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Hypersensitivity reactions to anticancer agents: data mining of the public version of the FDA Adverse Event Reporting System, AERS.

Previously, adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) database were reviewed to confirm platinum agent-associated hypersensitivity reactions. The present study was performed to confirm whether the database could suggest the hypersensitivity reactions caused by anticancer agents, paclitaxel, docetaxel, procarbazine, asparaginase, teniposide, and etoposide.

METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving candidate agents were analyzed. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 was applied to evaluate the susceptibility to hypersensitivity reactions, and standardized official pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean.

RESULTS: Based on 1,644,220 AERs from 2004 to 2009, the signals were detected for paclitaxel-associated mild, severe, and lethal hypersensitivity reactions, and docetaxel-associated lethal reactions. However, the total number of adverse events occurring with procarbazine, asparaginase, teniposide, or etoposide was not large enough to detect signals.

CONCLUSIONS: The FDA's adverse event reporting system, AERS, and the data mining methods used herein are useful for confirming drug-associated adverse events, but the number of co-occurrences is an important factor in signal detection.

Antenatal risk factors for peanut allergy in children.

BACKGROUND: Prenatal factors may contribute to the development of peanut allergy. We evaluated the risk of childhood peanut allergy in association with pregnancy exposure to Rh immune globulin, folic acid and ingestion of peanut-containing foods.

METHODS: We conducted a web-based case-control survey using the Anaphylaxis Canada Registry, a pre-existing database of persons with a history of anaphylaxis. A total of 1300 case children with reported peanut allergy were compared to 113 control children with shellfish allergy. All were evaluated for maternal exposure in pregnancy to Rh immune globulin and folic acid tablet supplements, as well as maternal avoidance of dietary peanut intake in pregnancy.

RESULTS: Receipt of Rh immune globulin in pregnancy was not associated with a higher risk of peanut allergy (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.51 to 1.45), nor was initiation of folic acid tablet supplements before or after conception (OR 0.53, 95% CI 0.19 to 1.48). Complete avoidance of peanut-containing products in pregnancy was associated with a non-significantly lower risk of peanut allergy (OR 0.53, 95% CI 0.27 to 1.03).

CONCLUSION: The risk of childhood peanut allergy was not modified by the following common maternal exposures in pregnancy: Rh immune globulin, folic acid or peanut-containing foods. Clinical implications: Rh immune globulin, folic acid supplement use and peanut avoidance in pregnancy have yet to be proven to modulate the risk of childhood anaphylaxis to peanuts. Capsule Summary: Identification of prenatal factors that contribute to peanut allergy might allow for prevention of this life-threatening condition. This article explores the role of three such factors.

Atopic dermatitis: from new pathogenic insights toward a barrier-restoring and anti-inflammatory therapy.

PURPOSE OF REVIEW: Recent published work on atopic dermatitis focusing on the pathogenesis and epidemiology, which have a direct effect on treatment, is presented.

RECENT FINDINGS: Worldwide, the incidence of atopic dermatitis is still increasing, although a plateau seems to be reached in certain industrialized countries. In addition to the filaggrin missense mutations, other mechanisms responsible for impaired skin-barrier function have been identified. These findings have a direct impact on therapy as well as behavior strategies. The barrier defect and the resulting inflammation in the skin, in particular interleukin (IL)-17-mediated responses, play an important role in promoting allergic airway responses and food allergy.

SUMMARY: These recent findings on epithelial barrier defects, as well as cells and cytokines important for atopic dermatitis development, provide new insights into its pathogenesis, help to characterize patient subgroups, and identify new therapeutic strategies.

Allergen immunotherapy: a history of the first 100 years.

PURPOSE OF REVIEW: To provide a historical perspective on the development of allergen immunotherapy and to describe the progress that has been made in both the clinical application and the scientific understanding of this therapeutic technique in the 100 years since its inception.

RECENT FINDINGS: Although allergen immunotherapy has been part of allergy practice for a century, it is only in relatively recent years that the cellular and molecular mechanisms which underlie its clinical efficacy have been elucidated. Most recent studies implicate the T-regulatory cell response as central to the development of a tolerogenic state in response to allergen immunotherapy, with both IL-10 and TGF-β playing crucial roles in the development of this cell subset. The clinical application of immunotherapy continues to advance, with promising contemporary studies noting improved safety and efficacy with pretreatment using omalizumab prior to an immunotherapy program as well as the potential for innate immune system modulation with allergen conjugates which can stimulate pattern recognition receptors such as the toll-like receptors.

SUMMARY: After 100 years of clinical application, allergen immunotherapy remains the only treatment modality with the potential for long-term immunologic amelioration of atopic diseases. Future treatment advances in allergen immunotherapy will likely harness the increasing power of molecular and genomic medicine to achieve greater allergen specificity, while improving overall efficacy and minimizing the potential for systemic reactions.

Anti-interleukin-5 antibody therapy in asthma and allerges.

Interleukin 5 (IL-5) has been shown to play an instrumental role in eosinophilic inflammation in allergic diseases. The purpose of this review is to explore clinical trials of anti-IL-5 antibody therapy that have been conducted in patients with asthma, hypereosinophilic syndromes, eosinophilic esophagitis, atopic dermatitis, Churg-Strauss syndrome, and nasal polyposis.

RECENT FINDINGS: Recent trials of anti-IL-5 in patients with severe asthma refractory to existing therapies and prominent sputum eosinophilia experienced significant reductions in asthma exacerbations. Studies in patients with hypereosinopihilic syndromes have shown that IL-5 antagonism allows significant reductions in systemic corticosteroid doses while maintaining or improving blood eosinophil counts and symptoms. In children and adults with eosinophilic esophagitis, anti-IL-5 treatment reduced eosinophil numbers in esophageal tissue; it is uncertain whether these findings are predictive of clinical improvement. Clinical studies of individuals with atopic dermatitis do not support efficacy of anti-IL-5 in either reducing allergen patch test intensity or symptoms of chronic dermatitis. In small trials in both Churg Strauss syndrome and nasal polyposis, anti-IL-5 shows promise but larger numbers of patients with these conditions will need to be studied.

SUMMARY: Anti-IL-5 is efficacious in treating patients with severe asthma and sputum eosinophilia and hypereosinophilic syndromes. Larger controlled trials with appropriate endpoints will be necessary to assess the role of anti-IL-5 in other eosinophilic disorders.

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