Increased susceptibility of a carrier of X-linked chronic granulomatous disease (CGD) to Aspergillus fumigatus infection associated with age-related skewing of lyonization.

Chronic granulomatous disease (CGD) is an inherited disorder characterized by the inability of phagocytes to generate normal amounts of superoxide (O2-), leaving patients susceptible to life-threatening infections. It was previously assumed that once carriers of the X-linked form of CGD were found to have 30% or more of functionally normal neutrophils, they would be free of risk for infection because the lyonization ratio was believed to be constant. Our report strongly contradicts this assumption. A 45-year-old X-CGD carrier had approximately 40% of normal neutrophils in her peripheral blood at age 21 years. Recently, she contracted a life-threatening pulmonary infection with Aspergillus fumigatus. After recovery, the ratio of normal-to-nonfunctional neutrophils was re-evaluated. She was found to have only 6-8% of normal neutrophils, suggesting that a striking decrease in the number of normal cells over the past 25 years was the reason for an increased susceptibility to Aspergillus infection. We conclude that age-related acquired skewing of the lyonization ratio can result in an increased susceptibility to life-threatening infections in X-CGD carriers.

Frequency of very late fatal sepsis after splenectomy for hereditary spherocytosis: impact of insufficient antibody response to pneumococcal infection.

Very late sepsis in splenectomized patients with hereditary spherocytosis has been seen rarely up to now; the frequency and the immunodeficiency causing it are largely unknown. Within the past 7 years we have learned of four cases of sepsis or meningitis (three fatal) in adult patients with hereditary spherocytosis who had been splenectomized years earlier. The estimated frequency of very late postsplenectomy infections is 0.69 cases of sepsis or meningitis in 1000 patient-years (0.46 deaths in 1000 patient-years). Pneumococci were proven in two patients. The surviving patient showed low antibody titers against pneumococcal serotypes even after pneumococcal meningitis and subsequent vaccination. There have been several reports of an insufficient response to pneumococcal vaccination in patients with severe infections. We recommend determination of pneumococcal antibody titers after immunization in every splenectomized patient: Nonresponders to vaccination may be at high risk for overwhelming postsplenectomy infection. Our data demonstrate that there is a lifelong risk for severe postsplenectomy infections and therefore the lasting need for immediate antibiotic therapy in any case with sudden onset of high fever.

Variability of house dust mite allergen exposure in dwellings.

The variability of repeated house dust mite (HDM) allergen determinations at the same site within 3-24 months was evaluated on previously collected samples. Between two and four repeated measurements of Der p 1, a major allergen of Dermatophagoides pteronyssinus and Der f 1, a major allergen of D. farinae, on 46 carpets and 31 mattresses were analyzed. In 90% of carpets and mattresses, HDM allergen concentrations were clinically relevant (at least one measurement >0.1 microg Der p 1 + Der f 1/g dust). The coefficients of variation (CVs) for allergen concentrations in repeated samples over time (55.3-82.0% for the two allergens in beds and carpets) were clearly greater than the CVs for multiple samples collected at the same time (4.0-32.6%). Determination of allergen mass per square meter of surface instead of concentration per gram of dust resulted in an even greater CV (72.3-86.7%). The 95% range of expected values was about 10-fold above and below the result of a single determination. We conclude that single determinations of HDM allergen in dust give very limited information about long-term exposure of an individual to the allergen. Repeated measurements are recommended. Studies of factors that affect HDM allergen exposure must be planned with appropriate sample sizes.

Sensitivity and specificity of quantitative determination of pancreatic elastase 1 in feces of children.

BACKGROUND: The secretin-pancreozymin test has been accepted as the gold standard for testing exocrine pancreatic function. However, this test is invasive, time-consuming, and expensive. Therefore, in daily practice, more simple, indirect methods are proposed. METHODS: The fecal concentration of human pancreatic elastase (E1) has been assessed for diagnostic sensitivity and specificity. For sensitivity, fecal E1 determination in 23 healthy children were studied. RESULTS: Sensitivity to detect pancreatic insufficiency was 100% and specificity 96%. CONCLUSIONS: Fecal E1 concentration appears to be a more sensitive and specific test of pancreatic function than other tests.