Adrian M. Casillas

Slow subcutaneous human intravenous immunoglobulin in the treatment of antibody immunodeficiency: use of an old method with a new product.

Human intravenous immunoglobulin (IVIG) is a valuable therapeutic agent for antibody immunodeficiency and certain immunoregulatory disorders. However, for some patients, intravenous administration is not feasible because of poor venous access, severe side effects, or rapid IgG catabolism. This report demonstrates that the slow subcutaneous infusion of IVIG is a suitable alternative in these patients. Berger et al.1 first reported the use of 16.5% intramuscular immunoglobulin given by slow subcutaneous infusions for antibody replacement in immunodeficiency. Gardulf and associates2, 3 have used the subcutaneous route in immunodeficient adults in Scandinavia for many years, and they report that it is less expensive, better tolerated, and preferable to intravenous infusions by most patients. Abrahamsen et al.4 report a similar experience in eight children with primary immunodeficiency. Because mercury-free 16.5% intramuscular immunoglobulin is not available in this country, we used preservative-free 10% IVIG in eight antibody-deficient patients, all of whom tolerated subcutaneous infusions well, including three patients with prior severe adverse reactions to IVIG infusions.

Differences among heat-treated, raw, and commercial peanut extracts by skin testing and immunoblotting

BACKGROUND Peanut allergenicity has been reported to be influenced by heat treatment, yet the commonly available extracts for skin prick testing (SPT) are derived from raw extracts. OBJECTIVE To assess the effect of heat treatment on the SPT reactivity and specific IgE binding to peanut. METHODS Three commercial extracts and 3 laboratory-prepared extracts, including raw, roasted, and boiled, were used for SPT in 19 patients with suspected peanut allergy and in 4 individuals who eat peanut without any symptoms. Serum samples were obtained to measure total IgE in addition to specific IgE binding to the study extracts by immunoblotting. Peanut allergy was confirmed with challenge test unless the individual had a convincing history of a severe reaction. RESULTS Eleven study participants were considered peanut allergic based on a strong history or positive challenge test result. SPT with the prepared and commercial reagents showed that the boiled extract had the highest specificity (67% vs 42%-63% for the other extracts). The prepared extracts showed similar SPT sensitivity (81%). Three patients with a history of severe reaction and elevated specific IgE levels to peanut to the 3 study extracts had variable SPT reactivity to 1 or more of the commercial extracts. IgE binding to Ara h 2 was found in nearly all patients, regardless of their clinical reactivity. CONCLUSIONS None of the extracts tested showed optimal diagnostic reliability regarding both sensitivity and specificity. Perhaps testing should be performed with multiple individual extracts prepared by different methods.

Assessment of high-sensitivity C-reactive protein as a marker of airway inflammation in asthma

BACKGROUND Limited data are available on the presence of a systemic measure of inflammation in asthma. One marker that has been reported is C-reactive protein (CRP). OBJECTIVE To examine the correlation between high-sensitivity CRP (hsCRP) and asthma activity. METHODS Fifty-four patients with physician-diagnosed asthma, ages 6 to 58 years, were enrolled in the study. In addition to medical history and physical examination, asthma was assessed according to the National Asthma Education and Prevention Program (NAEPP) control score, fractional exhaled nitric oxide (FeNO), and spirometry. The relationships between hsCRP and each of the asthma control measures (ie, NAEPP control scores, presence of wheeze, FeNO, and forced expiratory volume in 1 second [FEV1]) were calculated. RESULTS The hsCRP levels in all patients ranged from less than 0.5 to 14.1 mg/L, with a mean (SD) of 2.1 (2.9 mg/L), compared with less than 0.5 mg/L expected in healthy individuals. The FEV1 percentage predicted ranged from 48% to 130%, with a mean (SD) of 96.5% (17.5%). Correlation coefficients for hsCRP vs FEV1 and FeNO were 0.07 and -0.03, respectively. Neither of these values reached statistical significance. The chi2 analysis values for hsCRP vs the NAEPP scores, wheeze, FEV1, and FeNO were 0.00, 2.16, 1.32, and 2.08, respectively, with none being statistically significant. CONCLUSIONS Our study of patients with asthma, mostly of a mild severity, did not reveal any significant correlation between hsCRP and wheeze, NAEPP control score, FEV1, or FeNO. Larger studies with a more diverse level of asthma control are warranted in examining the utility of hsCRP in the evaluation of asthma.

Underexpression and overexpression of Fas and Fas ligand: a double-edged sword.

OBJECTIVE To compare autoimmune lymphoproliferative syndrome (ALPS) and Stevens-Johnson syndrome (SJS) with respect to the defects in Fas- and Fas ligand (FasL)-mediated apoptosis. DATA SOURCES Selected reviews, case reports, and original studies were searched in PubMed and MEDLINE for the keywords ALPS, SJS, Fas, FasL, and apoptosis. STUDY SELECTION Case reports of ALPS and SJS were selected as examples of Fas- and FasL-mediated diseases. In addition, we selected articles that examined the pathophysiology of apoptosis in the context of Fas-FasL interaction. RESULTS Failure to initiate apoptosis of abnormal T lymphocytes occurs in such diseases as ALPS, leading to the accumulation of double negative T cells with an increase in autoimmunity. In contrast to apoptotic failure, SJS is associated with a pathological increase in programmed keratinocyte cell death. CONCLUSION The consequences of dysregulated Fas- and FasL-mediated apoptosis leads to self-reactivity, malignant transformation, and immune dysfunction. An understanding of underlying mechanisms and qualitative assessment of Fas and FasL may have clinical benefits when control of these homeostatic mechanisms is in question.

Eliminating health disparities: what have we done and what do we do next?

The United States, one of the richest countries in the world, spends more than any other on health care, but does not provide the best nor does it provide healthcare equally. Much of this inequity stems from vast socioeconomic inequalities.1 Conversely, improving the overall health of our citizens depends in large part on eliminating health disparities.2 Although we face a battered economy, there is new attention to this problem and to diversifying the workforce; there is new hope that these disparities can be addressed. As detailed in our Journal, asthma, a treatable condition and the most common chronic disease of childhood, is one in which disparities in care and outcome are prominent.3–5 This issue of the Journal is devoted to describing health disparities, particularly as they apply to the management of asthma, along with a discussion of proposals for enhancing the care that we can deliver as a community. Three commentaries emphasize the multiple factors and levels of complexity that converge to form the disparity in health care that we have witnessed.6–8 Bryant-Stephens points out that although the prevalence of asthma is greater for Blacks than non-Latino Whites, the disparity in morbidity is far greater. Most disturbing is her reference to the Six City Study that found that even after controlling for factors anticipated to explain disparities such as environmental exposures, parental history, and demographic factors; Black children still had 1.6 times the odds of asthma diagnosis when compared to non-Latino White children.9 What are these other factors? Arguably, some are combinations of those multi-level factors presented by Canino et al.7 They could include other neighborhood exposures or effects of poverty not characterized in the study, problems with access to medications and health care, or health practice factors to name only a few of the possibilities. Both Bryant-Stephens and Valet et al comment on the burden of asthma for rural minority populations. Valet et al conducted an interesting analysis showing that differences in outcomes for rural versus urban dwellers is not well-established; however, in both rural and urban areas of the United States, poverty is associated with poorer health outcomes. Impoverished rural African Americans may have increased risk for poor asthma outcomes, but this requires further study. Together these three articles emphasize that health disparities operate through direct and indirect effects of unrelenting poverty on health. What has our subspecialty done to address these disparities? The AAAAI has made a number of efforts and Hugh Sampson MD set a goal for his presidency to address this immense and critical task. Below are some of the AAAAI initiatives.

Subcutaneous Human Intravenous Immunoglobulin (IVIG) in the Treatment of Antibody Deficiency. ♦ 60

Subcutaneous Human Intravenous Immunoglobulin (IVIG) in the Treatment of Antibody Deficiency. ♦ 60