Corticosteroid therapy for refractory infections in chronic granulomatous disease: case reports and review of the literature.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary phagocyte immunodeficiency. It is often accompanied by an exuberant and aberrant inflammatory response, with granulomata and obstruction of the gastrointestinal and genitourinary tracts and inflammatory bowel disease. Although corticosteroids are successful in managing the obstructive and inflammatory disorders of CGD, they are not ordinarily used for the management of infection because of the possibility of further compromising the patient's immune system. OBJECTIVES: To discuss the pros and cons of the use of corticosteroids for the treatment of infections in CGD. METHODS: We describe 2 patients with CGD and refractory infections who were successfully treated with systemic corticosteroids in addition to antimicrobial agents. We also review the medical literature in which corticosteroids have been used for CGD infection. RESULTS: Our cases add to 3 other reports in which antibiotics and corticosteroids were used successfully in patients with CGD. However, in the presence of a potential pathogen, notably, aspergilla, corticosteroids may mask or favor dissemination of the fungus, especially in adults. CONCLUSIONS: Corticosteroids may play an important adjunctive role in CGD refractory infections.

Potential costs and benefits of newborn screening for severe combined immunodeficiency.

OBJECTIVE: Severe combined immunodeficiency (SCID) is a rare, treatable disorder of the immune system. The incidence is unknown but may be more common than published estimates because infants frequently die of infection before diagnosis. SCID is a candidate for universal newborn screening, so there is a need to determine under which circumstances screening would be cost-effective. STUDY DESIGN: We assumed a screening program for SCID would use T-cell lymphopenia as the screening criterion and performed a cost-utility analysis comparing universal screening with screening only those with a family history of SCID. RESULTS: Assuming society is willing to pay $50,000 for every quality-adjusted life-year saved, a SCID screening test that cost less than $5 with a false-negative rate of 0.9% and a false-positive rate of 0.4% would be considered cost-effective. A nationwide screening program would cost an additional $23.9 million per year for screening costs but would result in 760 years of life saved per year of screening. The cost to detect 1 case of SCID would be $485,000. CONCLUSION: SCID screening could result in a large benefit to detected individuals, making screening relatively cost-effective in spite of the low incidence of the disease. However, an adequate test is critical to cost-effectiveness.

Compound-heterozygous mutations in the plasminogen gene predispose to the development of ligneous conjunctivitis

Homozygous type I plasminogen deficiency has been identified as a cause of ligneous conjunctivitis. In this study, 5 additional patients with ligneous conjunctivitis are examined. Three unrelated patients (1 boy, 1 elderly woman, and 1 man) had plasminogen antigen levels of less than 0.4, less than 0.4, and 2.4 mg/dL, respectively, but had plasminogen functional residual activity of 17%, 18%, and 17%, respectively. These subjects were compound-heterozygotes for different missense mutations in the plasminogen gene: Lys19 --> Glu/Arg513 --> His, Lys19 --> Glu/Arg216 --> His, and Lys19 --> Glu/Leu128 --> Pro, respectively. The other 2 patients, a 14-year-old boy and his 19-year-old sister, who both presented with a severe course of the disease, exhibited plasminogen antigen and functional activity levels below the detection limit (<0.4 mg/dL and <5%, respectively). These subjects were compound-heterozygotes for a deletion mutation (del Lys212) and a splice site mutation in intron Q (Ex17 + 1del-g) in the plasminogen gene. These findings show that certain compound-heterozygous mutations in the plasminogen gene may be associated with ligneous conjunctivitis. Our findings also suggest that the severity of clinical symptoms of ligneous conjunctivitis and its associated complications may depend on the amount of plasminogen functional residual activity