Silvia Caimmi

How Can We Better Classify NSAID Hypersensitivity Reactions? – Validation from a Large Database

Background: Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is one of the most common drug hypersensitivities. Several clinical subtypes have been distinguished depending on symptomatology (respiratory, cutaneous, anaphylaxis), timing (immediate, delayed), underlying chronic disease (asthma, chronic urticaria) or putative mechanism of the reaction (allergic, nonallergic mediated). The aim of the present study was to better classify the many hypersensitivity reactions to NSAIDs. Methods: In the present retrospective study, during an 11-year study period, we collected data from all patients with a proven NSAID hypersensitivity. Reactions were classified according to clinical patterns, chronology, underlying diseases and the results of oral provocation tests into 5 and 7 groups in line with two published classifications, respectively. Results: Forty-nine and 88 out of 307 reactions (in 122 patients) could not be classified on the basis of the two previously published classifications. We created a new classification which could include all patient reactions. Conclusions: Our new classification is more suitable for clinical expression of NSAID hypersensitivity. It allows clinicians to identify patients at a high risk, based on the clinical history and clinical manifestations. Moreover, it is helpful for a better understanding and teaching of these reactions.

Probiotics and food allergy.

The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.

Omalizumab in Children

Omalizumab is a recombinant humanized monoclonal antibody that reduces levels of circulating immunoglobulin E (IgE) and expression of IgE high-affinity receptors on mast cells and basophils, interrupting the subsequent allergic inflammatory cascade. Current indications for treatment with omalizumab in pediatric patients are clearly defined and are confined to moderate-to-severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU). Any other prescription can only be off label. Data available from clinical trials conducted in children suggest that omalizumab is clinically effective and generally well tolerated. Given its mechanism of action, recent reports have suggested its possible clinical use in other IgE-mediated disorders, such as allergic rhinitis, food allergy, and anaphylaxis. In recent years, several studies have also investigated the possible applications of omalizumab in a number of non IgE-mediated diseases. The aim of the present review is to assess all applications of omalizumab as therapy in the pediatric population. The approved indications—allergic asthma and CSU—are reviewed. Moreover, further potential applications of omalizumab are discussed in both IgE-mediated and non-IgE-mediated diseases.

Increased risk of otitis media with effusion in allergic children presenting with adenoiditis

Objective Otitis media with effusion (OME) is a common disorder in childhood. The aim of the study was to assess the association of atopy and endoscopic features with the presence of OME. Subjects and Methods This cross-sectional study evaluated 287 children presenting with acute upper-airway infections persistent for at least ten days and tested through nasal endoscopy and skin-prick test. Results Fifty-three patients had a diagnosis of OME; out of them, 23 showed acute rhinosinusitis, ten adenoiditis, and 20 both features. OME was diagnosed in 26 atopic children and in 27 nonatopic ones. On a multivariable analysis, allergic rhinitis, endoscopic pattern of adenoiditis, and younger age were all shown to be independently associated with a diagnosis of OME. Conclusions This study suggests that allergic rhinitis and adenoiditis are significant risk factors to OME development and that the risk becomes higher when these two conditions are con-comitantly present.

Adenoids in children: Advances in immunology, diagnosis, and surgery.

Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options. Clin. Anat. 27:346–352, 2014.

Gene-environment interaction in childhood asthma.

The importance of early life environmental influences on the etiology of asthma is implied by the observed geographic and temporal variation in the prevalence of the disease among children. There is evidence pointing to the role of exposure to allergen, various aspects of diet and hygiene-related factors in the etiology of asthma. There is also evidence that heritable factors influence the impact of hygiene-related exposures on the risk of having asthma. A number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Polymorphisms within genes coding for the toll-like receptor-lipopolysaccharide (TLR-LPS) signaling pathway may underlie variations in effects of hygiene-related exposures, including specifically endotoxin, on the risk of developing allergic sensitization and allergic disease. This review presents recent findings illustrating the role of gene-environment interactions in childhood asthma susceptibility.

From IgE to clinical trials of allergic rhinitis.

The current scientific research is continuously aiming at identifying new therapeutic targets with the purpose of modifying the immune response to allergens. The evolution in immunological methods has led to the identification of immunoglobulin E (IgE) as both a diagnostic biomarker and potential therapeutic target in allergic diseases, such as allergic rhinitis. Allergen immunotherapy has been used for more than 100 years to treat allergic diseases and it is today considered the only disease-modifying treatment capable of inducing a long-lasting immunological and clinical tolerance toward the causal allergen. During the past 20 years, major advances have been made in understanding the molecular and cellular mechanisms of allergen tolerance in humans. Moreover, there has been considerable progress in allergen extract modifications and additions to standard extracts. The recognition that IgE plays a pivotal role in basic regulatory mechanisms of allergic inflammation has recently stimulated research into the therapeutic potential of directly targeting this antibody. Omalizumab, the most advanced humanized anti-IgE monoclonal antibody, is currently approved for the treatment of uncontrolled allergic asthma and chronic spontaneous urticaria. Interesting results also arise from studies in which omalizumab was administered in patients with allergic rhinitis. The aim of this review is to provide an update on current findings on immunological and clinical effects of allergen immunotherapy and anti-IgE therapy, which have been shown to have synergistic modes of action for the treatment of allergic rhinitis.

Passive exposure to smoke results in defective interferon-γ production by adenoids in children with recurrent respiratory infections.

There is evidence that exposure to passive smoke is associated with an increased susceptibility to respiratory infections. Indeed, cigarette smoke extracts may interfere with the immune system, even though the precise mechanism has not been fully understood yet. Recurrent respiratory infections may be sustained by a defective immune response. The aim of the present study was to evaluate whether, in a cohort of children presenting both with recurrent respiratory infections and with a history of exposure to tobacco smoke, these factors were related to a lower local production of interferon-gamma (IFN-gamma) when compared to a similar non-exposed population. The study group included 128 children undergoing adenoidectomy, presenting with more than three respiratory infections per year, independently of exposure to passive smoke at home. The intracellular cytokine profile of lymphocyte subsets in adenoids was evaluated by flow cytometry analysis. Children exposed to tobacco smoke suffered from a significantly greater number of respiratory infections and had a lower percentage of IFN-gamma-producing CD8+ cells in adenoids than non-exposed children, while other T-cell subsets were not affected. The effect of smoke exposure seems to be specific to the IFN-gamma-producing CD8+ cells in adenoids and may contribute to the increased susceptibility to the recurrence of respiratory infections.

Current recommendations and emerging options for the treatment of allergic rhinitis

Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. The aim of this review is to provide an update on AR treatment, with a focus on current therapies defined by AR and its impact on asthma guidelines and with a particular emphasis on new and future therapeutic perspectives.

Safety of Cefuroxime as an Alternative in Patients with a Proven Hypersensitivity to Penicillins: A DAHD Cohort Survey

Objective: In patients sensitized to β-lactams, a safe β-lactam alternative is often needed. The objective was to assess the safety of cefuroxime in patients with a proven β-lactam allergy. Design: Using the Drug Allergy and Hypersensitivity Database cohort, patients with a proven β-lactam allergy and tested for cefuroxime between September 1996 and April 2007 were selected. The European Network of Drug Allergy recommendations were followed. Prevalence of sensitization to cefuroxime (as an alternative) was established in patients with a proven β-lactam allergy. Results: Amongst the 650 subjects tested, 143 (22.0%) presented at least one β-lactam sensitization other than cefuroxime [39–27.3% male, median age at test 44.0 (32.0–56.0) years]. One hundred and eighteen (82.5%) were sensitized to penicillins, 8 (5.6%) to cephalosporins and 17 (11.9%) to both penicillins and cephalosporins. Nine (6.3%) patients were sensitized to cefuroxime (6 diagnosed by provocation test): 5 (55.6%) in the penicillin-only allergic group and 4 (44.4%) in the penicillin and cephalosporin allergic group. Prevalence of cefuroxime hypersensitivity reaction in patients sensitized to β-lactams was 6.3% (95% CI 2.3–10.3%) and in those sensitized to penicillin 4.2% (95% CI 0.6–7.9). This rate decreased to 2.9% (95% CI 0–6.9) in patients with prior histories involving a penicillin only (without any history involving an unknown β-lactam). Conclusion: Cefuroxime appeared to be a safe alternative in β-lactam-allergic patients after testing. The risk of giving cefuroxime being not null, a thorough drug allergy work-up, including provocation test, is still needed.