Publications by authors named "Julia Upton"

42 Publications

Fruit-Induced Anaphylaxis: Clinical Presentation and Management.

J Allergy Clin Immunol Pract 2021 Mar 13. Epub 2021 Mar 13.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

Background: Data are sparse regarding the clinical characteristics and management of fruit-induced anaphylaxis.

Objective: To assess clinical characteristics and management of patients with fruit-induced anaphylaxis and determine factors associated with severe reactions and epinephrine use.

Methods: Over 9 years, children and adults presenting with anaphylaxis to seven emergency departments in four Canadian provinces and patients requiring emergency medical services in Outaouais, Quebec were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized form documenting symptoms, triggers, and management was collected. Multivariate logistic regression was used to identify factors associated with severe reactions and epinephrine treatment in the pre-hospital setting.

Results: We recruited 250 patients with fruit-induced anaphylaxis, median age 10.2 years (interquartile range, 3.6-23.4 years); 48.8% were male. The most common fruit triggers were kiwi (15.6%), banana (10.8%), and mango (9.2%). Twenty-three patients reported having eczema (9.3%). Epinephrine use was low in both the pre-hospital setting and the emergency department (28.4% and 40.8%, respectively). Severe reactions to fruit were more likely to occur in spring and among those with eczema (adjusted odds ratio [aOR] = 1.12, 95% confidence interval [CI], 1.03-1.23; and 1.17, 95% CI, 1.03-1.34, respectively). Patients with moderate and severe reactions (aOR = 1.23; 95% CI, 1.06-1.43) and those with a known food allergy (aOR = 1.38; 95% CI, 1.24-1.54) were more likely to be treated with epinephrine in the pre-hospital setting.

Conclusions: Severe anaphylaxis to fruit is more frequent in spring. Cross-reactivity to pollens is a potential explanation that should be evaluated further.
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http://dx.doi.org/10.1016/j.jaip.2021.02.055DOI Listing
March 2021

COVID-19 vaccine testing & administration guidance for allergists/immunologists from the Canadian Society of Allergy and Clinical Immunology (CSACI).

Allergy Asthma Clin Immunol 2021 Mar 15;17(1):29. Epub 2021 Mar 15.

Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, MN, Canada.

Background: Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists.

Methods: Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms "human" and "English" and limited the search to the relevant subject age range with the term "adult." Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance.

Results: Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination.

Interpretation: This review provides the first Canadian guidance regarding assessment of an adolescent and adult with a suspected allergy to one of the COVID-19 vaccines currently available, or any of their known allergenic components, and for patients who are immunocompromised who require vaccination for COVID-19. As information is updated this guidance will be updated accordingly.
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http://dx.doi.org/10.1186/s13223-021-00529-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957441PMC
March 2021

Community Use of Epinephrine for the Treatment of Anaphylaxis: A Review and Meta-Analysis.

J Allergy Clin Immunol Pract 2021 Feb 4. Epub 2021 Feb 4.

Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Center, Montreal, QC, Canada.

Background: Community use of epinephrine for the treatment of anaphylaxis is low. Knowledge of rates of epinephrine use in the pre-hospital setting along with identification of barriers to its use will contribute to the development of policies and guidelines.

Objectives: A search was conducted on PubMed and Embase in April 2020. Our systematic review focused on 4 domains: (1) epinephrine use in the pre-hospital setting; (2) barriers to epinephrine use in the pre-hospital setting; (3) cost evaluation and cost-effectiveness of epinephrine use; and (4) programs and strategies to improve epinephrine use during anaphylaxis.

Methods: Two meta-analyses with logit transformation were conducted to: (1) calculate the pooled estimate of the rate of epinephrine use in the pre-hospital setting among cases of anaphylaxis and (2) calculate the pooled estimate of the rate of biphasic reactions among all cases of anaphylaxis.

Results: Epinephrine use in the pre-hospital setting was significantly higher for children compared with adults (20.98% [95% confidence interval (CI): 16.38%, 26.46%] vs 7.17% [95% CI: 2.71%, 17.63%], respectively, P = .0027). The pooled estimate of biphasic reactions among all anaphylaxis cases was 3.92% (95% CI: 2.88%, 5.32%). Our main findings indicate that pre-hospital use of epinephrine in anaphylaxis remains suboptimal. Major barriers to the use of epinephrine were identified as low prescription rates of epinephrine autoinjectors and lack of stock epinephrine in schools, which was determined to be cost-effective. Finally, in reviewing programs and strategies, numerous studies have engineered effective methods to promote adequate and timely use of epinephrine.

Conclusion: The main findings of our study demonstrated that across the globe, prompt epinephrine use in cases of anaphylaxis remains suboptimal. For practical recommendations, we would suggest considering stock epinephrine in schools and food courts to increase the use of epinephrine in the community. We recommend use of pamphlets in public areas (ie, malls, food courts, etc.) to assist in recognizing anaphylaxis and after that with prompt epinephrine administration, to avoid the rare risk of fatality in anaphylaxis cases.
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http://dx.doi.org/10.1016/j.jaip.2021.01.038DOI Listing
February 2021

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

Allergy 2020 Dec 9. Epub 2020 Dec 9.

Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.

Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies.

Methods: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE.

Results: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC.

Conclusions: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.
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http://dx.doi.org/10.1111/all.14695DOI Listing
December 2020

Management and diagnosis of exercise-associated anaphylaxis cases in the paediatric population.

Clin Exp Allergy 2021 Jan 28;51(1):148-150. Epub 2020 Oct 28.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

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http://dx.doi.org/10.1111/cea.13763DOI Listing
January 2021

Risk of peanut- and tree-nut-induced anaphylaxis during Halloween, Easter and other cultural holidays in Canadian children.

CMAJ 2020 Sep;192(38):E1084-E1092

Division of Allergy and Clinical Immunology (Leung, Gabrielli, Ben-Shoshan), Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montréal, Que.; Division of Rheumatology (Clarke, Shand), Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alta.; Department of Emergency Medicine (Morris), Hôpital Sacré-Coeur; Division of Pediatric Emergency Medicine (Gravel), Department of Pediatrics, Centre hospitalier universitaire Sainte-Justine, Montréal, Que.; Division of Pediatric Emergency Medicine (Lim), Department of Pediatrics, Children's Hospital at London Health Sciences Centre, London, Ont.; Divisions of Allergy and Immunology (Chan) and Emergency Medicine (Goldman, Enarson), Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC; Department of Pediatrics (O'Keefe), Faculty of Medicine, Memorial University, St. John's, NL; Food Allergy Canada (Gerdts), Toronto, Ont.; Division of Clinical Immunology & Allergy (Chu), Department of Medicine, and Department of Health Research Methods, Evidence, and Impact (Chu), McMaster University, Hamilton, Ont.; Division of Immunology and Allergy (Upton), Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ont.; Centre for Outcomes Research and Evaluation (Zhang), Research Institute of McGill University Health Centre, Montréal, Que.

Background: It is not established whether the risk of anaphylaxis induced by peanuts or tree nuts in children increases at specific times of the year. We aimed to evaluate the risk of peanut-and tree-nut-induced anaphylaxis during certain cultural holidays in Canadian children.

Methods: We collected data on confirmed pediatric cases of anaphylaxis presenting to emergency departments in 4 Canadian provinces as part of the Cross-Canada Anaphylaxis Registry. We assessed the mean number of cases per day and incidence rate ratio (IRR) of anaphylaxis induced by unknown nuts, peanuts and tree nuts presenting during each of 6 holidays (Halloween, Christmas, Easter, Diwali, Chinese New Year and Eid al-Adha) versus the rest of the year. We estimated IRRs and 95% confidence intervals (CIs) using Poisson regression.

Results: Data were collected for 1390 pediatric cases of anaphylaxis between 2011 and 2020. Their median age was 5.4 years, and 864 (62.2%) of the children were boys. During Halloween and Easter, there were higher rates of anaphylaxis to unknown nuts (IRR 1.66, 95% CI 1.13-2.43 and IRR 1.71, 95% CI 1.21-2.42, respectively) and peanuts (IRR 1.86, 95% CI 1.12-3.11 and IRR 1.57, 95% CI 0.94-2.63, respectively) compared to the rest of the year. No increased risk of peanut- or tree-nut-induced anaphylaxis was observed during Christmas, Diwali, Chinese New Year or Eid al-Adha. Anaphylaxis induced by unknown nuts, peanuts and tree nuts was more likely in children aged 6 years or older than in younger children.

Interpretation: We found an increased risk of anaphylaxis induced by unknown nuts and peanuts during Halloween and Easter among Canadian children. Educational tools are needed to increase awareness and vigilance in order to decrease the risk of anaphylaxis induced by peanuts and tree nuts in children during these holidays.
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http://dx.doi.org/10.1503/cmaj.200034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532006PMC
September 2020

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

Allergy 2021 03 16;76(3):831-841. Epub 2020 Aug 16.

Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Background: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms.

Methods: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed.

Results: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9.

Conclusion: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.
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http://dx.doi.org/10.1111/all.14529DOI Listing
March 2021

The use of It's Never Too Late technology (iN2L) in enhancing well-being among the elderly in a residential setting.

J Women Aging 2020 Jul-Aug;32(4):481-487. Epub 2020 Jun 28.

Department of Pharmacy Administration and Public Health, St. John's University , Queens, New York, USA.

This study explored the benefits of using It's Never Too Late [iN2L] with the residents at Mercy Center.

Over 10-weeks, 30 study participants were consented and attended three workshops engaging with iN2L. Paired t-tests were used to detect significant differences.

An increase in residents' sense of well-being on the Warwick-Edinburgh Mental Wellbeing Scale (WEMWS) and additional questions indicating levels of distress and contentment. Significant improvements were noted for the WEMWS Scale and a decreased level of distress. iN2L is a promising technology that may be used with residents in long-term care facilities, regardless of cognitive impairment.
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http://dx.doi.org/10.1080/08952841.2020.1781508DOI Listing
June 2020

Production of allergen-specific immunotherapeutic agents for the treatment of food allergy.

Crit Rev Biotechnol 2020 Sep 9;40(6):881-894. Epub 2020 Jun 9.

National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

Allergen-specific immunotherapy (IT) is emerging as a viable avenue for the treatment of food allergies. Clinical trials currently investigate raw or slightly processed foods as therapeutic agents, as trials using food-grade agents can be performed without the strict regulations to which conventional drugs are subjected. However, this limits the ability of standardization and may affect clinical trial outcomes and reproducibility. Herein, we provide an overview of methods used in the production of immunotherapeutic agents for the treatment of food allergies, including processed foods, allergen extracts, recombinant allergens, and synthetic peptides, as well as the physical and chemical processes for the reduction of protein allergenicity. Commercial interests currently favor producing standardized drug-grade allergen extracts for therapeutic use, and clinical trials are ongoing. In the near future, recombinant production could replace purification strategies since it allows the manufacturing of pure, native allergens or sequence-modified allergens with reduced allergenicity. A recurring issue within this field is the inadequate reporting of production procedures, quality control, product physicochemical characteristics, allergenicity, and immunological properties. This information is of vital importance in assessing therapeutic standardization and clinical safety profile, which are central parameters for the development of future therapeutic agents.
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http://dx.doi.org/10.1080/07388551.2020.1772194DOI Listing
September 2020

Anaphylaxis as a presenting symptom of food allergy in children with no known food allergy.

J Allergy Clin Immunol Pract 2020 09 26;8(8):2811-2813.e2. Epub 2020 Apr 26.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, McGill University Health Centre, Montreal, QC, Canada.

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http://dx.doi.org/10.1016/j.jaip.2020.04.033DOI Listing
September 2020

Primary immunodeficiencies and their associated risk of malignancies in children: an overview.

Eur J Pediatr 2020 May 11;179(5):689-697. Epub 2020 Mar 11.

Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G1X8, Canada.

Primary immunodeficiency disorders represent a heterogeneous spectrum of diseases, predisposing to recurrent infections, allergy, and autoimmunity. While an association between primary immunodeficiency disorders and increased risk of cancer has been suggested since the 1970s, renewed attention has been given to this topic in the last decade, largely in light of the availability of large registries as well as advances in next generation sequencing. In this narrative review, we will give an insight of the primary immunodeficiencies that are commonly responsible for the greater number of cancers in the primary immunodeficiency disorders population. We will describe clinical presentations, underlying genetic lesions (if known), molecular mechanisms for carcinogenesis, as well as some management considerations. We will also comment on the future directions and challenges related to this topic.Conclusion: The awareness of the association between several primary immunodeficiencies and cancer is crucial to provide the best care for these patients.What is Known: • Patients with primary immunodeficiency have an increased risk of malignancy. The type of malignancy is highly dependent on the specific primary immunodeficiency disorder.What is New: • Survival in patients with primary immunodeficiency disorders has been improving, and conversely also their lifetime risk of malignancy. • International collaboration and multinational registries are needed to improve our knowledge and therapeutic strategies.
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http://dx.doi.org/10.1007/s00431-020-03619-2DOI Listing
May 2020

Oral food challenges: Special considerations.

Ann Allergy Asthma Immunol 2020 05 21;124(5):451-458. Epub 2020 Feb 21.

Department of Pediatrics, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Texas.

Objective: To reinforce special considerations when offering and conducting oral food challenges (OFCs).

Data Sources: Published studies and reviews.

Study Selections: Studies concerning OFCs and their conduct.

Results: Multiple OFC protocols for various clinical situations and foods were reviewed.

Conclusion: OFCs are used for the definitive diagnosis of food allergy. Risk and benefit assessment guide the OFC procedure. The conduct of OFCs is influenced by multiple factors, including age, food, and goal of the challenge.
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http://dx.doi.org/10.1016/j.anai.2020.02.008DOI Listing
May 2020

Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified by Whole-Exome Sequencing in 1000 Children at a Single Center.

Gastroenterology 2020 06 19;158(8):2208-2220. Epub 2020 Feb 19.

SickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada; Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Institute of Medical Science and Biochemistry, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address:

Background & Aims: A proportion of infants and young children with inflammatory bowel diseases (IBDs) have subtypes associated with a single gene variant (monogenic IBD). We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with IBD.

Methods: We performed whole-exome sequencing analyses of blood samples from an unselected cohort of 1005 children with IBD, aged 0-18 years (median age at diagnosis, 11.96 years) at a single center in Canada and their family members (2305 samples total). Variants believed to cause IBD were validated using Sanger sequencing. Biopsies from patients were analyzed by immunofluorescence and histochemical analyses.

Results: We identified 40 rare variants associated with 21 monogenic genes among 31 of the 1005 children with IBD (including 5 variants in XIAP, 3 in DOCK8, and 2 each in FOXP3, GUCY2C, and LRBA). These variants occurred in 7.8% of children younger than 6 years and 2.3% of children aged 6-18 years. Of the 17 patients with monogenic Crohn's disease, 35% had abdominal pain, 24% had nonbloody loose stool, 18% had vomiting, 18% had weight loss, and 5% had intermittent bloody loose stool. The 14 patients with monogenic ulcerative colitis or IBD-unclassified received their diagnosis at a younger age, and their most predominant feature was bloody loose stool (78%). Features associated with monogenic IBD, compared to cases of IBD not associated with a single variant, were age of onset younger than 2 years (odds ratio [OR], 6.30; P = .020), family history of autoimmune disease (OR, 5.12; P = .002), extra-intestinal manifestations (OR, 15.36; P < .0001), and surgery (OR, 3.42; P = .042). Seventeen patients had variants in genes that could be corrected with allogeneic hematopoietic stem cell transplantation.

Conclusions: In whole-exome sequencing analyses of more than 1000 children with IBD at a single center, we found that 3% had rare variants in genes previously associated with pediatric IBD. These were associated with different IBD phenotypes, and 1% of the patients had variants that could be potentially corrected with allogeneic hematopoietic stem cell transplantation. Monogenic IBD is rare, but should be considered in analysis of all patients with pediatric onset of IBD.
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http://dx.doi.org/10.1053/j.gastro.2020.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283012PMC
June 2020

Anaphylaxis to goat/sheep's milk in a 4-year-old boy tolerant to cow's milk.

BMJ Case Rep 2020 Jan 8;13(1). Epub 2020 Jan 8.

Department of Pediatrics, Division of Allergy, Immunology and Dermatology, Montreal Children's Hospital, Montreal, Québec, Canada.

Immune-mediated reactions to dairy products may vary depending on the mammalian source. We present a case of anaphylaxis to goat/sheep's milk with tolerance to cow's milk. A 4-year-old boy of Eastern European descent presented with gastrointestinal and respiratory symptoms within minutes after eating a goat/sheep's milk-derived food product. The tryptase level measured 1 hour post initial symptoms and 1 month after the allergic reaction were 14.6 µg/L and 5.1 µg/L, respectively (norm: 0.0-13.5 µg/L), confirming the diagnosis of anaphylaxis. A skin prick test performed 1 month after the reaction was highly positive for goat/sheep's milk, but negative for cow's milk. Skin prick tests may establish a life-threatening goat/sheep's milk allergy. Goat/sheep's milk allergy should always be considered in cow's milk-tolerant patients who present with an allergic reaction to dairy products, or when undergoing/have completed of oral immunotherapy for cow's milk allergy.
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http://dx.doi.org/10.1136/bcr-2019-232844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954805PMC
January 2020

When and how pediatric anaphylaxis cases reach the emergency department: Findings from the Cross-Canada Anaphylaxis Registry.

J Allergy Clin Immunol Pract 2020 04 31;8(4):1406-1409.e2. Epub 2019 Oct 31.

Division of Pediatric Allergy and Clinical Immunology, Department of Pediatrics, McGill University Health Centre, Montreal, QC, Canada.

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http://dx.doi.org/10.1016/j.jaip.2019.10.009DOI Listing
April 2020

Recent developments and highlights in food allergy.

Allergy 2019 12 30;74(12):2355-2367. Epub 2019 Oct 30.

Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features. Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development. Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit. More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that.
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http://dx.doi.org/10.1111/all.14082DOI Listing
December 2019

ICER report for peanut OIT comes up short.

Ann Allergy Asthma Immunol 2019 11 9;123(5):430-432. Epub 2019 Sep 9.

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Division of Pulmonary and Critical Care Medicine, Stanford University, Stanford, CA, USA; Division of Allergy, Immunology and Rheumatology, Stanford University, Stanford, California. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2019.09.001DOI Listing
November 2019

Live vaccines after pediatric solid organ transplant: Proceedings of a consensus meeting, 2018.

Pediatr Transplant 2019 11 9;23(7):e13571. Epub 2019 Sep 9.

Division of Infectious Diseases, Department of Paediatrics, Transplant and Regenerative Medicine Centre, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.

Growing evidence suggests receipt of live-attenuated viral vaccines after solid organ transplant (SOT) has occurred and is safe and needed due to lapses in herd immunity. A 2-day consortium of experts in infectious diseases, transplantation, vaccinology, and immunology was held with the objective to review evidence and create expert recommendations for clinicians when considering live viral vaccines post-SOT. For consideration of VV and MMR post-transplant, evidence exists only for kidney and liver transplant recipients. For MMR vaccine post-SOT, consider vaccination during outbreak or travel to endemic risk areas. Patients who have received antiproliferative agents (eg. mycophenolate mofetil), T cell-depleting agents, or rituximab; or have persistently elevated EBV viral loads, or are in a state of functional tolerance, should be vaccinated with caution and have a more in-depth evaluation to define benefit of vaccination and net state of immune suppression prior to considering vaccination. MMR and/or VV (not combined MMRV) is considered to be safe in patients who are clinically well, are greater than 1 year after liver or kidney transplant and 2 months after acute rejection episode, can be closely monitored, and meet specific criteria of "low-level" immune suppression as defined in the document.
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http://dx.doi.org/10.1111/petr.13571DOI Listing
November 2019

A perspective on the pediatric death from oral food challenge reported from the Allergy Vigilance Network.

Allergy 2019 06;74(6):1035-1036

Sean N. Parker Center for Allergy and Asthma Research, Stanford University, Stanford, California.

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http://dx.doi.org/10.1111/all.13791DOI Listing
June 2019

Primary immunodeficiency.

Allergy Asthma Clin Immunol 2018 12;14(Suppl 2):61. Epub 2018 Sep 12.

4University of Manitoba, Winnipeg, MB Canada.

Primary immunodeficiency disorder (PID) refers to a large heterogeneous group of disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T cell, B-cell or combined immunodeficiencies) or of innate immunity (e.g., phagocyte and complement disorders). Although the clinical manifestations of PIDs are highly variable, many disorders involve an increased susceptibility to infection. Early consultation with a clinical immunologist is essential, as timely diagnosis and treatment are imperative for preventing significant disease-associated morbidity. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig) levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The disorders affecting the activity of the T-cell arm of the adaptive system, such as severe combined immunodeficiency, require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article provides an overview of the major categories of PIDs and strategies for the appropriate diagnosis and management of these rare disorders.
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http://dx.doi.org/10.1186/s13223-018-0290-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157160PMC
September 2018

Use of CT for Head Trauma: 2007-2015.

Pediatrics 2018 10 4;142(4). Epub 2018 Sep 4.

Division of Emergency Medicine, Department of Pediatrics, Harvard Medical School, Harvard University and Boston Children's Hospital, Boston, Massachusetts.

Background And Objectives: International efforts have been focused on identifying children at low risk of clinically important traumatic brain injury in whom computed tomography (CT) neuroimaging can be avoided. We sought to determine if CT use for pediatric head trauma has decreased among US emergency departments (EDs).

Methods: This was a cross-sectional analysis of the National Hospital Ambulatory Care Medical Survey database of nationally representative ED visits from 2007 to 2015. We included children <18 years of age evaluated in the ED for head injury. Survey weighting procedures were used to estimate the annual proportion of children who underwent CT neuroimaging and to perform multivariable logistic regression.

Results: There were an estimated 14.3 million pediatric head trauma visits during the 9-year study period. Overall, 32% (95% confidence interval [CI]: 29%-35%) of children underwent CT neuroimaging with no significant annual linear trend ( trend = .50). Multivariate analysis similarly revealed no difference by year (adjusted odds ratio [aOR]: 1.02; 95% CI: 0.97-1.07) after adjustment for patient- and ED-level covariates. CT use was associated with age ≥2 years (aOR: 1.51; 95% CI: 1.13-2.01), white race (aOR: 1.43; 95% CI: 1.10-1.86), highest triage acuity (aOR: 8.24 [95% CI: 4.00-16.95]; < .001), and presentation to a nonteaching (aOR: 1.47; 95% CI: 1.05-2.06) or nonpediatric (aOR: 1.53; 95% CI: 1.05-2.23) hospital.

Conclusions: CT neuroimaging did not decrease from 2007 to 2015. Findings suggest an important need for quality improvement initiatives to decrease CT use among children with head injuries.
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http://dx.doi.org/10.1542/peds.2018-0814DOI Listing
October 2018

Early introduction without screening is a good deal, if caregivers will buy it.

Allergy 2019 02;74(2):213-215

Pediatric Allergy and Clinical Immunology, CHU Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.

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http://dx.doi.org/10.1111/all.13584DOI Listing
February 2019

A Toddler With Treatment-Resistant Iron Deficiency Anemia.

Pediatrics 2018 07;142(1)

General Pediatrics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Canada; and

A 19-month-old girl with a history of asthma and atopic dermatitis presented to her pediatrician because of parental concerns of pallor and fatigue. On dietary history, it was discovered that she was a picky eater and consumed 26 oz of homogenous milk daily. Her physical examination was unremarkable aside from pallor, and both her height and weight plotted between the 50th and 75th percentile for age. Therefore, she was investigated for iron deficiency anemia and indeed her blood work was consistent. Despite appropriate iron supplementation and dietary milk restriction, there was no improvement in her hemoglobin or iron studies. Our expert panel examines the case and offers a differential diagnosis for a child presenting with treatment-resistant iron deficiency anemia.
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http://dx.doi.org/10.1542/peds.2017-2971DOI Listing
July 2018

The Impact of Baked Egg and Baked Milk Diets on IgE- and Non-IgE-Mediated Allergy.

Clin Rev Allergy Immunol 2018 Oct;55(2):118-138

Jaffe Food Allergy Institute, Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Baked milk (BM) and baked egg (BE) diets are increasingly used in the management of milk and egg allergy, rather than avoidance. Children with tolerance versus reactivity to BM and BE may have smaller skin prick test and lower specific IgE, and BM-tolerant children have less basophil reactivity and more peripheral T regulatory cells. However, most milk- and egg-allergic children tolerate BM and BE and an individual's reactivity is unpredictable. Non-reactivity is due to conformational changes in the allergens. Significant differences in the published advice about methods of introduction exist from graded introduction at home to a medically supervised full dose. These approaches carry different risks and may have different immunological effects. Reactivity to BM is a predictor of a severe milk allergy. Therefore, medical supervision for BM and BE introduction is prudent. The baked diet allows dietary liberation. Most, but not all, BM- and BE-tolerant children continue eating the baked foods. The prognosis of children who can eat BM and BE is favorable with likely resolution of their allergy over the next few years. Murine models of BE diets demonstrate that heated egg can impart clinical protection against anaphylaxis and cause immune changes. Most observational human studies of BM and BE diets demonstrate clinical resolution of allergy and favorable immune changes versus regular care controls. However, the one randomized controlled trial for the BE diet in BE-tolerant children did not support an immune-modifying effect of the BE diet. Another study of BE immunotherapy is expected to be completed in 2018. There is currently no evidence for prevention of allergy with the baked diets. There may be a future role for BM and BE in liberating the diets of individuals with non-IgE-mediated allergy given recent studies that a subset of these patients can consume BM without a clinical reaction.
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http://dx.doi.org/10.1007/s12016-018-8669-0DOI Listing
October 2018

Autosomal Recessive Agammaglobulinemia Due to a Homozygous Mutation in PIK3R1.

J Clin Immunol 2018 01 25;38(1):88-95. Epub 2017 Nov 25.

Maritime Medical Genetics, Department of Pediatrics, Izaak Walton Killam (IWK) Health Centre, 5850/5980 University Avenue, PO Box 9700, Halifax, NS, B3K 6R8, Canada.

The role of class IA phosphoinositide 3 kinases (PI3Ks) in immune function and regulation continues to expand with the identification of greater numbers of genetic variants. This case report is the second reported case of a homozygous premature stop codon within the PIK3R1 gene leading to autosomal recessive agammaglobulinemia. The proband, born to consanguineous parents, presented at 10 months of age with a history of oropharyngeal petechiae and bleeding from the mouth, gums, and tear ducts. Initial investigations revealed thrombocytopenia, neutropenia and the absence of B cells. Further genetic testing via a custom next-generation sequencing panel confirmed the presence of a homozygous mutation in PIK3R1, c.901 C>T, a premature stop codon at amino acid position 301. Given their many roles in immune regulation, recessive mutations in the PlK3R1 gene should be considered in infants presenting with hypogammaglobulinemia or agammaglobulinemia, particularly in the setting of parental consanguinity.
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http://dx.doi.org/10.1007/s10875-017-0462-yDOI Listing
January 2018

Long-term immune reconstitution after matched unrelated hematopoietic stem cell transplantation for immunodeficiency.

J Allergy Clin Immunol 2018 03 8;141(3):1154-1157.e3. Epub 2017 Nov 8.

Division of Immunology & Allergy, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada; Canadian Centre for Primary Immunodeficiency, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.10.015DOI Listing
March 2018

Quality of life for parents of children with food allergy in peanut-restricted versus peanut-free schools in the United States and Canada.

J Allergy Clin Immunol Pract 2018 Mar - Apr;6(2):671-673.e7. Epub 2017 Oct 18.

Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Texas Children's Hospital, Houston, Texas; Department of Pediatrics, Section of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Houston, Texas.

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http://dx.doi.org/10.1016/j.jaip.2017.08.013DOI Listing
November 2019