Chronic granulomatous disease is characterized by WBCs that cannot produce activated O₂ compounds and by defects in phagocytic cell microbicidal function. Manifestations include recurrent infections; multiple granulomatous lesions of the lungs, liver, lymph nodes, and GI and GU tract; abscesses; lymphadenitis; hypergammaglobulinemia; elevated ESR; and anemia. Diagnosis is by assessing O₂ radical production in WBCs via a flow cytometric respiratory burst assay. Treatment is with antibiotics, antifungal drugs, and interferon-γ; granulocyte transfusions may be needed.

More than 50% of cases of chronic granulomatous disease (CGD) are inherited as an X-linked recessive trait and thus occur only in males; in the rest, inheritance is autosomal recessive. In CGD, WBCs do not produce hydrogen peroxide, superoxide, and other activated O₂ compounds because nicotinamide adenine dinucleotide phosphate oxidase activity is deficient. Phagocytic cell microbicidal function is defective; thus, bacteria and fungi are not killed despite normal phagocytosis.

Symptoms and Signs

CGD usually begins with recurrent abscesses during early childhood, but in a few patients, onset is delayed until the early teens. Typical pathogens are catalase-producing organisms (eg, Staphylococcus aureus; Escherichia coli; Serratia, Klebsiella; and Pseudomonas sp; fungi). Aspergillus infections are the leading cause of death.

Multiple granulomatous lesions occur in the lungs, liver, lymph nodes, and GI and GU tract (causing obstruction). Suppurative lymphadenitis, hepatosplenomegaly, pneumonia, and hematologic evidence of chronic infection are common. Skin, lymph node, lung, liver, and perianal abscesses; stomatitis; and osteomyelitis also occur. Growth may be delayed.

Diagnosis

Diagnosis is by a flow cytometric respiratory burst assay to detect O₂ radical production. The test can also identify female carriers of the X-linked form. Hypergammaglobulinemia and anemia can occur; ESR is elevated.

Treatment

• Prophylactic antibiotics, sometimes including antifungals
• Sometimes interferon (IFN)-γ
• For severe infections, granulocyte transfusions or bone marrow transplantation

Treatment is continuous prophylactic antibiotics, particularly trimethoprim/sulfamethoxazole 160/800 mg po bid alone or with cephalexin 500 mg po q 8 h. Oral antifungals are given as primary prophylaxis or are added if fungal infections occur even once; most useful are itraconazole po q 12 h (100 mg for patients < 13 yr; 200 mg for those ≥ 13 yr or weighing > 50 kg), voriconazole po q 12 h (100 mg for those weighing < 40 kg; 200 mg for those weighing ≥ 40 kg), or posaconazole (400 mg bid). IFN-γ may reduce severity and frequency of infections. Usual dose is 50 μg/m² sc 3 times/wk.

Granulocyte transfusions can be lifesaving when infections are severe. When preceded by pretransplantation chemotherapy, HLA-identical sibling bone marrow transplantation may be successful.

Last full review/revision September 2008 by Rebecca H. Buckley, MD