Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2020

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A parent satisfaction questionnaire was sent to families post AD education via Survey Monkey ™ . Program information was sent to all pediatricians in Winnipeg and advertised on our website (www.caaec .ca). Results: Of the 187 children referred to the program, 63 (34%) received education, 114 (61%) did not respond to multiple invitations and 10 (5%) declined education. Of the families who received education, 30 children (48%) had severe, 15 (24%) had moderate AD and SCORAD was unavailable for 18 (28%). Families reported a high level of program satisfaction with a sense of improved knowledge, increased skills, awareness, and benefits for their child. Conclusions: AD education programs are rare but help to enhance children's AD management. Information, demonstration and support provided to families can improve overall satisfaction, compliance and treatment efficacy for AD. Offering the education program to more families will give the CAAEC further feedback and evaluation on its effectiveness. Background: Food desensitization via Oral Immunotherapy (OIT) is gaining higher acceptance in clinical practice. Due to adverse reactions during OIT, the duration of the escalation phase until maintenance dose is achieved may be longer, and in a minority of cases, OIT is stopped. However, it is unclear what clinical factors are associated with longer duration of escalation phase. It is crucial to sort out these factors in order to allocate adequate resources for OIT. We aim to assess the clinical factors associated with longer milk OIT duration. Methods: Data was collected from patients undergoing milk OIT at the Montreal Children's Hospital, BC Children's Hospital, and Hospital for Sick Children. We aimed to assess the duration of OIT with respect to reaching a maintenance dose of 200 mL of milk. We compared uniand multivariable linear regressions to evaluate sociodemographic factors (age, sex), clinical characteristics (presence of co-morbidities such as asthma) and study entry variables (cumulative milk dose causing reaction, skin test wheal size, severity of entry challenge) associated with longer OIT duration. Results: Among 51 children who reached 200 mL of milk, the median age was 12 years [Interquartile Range (IQR 9, 15)] and 54.9% were males. 86.3% of children had controlled asthma. The median cumulative dose of milk causing a reaction upon entry challenge was 14.4 mL (IQR 4.4, 44.4) and 21.6% received more than 1 dose of epinephrine. The median duration of escalation phase to reach 200 mL was 31 weeks (IQR 21.5, 39.8). Multiple doses of epinephrine (2 or more) during entry challenge was associated with longer OIT duration by almost 15 weeks [14.74, 95% CI: (2.75, 26.74)]. Conclusions: The data suggests the severity of adverse reactions at entry challenge is associated with longer escalation phase duration. Performing a challenge prior to OIT can assist in predicting the duration of OIT.

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Skin prick test in milk allergic patients undergoing oral immunotherapy: randomized controlled crossover trial Esraa Bukhari 1  Background: Skin prick test (SPT) is the most commonly used confirmatory test for an IgE-mediated milk allergy. However, food SPTs are not standardized and it is not clear if commercial extracts are more appropriate than diluted/undiluted food in assessing food allergy resolution. We aimed to assess the accuracy of SPTs with extract, diluted (1:10), and undiluted milk to detect desensitization in children with milk allergy undergoing oral immunotherapy (OIT). Methods: Children with milk allergy undergoing OIT and controls were recruited from Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and The Hospital for Sick Children (SickKids). Participants in the active arm received a weekly increase in milk until 200 ml of pure milk was tolerated. SPT using milk extract (Omega), diluted 2% milk (1:10), and undiluted milk was done at the study entry and when 200 ml of pure milk was reached. Participants in the control arm had SPT at study entry and 12 months later before they entered the active arm. Results: Among 51 children who reached 200 ml, the median age was 12 years [Interquartile Range (IQR 9.25, 15.0)] and 52.9% were males. The mean decrease in wheal size at 200 ml from the baseline was 3.68 mm (95%CI 2.39-4.98), 5.01 mm (95% CI 3.57-6.44), and 4.97 mm (95% CI 3.12-6.82) for milk extract, diluted and undiluted milk respectively. Among 32 controls, the median age was 10 years (IQR7.0, 14.25) and 62.5% were males. There was no significant change in wheal diameter over a one-year period regardless of the skin test method. Conclusions: Response to extract behaved similarly to whole food (Diluted and undiluted) and thus can be used to follow sensitization in the context of a desensitization program. developed diffuse urticaria, facial angioedema, wheeze, and chest tightness. He was taken to the emergency department via ambulance and treated with epinephrine. On review, the store-bought "fruit smoothie" contained apple, pineapple, orange, banana, soy and whey protein. There were no cofactors. After the episode, he consumed all fruits and milk without reaction, but not soy. Prior to anaphylaxis, he was not actively avoiding soy protein and he consumed soy in infrequent quantities. Interestingly, he also has a chickpea allergy, but the index reaction was at age 6. He did not avoid other legumes for crossreactivity concerns. Skin prick testing was performed with appropriate controls. Whey protein was negative. Soy protein was strongly positive at 10 × 8 mm. Serum specific immunoglobulin E (IgE) was elevated to soybean at 12.92 kilounits/litre and whey was negative. Conclusions: It is highly unusual for a patient at this age to present with a new IgE-mediated soy allergy. This case is important as it highlights the potential for hidden allergens in "organic health foods". Our patient had a fruit smoothie without realizing it was a soy protein containing beverage and developed unexpected anaphylaxis. Although this patient was unaware of his new soy allergy, the case exemplifies why it is crucial to educate patients on the importance of reading labels. This case will contribute to food allergy literature, especially soy and legume allergy.

Statement of Consent:
Written informed consent for this case report was obtained from the patient.

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The impact of COVID-19 on food-allergy-specific anxiety: a cross-sectional survey of parents of children with food allergies Clara Westwell-Roper 1,2 , Sharon To 3 , Lianne Soller 3 , S. Evelyn Stewart 2,4,5 , Edmond S. Chan 3 Background: Parenting a child with food allergy (FA) is associated with reduced health-related quality of life (HRQOL), including FA-specific anxiety (FAA). We characterized effects of the COVID-19 pandemic on FAA among parents of children with FA in Canada. Methods: A survey link was distributed by Food Allergy Canada and the Metro Vancouver Anaphylaxis Group in May-June 2020. The survey included medical/demographic information, anxiety and HRQOL measures, a 31-item FAA questionnaire undergoing validation (querying current/pre-COVID-19 symptoms), and COVID-19 impact rating scales. Groups were compared by two-tailed t test, one-way ANOVA, or Chi squared test. Reflexive thematic analysis was applied to openended responses. Results: 293 consenting participants completed the FAA questionnaire. 92% were mothers, reporting a greater share of management responsibility than fathers (78.5% ± 17.6% vs. 57.6% ± 23.0%, p < 0.0001). 66.7% reported increased overall anxiety due to COVID-19. Only 28.1% reported increased FAA (p < 0.0001), which was unchanged (29.5%) or decreased (42.3%) among remaining respondents. Among those with increased overall anxiety attributed to COVID-19, FAA was decreased or unchanged in 35.4% and 24.0%, respectively. Global FAA correlated weakly with general anxiety measures (GAD-7 ρ = 0.273; STAI-S ρ = 0.371) and moderately with FA-specific HRQOL (FAQL-PB ρ = 0.688; all p < 0.0001). More respondents with past FA-related emergency visits reported COVID-19-related FAA than those without (33.0% vs. 16.0%, p = 0.0041). COVID-19 was associated with a decrease in all FAA dimensions (emotions, cognitions, physical symptoms, behaviours, and coping) and their functional impacts. Qualitative themes included both positive and negative impacts: decreased worry about out-of-home allergen exposures, lack of "safe" food availability, concern about health care system FA management capacity; and risks of infection associated with emergency care. Conclusions: Despite increased overall anxiety, most parents reported unchanged or decreased FAA associated with COVID-19-related restrictions. Further studies should evaluate methods for identifying families requiring mental health support for FA management, particularly as restrictive guidelines are relaxed and perceived allergen exposure risk increases. Background: Erythromycin is an antibiotic used as an alternative medication for patients with penicillin allergies. Recent studies determined that erythromycin mimics motilin, stimulating motilin receptors in the gut. Duodenal smooth muscles contract, ultimately accelerating food absorption. Case Presentation: We report a case of allergic reaction during peanut oral immunotherapy (OIT) associated with erythromycin use. A 17-year-old female undergoing peanut OIT was prescribed erythromycin 500-mg po QID for persistent sore throat. She has history of penicillin allergy. She was taking 75-mg of peanut protein each day for 7 days prior, without reaction. She took her first erythromycin dose the night before, feeling nauseous by morning. She took her second and third erythromycin doses by 11:00AM, then took 75-mg OIT dose at 4:15PM. 45 min post-OIT-dose, she felt intensified nausea and stomach pain. 1.5 h post-OIT-dose, she developed facial hives which gradually spread systemically, and severe nausea/stomach pain. She had not exercised, taken the protein on an empty stomach, or had a fever before taking dosage. She was taken to hospital and treated with Benadryl and prednisone. Erythromycin was stopped. She was challenged to 75-mg protein the next day. No reaction. Conclusions: Erythromycin use during OIT treatment increases reaction risk. This case may aid allergists conducting OIT programs to be wary of risks to patients using erythromycin and fellow reported motilin agonists; macrolide antibiotics-including clarithromycin, azithromycin, roxithromycin, and oleandomycin-during treatment. Of clinical importance is recognizing that erythromycin induces GI hypermotility and may cause reactions to OIT doses due to accelerated protein dose absorption.

Background:
The prevalence of food allergy has remained stable [1], but the rate of anaphylaxis has increased over the last decade [2]. Reactions may occur in different settings, including restaurants. There is lack of prospective data assessing the management of anaphylaxis in restaurants. Methods: We assessed cases of anaphylaxis occurring in restaurants through the Cross-Canada Anaphylaxis Registry, a cohort study established in 2011 that enrolls children and adult anaphylaxis cases of presenting to emergency departments in 5 Canadian provinces. Participants were recruited prospectively and retrospectively using ICD10 codes. Data were collected on baseline sociodemographic and clinical characteristics as well as location, clinical manifestations, and management of reactions using a standardized questionnaire. Cases were classified as mild, moderate, or severe according to the position paper of the European Academy of Allergology and Clinical Immunology on management of anaphylaxis in childhood [3]. Multivariate logistical regression was used to identify factors associated with epinephrine use in restaurants. Results: Among 187 cases of anaphylaxis occurring in restaurants, 73.3% involved children. Reactions were mainly triggered by food (94.7%) while the remainder were triggered by drug (0.5%) or unknown cause (4.8%). Of the reactions with known triggers, the most common triggers were peanut (18.2%), shellfish (9.6%), and tree nut (8%). Pre-hospital epinephrine use was documented in 39% of the cohort and in 48% of those with known food allergies. Epinephrine use in restaurants was more likely in cases with known food allergy (OR 1.12; 95% CI 1.12-1.50) and for moderate/severe reactions (OR 1.24; 95% CI 1.03-1.50). Conclusions: Epinephrine was not used in the majority of anaphylaxis occurring in restaurants, even among those with known food allergy. Educational programs promoting the use of epinephrine as well as policies encouraging restaurants to stock and train restaurant staff to use epinephrine auto-injectors are required. Results: 10 out of 29 patients assessed in our clinic met inclusion criteria. Average score was 20, indicating a high likelihood of reaction. Commonly reported clinical presentations were hypotension defined as systolic blood pressure of < 90 mmHg (N = 10), followed by bronchospasm (N = 4), and angioedema, and urticaria (N = 4). Other more severe presentations included cardiac arrest (N = 2). Acute tryptase was sent in 7 cases and was elevated in 6 cases. Identified triggers were cefazolin (N = 4), chlorhexidine (N = 4), patent blue dye (N = 1), and bacitracin (N = 1). For treatment, all patients received epinephrine.

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Conclusions: Hypotension appears to be the most common presentation associated with POA. Frequent triggers included cefazolin and chlorhexidine. Our findings are consistent with US data supporting antibiotics as the main cause of POA. Furthermore, similar to the UK, chlorhexidine POA is becoming more prevalent. In contrast to European data, no cases of neuromuscular blocking agent or latex anaphylaxis were observed. We highlight initial epidemiological data, which suggests differences in the specific causative agents of POA in British Columbia. Further studies are necessary to characterize Canadian POA epidemiology.

#19
Associations between age and the safety and efficacy of peanut oral immunotherapy Rongbo Zhu 1,2 , Jennifer L. Protudjer 3,4,5  Background: Peanut oral immunotherapy (POIT) is an effective treatment in peanut allergic children which improves quality of life. POIT is efficacious and safe in preschool-aged and older children, with some speculation that age-related differences in efficacy and safety may exist. However, these differences have not been studied via a standardized protocol. The aim of our study is to examine associations between age at start of POIT, and the efficacy and safety of POIT, using a standardized protocol. Methods: This is a single-center retrospective study of pediatric patients (< 18 years old), conducted between June 2016 and November 2019. Patients underwent monthly clinic visits over 14 months, and peanut dosing was escalated to 250 mg of peanut protein using formulary capsules containing peanut flour. Completion of POIT was defined by tolerance of at least 250 mg of peanut protein in capsules, peanut butter, or peanut M&Ms. Safety was defined as epinephrine use during POIT. Data were analyzed using n/N, %, mean ± standard deviation, and binary logistic regression analysis (OR, 95% CI). Results: Overall, 158 patients (61.4% male; mean age 8.40 ± 4.25 years) were included. Mean baseline skin prick test (SPT) for peanut was 8.49 ± 3.94 mm. Mean baseline peanut IgE was 50.79 ± 41.06 kU/L. In addition to peanut allergy, 41.2% (65/158) had at least one other food allergy and 82.3% (130/158) had comorbid allergic disease. In total, 70.9% (112/158) patients completed per protocol, and 5.1% (8/158) required epinephrine during POIT. Older age at baseline was inversely associated with the odds of completion (OR 0.70; 95% CI 0.54-0.92), whereas no association was found between age and epinephrine during OIT (OR 0.49; 95% CI − 0.97-1.95). Conclusions: Younger children are significantly more likely to successfully complete POIT using a standardized protocol, whereas the safety of POIT is not significantly associated with age. Background: Plant-based diets are becoming increasingly popular, resulting in an increased demand for plant-based protein substitutes, including chickpea, pea, lentil, and lupine. Recently, these legumes have been identified as the cause of allergic reactions and in some cases, anaphylaxis. However, there is limited knowledge about these emerging allergens, and the potential impact they may have on the consumer and on the food industry. The aim of this study is to summarize the available evidence on non-priority plant protein food allergy in the clinical context. Methods: Our scoping review will follow the PRISMA-ScR checklist and the Arksey and O'Malley framework, and will search MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The research question we intend to answer is "What is known from the existing literature about non-priority plant protein food allergy, including but not limited to, chickpea, pea, lentil, and lupine, but excluding peanut and soy, in the clinical context?" The study population includes all ages. Inclusion criteria will include peer-reviewed primary literature in English, French, Spanish, and Swedish languages, regardless of the country of study and date published. The gray literature will be searched, including the bibliographies of accepted full-articles, abstracts from relevant conferences, and associated government policies. We will exclude non-clinical and preclinical studies, as we want to determine how nonpriority plant protein food allergy affects patients. All screening and data charting will be performed by two independent reviewers, with disagreements solved by decision of a third reviewer. Results: Our comprehensive literature search retrieved 5644 unique records. We anticipate this scoping review will provide relevant information on novel non-priority plant protein sources as they are related to food allergy. Conclusions: In the future, this review will be used in combination with patient engagement to inform roundtable discussions with food manufacturers, health policy makers, and our national patient advocacy organization, Food Allergy Canada. Background: There is no research on how COVID-19 has affected rate of epinephrine autoinjector (EAI) use among food-allergic patients. We hypothesized that quarantine during COVID-19 would lead to lower rates of accidental exposure and subsequent use of EAI due to fewer opportunities for leaving the home and fewer instances of a non-primary caregiver preparing food. This study sought to determine whether COVID-19 affected the rate of EAI administration in foodallergic families. Methods: An online survey was sent to BC patients who had allergist confirmed food allergy, asking whether EAI was administered in the past year pre-COVID-19 or during COVID-19. The COVID-19 period included 4 months (33.3%) of the year (Mar/2020-Jun/2020) and the pre-COVID-19 period included 8 months (66.7%) of the year (Jul/2019-Feb/2020). A two-sample t-test was used to compare the proportion of patients administering EAI during COVID-19 with the proportion of the year that COVID-19 quarantine was in place. Results: Between May-Jun/2020, 66 of 309 (Response rate 21.4%) families completed the COVID-19 questionnaire. Of these, 8/66 (12.1%) administered EAI in the past year, with 1/8 (12.5%) during COVID-19. Had distribution been uniform and unchanged, we would expect instead 33.3% of episodes to occur during COVID-19. However, the t-test did not show a significant difference (p = 0.15) between these two proportions. Conclusions: This is the first study to examine accidental exposure requiring EAI during COVID-19. Although the proportion administering EAI during COVID-19 was less than expected, this was nonsignificant, possibly due to small sample size. Seasonal variation in anaphylaxis could also explain the rate of EAI during COVID-19. More studies with a larger sample size are needed to draw definitive conclusions about whether COVID-19 had an impact on the use of EAI by food-allergic families. Background: Fish allergy, both finned and shellfish has increased in recent years with prevalence rates of self-reported allergy ranging from 0.2% to 2.29% in the general population. The major allergy-eliciting protein in salmon is parvalbumin, a calcium-binding protein from the albumin family with a low molecular weight that is found in the white muscle. Allergy Asthma Clin Immunol 2021, 17(Suppl 1):33 Case Presentation: A 4-year-old presented to a local community clinic with a prior history of generalized urticaria and agitation after consumption of salmon. Skin prick testing (SPT) revealed negative responses to both extract and cooked salmon. He subsequently passed an oral food challenge (OFC) in which he consumed 7.5 g of salmon and was declared salmon tolerant. Four months later, he developed urticarial lesions and pruritus upon having a salmon dish at a restaurant. The reaction was successfully treated with diphenhydramine. Subsequent SPT to salmon revealed a negative response to salmon extract and a positive response to both raw (9 mm) and cooked (10 mm) wild Atlantic salmon. Patient went on to successfully pass a second OFC to farmed salmon and was recommended to avoid wild Atlantic salmon.
Conclusions: Based on current research, wild Atlantic salmon has a significantly larger muscle mass in comparison to farmed salmon. It is hypothesized that the patient developed an allergic reaction to wild Atlantic salmon because of increased exposure to parvalbumin in the higher concentrated protein form of salmon. However, further research is needed to elucidate the possibility of other allergenic proteins unique to the Atlantic salmon wild from farmed salmon. In addition, this report indicates the importance of testing with forms of the suspected allergen, beyond extract alone, to include both raw and cooked forms. Background: Plant food allergies are often related to inhalant allergens, such as grasses, trees and weeds. This relationship can be attributed to cross-reactive proteins. An example of this is birch tree and certain tree nuts, such as almond and hazelnut. Cross reactivity between cannabis and plant proteins has been reported. Based on available data, this link is due to non-specific lipid transfer proteins (LTP).

Case Presentation:
A 19 year old male with significant pollen allergies had a history of tree nut tolerance, with occasional mild oral pruritus to raw nuts. The patient inhaled cannabis and consumed a nut bar, which contained almond, sesame and rice. Soon after, he developed systemic urticaria and wheezing, requiring emergency treatment for anaphylaxis. In follow-up, skin prick testing (SPT) identified strongly positive responses to grasses and ragweed. SPT was positive to almond and hazelnut, despite previous clinical tolerance, and negative to sesame. The patient underwent an in office almond oral challenge and was able to tolerate initial dosing of 15 grams. Anaphylaxis occurred at a cumulative dose of 30 grams, characterized by systemic urticaria, dysphagia, nausea and rhinorrhea. He was treated with epinephrine, prednisone, saline and allergy medications. He was advised to carry epinephrine and to avoid almonds. Conclusions: The above patient experienced anaphylaxis to almond on two occasions; after cannabis inhalation and once consuming the final oral challenge dose. The initial anaphylaxis may have been facilitated by the preceding cannabis. Subsequent in office challenge at higher threshold dosing confirmed his almond allergy. It is hypothesized that cannabis inhalation may have reduced the threshold of anaphylaxis to almond, due to "allergic" LTP association. With the legalization of cannabis, the possibility of similar reactions occurring is increased. Further research on the effect of cannabis in relation to various food sensitization in the pollen food syndrome population is needed. Allergy Asthma Clin Immunol 2021, 17(Suppl 1):33 allergy diagnosis, sensitization measured by skin prick testing or specific IgE level, allergy resolution, and presence and severity of AD. We also recorded the child's gender, history of allergy to foods other than boney fish and family history of atopic conditions. We used multivariable logistic regression to examine the association between resolution of boney fish allergy and moderate-to-severe AD, after adjusting for potential confounders. Results: Of the 297 children with boney fish allergy (median age 4.3 years, range 4.7 months-18 years), 39.1% were female, 69.7% were sensitized to multiple types of boney fish, 67.3% had AD, 28.7% had moderate-to-severe AD, 50.8% had asthma and 64.3% were allergic to foods other than boney fish. Overall, 33 children had improvement of their AD until it was no more than mild. Among the 6 children who outgrew their fish allergy, 4 (2.5%) had absent-to-mild AD and 2 (1.9%) had moderate-to-severe AD. Children who outgrew their boney fish allergy were more likely to be sensitized to only one type of boney fish (p = 0.04). After adjusting for boney fish monosensitization, children with moderate-to-severe AD were no less likely to outgrow their boney fish allergy (OR 1.17, 95% CI 0.21-6.63). Conclusions: Children who outgrew their boney fish allergy were more likely to be monosensitized but no more likely to have moderate-to-severe AD. Background: COVID-19 has caused unprecedented fear of visiting public places, especially hospitals. As such, we assessed whether the rate of visits to a pediatric emergency department (ED) for anaphylaxis in 2020 had decreased compared to 2019. Methods: Children presenting to the Montreal Children's Hospital ED from February 2019 to May 2020 with anaphylaxis were recruited for the Cross-Canada Anaphylaxis REgistry (C-CARE). A standardized form documenting symptoms, triggers and management was collected. Total number of anaphylaxis visits were compared by an unpaired Wilcoxon test. Results: Between February and May 2019, there were 26,570 ED visits, 98 (0.37%) of which were anaphylaxis. Of these cases [median age 9.1, Interquartile Range (IQR) = 13.78, 3.25], 91 (92.86%) were food-induced and 16 (16.33%) were severe. 49 (50%) and 50 (51.02%) patients received out-of-hospital and in-hospital epinephrine, respectively. Between February and May 2020, there were 13,960 ED visits, 54 (0.39%) of which were anaphylaxis. Of these cases (median age 3.5, IQR = 8.83, 1.58), 49 (90.74%) were food-induced and 2 (3.70%) were severe. 34 (62.97%) and 20 (37.04%) patients received out-of-hospital and in-hospital epinephrine, respectively. Between these months in 2019 and 2020, there was no significant difference in proportion of overall and monthly anaphylaxis cases among all ED visits. Excluding February from the analysis did not change the significance. Furthermore, there was no significant difference in foodinduced anaphylaxis. However, there was a significant difference in severity, with 12.62% (95%CI: 2.30%, 22.94%) less in 2020.

Conclusions:
The decreased rate of severe reactions could show hesitancy to bring children with severe reactions to the ED. However, it is also possible that restricted social interactions and increased parental supervision, which increased supervised food introduction, reduced severe accidental reactions. The lower median age may indicate that only parents of younger children believe the risk of anaphylaxis outweighs that of COVID-19. Background: Atopic dermatitis affects 20% of children and 50% is diagnosed by age 1 year; 1% of children have egg allergy and 50% of egg allergy is outgrown. According to the dual allergen hypothesis, oral antigen exposure promotes tolerance while epicutaneous exposure promotes sensitization. Early, persistent, and severe atopic dermatitis has been associated with developing egg allergy. We hypothesize that infants with egg allergy are more likely to outgrow their allergy if they do not have atopic dermatitis. Methods: We reviewed charts of all infants with egg allergy referred to Pediatric Allergy Clinic in the first year of life and evaluated from 2013-2017. We collected data regarding egg allergy diagnosis, development of egg and baked egg tolerance, and the presence, severity and control of atopic dermatitis. We used multivariable logistic regression to evaluate the association between egg allergy resolution and presence of atopic dermatitis. Results: Of the 83 infants with egg allergy, median age of diagnosis was 8.4 months (range 3.1-42 months), 43.4% were female, 90.4% developed well-baked egg tolerance, 58.5% outgrew egg allergy, 80.7% had atopic dermatitis (11.0% severe, 24.4% moderate and 45.1% mild), 67.1% had food allergies other than egg, 25.6% had asthma and 63.9% had parental allergic conditions. After adjusting for sex, children without atopic dermatitis were more likely to outgrow their egg allergy (adjusted OR 4.15, 95% CI 1.05-16.1, p = 0.042). Absent or mild atopic dermatitis was not associated with developing well-baked egg tolerance (6.45, 0.63-65.8, p = 0.077). Among children who remained allergic to well-baked egg, none had severe atopic dermatitis. Conclusions: Children without atopic dermatitis were more likely to outgrow their egg allergy, although an association with atopic dermatitis severity could not be determined in this small study. Atopic dermatitis was not associated with development of tolerance to wellbaked egg.
Background: Early introduction of highly-allergenic foods has been associated with decreased risk of sensitization. We examined associations between maternal diet during pregnancy and child sensitization to egg, peanut, cow's milk, and dust mites at ages 1 and 3 years. Methods: CHILD participants were recruited from the general population before birth. Maternal diet, including number of days per week of egg consumption, was reported prenatally. Infant diet was reported at birth and every 3-6 months. At ages 1 and 3 years, sensitization to allergens, including egg, peanut, cow's milk, and dust mites, was measured by skin prick testing. Atopic dermatitis was diagnosed clinically starting at age 6 months. Multivariable logistic regression was used to examine associations between maternal prenatal consumption of egg and other food allergens, timing of infant dietary introduction of food allergens, and child sensitization to egg, peanut, cow's milk and dust mites. Results: Among 2912 CHILD participants at age 1 year, sensitization was: 7.4% egg, 5.0% peanut, 15.5% cow's milk, and 1.0% dust mites; at 3 years, sensitization was: 2.2% egg, 3.8% peanut, 1.1% cow's milk, and 1.8% dust mites. After adjusting for potential confounders, such as moderate-severe atopic dermatitis, 1-year-old infants of mothers who ate egg at least daily during pregnancy (3.8%) were over twice as likely to be sensitized to egg (OR 2.63; 95%CI: 1.46-4.72), peanut (OR 2.48, 95% CI: 1.24-4.99) and cow's milk (OR 2.34; 95%CI: 1.00-5.46), but not to dust mites. Results were similar for sensitization at age 3 years and persisted after stratification by age of introduction to the highly allergenic foods. Conclusions: Infants were more likely to be sensitized to egg, peanut, and cow's milk if their mothers ate egg daily during pregnancy. These associations persisted after accounting for age of highly-allergenic food introduction into the infants' diets. Background: Biphasic anaphylaxis is unpredictable and has wide range 1%-23% of incidences. Previous studies recognized delayed epinephrine administration as a risk factor for biphasic reactions. We have previously demonstrated an incidence rate of 19% for biphasic anaphylactic reactions in the Kingston. The purpose of this study is to determine the incidence of, and predictors for, biphasic anaphylaxis in a single centre via a prospective evaluation of patients with diagnosed anaphylaxis.
Methods: All patients with emergency department visits given a diagnosis of "allergic reaction", "anaphylaxis", "drug allergy", or "insect sting allergy" during 1.5 year period were evaluated. Patients were contacted within 72 h to establish symptoms and determine the presence of biphasic reactivity. A full medical record review of the incident ensued, and uniphasic and biphasic cases were compared using the unpaired t test for continuous data and Fisher's exact tests for ordinal data. Results: A total of 155 patients with anaphylaxis were identified; complete follow-up was obtained for 138 patients. Twenty-two patients (16%) experienced confirmed biphasic reactivity, seven patients (5%) experienced secondary non-biphasic (SnBi) reactivity. Nineteen patients had their second phase occur > 8 h after the initial reaction; 63.6% were biphasic, and 71.4% were SnBi. There were no consistent clinical features or management differences predictive of biphasic reactors. The SnBi reactions were limited cutaneous manifestations. Conclusions: Biphasic anaphylaxis incidence in this study was 16%. The second-phase onset can occur > 8 h after initial symptom resolution. Predicting biphasic anaphylaxis is still challenging as clinical presentations, and management were similar in this study. Background: Sesame seed is an emergent global food allergen with limited data on seed cross-reactivity [1]. Allergenic seed storage proteins such as 11S, 7S globulins, and 2S albumins found in tree nuts share homologous amino acid sequences in botanically-related plants and seeds [1], attributing to cross-reactivity. Sesame seed cross-reactivity is found in poppy seed [1]. Clinical cross-reactivity is also found between sesame and sunflower seeds shared by similar 2S albumin proteins [1]. Patients with single seed allergies often request information for risk to other seed allergies. Case Presentation: A 31-year-old female patient with a history of allergy to tree nuts, sesame seed, and asthma, consumed a poppy seed cracker and developed throat hoarseness and gastrointestinal (GI) allergic symptoms. Treatment with epinephrine and antihistamine therapy resulted in prompt resolution of symptoms. Skin prick test (SPT) identified positive responses to sesame seed, poppy seed, pumpkin seed, peanut, and tree nuts including almond, brazil nut, pecan, walnut, hazelnut, pistachio, and cashew. SPT was negative to sunflower seed and all indoor and outdoor inhalants.

Conclusions:
The positive SPT responses to sesame, poppy, and pumpkin seeds suggest rare cross-reactivity among seed allergens. It is interesting to note, the negative SPT result to sunflower seed does not support observed cross-reactivity between sunflower and sesame seeds which both contain 2S albumin. Limited research regarding seed cross-reactivity is available but it is important to note that in vitro cross-reactivity may or may not reflect clinical cross-reactivity [1]. Testing and in-office oral challenge to seeds are necessary to clarify the extent of seed allergies in these patients.
Background: Data on fruit-induced anaphylaxis is sparse. We aimed to assess the clinical characteristics and management of patients presenting to Emergency Departments (ED) across Canada and to determine factors associated with severe reactions and epinephrine use. Methods: Between April 2011 and May 2020, children and adults presenting with anaphylaxis to seven EDs in four Canadian provinces were recruited as part of the Cross-Canada Anaphylaxis Registry (C-CARE). 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: Over a 9-year period, 248 patients with fruit-induced anaphylaxis presented to the EDs, median age was 10.2 [Interquartile Range (IQR) 3.7, 23.5] and 48.4% were males. The most common fruit triggers were kiwi (15.7%), banana (9.7%), and mango (9.7%). Only 23 patients (9.3%) reported having eczema. Epinephrine use was low in both the pre-hospital setting and the ED (28.6% and 40.7%, respectively), and 157 (63.3%) patients did not receive treatment with epinephrine at all. Severe reactions to fruit were more likely to occur in spring and among those with known eczema [adjusted Odds Ratio (aOR) 1 were more likely to be treated with epinephrine in the pre-hospital setting, while adjusting for age, sex, fruit trigger, known asthma, known eczema, and prescription of an epinephrine auto-injector. Conclusions: Severe anaphylaxis to fruit could be due to cross-reactivity to pollens present in the spring. Epinephrine use in fruit-induced anaphylaxis is suboptimal therefore education programs prompting the use of epinephrine are needed. Background: Children with anaphylaxis are often not appropriately managed by caregivers. We aimed to develop and test the effectiveness of an education tool to help pediatric patients and their families better understand anaphylaxis and its management, and to improve current knowledge and treatment guidelines adherence. Methods: From June 2019 to March 2020, 103 pediatric patients with history of food-triggered anaphylaxis who presented to the allergy outpatient clinics at the Montreal Children's Hospital and The Children's Clinic located in Montreal, Quebec were recruited. The patients and parents, together, were asked to complete six questions related to the triggers, recognition and management of anaphylaxis at the time of presentation to the clinic. Participants were automatically shown a 5-min animated video addressing the main knowledge gaps related to the causes and management of anaphylaxis. At the end of the video, participants were redirected to the same 6 questions to respond again. The scores were recorded in percentage of correct answers (minimum 0.0; maximum 1.0). Results: The mean age of the patients was 5.4 ± 4.3 years (range: 0.6-17.9 years). The majority were males (54 patients; 52.4%). The mean baseline pre-video education questionnaire score was 0.77 ± 0.16 (range: 0.3-1.0), while the mean follow-up score was 0.82 ± 0.17 (range: 0.3-1.0). This score difference of 0.05 was statistically significant (p = 0.001). There were no significant associations between change in scores and age or sex of the participants. Conclusions: Our video teaching method was successful in educating patients and their families to better understand anaphylaxis and its management at the moment of the clinical encounter. The test will be repeated at a 1-year interval to determine their retention of knowledge. Other educational methods should be developed and investigated to improve the knowledge of participants with worse (or no change) follow-up scores in our study. Acknowledgement: This project received support from AllerGen, the Allergy, Genes and Environment Network, which is a national research network funded by Innovation, Science and Economic Development Canada through the Networks of Centres of Excellence (NCE) Program. Background: This study sought to examine the temporal sequence of manifestations of anaphylaxis within individuals and between individuals across multiple reactions. Methods: Patients evaluated for recurrent anaphylaxis in a tertiary care allergy clinic between 2012-2018 were included. At each visit, patients were asked to record the temporal sequence in which symptoms of anaphylaxis appeared. The Fleiss' Kappa method was used to assess reproducibility of the order of appearance of specific symptoms during anaphylaxis in individual patients and across individuals with similar triggers. Results: Mean patient age was 35.7 years (SD = 14.0; range 1-71) of whom 77% were female. A total of 3129 anaphylactic reactions were analyzed in 159 patients. The mean kappa within individuals was 0.93, 5th percentile was 0.49 and 95th percentile was 1.0. The mean kappa between individuals of the same allergic trigger was − 0.029 [range, 0.11-0.05]. Among the 19 patients who recorded reactions of varying severity levels, the mean within-patient kappa was 0.94, with 15/19 patients having values of 1.0. Conclusions: These data suggest that patients will continue to experience reproducibly stereotypic anaphylactic reactions over time. Furthermore, when reactions escalate in severity, the sequence of early symptoms remains unchanged. The sequence of symptoms of anaphylaxis is unique to a given individual, but not across individuals who share a common allergic trigger. By recognizing the stereotypic nature of anaphylactic reactions, especially the earliest symptoms, patients will be better able to identify incipient reactions and intervene appropriately with self-administration of epinephrine and by activating emergency medical services. Background: For many children, exposure to foods to which they are allergic commonly occur through accidental exposure or food contamination. We present a case of an infant with cow milk allergy exposed to partially digested cow milk in vomitus who experienced a significant allergic reaction. Case Presentation: A 1 year old male was diagnosed at age 6 months with allergies to cow milk, egg and possibly mustard. He attends a day care with five other infants in the same room. Another infant was fed cow milk from a bottle. Approximately 2 h and 15 min later that infant vomited close to the subject. He was exposed to the vomitus on his clothes, hands and face. He was cleaned immediately but urticaria were noted on areas where the vomitus had touched his skin. Within minutes he started to drool and he began to cough. He was given i.m. epinephrine (EpiPen ® ) and transported to the local emergency department. The cough and drooling rapidly improved. On arrival to the emergency department there were no other symptoms and his vital signs were normal. He was observed there for 4 h. The specific IgE level (ImmunoCAP ® ) to cow milk was subsequently measured and was greater than 100 kU/L. Conclusions: This was an unusual exposure to cow milk. Even after 2 h in an infant's stomach, the cow milk allergens had not completely digested and were still capable of triggering an allergic reaction. This reinforces the need for close supervision of infants and young children with food allergies and immediately cleaning food waste, including vomitus, from surfaces to prevent accidental exposure.

Statement of Consent:
Written informed consent for this case report was obtained from the patient. Background: Food allergies are mediated by allergen-specific (as) -IgE which binds to the surface of mast cells and basophils, and when bound by allergen, causes these cells to release inflammatory mediators that result in allergic symptoms. A recent randomized trial found that allergen exposure in the first 6 months of life reduced the likelihood of allergic sensitization compared to later exposure [1], suggesting that sensitization events in allergic patients may occur very early in life. However, the transition from early sensitization to clinical manifestation of allergic responses is a critical phenomenon that requires further elucidation. Therefore, our objective is to characterize the early sensitization phase and the mechanisms that lead to overt allergy. Methods: Our novel murine model illustrates that a single intragastric administration of an allergen that in itself is not associated with the generation of IgE, does establish lifelong immunological memory such that subsequent allergen exposures lead to the production of IgE and anaphylaxis. Results: Using a novel model of allergic priming to investigate the early, incipient presentation of food allergy, we found that the memory phenotype imprinted during priming is long-lived and potentially permanent. T cell proliferation in vitro and functional measures of T cell activity suggest the presence of activated memory Th2 cells. Additionally, allergen-specific B cells seem naive in secondary lymphoid tissues post-priming. Conclusions: Overall, we propose that the trajectory of allergic immunity starts with a pre-clinical, activated T cell phase which is insufficient to activate B cells. These T cells hold the memory of IgE responses. Upon secondary exposure, these T cells show a capacity to interact with naive B cells and facilitate differentiation and IgE class switching.

Background:
The pathogenesis of food allergy remains unclear, though several theories have been proposed. Determining predictors for food allergy may guide investigations of its pathogenesis and help to detect patients at risk before a serious life-threatening reaction occurs. This study aimed to identify predictors of food allergy from a patient's clinical history. Methods: A retrospective chart review of patients referred for assessment of food allergy at a Canadian hospital-based allergy clinic was conducted. Patients were considered to have food allergy based on unsuccessful oral food challenge or clinical judgment. Complete-case analysis was conducted. Patients missing data and those for whom a diagnosis of food allergy could not be confirmed or ruled out were excluded from further analysis. Logistic regression was used to determine factors that predict food allergy. Results: 41 (72%) of referred patients were ultimately diagnosed with food allergy. In our patient population, univariate analysis identified that the following factors were associated with a food allergy: family history of atopy (Odds Ratio (OR) = 2.85, 95% Confidence Interval (CI) = 1.51, 5.35), asthma (OR = 2.86, 95% CI = 1.21, 6.76), eczema (OR = 3.71, 95% CI = 1.61, 8.56), allergic rhinitis (OR = 3.25, 95% CI = 1.47, 7.18), having a pet at home (OR = 3.5, 95% CI = 1.59, 7.68) and male sex (OR = 2.67, 95% CI = 1.24, 5.74). Multivariate analysis identified age over 18 as a negative predictor (OR = 0.10, 95% CI = 0.012, 0.72). Conclusions: Personal and family history of atopy increase risk of food allergy, supporting the findings of previous studies. The factors identified in this study may be intercorrelated, requiring a larger sample size to separate their effects. Other factors not investigated may also play a greater role in predicting food allergy, highlighting the need for further research to identify and quantify predictors of allergic reactions. Background: Oral food challenges (OFCs) involve the ingestion of a suspected food allergen under medical supervision and are the diagnostic standard of food allergies. OFCs are recommended for patients below positive decision points, where there is a 95% probability of a reaction. However, global consensus on approach is lacking. This study investigated OFC use in an allergy clinic and sought to identify clinical factors that influence the decision to pursue OFC. Methods: A retrospective chart review of patients referred for investigation of food allergy at a hospital-based, Canadian allergy clinic was conducted. Patients with missing data and those ultimately diagnosed with eosinophilic esophagitis, protein intolerance, celiac disease, and food protein induced proctocolitis/enterocolitis were excluded from further analysis. Clinical factors associated with OFC decision-making were modelled using multivariate logistic regression. Results: Out of 71 cases presenting with a query of food allergy, 15 (21%) completed OFC, while 56 (79%) did not complete OFC. Of patients tested with OFC, 9 (60%) passed OFC and were determined not to have food allergy. No patients experienced an anaphylactic reaction above a grade 3 on the World Allergy Organization systemic allergic reaction grading system. Factors associated with the decision to pursue OFC were skin prick test wheal size (Odds Ratio (OR) = 0.78, 95% Confidence Interval (CI) = 0.65, 0.94), age at index reaction (OR = 0.89, 95% CI = 0.80, 0.99), and the report of oral symptoms in the index reaction (OR = 6.69, 95% CI = 1.28, 34.88). Conclusions: In this study, OFCs were used in approximately 1 in 5 investigations of food allergy. Age and oral symptoms at index reaction and skin prick test wheal size predict OFC use but may not adequately predict risk for anaphylaxis during OFC. Further research is needed to identify predictors of likelihood and severity of allergic reactions and provide consensus in the use of OFCs.

#38 Multivariate analysis of factors influencing oral food challenge decision-making
compare West and East coasts, and to assess factors associated with severe reactions (defined as including stridor, cyanosis, circulatory collapse, or hypoxia). Methods: Between 2011 and 2020, children presenting to five emergency departments (EDs) were recruited as part of the Cross-Canada Anaphylaxis REgistry (C-CARE). A standardized form documenting symptoms, triggers and management were collected. The leading culprits, symptoms and epinephrine use between West coast (one center in British Columbia) and East coast (three centers in Quebec, one center in Ontario) EDs were compared. Multivariate logistic analysis was used to evaluate factors associated with severe reactions. Results: A total of 1310 cases of anaphylaxis were included, among which 540 (41%) were induced by tree nuts. The median age was 5.20 years [Interquartile range (IQR): 2.50-9.50] and 65.4% were males. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew, hazelnut and pistachio (32.8%, 20.0% and 9.3%, respectively). Cashew-induced anaphylaxis was more common in the West coast [14.0% difference (95% CI, 1.6%-27.6%)], whereas pistachio-induced anaphylaxis was more common in the East coast [6.3% difference (95% CI, 0.5%-12.2%)]. Pre-hospital and ED epinephrine administration was documented in 35.2% and 52.5% of cases, respectively. Severe reactions were more likely among males [adjusted Odds Ratio (aOR) 1.05 (95% CI, 1.01-1.10)] and among older children [aOR 1.00 (95% CI, 1.00-1.01)], while adjusting for location and type of tree nut. Conclusions: Different tree nut-induced anaphylaxis patterns within Canada may be due to differences in lifestyle. Educational programs promoting prompt epinephrine use and vigilance regarding the risk of severe reactions are required, especially among males and older children. Background: Deficiency of adenosine deaminase type 2 (DADA2) resulting from recessive loss-of-function mutations in ADA2 was identified in 2014 and described as new auto-inflammatory syndrome presenting with recurrent fevers, early-onset stroke, systemic vasculitis and mild immunodeficiency. Our understanding of this pathology has since expanded. A genotype-phenotype spectrum in DADA2 was recently identified with three distinct presentations depending on the ADA2 mutation: vasculitis, pure red cell aplasia and bone marrow failure. We present a case of DADA2 presenting with bone marrow failure 25 years after diagnosis of common variable immune deficiency (CVID). Case Presentation: Our patient is a 33-year-old gentleman coming from a non-consanguineous French-Canadian family. After a diagnosis of immune thrombocytopenia at age 3 and several respiratory tract infections, he was evaluated in immunology at age 6. Work-up revealed panhypogammaglobulinemia and suboptimal vaccine responses. Complete blood count, lymphocyte subset enumeration as well as T cell proliferation to mitogens were normal. CVID was diagnosed and he was started on immunoglobulin replacement therapy without further significant infections. Abdominal ultrasounds revealed a gradual increase in splenomegaly, with thrombocytopenia noted at age 27. Abdominal imaging at age 31 revealed a 30 cm spleen, noncirrhotic portal hypertension with esophageal varices as well as axillary and inguinal lymphadenopathies. A homozygous pathogenic missense mutation in ADA2 c.1072G>A (p.Gly358Arg) was detected on genetic panel testing. Subsequent bone marrow biopsy revealed myelofibrosis. The patient was started on adalimumab with consideration for future bone marrow transplant.

#40
Conclusions: ADA2 is likely involved in bone marrow microenvironment but its physiologic functions are not fully understood. DADA2 can present clinical overlap with CVID, but whether CVID is a distinct phenotype in DADA2 remains to be clarified.

Statement of Consent:
Written informed consent for this case report was obtained from the patient. Allergy Asthma Clin Immunol 2021, 17(Suppl 1):33 Background: Common variable immunodeficiency (CVID) is characterized by reduced serum immunoglobulins, and deregulation of the immune system. CVID has been associated with an increased incidence of some forms of cancers and autoimmune conditions. Case Presentation: We describe a patient, diagnosed with CVID in her fourth decade of life, who subsequently developed autoimmune hepatitis after 2 years of immunoglobulin replacement therapy. Histological, and serological analyses were in keeping with the diagnosis of autoimmune hepatitis. She was initiated on azathioprine 75 mg orally once daily, with normalization in liver biochemistry and synthetic function.
Conclusions: This case suggests that although immunoglobulin replacement alleviates the general state of chronic immune activation, not all abnormalities in cellular immunity are normalized. There are few reported cases of autoimmune hepatitis associated with CVID in the current literature; there remains no specific therapy for liver involvement in CVID. We demonstrate clinical and biochemical control of autoimmune hepatitis with azathioprine in conjunction with continued immunoglobulin replacement therapy. Further research is needed to better understand what is driving immune activation, and to further characterize why patients still suffer from inflammatory complications even when on replacement therapy. Written informed consent for publication of clinical details was obtained from the patient. A copy of the consent is available for review by the Editor of this journal. Background: Healthcare for immunodeficiency has been fragmented, resulting in no uniform standard for diagnosis and management. A mainstay treatment, Immunoglobulin replacement therapy (IGRT) reduces infection, improve quality of life and survival. Cases of immunodeficiency, IG indications and utilization are increasing. Homebased, self-administered subcutaneous immunoglobulin (SCIG) has better patient satisfaction and decreased costs versus in-centre IVIG. However, evaluation of diagnosis, indication, adherence, dose and titration, therapeutic and adverse outcomes requires real-time population-based data, and has generally not been done. Methods: We began a pilot multicentre clinical program dedicated to immunodeficiencies and IGRT. A key component of the clinic-based program is case management with specialized nursing care to educate, coordinate, support and monitor IGRT. We created a consented case registry using the ONIT infrastructure to register clinical and demographic data prospectively from the point of care. Clinical data include diagnosis, comorbidities, therapeutic indication for IGRT, specific treatment regimen, health outcomes, infection rates, adverse events and health-related quality of life to name a few. Results: ONIT was approved by the Ontario MOHLTC in 2019 to promote and support SCIG, and evaluation. We have started at The Ottawa Hospital, St. Michael's Hospital, and Hamilton Health Sciences. Recruitment of program nurses (4.0 FTE) was completed in March 2020. As of March 2020, we identified 564 SCIG and 118 IVIG patients in our program (uncurated data, before ONIT case registry). Case Report Forms were created and agreed upon, the case registry was approved by Clinical Trials Ontario (#1978), and a web-based case registry was successfully created by the Ottawa Methods Centre. The first patient was consented and enrolled in June 2020.

Conclusions:
This pilot initiative is intended to generate high-quality data that can be used for healthcare evaluation, standardization and research for immunodeficient patients, which may improve IG stewardship and be used in other centres. Background: Identifying the genetic etiology in patients with primary immunodeficiency (PID) is becoming increasingly important, both for patient prognosis, management and for estimating the risk for relatives. The diagnostic yield in this patient cohort varies between 15-79% depending on multiple factors including methodological differences such as platform used, the number of genes included and the risk for a monogenetic cause of disease. We report our experience with 2162 patients suspected to have a genetic cause of their PID. We describe the supplementary methods used for genes that cannot be reliably analysed by next-generation sequencing (NGS). Methods: We performed a retrospective review of the NGS results of 2162 patients referred to our laboratory with a clinical suspicion of a PID and tested with one of our 10 immunology-related panels. Results: The cumulative diagnostic yield of all immunology-related panels was 14.4% (311/2162). The diagnostic yield in patients between 0-5 years of age was 19.9%. Phenotypic-specific panels, like the Severe Combined Immunodeficiency Panel and the Chronic Granulomatous Disease had a higher diagnostic yield (47.4% and 46%, respectively) than the comprehensive Primary Immunodeficiency Panel (12.8%). Of the 270 reported pathogenic and likely pathogenic diagnostic sequence variants, 217 (80%) were unique. Thirty diagnostic copy number variants (CNVs) were reported in 29 patients. In 3 index cases, our CNV detection algorithm identified a homozygous whole NCF1 gene deletion. Because the analysis of NCF1 is complicated by two highly homologous pseudogenes, additional bioinformatic analysis and a custom Sanger assay was performed to confirm these findings. Conclusions: This study provides further evidence about the diagnostic yield of panel genetic testing in patients with PID. Younger patients and phenotype-specific panels have a higher diagnostic yield. Additional methods are needed to identify variants in difficult to sequence regions. Allergy Asthma Clin Immunol 2021, 17(Suppl Background: Immune Globulin Subcutaneous (Human) 20% (Cuvitru; Ig20Gly) is a subcutaneous immunoglobulin (SCIG) formulation allowing for infusions at increased rates and reduced times compared with other conventional SCIG therapies. Real-world data on Ig20Gly use in Canada are limited. CANCUN (NCT03716700) is assessing real-world Ig20Gly infusion parameters in patients with primary and secondary immunodeficiencies (PID and SID, respectively) transitioning to Ig20Gly. Methods: Patients (> 2 y) with PID or SID receiving SCIG for ≥ 3 months before transitioning to Ig20Gly were eligible for this ongoing Canadian multicenter phase 4, noninterventional, prospective, single-arm study. A prespecified interim analysis assessed baseline characteristics and Ig20Gly utilization at Ig20Gly initiation and 3, 6, and 12 months later. Safety data will be evaluated at final analysis. Results: As of December 31, 2019, 121 patients were enrolled (64.5% female; 51.2% aged ≥ 65 y [mean; range: 61.9; 19-83 y]) at 6 centers. 57 (47.1%) patients had PID, 63 (52.1%) had SID (of whom 57.8% had chronic lymphocytic leukemia), and one had both. Most patients used 2 infusion sites (range: 1-6 sites; primarily lower and upper abdomen); mean site number (2.5) remained unchanged 3 months postinitiation. The mean maximal infusion rate was 28.8 mL/h/site at initiation but ≥ 48.3 mL/h/site at all postinitiation timepoints. The mean infusion duration was < 1 h at all timepoints (range: 5-135 min). The median dose was 8 g at all timepoints except 3 months (6.5 g). Most patients (> 70%) administered treatment once weekly. Interrupted or slowed infusions were rare (one at 6 months; two at 12 months). Conclusions: In patients with PID or SID transitioning to Ig20Gly, infusions were more rapid after initiation, requiring < 1 h on average. Most commonly, patients used 2 infusion sites and administered Ig20Gly once weekly. Shire US Inc. (a Takeda company) funded this study. Baxalta US Inc. (a Takeda company) funded writing support. Background: X-linked lymphoproliferative disease type 1 (XLP1) is a very rare condition that commonly manifests as: hypogammaglobulinemia, lymphoma and hemophagocytic lymphohistiocytosis (HLH). Patients commonly present prior to the age of 10 and survival is poor without hematopoietic stem cell transplantation (HSCT). Here we present a rare case of an adult patient presenting with hypogammaglobulinemia diagnosed with XLP1. Case Presentation: A 34-year-old man was referred for evaluation of hypogammaglobulinemia. He was found to have recurrent sinopulmonary infections and otitis media since infancy. He also had a history of Burkitt lymphoma diagnosed and treated at the age of 15 and has since been in remission. Baseline immunologic testing revealed evidence of hypogammaglobulinemia with a total IgG of 1.95 g/l, IgA of 0.179 g/l and IgM of 0.18 g/l. Absolute CD19 count was slightly low at 0.061 × 10 9 /L. A thorough family history revealed a pedigree suggestive of an X-linked disorder, prompting genetic testing. Molecular genetic testing found a likely pathogenic mutation in SH2D1A leading to a diagnosis of XLP1. In addition to his treatment with subcutaneous immunoglobulin replacement therapy he was also referred to a lymphoma specialist, due to concerns for lymphoma recurrence and HLH.
Conclusions: This case highlights the importance of a detailed family history in the assessment of adult patients with hypogammaglobulinemia. XLP1 is associated with unique risks and management considerations when compared with most other primary humoral immunodeficiencies diagnosed in adults, such as common variable immunodeficiency.

Statement of Consent:
Written informed consent for this case report was obtained from the patient. Background: Cancer is one of the most common causes of death in patients with primary immunodeficiencies (PIDs). The immune surveillance concept postulates that PIDs are an important contributor to cancer growth and outcomes, as the integrity of the immune system is critical in the surveillance of abnormal cellular transformations and cancer cell survival. Although several immunodeficiency syndromes have been known to be associated with malignancies in children and adults, currently, the molecular mechanisms that link immune functions to cancers are poorly understood. We identified distinct molecular characteristics in cancers with respect to PID-related genes that impact survival outcomes in affected patients. Methods: In this study, we integrated transcriptomic and somatic mutation data of 29 adult cancers and 5 pediatric cancers from publicly available databases such as The Cancer Genome Atlas (TCGA) and TARGET with respective healthy tissues as control from the Genotype-Tissue Expression (GTEx) project. PID-related genes were curated from the Fulgent Genetics "Comprehensive Primary Immunodeficiency NGS Panel." Unified datasets integrating GTEx healthy samples and TCGA data were provided by the Recount2 protocol and differential gene expression (DEG) analyses were carried out using the limma-voom pipeline in the TCGAbiolinks R package. Gene ontology (GO) enrichment analysis was performed using the pathfindR R package. Mutational and clinical data were acquired from cBioPortal and used to generate Kaplan-Meier survival curves. Results: Of 472 PID-related genes, 151 (32.0%) up-regulated and 88 (18.6%) down-regulated genes were identified across the 29 unified TCGA-GTEx datasets. GO analysis revealed enriched pathways related to complement and coagulation cascades (27/29), systemic lupus erythematosus (25/29), along with Fanconi anemia (22/29) for the DEGs. Top mutated PID-related genes were FAT4 (12.61%), KMT2D (12.30%), and PTEN (10.84%) across all cancer types, with a total of 72 affected PID-related genes. Conclusions: Our integrative approach aids in the elucidation of molecular mechanisms that bridge PIDs to tumour biology. Background: There is currently little Canadian data to assess how well traditional time-based residency training programs have prepared residents for careers in Clinical Immunology and Allergy (CIA). This study aims to identify the perceived preparedness of residents in various areas of practice upon the completion of a Canadian CIA residency training program. In addition, this study will provide a baseline for future research comparing Competence by Design (CBD) and traditional time-based residency programs, with respect to transition to practice competencies. Methods: In the summer of 2020, an electronic survey was sent to 2018 and 2019 graduates of Canadian CIA training programs by the Canadian Society of Allergy and Clinical Immunology (CSACI). Several reminder emails were sent and Program Directors were encouraged to share the survey with their former residents. Results: Former residents felt well prepared in most medical expert areas, particularly to treat allergic rhinitis, urticaria/angioedema, venom allergies, and drug allergies. Residents felt less prepared to treat autoimmune diseases, autoinflammatory disorders, inborn errors of immunity, and to conduct various aspects of practice set-up and management. For example, they felt less prepared to hire office staff, set up a research lab, provide virtual care, and set up an office. The majority of these intrinsic competencies were learned through mentorship and on the job after finishing training. Conclusions: Upon completion of training, Canadian CIA residents felt well prepared for many competencies, particularly in medical expert areas. Training programs may wish to focus on various intrinsic competencies, specifically the Leader role, in order to better prepare residents for transition to practice. Academic half-day was not identified as a primary learning centre, suggesting that new teaching strategies may be required. Background: Tiotropium is a long-acting bronchodilator authorized by Health Canada as an adjunct therapy to inhaled corticosteroids in severe asthmatic adults. International and Canadian guidelines recommended its use in severe asthmatic children ≥ 6 or ≥ 12 years, respectively. The objective of this study was to describe the context of use of and clinical experience with tiotropium in Canadian asthmatic children.

Other Allergy/Immunology
Methods: This mixed-method case series study collected parents' and physicians' independent perceptions of tiotropium' use. Asthmatic children aged 1 to 17 years were eligible if enrolled in the Pediatric Asthma Database and Biobank (PADB) of the Sainte-Justine University Health Centre and received a tiotropium prescription. Clinical data were collected from the PADB electronic records. The parents/children's and treating physicians' perceptions were collected independently by electronic surveys inquiring about reasons for initiation, perceived efficacy and perceived safety on 7-point Likert scales, and overall satisfaction. Results: Between May-August 2020, 34 children were included; 11 (32%) were female with a median (range) age of 10.6 (1.4, 17.8) years, with 79% surveys completed by families and 100% by physicians. All patients initiated tiotropium. Physicians' non-exclusive prescription objectives were to improve lung function (68%), reduce chronic symptoms (65%), exacerbation severity (32%), exacerbation frequency (29%), and/or to replace medications causing side effects (47%). Most parents (89%) and physicians (71%) were conformable with initiating tiotropium. Overall, 93% of parents and 71% of physicians reported improvement in the child's asthma. Side effects related to tiotropium occurred infrequently. Adding tiotropium generally didn't affect the parents' ability to give other prescribed medications. Most parents (93%) and all physicians would try tiotropium again. Conclusions: Pediatric off-label use of tiotropium, mostly prescribed to relieve chronic symptoms, lung impairment, or side effects, was perceived safe and effective in most children. The later two treatable traits, not previously considered as treatment indication, deserve confirmation in prospective pediatric studies. Background: Systemic mastocytosis (SM) and hereditary alpha-tryptasemia (HαT) can have overlapping presentations of mast cell activation and are difficult to distinguish on clinical grounds. SM diagnosis requires bone marrow or tissue biopsy whereas HαT can be diagnosed with buccal swab for genetic testing [1]. The Spanish Network on Mastocytosis (REMA) score has been validated as a way to predict mast cell clonality and SM using basal serum tryptase levels, clinical symptoms, and sex [2]. This study aims to determine whether REMA scores differ sufficiently between individuals with SM and HαT such as to confidently rule in or out the need for more invasive investigations like bone marrow or tissue biopsy. Methods: A retrospective chart review of 39 patients with SM and 24 patients with HαT was performed in order to calculate individual REMA scores. A two sample Wilcoxon test was conducted in order to assess the difference in median REMA scores between patients with SM and HαT. Subgroup analysis was done within the SM cohort to compare REMA scores based on KIT D816V mutation and SM subtype. Area under the curve was calculated in order to evaluate the discriminatory property of the REMA score. Results: Median REMA score within the SM cohort was 2 (0.50, 4.00) compared to − 1 (− 1.50, 0.00) within the HαT cohort (p < 0.001). REMA scores in patients with SM did not differ based on KIT mutation status. A REMA score cut-off of 0.5 was able to distinguish SM and HαT with a specificity of 83.3% (67%, 96%). Conclusions: This novel comparison of REMA scores in patients with SM and HαT highlights a potential role for calculated REMA score in informing decisions about the need for invasive testing in patients presenting with symptoms of mast cell activation. Larger, comparative studies should be performed before incorporating REMA scoring into routine care. Background: Cannabis use has increased in Canada over the last few years. While the adverse effects of cannabis use has been extensively documented, little has been reported about it's association with adverse allergic events. Studies have shown clinical presentation of cannabis use varies from mild to life threatening allergic reactions, depending on the route of exposure. Chronic inhalation of cannabis leads to severe manifestations of bronchitis, asthma and worsening pulmonary function. The case below aims to highlight cannabis hypersensitivity and its associated pulmonary sequelae. Case Presentation: A 26 year old female presented with congestion, throat pruritus, and coughing post inhalation of cannabis. Further questioning revealed emesis to edible cannabis with systemic urticaria. Handling of cannabis products also led to contact urticaria. Past medical history was positive for asthma with a drug history of multiple analgesic medications for treatment of chronic pain. Medical marijunana was used as a daily adjunct for pain relief. Skin prick testing was negative to common indoor and outdoor inhaled allergens and was strongly positive to the patient's sample of medical marijunana, and hemp seeds. Initial pulmonary function testing revealed FEV1 to be 3.15 L (91%) which decreased to 2.78 L (80%) post cannabis inhalation with reversibility post broncho-dilator. The patient was advised to avoid edible cannabis and when possible decrease marijunana inhalation.

Conclusions:
Previously there were few reported cases of allergic disease associated with cannabis use. Our case confirmed that edible cannabis induced anaphylaxis and allergic asthma can be exacerbated by inhalation of cannabis, generally used for management of chronic pain. Allergic cannabis reactions may increase as cannabis becomes more socially and legally acceptable. Currently, in Canada, there is no approved therapeutic option in suspected cannabis hypersensitivity; strict avoidance remains the recommended treatment. As cannabis becomes increasing medically indicated, awareness of allergic manifestations is needed for appropriate counselling.

Statement of Consent:
Written informed consent for this case report was obtained from the patient. environmental risk factors that could explain the earlier onset of disease in South Asians demand further investigation.

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Successful desensitization for rabies vaccine in a pregnant woman: a case report Shorooq Banjar 1,2 , Salma AlKhammash 3 , Maryse Peterlini 4 , Natacha Tardio  Background: Good's Syndrome is a rare adult-onset condition often affecting patients between 40 and 70 years of age and is characterized by immunodeficiency and thymoma. Patients with Good's Syndrome exhibit features of hypogammaglobulinemia, a reduction of peripheral B-cells and CD4+ lymphopenia. These patients are reported to have increased susceptibility to various infections as well as autoimmunity, however, the literature has not identified oral mucositis as a manifestation of Good's Syndrome. Case Presentation: A 63-year-old female was diagnosed with Good's Syndrome following a thymectomy in 2013 with a history of recurrent sinopulmonary infections, absent B-cells and significantly low immunoglobulin levels. Prior to the discovery of the thymoma, there was no history of recurrent or invasive viral, bacterial or fungal infections. She was then initiated on monthly intravenous immunoglobulin (IVIG) replacement therapy that resulted in an improvement in the burden of infections. She was well until May 2019, when she began experiencing painful oral mucositis. There was no history of recent chemotherapy or radiation therapy to suggest a secondary cause and oral swabs were negative for herpes. She was evaluated by a dermatologist and oral pathologist and a diagnosis of oral lichenoid mucositis was made. Despite an increase in the IVIG dose, the oral ulcers did not improve. She was advised to use dexamethasone mouthwash for symptom relief. Conclusions: Good's Syndrome is a rare acquired disease of combined T-and B-cell immunodeficiency with a thymoma and although there have been reported cases of recurrent oral herpetic infections, the literature has not described presentations of oral mucositis as a manifestation of the disease. This case may describe a new clinical profile and provide a better understanding of morbidity for this complex disease. Consent to publish was obtained from the patient involved in this study. Background: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent febrile episodes and serositis. First attacks usually occur during childhood and rarely after 50 years old. We present here the first case to our knowledge of very late-onset FMF associated with isolated IgG deficiency and poor response to conjugated pneumococcal vaccination. Case Presentation: A 77-year-old man of Ashkenazi Jewish descent consulted the emergency department with fever, hypotension, tachycardia, and myalgias. Investigations revealed leukocytosis (WBC 17) and elevated C-reactive protein (54.4 mg/L), however blood and urine cultures were negative. CT-scan of the head, neck, chest and abdomen ruled out infection and neoplasia. His symptoms resolved within days with supportive care and empiric antibiotics. He had experienced similar symptoms twice in the past 5 years without identifiable etiology. The patient had a history of isolated IgG deficiency, one episode of pneumonia and one episode of sinusitis in his lifetime, but no family history of immunodeficiency or autoinflammatory disease. Immunologic evaluation showed low IgG at 4.88 g/L (normal 7.00-15.00), mildly low IgM at 0.44 g/L (normal 0.50-3.00), normal IgA, normal T and B cell enumerations, and low switched memory B cells (2%). He had a good serologic response to tetanus and haemophilus conjugated vaccines, but a poor response to conjugated pneumococcal vaccination (2/14 serologies measured). In light of hypogammaglobulinemia and unexplained febrile attacks, genetic testing was done, revealing heterozygous MEFV pathogenic variant p.Val726Ala (V726A) on exon 10. The patient was started on low-dose colchicine 0.3 mg/ day for recurrent gout and has had no FMF attacks since then. Conclusions: FMF is a clinical diagnosis and should be included in the differential diagnosis of unexplained recurrent febrile episodes, regardless of patient's age. Infections are a well-known trigger of FMF attacks, and patients with humoral immunodeficiencies and FMF may benefit from earlier immunoglobulin replacement therapy. Allergy Asthma Clin Immunol 2021, 17(Suppl 1):33 surgery with a total of 1,902 prescriptions, followed by internal medicine (1,660), obstetrics and gynecology (875), and intensive care (713). Conclusions: We have identified wards at our institution with the highest rates of first generation-antihistamine prescribing with the surgical, obstetrical and medicine wards being the top three. Physicians, pharmacists, and nurses-especially in these identified areas of the hospital-may benefit from education around the potential for serious harm of first-generation antihistamines and the availability of safer alternatives. Additionally, limiting access to first-generation antihistamines in hospital would encourage safer prescribing habits and familiarity with second-generation agents. Background: While the pathogenesis of chronic spontaneous urticaria (CSU) remains unknown, autoantibodies have been found in subjects with CSU. It has been speculated that these autoantibodies cause the condition. Thus, the objective of this review was to investigate the presence of autoantibodies in CSU subjects. Methods: A systematic review was conducted within the PubMed, Medline and CENTRAL databases to identify all studies that assessed the presence of IgG anti-FcεR1α, IgG anti-IgE and anti-TPO antibodies in CSU subjects. Results: 27 papers were included in this review. 14 assessed the presence of IgG anti-FcεR1α antibody in CSU subjects. In five papers that studied CSU subjects with positive-autologous serum skin tests (ASST), 58% had IgG anti-FcεR1α, while in 3 papers that studied CSU subjects with negative-ASSTs, 22.9% had IgG anti-FcεR1α. In nine studies where ASST was not performed, IgG anti-FcεR1α was detected in 43.1% of CSU subjects. In 11 controlled studies, 38.8% of the CSU population had IgG anti-FcεR1α, compared to 6.7% of healthy controls (p < 0.0001). CSU subjects were 6.5 times more likely to have IgG anti-FcεR1α present (p = 0.001). Five studies found IgG anti-IgE antibody in 41.8% of CSU subjects. In four controlled studies, 44% of CSU subjects had this autoantibody present, compared to 15.3% in healthy controls (p = 0.09). CSU subjects were 2.4 times more likely to have IgG anti-IgE present (p = 0.03). In 11 studies, anti-TPO antibody was detected in 17.8% of CSU subjects. In six controlled studies, anti-TPO was found in 16.9% of CSU subjects compared to 5.1% in healthy controls (p = 0.03). CSU subjects were 5.0 times more likely to have anti-TPO present (p = 0.02). Conclusions: Elevated levels of FcεRIa-specific, IgG anti-IgE and anti-TPO autoantibodies were found in CSU subjects compared to healthy controls, which may indicate that autoimmunity may contribute to the pathogenesis of this disease or be an inflammatory marker associated with the condition. Background: Chronic spontaneous urticaria (CSU) is defined by spontaneous appearance of wheals, angioedema or both for at least 6 weeks. Previous studies have reported an association between parasitic infections and CSU in pediatric patients. While the etiology of CSU is restricted for pediatric patients, there are commonly known etiological factors including thyroid diseases, infections and autoimmune diseases. Currently there is extensive research on these etiological factors, however there is limited literature exploring parasitic infections as a cause for CSU. Case Presentation: A 5 year old female presented with chronic urticaria for the past 4 years. The rash presented as typical urticarial lesions: transient, pruritic skin lesions located ubiquitously. Further examination revealed intermittent angioedema located on the lips and ears. The patient's urticaria was spontaneous in nature though exacerbated by various: unrelated foods, frigid surfaces, heat, stress, and pressure. Additional questioning precluded common inducible forms of urticarial. Blood work indicated normal thyroid function, negative celiac screening, negative inflammatory markers, and negative autoimmune work up. IgE was elevated at 131 kU/L. Analysis of a stool culture revealed the presence of an amoeba, Dientamoeba fragilis, often felt to be non-clinical relevant in the pediatric gastrointestinal literature. The patient was prescribed Paromomycin for the resolution of the parasitic infection. Subsequently, the patient's urticarial symptoms reduced in severity by 90%. Patient was advised to perform a repeat stool test. Conclusions: Parasitic infection in relation to CSU have been reported. This case identifies the benefit of further investigational screening in select CSU patients and the eradication for a low toxicity parasitic agent. The gradual increase of parasitic related cases in tropical and non tropical countries would suggest that parasitology should become a part of the routine screening for childhood CSU. Further research is required to determine a causal relationship between parasitic infections and CSU.

Statement of Consent:
Written informed consent for this case report was obtained from the patient. Background: Viruses, including COVID-19, are known triggers of urticaria. Omalizumab, an anti-IgE monoclonal antibody, is indicated in chronic spontaneous urticaria (CSU) patients who are refractory to antihistamines. Omalizumab has been found to reduce the duration, frequency, and viral shedding of rhinovirus infections. We hypothesize that CSU patients on omalizumab may have a decreased risk of severe infection with COVID-19. As such, we describe a long-term care worker on omalizumab who experienced a mild COVID-19 infection with CSU flare. Case Presentation: We present a 43-year old Caucasian, non-obese, non-atopic female with a 20-year history of CSU with eosinopenia who was well-controlled on cetirizine 10 mg/day and omalizumab 300 mg SC q4weeks since 2017 with an Urticaria Activity Score 7 (UAS7) of 0 on a background of severe anxiety/depression and active smoking (20-pack year). She had normal lung function and no cardiac comorbidities. On March 30th, 2020, she tested positive for COVID-19 after 5 days of worsening nasal congestion, headache, and fever, while working at a long-term care facility heavily impacted by a COVID-19 outbreak. Her COVID-19 symptoms resolved without intervention after 7-days, which was followed by a moderate flare of her CSU (UAS7 16). Omalizumab was given the week before symptom onset and 14-days after symptom resolution. She did not require a burst of prednisone to control her urticarial flare.