Philippe Bégin

Treatment of Patients with a History of Penicillin Allergy in a Large Tertiary-Care Academic Hospital

BACKGROUND Prescribing antibiotics to patients with a history of penicillin allergy is common in clinical practice. Opting for non-beta-lactam antibiotics has its inconveniences and is often unnecessary, because most of these patients are in fact not allergic. OBJECTIVE This study aimed to determine how physicians in a large Canadian tertiary-care academic hospital without allergists on staff treat patients with a history of penicillin allergy. METHODS A retrospective study was conducted during a 1-year period among all patients hospitalized in the intensive care unit, coronary care unit, and internal medicine wards. Files of patients with a record of penicillin allergy were reviewed to assess the need for antibiotics during their hospitalization and the decision-making process underlying the choice of antibiotic. The additional costs of alternative antibiotics were calculated. RESULTS The files of 1738 patients admitted over a 1-year period were hand reviewed. A history of penicillin allergy was found in 172 patients (9.9%). The allergic reaction was described in only 30% of cases and left unmentioned in 20.7%. Beta-lactam antibiotics were used on 56 occasions despite a history of penicillin allergy. The use of alternative antibiotics in place of the beta-lactam standard of care carried an additional cost of

Epigenetic regulation of asthma and allergic disease

15,672 Canadian. CONCLUSION Alleged penicillin allergy is common among hospitalized patients and leads to substantial additional costs. Poor documentation of penicillin allergy likely reflects a lack of knowledge on this issue in the medical community, which impairs optimal treatment of these patients. Increased education on this matter is needed, and allergists on staff could be part of the solution.

Egg-allergic patients can be safely vaccinated against influenza

Epigenetics of asthma and allergic disease is a field that has expanded greatly in the last decade. Previously thought only in terms of cell differentiation, it is now evident the epigenetics regulate many processes. With T cell activation, commitment toward an allergic phenotype is tightly regulated by DNA methylation and histone modifications at the Th2 locus control region. When normal epigenetic control is disturbed, either experimentally or by environmental exposures, Th1/Th2 balance can be affected. Epigenetic marks are not only transferred to daughter cells with cell replication but they can also be inherited through generations. In animal models, with constant environmental pressure, epigenetically determined phenotypes are amplified through generations and can last up to 2 generations after the environment is back to normal. In this review on the epigenetic regulation of asthma and allergic diseases we review basic epigenetic mechanisms and discuss the epigenetic control of Th2 cells. We then cover the transgenerational inheritance model of epigenetic traits and discuss how this could relate the amplification of asthma and allergic disease prevalence and severity through the last decades. Finally, we discuss recent epigenetic association studies for allergic phenotypes and related environmental risk factors as well as potential underlying mechanisms for these associations.

Regulatory T cells and their roles in immune dysregulation and allergy.

that additional factors are required. Our study also confirmed the association of FLG mutations and early-onset infantile eczema, which is in line with previous work. Our ability to interrogate the role of sensitization in the relationship between FLG mutations and food allergy in a large population-based, age-matched, challenge-proved food allergy cohort is a major and novel strength of this work. There is some potential participation bias among negative control subjects (higher immediate family history of allergic diseases compared with the general population); however, such a bias would be more likely to create a false-negative than a false-positive association. In conclusion, FLG mutations do not increase the risk of food allergy over and above that of food sensitization among 1-year-old infants. These results confirm the biological plausibility that decreased skin barrier function increases the risk of food sensitization in early life, but other as yet undetermined factors are important in the conversion from food sensitization to allergy.

Basophils are recruited to inflamed lungs and exacerbate memory Th2 responses in mice and humans.

The main function of the immune system is to fight off potential infections, but also to maintain its activity below a level that would trigger self-reactivity. Regulatory T cells (Tregs) such as forkhead box P3+ (FOXP3) Tregs and type 1 regulatory T cells (Tr1) play an essential role in this active process, using several distinct suppressive mechanisms. A wide range of pathologies have been associated with altered Treg cell function. This is best exemplified by the impact of mutations of genes essential for Treg function and the associated autoimmune syndromes. This review summarizes the main features of different subtypes of Tregs and focuses on the clinical implications of their altered function in human studies. More specifically, we discuss abnormalities affecting FOXP3+ Tregs and Tr1 cells that will lead to autoimmune manifestations and/or allergic reactions, and the potential therapeutic use of Tregs.

Human basophils interact with memory T cells to augment Th17 responses

Although the contribution of basophils as inducers or amplifiers of Th2 responses is still debated, prolonged basophil/CD4 T cell interactions were observed in lungs but not lymph nodes (LNs) of parasite‐infected mice. However, the impact of basophils on the function of tissue CD4 effector T cells remains unknown.

Freezing does not alter antigenic properties of fresh fruits for skin testing in patients with birch tree pollen–induced oral allergy syndrome

Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3- or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T(EM)), central memory T cells (T(CM)), and CCR6(+) CD4 T cells. More specifically, basophils promoted the emergence of IL-17(+)IFN-γ(-) and IL-17(+)IFN-γ(+), but not IL-17(-)IFN-γ(+) CD4 T cells in T(EM) and T(CM). Mechanistic analysis revealed that the enhancing effect of IL-17 production by basophils in T(EM) involved the ERK1/2 signaling pathway, occurred in a contact-independent manner, and was partially mediated by histamine via H(2) and H(4) histamine receptors. The results of the present study reveal a previously unknown function for basophils in augmenting Th17 and Th17/Th1 cytokine expression in memory CD4 T cells. Because basophils accumulated in inflamed inflammatory bowel disease tissues, we propose that these cells are key players in chronic inflammatory disorders beyond Th2.

Oral immunotherapy for the treatment of food allergy

To the Editor: The oral allergy syndrome (OAS) describes an allergic reaction that occurs on ingestion of certain fresh fruits and vegetables in pollen-sensitized subjects. The culprit allergens found in associated fresh foods are rapidly inactivated by digestion and cooking. As a result, symptoms are usually limited to the mouth and throat and preferably observed with raw forms of the food. When evaluating patients with OAS, skin prick tests (SPTs) with commercial extracts will often yield negative responses because the allergens are thought to be altered in the fabrication process of food extracts. Specific serum IgE (ssIgE) assays are also of limited value, and although recombinant allergens appear to be promising, they are not yet widely available. At present, the preferred method for evaluating patients with OAS is the use of SPTs with fresh fruits and vegetables using the prick-prick technique, which consists of pricking the fruit directly with a lancet and then using the same lancet immediately for the skin prick. This method has been shown to be much more sensitive than SPTs with commercial extracts for most foods implicated in the syndrome. A practical limitation to this approach is the access to fresh food at the clinic. One solution is to have the patient return for a second appointment with his own fresh food, but this is time consuming for both the patient and the physician and delays diagnosis. Another potential pitfall is that the culprit fruit might not be available in its fresh form depending on the harvest season. Although the effect of cooking is well established, much less is known about the effect of freezing on the allergenic properties of the proteins responsible for OAS. During freezing, soluble proteins are progressively entrapped in newly formed crystals and might experience shear tension at the ice-liquid interface. Although this phenomenon has been shown to decrease the enzyme activity of some soluble proteins, the effect on antigenicity has not been studied. We hypothesized that frozen fruits would have the same value as fresh fruits for the purpose of skin testing patients with OAS. Twenty-three patients with OAS were recruited from the allergy clinic at our center. Inclusion criteria were as follows: (1) sensitivity to birch pollen on skin testing, (2) oral symptoms to a plant food related to birch, (3) and sensitivity to this fresh plant food on skin testing. Demographic data and medical history were collected for each subject. They were also asked to fill out a questionnaire regarding their upper respiratory tract symptoms, and scores for rhinoconjunctivitis symptoms were calculated. Fruits were bought fresh and frozen in a regular home freezer at 2188C for 48 to 72 hours. Frozen fruits were thawed at room temperature for 15 minutes before evaluation. Skin tests were performed with aeroallergens and commercial fruit extracts (Omega Laboratories, Montreal, Quebec, Canada), as well as with fresh and thawed fruits, by using the prick-prick method. ssIgE levels were measured for each fruit by using UNICAP technology (Phadia, Uppsala, Sweden). Twenty-three control subjects without symptoms of OAS and with negative SPT responses to birch pollen were also recruited from the clinic staff and underwent skin testing. Agreement between allergy tests was analyzed by using the Pearson correlation coefficient (PCC). Sensitivity was calculated as described elsewhere. All statistical analyses were performed with the SPSS software package (SPSS, Inc, Chicago, Ill). The study was reviewed and approved by the local ethics committee. All subjects provided written informed consent before enrollment into the study. Demographic and clinical data are presented in Table I. Table II shows allergy test results and agreement between tests for each fruit. Although correlation between fresh and frozen fruit SPT responses is shown to be systematically high and significant, correlation between fresh fruit and extract SPT responses remains very low and seldom significant. Somewhat lower PCCs were found between fresh and frozen plum, peach, nectarine, and Golden Delicious apples when compared with other fruits. This could be explained in part by the fact that these fruits elicited some of the largest SPT responses because marginally high results are expected to have lower reproducibility (regression toward the mean phenomenon). When considering all Bet v 1–related fruits (ie, excluding cantaloupe and watermelon, which are associated with allergy to the birch allergen Bet v 2), the size of the wheal from fresh fruit tests did not correlate with that obtained with birch tree extracts or with rhinoconjunctivitis scores (PCC, 0.011 and20.021, respectively; not significant). There was, however, a poor but significant correlation between fresh fruit SPT responses and ssIgE values (PCC, 0.227;P5 .003). Similar findings were observed for watermelon and cantaloupe, although correlation with ssIgE levels was nonsignificant, possibly because of the small numbers of patients sensitized to these fruits. Overall sensitivities of SPTs with fresh (81%) and frozen (82%) fruits were similar and in line with those reported in the literature. Overall sensitivity of SPTs with fruit extracts (12%) and ssIgE levels (69%) also fell within the expected range. Interestingly, ssIgE levels and extract SPT responses did not correlate TABLE I. Clinical characteristics of subjects

Variable yield of allergy patch testing in children with eosinophilic esophagitis.

Oral immunotherapy (OIT) is an emerging new therapy for food allergy. With multiple small exploratory trials and some large randomized-controlled phase 2 trials recently published and under way, there is a clear progress and interest toward making this a treatment option for patients suffering from food allergies. However, there are still many questions to be answered and parameters to fine-tune before OIT becomes an accepted option outside of the research setting. This review covers the main milestones in the development of OIT for food allergy and further discusses important specific issues that will have direct impact on its clinical application. More specifically, previous publications showing evidence for the induction of tolerance are specifically reviewed and varying safety, tolerability and efficacy parameters from previous reports are also discussed.

Risk of allergic reaction and sensitization to antibiotics in foods

To the Editor: Molina-Infante et al published a prospective study in which they performed selective elimination diets in a cohort of 22 adults with eosinophilic esophagitis (EoE). They reported poor performance of skin prick and allergy patch tests (APTs) at identifying relevant foods. Another striking observation was their low rate of positive patch test results to foods (only 5 patients [23%] having a positive result), which contrasts with the very high rate reported in a previous large pediatric cohort, reaching up to 85%. They proposed that the difference in age might account for these diverging results. We find their results very interesting as we have also had a similar disappointing experience with very low APT positivity in our pediatric patientswithEoE.Hence, the older ageof thepatients is probably not the sole explanation for the poor yield of APT. We retrospectively analyzed 61 cases of children with confirmed diagnosis of EoE referred to our allergy service between 2004 and 2012. All patients (median age 10.9 years) had typical symptoms and esophageal eosinophilia (>20 eosinophils/highpowered field) on biopsy. Fifty-seven patients underwent APT with the same technique already described by Spergel et al with the same offending food, aswell aswith chicken, beef, and peanut. We found only 8 patients (14%) with positive APT result. Other pediatric cohorts, by Rizo Pascual et al and Assa’ad et al, also reported low positivity rates of APT (12% and 37%, respectively). In the few previous studies in children, this positivity rate varies greatly and the use of APT is not yet standardized or validated. As with asthma, it appears that a certain heterogeneity exists in EoE and diverging clinical phenotypes could account for some of the differences between cohorts. Thus, age could be a factor in the equation, but one should keep in mind that high positive rates of APT are not necessarily the rule in children. Hence, considering the time and cost investment, the low positivity rate of APT, and the nonsuperiority of subsequent specific elimination diet compared with empiric 6-food elimination diet, we also come to question the use of APT in the pediatric population. Brenda Paquet, MD Philippe B egin, MD, MSc, FRCPC Louis Paradis, MD, FRCPC, FAAAAI Eric Drouin, MD, FRCPC Anne Des Roches, MD, FRCPC, FAAAAI