Comparing the risk of anaphylaxis requiring epinephrine in oral immunotherapy and subcutaneous immunotherapy: A review of recent Canadian real-world literature.

Background: The safety of pediatric food oral immunotherapy (Ped-OIT) has been depicted by some as less favorable than subcutaneous immunotherapy (SCIT) owing to the increased number of serious adverse events requiring epinephrine. A review of real-world data comparing Ped-OIT and SCIT safety is necessary to guide shared decision making. Objectives: Our aim was to compare the safety and adverse event profiles of peanut Ped-OIT and SCIT using Canadian real-word literature. Methods: We performed a retrospective review of recent Canadian real-world literature on peanut Ped-OIT and SCIT safety and adverse events. Results: The incidences of systemic reactions requiring epinephrine were 11 in 270 patients (4.07%) and 12 in 41,020 doses (0.029%) in a multicenter study in British Columbia, Alberta, Manitoba, and Nova Scotia studying 270 preschool-age children treated with peanut OIT. Similarly, a multicenter study in South-Western Ontario examining 160 patients between the ages of 1 and 17 years who were treated with peanut OIT showed that the incidences of systemic reactions requiring epinephrine were 5 in 160 patients (3.1%) and 8 in 52,751 doses (0.015%). A single-center retrospective review of 380 patients receiving aeroallergen SCIT showed that the incidences of systemic reactions requiring epinephrine were 28 in 380 patients (7.4%) and 1 in 1047 injection visits (0.095%). These findings are comparable to those of a review of 860 patients in Ontario who received either aeroallergen or venom SCIT, in which the incidence of systemic reaction requiring epinephrine was 10 in 4242 injections (0.24%). Conclusion: Despite differences in the OIT protocols used and age groups studied, recent real-world data suggest that the safety of preschool peanut OIT or peanut OIT using a slower buildup schedule is comparable to that of SCIT.

Utility of eConsults for COVID-19 vaccine-related concerns in Ontario: a cross-sectional analysis.

BACKGROUND: The Champlain BASE™ and Ontario eConsult services are virtual platforms that serve to facilitate contact between primary care providers and specialists across Ontario, relaying patient-specific questions to relevant specialists via a secure web-based platform. Despite ample evidence regarding the general effectiveness of these platforms, their utility as it pertains to clinical concerns regarding COVID-19 vaccines has not yet been explored. METHODS: We performed a cross-sectional descriptive analysis of COVID-19 vaccine related eConsults on Ontario patients completed by five allergy specialists between February and October of 2021. 4318 COVID-19 vaccine-related eConsults were completed in total during this time; with 1857 completed by the five allergists participating in this analysis. Question types/content were categorized using a taxonomy developed through consensus on a weighted monthly sample of 499 total cases. Data regarding whether external resources were required to answer each eConsult, impact on primary care provider referral decisions, and allergy consultant response times were collected. A 2-question survey was completed by primary care providers following eConsultation and results were collected. RESULTS: 41.08% of eConsults received involved safety concerns regarding COVID-19 vaccine administration in the setting of prior allergic disease and another 36.1% involved a potential reaction the first dose of a COVID-19 vaccine. 72.1% of eConsults were answered by specialist without needing external resources, and only 9.8% of all eConsults received resulted in a recommendation for formal in-person referral to Clinical Immunology & Allergy specialist or another subspecialty. Average time to complete eConsult was 16.4 min, and 79.7% of PCP eConsult queries which would have traditionally resulted in formal consultation were resolved based on advice provided in the eConsult without need for in-person assessment. CONCLUSIONS: Our study demonstrates the utility of the eConsult service as it pertains to COVID-19 vaccine-related concerns. The eConsult platform proved an effective tool in diverting the need for in-person assessment by an Allergist or other medical specialty. This is significant given the large volume of eConsults completed by Allergists, and demonstrates the impact of an effective electronic delivery of care model during a time of strained resources and public health efforts directed at mass vaccination.

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.

Geographical discrepancy in oral food challenge utilization based on Canadian billing data.

BACKGROUND: Oral food challenges (OFC) confer the highest sensitivity and specificity in diagnosis; however, uptake has been variable across clinical settings. Numerous barriers were identified in literature from inadequate training to resource access. OFC utilization patterns using billing data have not been previously studied. OBJECTIVE: The objective of this study is to explore the geographic differences in utilization of OFCs across Ontario and Québec using anonymized billing data from 2013 to 2017. METHODS: Anonymized OFC billing data were obtained between 2013 and 2017 from Ontario Health Insurance Plan (OHIP) and Régie de l'Assurance Maladie du Québec (RAMQ). The number of OFCs was extracted by location, billings, and physician demographics for clinic and hospital-based challenges. RESULTS: Over the period studied, the number of OFCs increased by 92% and 85% in Ontario clinics and Québec hospitals, respectively. For Ontario hospitals, the number of OFCs increased by 194%. While Québec performed exclusively hospital-based OFCs, after controlling for the population, the number of OFCs per 100,000 residents annually were similar to Ontario at 50 and 49 OFCs, respectively. The number of OFCs varied across the regions studied with an annual rate reaching up to 156 OFCs per 100,000 residents in urban regions and as low as 0.1 in regions furthest from city centers. CONCLUSION: OFC utilization has steadily increased over the last decade. There has been marked geographical discrepancies in OFC utilization which could be driven by the location of allergists and heterogeneity in their practices. More research is needed to identify barriers and propose solutions to them.

Impact of cannabis knowledge and attitudes on real-world practice.

BACKGROUND: Increased cannabis consumption worldwide challenges allergists because of an upsurge in cannabis allergy and need to discuss cannabis with patients. OBJECTIVE: To determine the knowledge, attitudes, and practices regarding cannabis among allergists and their approach to recognizing and diagnosing suspected cannabis allergy. METHODS: The International Allergist Canna Knowledge, Attitudes, and Practices Survey was completed by members from 3 International Allergy Societies. Survey questions included the following: 13 on cannabis attitudes, 7 on cannabis knowledge, and 4 on real-world allergy practices. Knowledge level was dichotomized and Statistical Package for the Social Sciences TwoStep Cluster Analysis grouped participants by attitudes. Multivariate analysis determined the relationship of knowledge and attitude to practice delivery. RESULTS: Of 570 eligible surveys started, 445 (78.1%) were completed. Participants were 49.7% of female sex, 65.9% aged 24 to 56 years, approximately 70% in practice for more than or equal to 10 years, and 29.2% practicing in an area where cannabis use is illegal. Of the respondents, 43.1% reported consulting on patients with suspected cannabis allergy and 54.7% had undertaken skin prick testing, in vitro cannabis testing, or both. Statistically significant differences were found between the 3 societies for most variables analyzed. Analysis of attitudes revealed 3 clusters named Traditional, Progressive, and Unsure. Those with more progressive attitudes toward cannabis and who had more knowledge were more comfortable speaking to patients about cannabis and more often asked patients on how often and how they used cannabis (all P < .001). CONCLUSION: Varying knowledge and attitudes toward cannabis affecting comfort communicating with patients about cannabis were found in members of 3 allergy societies supporting the need for more cannabis research and education.

Asthma Control, Airway Mucus, and 129Xe MRI Ventilation After a Single Benralizumab Dose.

BACKGROUND: Patients with eosinophilic asthma often report poor symptomatic control and quality of life. Anti-IL-5 therapy, including anti-IL-5Rα (benralizumab), rapidly depletes eosinophils in the blood and airways and also reduces asthma exacerbations and improves quality of life scores. In patients with severe asthma, eosinophilic inflammation-driven airway mucus occlusions have been measured using thoracic x-ray CT imaging. Pulmonary 129Xe MRI ventilation defect percentage (VDP) also sensitively measures asthma airway dysfunction caused by airway hyperresponsiveness, remodeling, and luminal mucus occlusions. Using 129Xe MRI and CT imaging together, it is feasible to measure both airway luminal occlusions and airway ventilation in relationship to anti-IL-5 therapy to ascertain the direct impact of therapy-induced eosinophil depletion on airway function. RESEARCH QUESTION: Does 129Xe MRI detect airway functional responses to eosinophil depletion after a single benralizumab dose and do airway mucus occlusions mediate this response? STUDY DESIGN AND METHODS: MRI, eosinophil count, spirometry, oscillometry, Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ), and St. George's Respiratory Questionnaire were completed on day 0 and 28 days after a single 30-mg subcutaneous benralizumab dose. CT scan mucus plugs were scored on day 0, and MRI VDP was quantified on days 0 and 28. RESULTS: Twenty-nine participants (27 with baseline CT imaging) completed day 0 and day 28 visits. On day 28 after a single benralizumab dose, significantly improved blood eosinophil counts, VDP, ACQ 6 scores, AQLQ scores (all P < .001), and peripheral airway resistance (P = .04) were found in all participants. On day 28, significantly improved VDP and ACQ 6 scores also were found in the subgroup of nine participants with five or more mucus plugs, but not in the subgroup (n = 18) with fewer than five mucus plugs. Based on univariate relationships for change in ACQ 6 score, multivariate models were generated and showed that day 0 VDP (P < .001) and day 0 CT scan mucus score (P < .001) were significant variables for change in ACQ 6 score on day 28 after benralizumab injection. INTERPRETATION: 129Xe ventilation significantly improved in participants with uncontrolled asthma and in those with significant mucus plugging after a single dose of benralizumab. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03733535; URL: www. CLINICALTRIALS: gov.

Telemedicine in allergy/immunology in the era of COVID-19: a Canadian perspective.

BACKGROUND: In the era of COVID-19, utilization of telemedicine has dramatically increased. In addition to reduced travel times, patient expenses, and work or school days missed, telemedicine allows clinicians to provide continued care while minimizing face-to-face interactions, maintaining social distancing, and limiting potential COVID-19 exposures. Clinical Immunology and Allergy (CIA), like many specialties, has adapted to incorporate telemedicine into practice. Previous studies have demonstrated similar patient satisfaction between virtual and in-person visits. However, evidence from fully publicly funded health care systems such as Canada has been limited. METHODS: We performed a quality improvement (QI) initiative to assess the feasibility of telemedicine. Between 1 March and 30 September 2020, patient encounters of two academic allergists at a single institution in London, Ontario, Canada were analyzed. Assessments were categorized into in-person or telemedicine appointments. A random sample of patients assessed virtually completed a voluntary patient satisfaction survey. Qualitative analysis was performed on survey comments. RESULTS: In total 3342 patients were seen. The majority were adults (n = 2162, or 64.7%) and female (n = 1872, or 56%). 1543 (46.2%) assessments were virtual and 1799 (53.8%) assessments were in-person. 67 of 100 random patient surveys sent to those in the virtual assessment group were completed. 89.6% (n = 60) agreed or strongly agreed when asked if they were satisfied with their telemedicine visit. 64.2% (n = 43) felt they received the same level of care compared to in-person assessments and 91% (n = 61) stated they would attend another virtual appointment. 95.4% (n = 62) of patients reported saving time with virtual assessment, the majority (n = 42, 62.7%) estimating between 1-4 h saved. Reported shortcomings included technical difficulties, "feeling rushed", and missing in-person interactions. CONCLUSIONS: Our quality improvement initiative demonstrated high patient satisfaction and time savings with virtual assessment in a publicly funded health care system. Studies suggest that CIA may be uniquely situated to benefit from permanent integration of virtual care into regular practice for both new and follow-up appointments. We anticipate continued increased utilization of telemedicine, signifying a lasting beneficial change in the delivery of healthcare.

Cannabis-related allergies: An international overview and consensus recommendations.

Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic. Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein. Other allergens may also be relevant, and recognition of allergens may vary between countries and continents. Cannabis also has the potential to provoke allergic cross-reactions to plant foods. Since cannabis is an illegal substance in many countries, research has been hampered, leading to challenges in diagnosis since no commercial extracts are available for testing. Even in countries such as Canada, where cannabis is legalized, diagnosis may rely solely on the purchase of cannabis for prick-to-prick skin tests. Management consists of avoidance, with legal issues hindering the development of other treatments such as immunotherapy. Education of healthcare professionals is similarly lacking. This review aimed to summarize the current status of cannabis allergy and proposes recommendations for the future management of this global issue.

Multicenter real-world experience with epinephrine 0.5 mg dosing for anaphylaxis with allergen immunotherapy.

Aim: To determine the safety and efficacy of 0.5 mg intramuscular (IM) epinephrine for the treatment of subcutaneous allergen immunotherapy induced anaphylaxis. Patients & methods: Retrospective chart review of patients who received 0.5 mg of IM epinephrine for treatment of anaphylaxis from subcutaneous allergen immunotherapy at two outpatient allergy and immunology practices. Results: Thirty-eight patients received 0.5 mg IM epinephrine. Eleven patients (29%) required a second dose, and two patients (5%) required a third dose of IM epinephrine. Sixteen patients (42%) were transferred to the emergency department with ongoing symptoms. All had eventual resolution of anaphylaxis. There were no adverse reactions or fatalities. Conclusion: IM epinephrine at a dose of 0.5 mg is safe and effective for treatment of anaphylaxis from subcutaneous allergen immunotherapy.

Lay abstract The aim of this study to understand whether a 0.5 mg dose of epinephrine injected into the muscle is safe and effective in treating anaphylaxis (a life-threatening allergic reaction) caused by subcutaneous allergen immunotherapy (allergy shots). We reviewed the charts of all patients who received 0.5 mg of epinephrine at two allergy clinics. Thirty-eight patients received 0.5 mg of epinephrine. Twenty-nine percent of patients required a second dose of epinephrine and 5% required a third dose. Forty-two percent of patients were sent to the emergency department due to ongoing symptoms. Anaphylaxis was successfully treated in all patients. There were no side effects or deaths. Epinephrine at 0.5 mg is safe and effective in treating anaphylaxis from subcutaneous allergen immunotherapy.

Fatal anaphylaxis due to peanut exposure from oral intercourse.

BACKGROUND: Intimacy-related allergic reactions, including anaphylaxis, are under-reported due to social stigma, lack of awareness, and misdiagnosis. The differential diagnosis for intimacy-related anaphylaxis is extensive and includes systemic human seminal plasma allergy, exercise-induced anaphylaxis, asthma exacerbation, latex allergy, and transference of food or drug allergens through saliva or seminal fluid. CASE PRESENTATION: Two adolescents met on a popular dating phone application. One individual had a long-standing history of asthma and peanut allergy. Although they never kissed, the male with peanut allergy received fellatio, while the other male had eaten peanut butter before they met. During fellatio, the peanut allergic male developed respiratory symptoms, used his bronchodilator, and collapsed. He remained unconscious despite aggressive interventions by emergency personnel called to the site. The clinical history and autopsy results suggested anaphylaxis to peanut allergen exposure from the intimate exposure as the cause of death. DISCUSSION AND CONCLUSIONS: To date, nearly all reported cases of intimacy-related anaphylaxis involve symptomatic women. This is the first report of intimacy-related anaphylaxis involving men who have sex with men and the first report of potential allergen transfer from oral mucosa to a patient receiving fellatio. Based on the paucity of published cases, death from intimacy-related anaphylaxis is exceedingly rare. Post-mortem analysis is inherently difficult, as an elevated tryptase level has myriad potential causes; nevertheless, the authors suggest that intimacy-related anaphylaxis due to peanut allergy is the most likely diagnosis. With increasing popularity of relationship applications, especially amongst stigmatized populations, this case highlights the importance of allergy awareness and patient education to decrease risk, particularly in the adolescent population, who are already at increased risk of severe anaphylaxis. Especially amongst those participating in intimate activities, disclosure of one's allergies warrants discussion, as the outcome can be fatal. Our case demonstrates the crucial need for increased advocacy in food allergy, education around intimacy-related anaphylaxis, and the importance of allergy awareness and prevention across all populations.

Systemic reactions to subcutaneous allergen immunotherapy: real-world cause and effect modelling.

BACKGROUND: Subcutaneous immunotherapy (SCIT) is an effective treatment for allergic rhinoconjunctivitis. However, adverse events, including life-threatening systemic reactions, may occur. The purpose of this project is to identify risk factors for systemic reactions to SCIT and to provide practice-based solutions using a quality improvement (QI) framework. METHODS: A QI initiative was performed in a hospital-based, Canadian Allergy clinic administering SCIT in a 12-month period. RESULTS: A total of 4242 injections of SCIT were performed over a period of 12 months. Of these, 10 injections resulted in a systemic reaction requiring epinephrine administration (i.e., an incidence of 1 in 424 injections, or 0.24%). Eight patients had at least one documented risk factor for a systemic reaction, and six had multiple risk factors. Major risk factors included seasonal exacerbation of allergic rhinitis, uncontrolled asthma, and an error in route of administration. All reactions occurred with the highest allergen extract concentration. CONCLUSION: This QI initiative highlights the need for improved patient and health care practitioner education and pre-administration screening. We suggest several considerations for SCIT administration: provide patients with written information on safety; screen patients before injections, including a review of treatment plan adherence and asthma control; adjust dosing to slow down buildup of the most concentrated immunotherapy extract, particularly in high risk patients; and apply additional safety measures in patients with multiple risk factors.

The complexities of insulin allergy: a case and approach.

BACKGROUND: Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). CASE PRESENTATION: A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. CONCLUSIONS: Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective.