomatous Disease (CGD) has improved remarkably with knowledge of the phagocytic cell abnormality and appreciation of the need for early, aggressive antibiotic therapy when infections occur. Recurrent hospitalization may be required in CGD patients since multiple tests are often necessary to locate the exact site and cause of infections, and intravenous antibiotics are usually needed for treatment of serious infections. Disease-free intervals are increased by prophylactic antibiotics and treatment with gamma interferon. Serious infections tend to occur less frequently when patients reach their teenage years. In fact, many patients with CGD complete high school, attend college, and are carrying on relatively normal lives. |
Chronic Granulomatous Disease is a genetically
determined (inherited) primary immune deficiency
disease characterized by an inability of the body's
phagocytic cells (polymorphonuclear leukocytes and
monocytes) to kill certain microorganisms.
