Antepartum versus postpartum amoxicillin oral challenge in pregnant patients with a reported penicillin allergy: A two-center prospective cohort study.

INTRODUCTION: While 10% of pregnant individuals report a penicillin allergy, there is no established best practice for penicillin allergy delabeling in pregnancy. To better understand options for penicillin delabeling, we aimed to evaluate two penicillin allergy delabeling protocols in pregnancy regarding efficacy, adverse events, and patient satisfaction. MATERIAL AND METHODS: From July 2019 to December 2022, we completed a two-center prospective cohort study, where each site recruited pregnant patients over 24 weeks gestational age with a reported penicillin allergy. One center offered antepartum amoxicillin oral challenges, either directly or after negative skin testing (i.e., antepartum oral challenge site). Our other centers completed a two-step approach with antepartum penicillin skin testing only and deferred oral challenges to the postpartum period (i.e., postpartum oral challenge site). Our primary outcome was the rate of penicillin allergy delabeling, defined as tolerating an antibiotic challenge with penicillin or amoxicillin. Univariate analyses were completed using chi-squared, Fisher's exact, and Wilcoxon rank tests. RESULTS: During the study period, 276 pregnant patients were assessed, with 207 in the antepartum oral challenge site and 69 in the postpartum oral challenge site. Among the 204 patients who completed antepartum oral challenges, 201 (98%) passed without reactions. Deferring oral challenges to the postpartum period led to a loss of follow-up for 37/53 (70%) of eligible individuals. Overall, 97% (201/207) of patients at the antepartum oral challenge site were delabeled from their penicillin allergy-compared to 38% (26/69) of patients referred to the postpartum oral challenge site (p < 0.0001). Three antepartum oral challenge reactions were noted, including two mild cutaneous reactions and a case of transient abdominal discomfort. CONCLUSIONS: Antepartum amoxicillin oral challenge is a more effective method to delabel pregnant patients from their penicillin allergy. Deferral of oral challenges to the postpartum period introduces a significant barrier for penicillin allergy delabeling.

Cow's milk alternatives for children with cow's milk allergy and beyond.

Cow's milk allergy (CMA) is one of the most common food allergies in the first years of life, with worldwide prevalence estimated to range from 2% to 5%. While the majority of children with CMA will eventually develop tolerance to cow's milk proteins (it is estimated that >75% of children with CMA develop tolerance to cow's milk proteins by the age of 3 years, and >90% develop tolerance by the age of 6 years), the selection of an appropriate cow's milk (CM) alternative for those with CMA is vital to ensure adequate growth and development during childhood. The increasing number of CM alternative products on the commercial market with markedly different nutritional content and micronutrient fortification adds a layer of complexity that can be challenging for both families and clinicians to navigate. This article aims to provide guidance and clarity to Canadian paediatricians and primary care clinicians on recommending the most appropriate, safe, and nutritionally optimal CM alternatives for individuals with CMA, and beyond.

How to Incorporate Oral Immunotherapy into Your Clinical Practice.

PURPOSE OF REVIEW: The purpose of this review is to discuss how to best incorporate oral immunotherapy into your clinical practice based on recent evidence and guidelines, and address controversies. RECENT FINDINGS: Oral immunotherapy is the food immunotherapy treatment with the most literature supporting its use. Recent data from both randomized clinical trials and real-world studies show OIT is especially safe and effective in preschoolers, while avoidance may be less safe than previously thought. OIT guidelines support its use outside of research. Oral immunotherapy can be safely and effectively incorporated into your clinical practice, with careful planning and consideration of scenarios where benefits outweigh risks. Baseline oral food challenges are necessary in clinical trials, but in clinical practice, these are best done when the history is unclear due to resource limitations. There is a role for both regular food and FDA-approved products. Future research should focus on optimizing safety and adherence in the real-world setting.

Idiopathic splenomegaly in childhood and the spectrum of RAS-associated lymphoproliferative disease: a case report.

BACKGROUND: KRAS (KRAS proto-oncogene, GTPase; OMIM: 190,070) encodes one of three small guanosine triphosphatase proteins belonging to the RAS family. This group of proteins is responsible for cell proliferation, differentiation and inhibition of apoptosis. Gain-of-function variants in KRAS are commonly found in human cancers. Non-malignant somatic KRAS variants underlie a subset of RAS-associated autoimmune leukoproliferative disorders (RALD). RALD is characterized by splenomegaly, persistent monocytosis, hypergammaglobulinemia and cytopenia, but can also include autoimmune features and lymphadenopathy. In this report, we describe a non-malignant somatic variant in KRAS with prominent clinical features of massive splenomegaly, thrombocytopenia and lymphopenia. CASE PRESENTATION: A now-11-year-old girl presented in early childhood with easy bruising and bleeding, but had an otherwise unremarkable medical history. After consulting for the first time at 5 years of age, she was discovered to have massive splenomegaly. Clinical follow-up revealed thrombocytopenia, lymphopenia and increased polyclonal immunoglobulins and C-reactive protein. The patient had an unremarkable bone marrow biopsy, flow cytometry showed no indication of expanded double negative T-cells, while malignancy and storage disorders were also excluded. When the patient was 8 years old, whole exome sequencing performed on DNA derived from whole blood revealed a heterozygous gain-of-function variant in KRAS (NM_004985.5:c.37G > T; (p.G13C)). The variant was absent from DNA derived from a buccal swab and was thus determined to be somatic. CONCLUSIONS: This case of idiopathic splenomegaly in childhood due to a somatic variant in KRAS expands our understanding of the clinical spectrum of RAS-associated autoimmune leukoproliferative disorder and emphasizes the value of securing a molecular diagnosis in children with unusual early-onset presentations with a suspected monogenic origin.

Penicillin allergy de-labeling: Adaptation of risk stratification tool for patients and families.

Penicillin allergy is reported in 10% of the population; however, over 90% of patients are deemed non-allergic upon allergist assessment. The goal of this quality improvement project is to validate a patient-driven assessment tool to safely identify patients at low risk of penicillin allergy and de-label them. Pediatric patients and pregnant women referred to the institution's allergy clinics for penicillin allergy assessment were invited to use the patient tool to complete a self-assessment, resulting in the assignment of a risk category. The risk stratification determined using the patient tool was compared against the allergist's assessment. The patient tool demonstrated agreement with the allergist assessment in 57/84 (67.9%, 95% CI [56.7%,77.4%]) assessments, intra-class correlation (ICC) = 0.618, p < 0.001. In 22/84 (26.2%) assessments, the patient tool determined a higher risk category, primarily due to differences in patients' perceived timing and description of symptoms. Only 5/84 (6.0%) patients were placed in a lower risk category by the patient tool compared to the allergist assessment. The patient tool demonstrates good validity in determining penicillin allergy risk, offering potential as a method of empowering patients to advocate in their care. Iterative changes to the patient tool will be applied to increase agreement.

Safety and Effectiveness of Bypassing Oral Immunotherapy Buildup With an Initial Phase of Sublingual Immunotherapy for Higher-Risk Food Allergy.

BACKGROUND: Because of its favorable safety, sublingual immunotherapy (SLIT) for food allergy has been proposed as an alternative treatment for those in whom oral immunotherapy (OIT) is of higher risk-older children, adolescents, adults, and those with a history of severe reactions. Although safe, SLIT has been shown to be less effective than OIT. OBJECTIVE: To describe the safety of multifood SLIT in pediatric patients aged 4 to 18 years and the effectiveness of bypassing OIT buildup with an initial phase of SLIT. METHODS: Patients aged 4 to 18 years were offered (multi)food SLIT. Patients built up to 2 mg protein SLIT maintenance over the course of 3 to 5 visits under nurse supervision. After 1 to 2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC) (cumulative dose, 300 mg protein) with the goal of bypassing OIT buildup. RESULTS: Between summer 2020 and winter 2023, 188 patients were enrolled in SLIT (median age, 11 years). Four patients (2.10%) received epinephrine during buildup and went to the emergency department, but none experienced grade 4 (severe) reaction. A subset of 20 patients had 50 low-dose OFCs to 300 mg protein and 35 (70%) OFCs were successful, thereby bypassing OIT buildup. CONCLUSIONS: In combination with very favorable safety of SLIT, with no life-threatening reactions and few reactions requiring epinephrine, we propose that an initial phase of SLIT to bypass supervised OIT buildup be considered for children in whom OIT is considered to be of higher risk.

Bypassing the build-up phase for oral immunotherapy in shrimp-allergic children.

Background: Oral immunotherapy is an effective treatment for food allergies; however, its use in clinical practice is limited by resources and lack of standardized protocols for foods other than peanut. Previous studies have suggested that shrimp has a higher threshold for reaction than other allergenic foods, suggesting it may be safe to directly administer maintenance doses of immunotherapy. Methods: Children aged 3-17 years who had 1) skin prick test ≥3 mm and/or specific IgE level ≥0.35 kU/L and convincing objective IgE-mediated reaction to shrimp, or 2) no ingestion history and specific IgE level ≥5 kU/L, underwent a low-dose oral food challenge to 300 mg shrimp protein, with the goal of continuing daily ingestion of the 300 mg maintenance dose as oral immunotherapy. Results: Between January 2020 and April 2023, 17 children completed the low-dose oral food challenge. Nine (53%) tolerated this amount with no reaction, and 8 (47%) had a mild reaction (isolated oral pruritis or redness on chin). Sixteen (94%) continued maintenance low-dose oral immunotherapy eating 300 mg shrimp protein daily. None of the patients developed anaphylaxis related to the immunotherapy. Conclusion: Our case series suggests that some shrimp allergic patients being considered for oral immunotherapy should be offered a low-dose oral food challenge, to potentially bypass the build-up phase of immunotherapy.

Using the canadian egg ladder in children with food protein-induced enterocolitis syndrome: a case series.

BACKGROUND: Current management of food protein-induced enterocolitis syndrome (FPIES) involves strict avoidance of the offending food for 12-18 months, followed by oral food challenge (OFC) under physician supervision. OFCs are resource-intensive and there is a lack of a universal standardized protocol for FPIES. Prolonged avoidance may increase the risk of IgE-mediated allergy, particularly in atopic patients. Food ladders have shown success in promoting accelerated tolerance in patients with IgE-mediated allergy. Our case series evaluated the safety of use of the Canadian Egg Ladder in patients with mild-to-moderate FPIES to egg. METHODS: From May 2020 to November 2021, patients with mild-to-moderate FPIES to egg, defined as no history of lethargy or intravenous fluid administration, were started on the Canadian Egg Ladder. Instructions for advancing up the ladder were identical to using the Canadian Egg Ladder in patients with IgE-mediated allergy. Patients were followed every 3-6 months, at which time information was collected regarding progression up the ladder, symptoms while on treatment and interventions required. Treating allergists completed a survey to capture baseline demographic characteristics and prior tolerance to egg. Descriptive statistics were analyzed using MS Excel. RESULTS: Twenty-one patients with mild-to-moderate FPIES were started on the Canadian Egg Ladder. Median age at initiation of the ladder was 10 months (IQR, 9-11). Nineteen (90.5%) patients completed the ladder, tolerating a serving size amount of cooked egg, over a median duration of 7 month (IQR, 4-9 months). Four patients (19.0%) had mild symptoms including vomiting (9.5%), pallor (9.5%), belching (4.8%), irritability (4.8%) and small spit up (4.8%). In three of the four patients, symptoms were the result of accidental exposure to a higher step of the ladder. There were no reports of lethargy. No patients required health care presentation or intravenous fluid administration. No patients discontinued the ladder. CONCLUSIONS: The Canadian Egg Ladder can safely guide the dietary advancement of egg-containing foods in patients with mild-to-moderate FPIES to egg, without the need for prolonged avoidance and resource-intensive OFCs.

Virtually supported penicillin allergy de-labelling during COVID-19.

BACKGROUND: Penicillin allergy is a commonly listed medication allergy despite rare overall incidence. Many patients erroneously have this label, which has personal, health, and societal costs. Penicillin allergy delabelling requires an oral challenge, which can be a rate limiting step in the de-labeling process; this is even more relevant with the reduction of in-person visits during the COVID-19 pandemic. OBJECTIVE: To identify the utility and broader applicability of using a virtually supported platform, initially adopted given COVID-19 restrictions, to expedite penicillin oral provocation challenge and penicillin de-labeling in patients at low to moderate risk of immediate hypersensitivity reaction and based on shared decision making. METHODS: Patients in Vancouver catchment area were referred for penicillin allergy and virtually assessed by the consulting allergist between July 2020 and April 2021. Those deemed appropriate for oral challenge based on the allergist consultant were offered the option of a virtual oral provocation challenge to oral amoxicillin in a subsequent virtual visit. Patients who agreed and were consented underwent a virtually supervised oral amoxicillin challenge during the second virtual visit. Findings are summarized in this case series. RESULTS: Twenty-three patients, both adult and pediatric, ranging from no to significant co-morbidities were consented and underwent the virtual challenge. One hundred percent of patients were successful with no reaction after an hour post virtual oral provocation challenge with amoxicillin. CONCLUSION: Virtual medicine is likely to remain in the allergist's practice. Virtually supported penicillin allergy delabelling, based on shared decision making and risk stratification, presents another pathway for penicillin allergy delabelling.

Real-World Safety Analysis of Preschool Tree Nut Oral Immunotherapy.

BACKGROUND: Our group previously described preschool peanut oral immunotherapy (OIT) in a real-world, multicenter setting, suggesting that this therapy is safe for most preschoolers. OBJECTIVE: To examine the safety and tolerability of tree nut (TN) OIT in preschoolers in the real world. METHODS: As part of a Canada-wide quality improvement project, TN-OIT (cashew/pistachio, walnut/pecan, hazelnut, almond, and macadamia nut) was performed in preschoolers who had (1) a skin prick test wheal diameter greater than or equal to 3 mm or a specific IgE level greater than or equal to 0.35 kU/L and a convincing objective IgE-mediated reaction or (2) no ingestion history and a specific IgE level greater than or equal to 5 kU/L. Dose escalations were performed every 2 to 4 weeks till a maintenance dose of 300 mg of TN protein was reached. Symptoms were recorded and classified using the modified World Allergy Organization Subcutaneous Immunotherapy Reaction Grading System (1, mildest; 5, fatal). RESULTS: Of the 92 patients who started TN-OIT from 2018 to 2021, 79 (85.9%) underwent single-food TN-OIT and 13 (14.1%) underwent multifood TN-OIT to 2 (10.8%) or 3 (3.3%) TNs. Eighty-nine (96.7%) patients reached maintenance, and 4 (4.3%) dropped out. Sixty-five (70.7%) patients experienced reactions during buildup: 35 (38.0%) grade 1 reactions, 30 (32.6%) grade 2 reactions, no grade 3 or 4 reactions, and 2 (2.17%) received epinephrine. CONCLUSIONS: Preschool TN-OIT in a real-world, multicenter setting appears safe and tolerable, with results comparable with our previously reported peanut OIT findings.

How We Manage Gastrointestinal Symptoms During Oral Immunotherapy Through a Shared Decision-Making Process-A Practical Guide for the Community Practitioner.

Allergists addressing gastrointestinal (GI) symptoms during oral immunotherapy (OIT) may be biased toward diagnoses related to OIT; however, non-OIT causes may occur. Although there is currently a lack of robust data for evidence-based treatment recommendations, we provide 3 real-world illustrative cases along with a proposed management algorithm for GI symptoms encountered during OIT. This algorithm was developed because of a significant clinical need, given the number of new-to-OIT providers that include practicing allergists, trainees transitioning into practice, and allied health care providers who manage GI symptoms in OIT patients. We developed the algorithm based on the opinions of community and academic allergy clinics across Canada with significant clinical experience offering infant, preschool, and school-aged OIT patients, with gastroenterologist input. Further research is needed to fill the knowledge gaps in the management of GI symptoms during OIT before formal recommendations can be suggested.

Risk factors associated with safety of preschool peanut oral immunotherapy.

Background: An understanding of how patient characteristics such as age, baseline peanut-specific IgE, and atopic comorbidities may influence potential safety outcomes during peanut oral immunotherapy (P-OIT) could aid in shared decision making between clinicians and patient families. Objective: This study explored the relationship between baseline patient characteristics and reactions during P-OIT using a large sample size to better understand potential risk factors influencing P-OIT safety. Methods: Data were obtained from the Food Allergy Immunotherapy (FAIT) registry, which collects real-world OIT data from community and academic allergy clinics across Canada. Multivariable logistic regression modeling was performed to examine the relationship between baseline patient characteristics and reactions during P-OIT. Multiple imputation was applied to reduce potential bias caused by missingness and to maximize the use of available information to preserve statistical power. Results: Between April 2017 and June 2021, a total of 653 eligible patients initiated P-OIT. Multivariable regression analysis showed pre-OIT grade 2+ initial reaction (odds ratio [OR] = 1.33, 95% confidence interval [CI] 1.10, 1.61), allergic rhinitis (OR = 1.60, 95% CI 1.08, 2.38), older age (OR = 1.01, 95% CI 1.00, 1.02), and higher baseline peanut-specific IgE (OR = 1.02, 95% CI 1.02, 1.03) were associated with grade 2+ reaction during P-OIT after adjusting for potential risk factors. Conclusion: Our study identified several clinically important risk factors for grade 2+ reactions during P-OIT: pre-OIT grade 2+ initial reaction, allergic rhinitis, older age, and higher baseline peanut-specific IgE. These results highlight the need for individualized risk stratification for OIT.

Penicillin de-labelling in vancouver, British Columbia, Canada: comparison of approaches, outcomes and future directions.

BACKGROUND: Inaccurate penicillin allergy labels lead to inappropriate antibiotic prescriptions and harmful patient consequences. System-wide efforts are needed to remove incorrect penicillin allergy labels, but more health services research is required on how to best deliver these services. METHODS: Data was extracted from five hospitals in Vancouver, British Columbia, Canada from October 2018-May 2022. The primary outcomes of this study were to outline de-labelling protocol designs, identify the roles of various healthcare professionals in de-labelling protocols and identify rates of de-labelling penicillin allergies and associated adverse events at various institutions. Our secondary outcome was to describe de-labelling rates for special populations, including pediatric, obstetric and immunocompromised subpopulations. To achieve these outcomes, participating institutions provided their de-labelling protocol designs and data on program participants. Protocols were then compared to find common themes and differences. Furthermore, adverse events were reviewed and percentages of patients de-labelled at each institution and in total were calculated. RESULTS: Protocols demonstrated a high level of variability, including different methods of participant identification, risk-stratification and roles of providers. All protocols used oral and direct oral challenges, heavily involved pharmacists and had physician oversight. Despite the differences, of the 711 patients enrolled in all programs, 697 (98.0%) were de-labelled. There were 9 adverse events (1.3%) with oral challenges with mainly minor symptoms. CONCLUSIONS: Our data demonstrates that de-labelling programs effectively and safely remove penicillin allergy labels, including pediatric, obstetric and immunocompromised patients. Consistent with current literature, most patients with a penicillin allergy label are not allergic. De-labelling programs could benefit from increasing clinician engagement by increasing accessibility of resources to providers, including guidance for de-labelling of special populations.