Renata J. M. Engler

Adequacy of the epinephrine autoinjector needle length in delivering epinephrine to the intramuscular tissues

BACKGROUND Epinephrine injected by an autoinjector in the anterolateral aspect of the thigh is the standard of care in the emergency self-treatment of anaphylaxis. In the United States, the autoinjector EpiPen is widely used for the self-treatment of anaphylaxis. OBJECTIVE To investigate whether EpiPen autoinjector, with a needle length of 1.43 cm, is sufficient for intramuscular delivery of epinephrine in men and women. METHODS The distance from skin to muscle in the anterolateral aspect of the thigh was measured in 50 men and 50 women who had undergone computed tomography of the thighs for other medical reasons. For each individual, body mass index (BMI; a measure of weight in kilograms divided by the square of height in meters) was also calculated, and the individuals were classified as underweight (BMI, < 18.5), normal (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) using standard definition. RESULTS In the study participants the mean +/- SD distance from skin to muscle was 0.66 +/- 0.47 cm for men and 1.48 +/- 0.72 cm for women (P < .001). One man (obese at a BMI of 42.2) and 21 women (11 obese with a mean BMI of 35.2, 6 overweight with a mean BMI of 30.1, and 4 normal with a mean BMI of 24.5) had a greater distance from skin to muscle than the EpiPen needle length of 1.43 cm. CONCLUSION The distance from skin to muscle for the anterolateral aspect of the thigh is higher in women compared with men. This difference suggests that EpiPen may not deliver epinephrine to the intramuscular tissue in many women.

Cell-Mediated Immune Response to Tuberculosis Antigens: Comparison of Skin Testing and Measurement of In Vitro Gamma Interferon Production in Whole-Blood Culture

ABSTRACT Although delayed-type hypersensitivity skin testing with tuberculin purified protein derivative (PPD) is the standard for tuberculosis screening, its variability suggests the need for a more sensitive, noninvasive test. An in vitro whole-blood assay has been proposed as an alternative. Using health care worker volunteers, we confirmed the correlation between PPD skin test (PPD-ST) results (positive, induration of >15 mm) and a standardized gamma interferon (IFN-γ) assay, QuantiFERON-TB (Q-IFN), manufactured by CSL Biosciences in Australia, and we evaluated Mycobacterium tuberculosisculture subfractions as potential substitutes for PPD. Twenty healthy volunteers with positive PPD-ST results and 20 PPD-ST-negative controls were enrolled. Whole blood was cultured with human PPD antigens (HuPPD), Mycobacterium avium complex (MAC) PPD, phytohemagglutinin (PHA), and four M. tuberculosis culture subfractions: low-molecular-weight culture, filtrate, culture filtrate without lipoarabinomannan, soluble cell wall proteins, and cytosolic proteins, all developed from M. tuberculosis strain H37RV. Secretion of IFN-γ (expressed as international units per milliliter) was measured by an enzyme immunoassay. The PPD or subculture fraction response as a percentage of the PHA response was used to determine positivity. Sixteen of 20 PPD-ST-positive individuals were classified as M. tuberculosis positive by Q-IFN, and 1 was classified as MAC positive. Sixteen of 20 PPD-ST-negative individuals were M. tuberculosis negative by Q-IFN, 2 were MAC positive, and 2 were M. tuberculosis positive. The tuberculosis culture subfractions stimulated IFN-γ production in PPD-ST-positive volunteers, and significant differences could be seen between the two PPD-ST groups with all subfractions except soluble cell wall protein; however, the response was variable and no better than the Q-IFN PPD. The agreement between the Q-IFN test and the PPD-ST was good (Cohens kappa = 0.73). The Q-IFN assay can be a useful tool in further studies of immune responses to M. tuberculosisantigens.

Select Human Anthrax Protective Antigen Epitope-Specific Antibodies Provide Protection from Lethal Toxin Challenge

Bacillus anthracis remains a serious bioterrorism concern, and the currently licensed vaccine remains an incomplete solution for population protection from inhalation anthrax and has been associated with concerns regarding efficacy and safety. Thus, understanding how to generate long-lasting protective immunity with reduced immunizations or provide protection through postexposure immunotherapeutics are long-sought goals. Through evaluation of a large military cohort, we characterized the levels of antibodies against protective antigen and found that over half of anthrax vaccinees had low serum levels of in vitro toxin neutralization capacity. Using solid-phase epitope mapping and confirmatory assays, we identified several neutralization-associated humoral epitopes and demonstrated that select antipeptide responses mediated protection in vitro. Finally, passively transferred antibodies specific for select epitopes provided protection in an in vivo lethal toxin mouse model. Identification of these antigenic regions has important implications for vaccine design and the development of directed immunotherapeutics.

Anthrax vaccination induced anti-lethal factor IgG: Fine specificity and neutralizing capacity

The efficacy biomarker of the currently licensed anthrax vaccine (AVA) is based on quantity and neutralizing capacity of anti-protective antigen (anti-PA) antibodies. However, animal studies have demonstrated that antibodies to lethal factor (LF) can provide protection against in vivo bacterial spore challenges. Improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin preparations to treat and prevent inhalation anthrax morbidity and mortality. This study (n=1000) was designed to identify AVA vaccinated individuals who generate neutralizing antibodies and to determine what specificities correlate with protection. The number of vaccine doses, years post vaccination, and PA titer were associated with in vitro neutralization, reinforcing previous reports. In addition, African American individuals had lower serologic neutralizing activity than European Americans, suggesting a genetic role in the generation of these neutralizing antibodies. Of the vaccinated individuals, only 69 (6.9%) had moderate levels of anti-LF IgG compared to 244 (24.4%) with low and 687 (68.7%) with extremely low levels of IgG antibodies to LF. Using overlapping decapeptide analysis, we identified six common LF antigenic regions targeted by those individuals with moderate levels of antibodies to LF and high in vitro toxin neutralizing activity. Affinity purified antibodies directed against antigenic epitopes within the PA binding and ADP-ribotransferase-like domains of LF were able to protect mice against lethal toxin challenge. Findings from these studies have important implications for vaccine design and immunotherapeutic development.

Complementary and alternative medicine for the allergist-immunologist: where do I start?

Complementary and alternative medicine (CAM) therapies present a growing information management challenge for physicians because nearly 40% of their patients may be using and another 50% may be considering use of CAM as part of their healthcare regimen. The National Health Statistics Reports for 2007 described the most commonly used nonvitamin, nonmineral therapy as natural products (eg, herbals at 17.7%). More than 5% of children under the age of 18 years used CAM for allergic conditions including asthma. The amount and quality of information available and concerns about liability risk represent a challenge for most physicians. This review focuses on considerations for approaching a CAM-related consultation, incorporating legal and logistic factors affecting how such an encounter should be approached. A 10-step process is presented that addresses different components of CAM consultations and what should be documented. Access to timely, high-quality information regarding product specific efficacy and safety data, as found in the Natural Medicines Comprehensive Database, is needed to support CAM consultation efficiently. Understanding of serious adverse events associated with CAM is limited; an international need exists for improved safety surveillance and information sharing. Allergy-immunology, as a specialty with expertise in adverse drug reaction evaluation and management, has a unique opportunity to support enhanced CAM-related adverse events evaluations, reporting, and research.

Using a structured medical note for determining the safety profile of anthrax vaccine for US soldiers in Korea

Selected military personnel are immunized with an FDA-licensed anthrax vaccine unless there are clinical contraindications. The objective of this analysis is to capture the experience of soldiers receiving anthrax vaccine to assist in better patient-provider communication and clarify the safety profile of the vaccine in this population as a quality-assurance initiative. Between August 1998 and July 1999, 2824 soldiers immunized against anthrax at one military clinic completed a structured medical note that was reviewed by a clinician. Female gender, prior vaccine-associated adverse events, and medication use were significantly related to higher reports of adverse events. All reported immediate consequences resolved.

Anaphylaxis following psyllium ingestion

Psyllium is a hydrophilic agent found in many bulk laxative preparations. We report the occurrence of an anaphylactic reaction in a patient after ingestion of a psyllium-containing laxative. IgE mediation of the reaction was suggested by a positive immediate skin test to psyllium, positive passive transfer skin test, lack of skin response during passive transfer with heat treated serum, and an elevated IgE (RAST) to psyllium seed.

Adverse reactions to vaccines

Abstract(The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.)Immunization healthcare is becoming increasingly complex as the number and types of vaccines have continued to expand. Like all prescription drugs, vaccines may be associated with adverse events. The majority of these reactions are self-limited and not associated with prologned disability. The media, Internet and public advocacy groups have focused on potentially serious vaccine-associated adverse events with questions raised about causal linkages to increasing frequencies of diseases such as autism and asthma. Despite a lack of evidence of a causal relationship to a variety of vaccine safety concerns, including extensive reviews by the Institute of Medicine, questions regarding vaccine safety continue to threaten the success of immunization programs. Risk communication arid individual risk assessment is further challenged by the public health success of vaccine programs creating the perception that certain vaccines are no longer necessary or justified because of the rate reaction risk.There is a need for improved understanding of true vaccine contraindications and precautions as well as host factors and disease threat in order to develop a patient specific balanced treated, documented and reported through the VAERS system. The increasing complexity of vaccination health care has led the Center of Disease Control and Prevention (CDC) to identify Vaccine Safety Assessment and Evaluation as a potential new specialty.

Severe Postvaccinia Encephalitis with Acute Disseminated Encephalomyelitis: Recovery with Early Intravenous Immunoglobulin, High-Dose Steroids, and Vaccinia Immunoglobulin

We report the second case of severe postvaccinial encephalitis with acute disseminated encephalomyelitis since smallpox vaccination was reintroduced in 2002. Both affected patients responded dramatically with early intervention of intravenous immunoglobulin. Our patient, who also received concurrent vaccinia immunoglobulin and corticosteroids, demonstrated full recovery.

Improved in vitro antigen-specific antibody synthesis in two patients with common variable immunodeficiency taking an oral cyclooxygenase and lipoxygenase inhibitor (ketoprofen)

In the process of performing a previously published study examining B cell function in 16 patients with common variable immunodeficiency (CVI)(J Allergy Clin Immunol 1991; 87:1138-49), we noted improved in vitro antibody (Ab) synthesis in a patient, H. B., while he was taking a cyclooxygenase and lipoxygenase inhibitor, ketoprofen. Addition of ketoprofen in vitro to B cells from patients with CVI resulted in improved proliferation and differentiation in four of five additional patients with CVI studied. One patient, besides H. B., M. K. B., whose B cells secreted increased amounts of antigen (Ag)-specific Ab in response to in vitro ketoprofen, underwent a trial of oral ketoprofen M. K. B., like H. B., demonstrated improved in vitro Ag-specific Ab production while she was taking oral ketoprofen. No increase in serum Ab levels was noted in either patient taking ketoprofen, but both patients remained infection free during the time of their ketoprofen trials (H. B., 9 months, and M. K. B., 36 months). No improvement in in vitro Ag-specific Ab synthesis was noted when H. B. and M. K. B. took oral cyclooxygenase inhibitors (naproxen or ibuprofen). Thus, additional study is warranted to examine the role of lipoxygenase products of arachidonic acid in the B cell dysfunction of CVI.