Proceedings of the Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting 2019

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Background: Cricket powder form a new high protein source with growing popularity among North American consumers. Previous studies have reported anaphylaxis following the consumption of insects and cross reactivity between shellfish and insects such as crickets and mealworm has been identified [1][2][3]. Here in, we describe a case that demonstrates a clinically relevant co-sensitisation to crickets powder in a patient with shellfish allergy. Case presentation: A 22 years old male with Crhon's disease was referred to the Allergy Clinic at Queen's University for evaluation of anaphylaxis caused by ingestion of cricket powder. He presented to the Emergency Department with epigastric pain, generalized pruritus, hives with erythema and swelling of his hands and forearms. His symptoms developed 40 min after ingestion of cookies made with cricket powder. He was treated with intravenous antihistamines. He had never consumed cricket powder or other edible insects before. He had a history of allergic rhinitis to environmental allergens. He was told he had a shellfish allergy, but did not recall prior reaction. He denied history of anaphylaxis, or childhood asthma. In clinic, he underwent skin prick testing (SPT) to environmental and shellfish allergens. He reacted to dust mites, cockroaches, grass, ragweed, and birch pollen. SPT was positive for shrimp, crab and lobster, but negative to molluscs. SPT with diluted saline slurry of cricket powder produced a strongly positive reaction, with appropriate controls and was negative when applied on a healthy volunteer. He was diagnosed with IgE mediated cricket powder allergy. He was advised to avoid consumption of cricket powder and traces and carry an epinephrine autoinjector. He preferred to continue avoiding all shellfish. Conclusion: Shellfish allergic/sensitive patients are at risk of developing an allergy to edible cricket. Therefore, these patients should be notified about this allergy risk and consider for evaluation before consumption of cricket. Statement of consent: Written informed consent was obtained from the patient. Allergy Asthma Clin Immunol 2020, 16(Suppl 1):47 hypotension followed by cardiac arrest. Cardiopulmonary resuscitation was initiated as well as epinephrine infusion which results in return of spontaneous circulation. Skin testing for all possible culprits was negative except for PB (25 mg/mL) which was positive for both 1:10 and full-strength dilutions. He subsequently underwent successful surgery without the use of Patent Blue. Case 2: A 32-year-old female diagnosed with cervical squamous cell carcinoma was admitted for radical hysterectomy and sentinel lymph node dissection. At induction, she received Ancef, Fentanyl, Propofol, Succinylcholine, topical Chlorhexidine 2%, followed by injection of 99-Technecium-Sulfur-Colloid and Patent Blue. Shortly after the injection of Sulfur Colloid and PB, the patient developed urticaria and angioedema and became severely hypotensive. She required resuscitation with vasopressors and the surgery was aborted. Skin testing to PB (25 mg/mL) was positive for both 1:10 and full-strength dilutions. Repeat surgery was performed successfully without the use of Patent Blue. Conclusion: Patent Blue is a rare but important cause of severe perioperative anaphylaxis. It is important to consider all perioperative agents when evaluating patients including dyes, radiopharmaceuticals, and antiseptics in addition to medications. Statement of consent: Written informed consent was obtained. Background: Castleman disease (CD) is a rare heterogeneous group of lymphoproliferative disorder of unknown etiology most often presenting in adulthood with nonspecific symptoms. It can be localized to one lymph node (monocentric) or generalized with constitutional symptoms (multicentric). Its definitive diagnosis requires specific histopathological features. Case presentation: A 16-year-old male was referred by hematology to our immunology service for persistent fever, weight loss, mild splenomegaly and generalized fatigue for 3 months. He had a mild anemia and a thrombocytopenia. He underwent initially a PET scan and two bone marrow aspirations ruling out a malignant etiology. Genetic testing for a panel of genes involved in auto-inflammatory syndromes did not reveal any relevant mutation. His evaluation and extensive investigation by infectious disease and rheumatology services did not reveal a cause to his persistent symptoms. The Patient was eventually readmitted again after a year. Upon further investigation, the PET scan showed a positive signaling in multiple lymph nodes (LN). A biopsy of the supraclavicular LN was compatible with a definitive diagnosis of CD. A regimen of corticosteroids and anti-IL6 monoclonal antibody therapy led to significant improvement of his symptoms. Conclusion: Castleman disease is a rare disease in the pediatric population. Given the nonspecific manifestations, a high index of suspicion and repeated investigations are required for its proper diagnosis and management. Statement of consent: Written informed consent was obtained.

#15
Anaphylaxis caused by trace exposure to angiotensin II blocker in a healthcare worker: a case report Angeliki Barlas 1 , Raymond Mak 2 1 Clinical Immunology and Allergy, University of British Columbia, Vancouver, BC, Canada; 2 Clinical Immunology and Allergy, University of British Columbia, Vancouver, BC, Canada Correspondence: Angeliki Barlas Allergy Asthma Clin Immunol 2020, 16(Suppl 1):#15 Background: Angiotensin-converting enzyme inhibitor (ACEI)-related angioedema is well described in the medical literature. However, angiotensin II receptor blocker (ARB)-related angioedema and anaphylaxis is not as well elucidated due to its lower incidence. There are limited reports of severe ARB-related adverse drug reactions in the literature and its definitive mechanism remains unknown. In healthcare workers, one of the possible aetiologies of anaphylaxis includes occupational exposures to medications. Case presentation: A 57-year-old female was referred to our clinic for evaluation of unexplained anaphylaxis. On detailed history, the patient, who works as a Care Aide, handled Irbesartan and Atenolol at a client's house earlier that day and then subsequently rubbed her eyes. Within 10 min of contact she developed lip swelling, flushing and rashes on the face. She presented to the emergency department where she was noted to be stridorous. She was treated with epinephrine, antihistamines and steroids but required intubation for respiratory distress. Later in the clinic, a graded oral challenge to Irbesartan resulted in substantial hypotension, dizziness, nausea and visible lip angioedema. She required two doses of epinephrine in the office which led to resolution of her symptoms. Subsequently, she tolerated a graded Atenolol challenge. She was diagnosed with an ARB allergy. Suggestions were provided for a modified workplace to ensure ongoing safety. Conclusion: Occupational allergy in health care workers can result in anaphylaxis. In healthcare workers, medications as a cause for anaphylaxis is often overlooked, especially when the causative agent is seemingly benign. Although an ARB allergy is rare, unusual drug allergies may be the cause of "unexplained" anaphylaxis even with trace exposures. When evaluating such a patient, a detailed history of medication exposure in the workplace and pursuing drug provocation testing are necessary for accurate diagnosis. Consent to publish was obtained from the patient involved in this study.

Failure of immunotherapy as treatment of Post-orgasmic Illness Syndrome (POIS)
Ana-Maria Bosonea, Amin S. Kanani Division of Allergy and Immunology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada Correspondence: Ana-Maria Bosonea Allergy Asthma Clin Immunol 2020, 16(Suppl 1):#16 Background: POIS is a rare disease first defined in 2002. Since then, 50 cases have been described in literature, but it remains largely underrecognized in the medical community. Although the pathophysiology is unknown, various treatments have been tried on a small scale including 3 published case reports of immunotherapy successfully decreasing POIS symptoms. We present a case of unsuccessful immunotherapy in a patient with positive autologous seminal fluid skin testing. Case Presentation: The patient is a 23-year-old male, meeting criteria for POIS with headaches, fatigue, generalized weakness, myalgias, arthralgias, sore throat and concentration problems within 1-h postejaculations lasting 1 week, occurring since puberty. On intradermal testing he had a positive reaction to seminal plasma 1:10 dilution (12 mm) and negative reaction to sperm. An immunotherapy preparation was made to the seminal plasma at a starting concentration of 1:100,000 and a maintenance concentration of 1:10 seminal fluid. The patient was treated with immunotherapy to autologous seminal fluid for a total of 4 years. Although after 3 years, the skin reaction to the 1:10 intradermal seminal fluid decreased from 12 to 3 mm, the symptoms were only minimally improved. Other treatments trialed include antihistamines, NSAIDs, and prednisone all without significant improvement. Conclusions: Although there are previous case reports documenting the success of immunotherapy as treatment for POIS, this is the first publication reporting its' unsuccessful use in a patient with POIS and positive skin testing, thus highlighting the gap in knowledge of the pathophysiology of this rare disease. Statement of consent: Written informed consent was obtained.
Background: IgE-mediated cow's milk allergy is a common food allergy in childhood but is rare in adulthood. We report a case of a woman developing IgE-mediated cow's milk allergy after the birth of her child. While there are rare case series noting adult-onset of cow's milk allergy, this is the first reported in North America in the literature of this food allergy developing after pregnancy [1,2]. Case presentation: We present a 43-year old female who tolerated cow's milk products on a regular basis with no reaction prior to the birth of her child. After the birth of her child she noted that each ingestion of milk products would result in cutaneous symptoms (urticaria,) oral pruritus and many ingestions resulted in shortness of breath/ cough. Total avoidance of milk was initiated following a severe reaction after ingesting a smoothie containing cow's milk. This reaction resulted in requiring 2 doses of epinephrine for symptoms of urticaria, shortness of breath, cough, light-headedness and an episode of emesis. Epicutaneous testing was performed in clinic and highly positive(8 mm) to commercial cow's milk extract (histamine control 6 mm, saline control negative) Conclusion: This case is the first to our knowledge to document emergence of IgE-mediated cow's milk allergy after pregnancy in North America. This case demonstrates that new food allergies after pregnancy should be considered and reiterates that adult cow's milk allergy, as noted in previous case series, can be phenotypically severe. Statement of consent: Written informed consent was obtained. Background: The infectious susceptibility to Streptococcus Pneumoniae remains a typical presentation of defects in the classical complement pathway. The regulatory proteins of the alternative complement pathway play a major role in the homeostasis of the latter. An abnormality of Factor I protein classically results in complement-mediated thrombotic microangiopathy, C3-glomerulonephritis or age-related macular degeneration. This unique case series reports a compound heterozygous pathogenic mutations of factor I in relation to pneumococcal invasive infections. Case presentation: Two brothers of 3 and 7 years-old, coming from an unremarkable non-consanguine family, were evaluated in immunology in the context of pneumococcal pulmonary sepsis and repetitive acute otitis. Functional complement tests have demonstrated a complete inactivation of the alternative pathway (AH50 0%) and a major decreased activity in the classical (CH50 11-15%) and lectin pathway (MBL 0-46%). Serum sC5b9 is normal and Factor B as well as C2 to C9 were quantitatively decreased. These siblings carry 2 heterozygous mutations of CFIc.1429 + 1G>C and CFIc.485G>A(Gly162Asp) for which each parent is a healthy carrier. The in silico studies revealed major changes in the functioning of CFI, namely a major amputation of the serine protease domain as well as in the C5 domain. The qualitative measurement also confirms a significant decrease in factor I serum.

A compound heterozygous Factor I mutation family and invasive pneumococcal infection
Conclusions: This rare family case proves the importance of CFI in the defense of the host. Indeed, this mutation generates a continuous and unregulated activation of the alternative complement pathway leading to depletion of main complement's protein and encapsulated germs susceptibility. Depending on the factor I mutation, disparate clinical presentation could occur whether infectious, nephrological or microangiopathic. Identifying these patients early in life and providing them vaccination and antibioprophylaxis is important. Statement of consent: Written informed consent was obtained. is a non-IgE-mediated food allergy that occurs in infancy during solid food introduction. FPIES manifests as delayed vomiting, irritability, ± diarrhea. Severe dehydration and shock may follow. Oral food challenges (OC) are needed to confirm FPIES triggers with IV fluids, ondansetron and adequate observation. Guidance for other grain introduction in single FPIES infants remains unknown. Case presentation: A non-atopic 6 month-old female presented to a SW Ontario ER with recurrent emesis, cyanosis, and peripheral hypotonia 1-2 h after ingestion of rice cereal. Blood work revealed an elevated total WBC of 28.9 × 10 9 /L. Intravenous fluids and ondansetron were needed to recover the infant. The child was diagnosed with FPIES to rice based on presentation. Subsequent in-patient admissions were arranged to help assess tolerance to other grains, using published protocols (0.6 g protein/kg exposure) (1). Physician-supervised OC was performed to wheat and oats, on separate admissions. Neither of these grains were tolerated with profuse emesis occurring 2 h postingestion that required intravenous fluid rehydration and ondansetron for recovery. Blood work revealed elevated platelets, but not total WBC from in hospital challenge. Conclusions: Multiple grain FPIES is rare; most FPIES to grains are single. This case highlights the benefits of structured in-hospital OC that confirmed multiple FPIES. In-hospital challenge was safe, in light of severe initial FPIES presentation to rice. Severe elevated WBC may be a marker of more complicated FPIES presentation. Statement of consent: Written informed consent for publication of their clinical details and/or images was obtained from the parent of the patient. A copy of the consent form is available for review by the Editor of this journal. Allergy Asthma Clin Immunol 2020, 16(Suppl 1):47

#19
Background: Cephalosporins and vancomycin are increasingly used together to treat infections. With increase use, more adverse drug reactions have been reported. Currently, there is no clear evidence for the potentiation of rash when the two drugs are used together. Our case demonstrates this possibility. Case presentation: A 63-year-old male, no history of drug allergy, developed a diffuse, pruritic maculopapular rash 5 days after initiation of ceftriaxone and vancomycin for severe lower leg cellulitis. Rash resolved within 4 days of discontinuing ceftriaxone and vancomycin. One week later, delayed intradermal testing (IDT) to ceftriaxone and vancomycin was negative, however testing precipitated recurrence of rash. Testing each antibiotic individually did not result in rash. Conclusions: Further studies are needed to define ceftriaxone and vancomycin IDT sensitivity. Based on this case, we postulate that there is possible potentiation of rash when ceftriaxone and vancomycin are used together. Ethics approval: The University of Manitoba ethics requirements for Case Report state that consent is required, and submission for ethics review is to be done before publication. Therefore submission for ethics review will be done if abstract is accepted for presentation. Background: The use of the basophil histamine release assay has expanded its use from being a diagnostic tool for the autoimmune subtype of chronic spontaneous urticaria, to depicting disease duration and severity, depending on a positive or negative assay result. Case presentation: We describe a patient, diagnosed with the autoimmune subtype of chronic spontaneous urticaria with a positive basophil histamine release assay, who was treated with anti-histamine therapy until disease remission. Conversion of the assay to negative correlating with disease remission was observed. This is the first description, in current literature, that a positive to negative conversion has been observed. Conclusion: This case suggests further research into the utility of the basophil histamine release assay as a biomarker for disease remission in the subset of patients with a positive assay at the time of diagnosis should be considered. 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: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare delayed hypersensitivity reaction, typically with a long latency period. DRESS is uncommon but potentially life-threatening in children. The lymphocyte toxicity assay (LTA) is an investigational assay measuring cell viability upon incubation with the suspected drug. We describe two cases of pediatric DRESS syndrome caused by amoxicillin-clavulanic acid. Case presentation: Case 1 involves an 11-month-old male prescribed amoxicillin-clavulanic acid for a respiratory infection. 14 days after antibiotic exposure, he presented with fevers, lethargy, a generalized erythematous maculopapular rash, and facial, hand, and scrotal edema. Laboratory investigations revealed reactive lymphocytes, peripheral eosinophilia (0.72 × 10 9 /L) and hepatitis. Testing for ANA, Hepatitis A and B, EBV, CMV, HHV6, Mycoplasma, Chlamydia, and blood cultures were negative. A RegiSCAR-Group Diagnosis Score of 6 confirmed definite DRESS. LTA testing revealed a concentration-dependant decline in viability after incubation with penicillin and penicillin metabolites. Parental samples also displayed concentration-dependent decreased cell viability. Case 2 involves an 11-year-old female with atopic dermatitis prescribed amoxicillin-clavulanic acid for a secondary bacterial skin infection. She developed fevers and decreased appetite 11 days after antibiotic exposure with progression to diffuse erythrodermic, maculopapular eruption, superficial desquamation, facial angioedema, peripheral eosinophilia (6.8 × 10 9 /L), hepatitis, and lymphadenopathy. Her RegiSCAR-Group Diagnosis Score was 5, confirming probable DRESS. LTA revealed a substantial decline in viability when exposed to penicillin. Both cases were treated with systemic steroids with normalization of labwork and improvement of symptoms. Conclusions: Amoxicillin-clavulanic acid is a commonly used antibiotic which should be recognized as a potential cause of DRESS in pediatric patients. The LTA can be a helpful tool in DRESS cases and may have potential implications for family members. Furthermore, these cases add to current literature supporting that there is a shorter latent period in DRESS induced by antibiotics in children. Statement of consent: Written informed consent for publication was obtained from the parents of the patients.

Background:
Hereditary angioedema with normal C1 inhibitor (HAEn-C1inh) is characterized by bradykinin-mediated swelling with normal level and function of C1 inhibitor (C1inh), family history of angioedema, no response to high-dose antihistamines, and exclusion of alternative causes. Genetic variations in factor XII, angiopoietin-1, and plasminogen have been described in some HAE-n-C1inh patients; however, diagnostic testing is limited. Angiotensin-converting enzyme inhibitors (ACEi) can cause bradykinin-mediated angioedema, lasting up to 2 months after ACEi discontinuation. Vocal cord dysfunction (VCD) causes respiratory symptoms including stridor, dyspnea, dysphonia and throat tightness secondary to abnormal vocal cord movements but is a benign condition. Case presentation: A 58 years-old female with hypertension on ramipril presented with cough and stridor to a rural hospital. CT scan revealed epiglottic swelling. C1inh level and function were normal. The patient was intubated and treated with antihistamines and prednisone. Ramipril was discontinued with a provisional diagnosis of ACEiinduced angioedema. The patient continued to present with stridor for the next 7 months, for which she was intubated multiple times, and a tracheostomy performed. Further history revealed possible angioedema affecting several generations. A clinical diagnosis of HAE-n-C1inh was made. Testing for genetic variations in SERPING1, F12, and PLG was negative. Daily attacks continued despite prophylaxis with tranexamic acid, danazol, and C1 inhibitor. Acute attacks had minimal response to icatibant and C1 inhibitor. Upon transfer to tertiary care for reassessment, provocative maneuvers performed by otolaryngologists discovered VCD. Conclusions: Common diagnoses in combination may mimic rare disorders. Initial angioedema may be explained by ACE inhibitors and subsequent episodes of stridor by VCD. Earlier reconsideration of the diagnosis may have prevented harm secondary to intubation and inappropriate treatment. The diagnosis of HAE-n-C1inh is difficult without reliable diagnostic testing; thus, caution in the exclusion of alternative diagnoses, and frequent re-evaluation is crucial for accurate patient management. Written informed consent was obtained from the patient for publication of the case details. Background: Angioedema induced by treatment with angiotensin converting enzyme (ACE) inhibitors accounts for one-third of all cases of angioedema treated in the emergency room [1]. ACE inhibitors block the effects of the enzyme ACE, altering the renin-angiotensin-aldosterone pathway and ultimately leading to decreased degradation of bradykinin. High levels of bradykinin stimulate vasodilation and increased vascular permeability, leading to angioedema, which rarely may progress to airway obstruction. C1 inhibitor concentrate is used to treat hereditary angioedema by inhibiting the formation of bradykinin. Few case reports have also demonstrated its efficacy in ACE inhibitor induced angioedema [2][3][4]. Case presentation: A 71-year old male presented to the emergency department with angioedema (without urticaria) of the face, lips and tongue following 4 years of ACE inhibitor therapy. He developed respiratory distress in the emergency department that was not responsive to epinephrine or antihistamines. C1 esterase and complement (C3/C4) levels later measured were normal. He received C1 inhibitor concentrate and responded with significant improvement in edema and resolution of respiratory distress within 1 h of administration. Conclusions: There is limited documentation in the literature to guide treatment of acute ACE inhibitor induced angioedema in the emergency department. We report an additional case treated successfully with C1 inhibitor concentrate. Written informed consent for publication of their clinical details was obtained from the patient. A copy of the consent form is available for review by the Editor of this journal. Background: Adverse reactions to tattoos are frequently diagnosed as allergic contact dermatitis (ACD) to dyes. Patch testing is often inconclusive in diagnosing contact allergy in these patients. Case presentation: Two patients were seen in the clinic for suspected ACD reactions to the red dye in their tattoos. A 65-year-old male with pre-existing tattoos containing red dye presented with pruritus and well-demarcated red, raised, and localized patches over the red dye tattoo (RDT) sites. Symptoms were treated with topical moisturizers and antihistamines. Assessment was carried out to ACD, dye and metal panels. Patch testing was only positive to copper. The patient was treated with Betaderm 0.1% cream. Five months later, he returned due to exacerbations of his dermatitis. Interestingly, only the RDT sites exposed to sunlight developed pruritus and rash, but unexposed RDT areas were unremarkable. The patient was diagnosed with photodermatitis of red dye, facilitated by the presence of copper, advised to cover affected areas while in the sun, and discharged home with oral prednisone. A 38-year-old male was seen for localized pruritic rashes over red/orange sites on his tattoo. Topical steroids were helpful, but symptoms returned upon sunlight exposure. The patient tested negative for ACD on all patch testing. Both patients denied adverse reactions to other colours in their respective tattoos. Conclusions: It is hypothesized that composite pigments in RDT react strongly to UV-radiation, causing decomposition, fragmentation and formulation of reactive oxidative species, leading to compromised skin integrity, which is often misdiagnosed as ACD. Clinicians should be aware of this risk with RDT sites in sunlight for proper treatment and counsel. Consent to publish: Written informed consent for publication of their clinical details and images was obtained from the patients. A copy of the consent form is available for review by the Editor of this journal. Background: Goat's and sheep's milk (GSM) allergies are rare in patients who display tolerance to cow's milk (CM). Despite high cross reactivity of milk caseins between the three dairy products, immunological response may vary depending on the mammalian source. Patients with IgE antibodies that are unreactive to bovine β-casein are reported to be reactive to caprine β-casein, despite the significant sequence homology between the two proteins [1]. We present a case of anaphylaxis to sheep/goat cheese in a 4 year old boy who is tolerant to CM products, demonstrating a mammalian-specific dairy allergy. Case presentation: A 4-year-old boy who is tolerant to CM presented with an allergic reaction within minutes after eating feta cheese (consisting of a mixture of GSM). The patient experienced drowsiness, abdominal cramps, angioedema, and was wheezing. He had known intermittent asthma, but no previous history of food allergies. The tryptase level measured 1 h post initial symptoms was 14.6 µg/L (norm: 0.0-13.5 µg/L). A tryptase repeated a month later was within normal limits (5.1 µg/L), confirming the diagnosis of anaphylaxis. A skin prick test performed 1 month after the reaction was highly positive for GSM (17 mm and 16 mm respectively), but negative for CM. Conclusions: Care givers and patients with CM tolerance should be aware of the risk of allergy to milk caseins found in different mammals. Specific skin prick tests may help establish a GSM allergy, while allowing continuous consumption of CM. Finally, patients who successfully complete oral immunotherapy for CM allergy should be informed that their increased tolerance may be restricted to CM protein, and not to other mammals. This is the first case of a patient who is unreactive to CM, but reactive towards GSM to be reported in Canada. Written informed consent for publication of the patient's clinical details and clinical images was obtained from their parents. A copy of the consent form is available for review by the Editor of this journal. Background: Allergen exposure through skin barrier is a known cause of sensitization in food allergy but has not been reported in drug allergy.

Reference
Case presentation: A 14-year-old boy was admitted to the intensive care unit for a suspected staphylococcus toxic shock syndrome. He presented multiples skin abscess, fever, headache, macular rash and low blood pressure at 102/49. He was treated with iv cefazolin and clindamycin. Five minutes after starting the clindamycin perfusion, he complained of throat tightening and dyspnea. Physical examination revealed angioedema, conjunctival hyperemia, generalized hives and wheezing. Saturation decreased to 88%. He was immediately treated with epinephrine, oxygen, diphenhydramine, salbutamol, hydrocortisone, and symptoms were rapidly controlled except for remaining low diastolic blood pressure. As he continued to be febrile and considering that clindamycin allergy is rare, moreover as he never received it before, we decided to perform a drug challenge. After perfusion of 380 mg, he presented throat tightness, hand pruritus, dyspnea, wheezing, and desaturation to 84%. Symptoms were rapidly controlled with epinephrine. At follow-up, prick and intradermal skin tests were performed, and both were positive. After verification, the mother reported the use of clindamycin gel for acne at one or two occasions in the previous year.

Conclusion:
We believe this is the first reported case of clindamycin anaphylaxis where sensitization may have occurred through previous skin exposure. Background: Food-dependent exercise-induced anaphylaxis (FDEIA) is a rare subtype of anaphylaxis that develops in association with physical exertion within a few hours of ingestion of a causative food. In this condition, neither food ingestion nor exercise alone is sufficient to trigger anaphylaxis. Although rare, this is an important condition to recognize, as it can lead to death. Case presentation: A healthy 22-year-old male athlete presented with anaphylaxis requiring epinephrine administration in the emergency room. The episode occurred within 30 min of consuming almonds immediately following exercise. He consumed the same brand and quantity of almonds the same week, in the absence of physical activity, without issue. He also exercised at the same intensity on several occasions that week, in the absence of almond consumption, without adverse reaction. Skin prick testing was positive to almond, along with almond serum-specific IgE, confirming almond to be the culprit allergen. Skin prick testing for environmental aeroallergens was positive for dust mite, grass pollen, and cat, but negative to birch. The patient was successful with oral food challenge to almond in hospital.
Conclusions: This is the first report of FDEIA isolated to almond in a patient without birch sensitization or food pollen syndrome. There is only one published case report of FDEIA to almond in a female patient with food pollen syndrome, sensitized to birch. Our case eliminates food pollen syndrome as a possible cause of anaphylaxis in a patient sensitized to almond. This case is an important reminder that although rare, FDEIA exists and confirming a diagnosis can lead to life-saving preventative strategies. As tree nuts, especially almond, are not commonly associated with FDEIA, this case will serve to expand our differential for anaphylaxis and contribute to current allergy literature. Background: Food induced pancreatitis (FIP) is a very rare entity, only 17 cases have been published, with half coming out of Japan, and most cases had IgE sensitization to the culprit food [1]. The pathophysiology of this condition is not well understood, proposed mechanisms are activation of pancreatic enzymes during anaphylaxis, or localized eosinophilic gastroenteritis at the Ampulla of Vater. Case presentation: An 18-year-old Japanese male with allergies to peanuts, tree nuts and fish, had an accidental exposure to cashews and developed anaphylaxis with symptoms of vomiting, diarrhea, abdominal pain, urticaria and throat tightness. He was treated with epinephrine, dimenhydrinate, buscopan, ondansetron, and prednisone. He continued to have severe epigastric pain 7 h after ingestion and was found to have pancreatitis based on a lipase of 6104 U/L (0-393 U/L) and a CT scan showing an edematous pancreas with multifocal non-enhancing areas. Subsequent ultrasounds did not show ductal dilation or gall stones. He did not have eosinophilia or abnormal IgG subclasses. He had 3 beers, 2 days prior to onset of symptoms, and his liver enzymes were normal. Symptoms resolved 3 days after ingesting the cashews, and his lipase was normal after 5 days. Cashew skin prick testing was 10 mm wheal and specific IgE 72.3 KU/L.

Conclusion:
We believe this is the first case report of cashew FIP. There is no biochemical or clinical evidence of autoimmune, alcoholic, gall stone and drug induced pancreatitis. The patient alcohol's consumption was minimal. The medications described above are not associated with pancreatitis. In the future, practitioners should be aware of FIP in patients with persistent abdominal pain after a food anaphylaxis event. Background: XLA is a hereditary primary immunodeficiency that results from Bruton's tyrosine kinase (BTK) gene mutations leading to early-onset agammaglobulinemia and recurrent infections. There have been over 1000 mutations in BTK gene reported to be responsible for XLA. These mutations lead to defective B-cell development, profound deficiency of immunoglobulins and an increased susceptibility to infections. Case report: A 55 year old gentleman presented to our clinic with recurrent sinopulmonary inections. At age 4 he was found to have hypogammaglobulinemia and was diagnosed with common variable immunodeficiency (CVID) and was treated with IVIG; despite this he continued to have recurrent infections. Blood work from 2009 had revealed no mature B-cells and therefore the suspicion of X-linked agammaglobulinemia was raised. BTK gene analysis was done revealing a novel T354I missense mutation in the BTK gene, reported as highly likely to be associated with XLA. Discussion: BTK mutations in XLA consist of missense mutations, small insertion and deletions, Splice-site mutations, and nonsense mutations. The patient we describe was found to have a novel T354I missense mutation of BTK gene. T354I is a non-conservative amino acid substitution in that a polar Threonine residue is replaced with a non-polar Isoleucin at a position conserved across mammals in the SH2 domain of BTK. Early diagnosis, treatment, and genetic counseling are essential to reducing mortality and morbidity. This case emphasizes that suspicion for XLA and gene-study is essential for patients presenting with clinically overlapping disorders that would include XLA as a differential diagnosis. Consent was obtained from the patient for this case report Background: Hereditary angioedema (HAE) is a rare genetic condition characterized by recurrent episodes of angioedema. Angioedema results from a bradykinin-mediated process, although patients are often treated as if this is histamine induced, resulting in ineffective management. Although rare, this condition is important to recognize as laryngeal edema can lead to fatal asphyxiation. The most commonly characterized forms of HAE arise from deficiency or dysfunction of C1 inhibitor. HAE types 1 and 2 are secondary to autosomal dominant mutations in the SERPING1 gene, with about 25% of mutations being de novo. HAE rarely has been associated with systemic lupus erythematosus (SLE).

Case presentation:
A 26 year old female presented with a ten year history of undiagnosed, recurrent angioedema involving the larynx, abdomen, genitourinary tract, and face. There was no family history of angioedema. She subsequently experienced inflammatory arthritis, a malar rash, recurrent aphthous ulcers, and a positive ANA, all suggestive of lupus. Investigations confirmed a low C1 esterase inhibitor level on two occasions.

Conclusion:
The association between SLE and HAE is rare. We report an interesting case of a patient with SLE and a classic presentation of HAE, versus acquired angioedema. Those rarely reported with Type 1 HAE and SLE are most often females and symptomatic (prominent gastrointestinal symptoms) with HAE, before developing lupus. This is consistent with our case. We suspect our patient has a de novo mutation and genetic testing is pending. Our case adds to the small body of literature recognizing a complex patient population with HAE and lupus, and will serve to contribute to current literature and assist in timely diagnosis.

#32
A systemic allergic reaction in oral challenge-confirmed hazelnut "tolerant" individual Sydney A. The patient was skin prick tested to hazelnut (10 mm), raw hazelnut (9 mm), and histamine (4 mm). The standard OC dosing in the clinic is 0.5 g, 1 g, 2 g, and 4 g at 15-min intervals with a 30-minmonitoring period after the final dose. The patient went on to tolerate 7.5 g of hazelnut flour (1.34 g hazelnut protein) in clinic. She was labeled as hazelnut-tolerant and discharged home. Four to 5 h after the OC, the patient consumed four hazelnut chocolate balls at home. Approximately 30 min after consumption, the patient complained of nausea, congestion, and facial swelling. The patient was treated with diphenhydramine and symptoms resolved. Analysis of the hazelnut chocolate ball protein content identified a total of 4 g hazelnut protein (1 g per ball).

Conclusions:
The clinic has adapted their OC protocol to add a fifth dose of 8 g of hazelnut flour (3.3 g pure hazelnut protein) to reduce the risk of false negative challenges where threshold dosing in hazelnut allergic children may be higher. This case emphasizes the need for an international standard for hazelnut OC dosing. Written informed consent for publication of their clinical details was obtained from the parent of the patient. A copy of the consent form is available for review by the Editor of this journal. Background: Cilantro is a member of the Apiaceae family, which includes carrots, parsley, aniseed and fennel seeds. Allergens are present in both the leaves and seeds of the plant. Reported hypersensitivity reactions include stomatitis, dermatitis, and contact urticaria.

Case presentation:
A 20 year old female underwent an oral challenge for cilantro. She had contact urticaria with exposure to cilantro at the workplace, and urticaria with emesis when eating salsa containing cilantro. She had dermatographism resulting in equivocal cilantro skin prick testing. She had negative aeroallergen testing, including with birch and mugwort pollen. We did not have access to cilantro specific IgE. The graded oral challenge began with one-eighth of a cilantro leaf. In 20 min she developed facial and neck erythema and urticaria, as well as mouth pruritis and lip tingling. She then developed emesis, diarrhea, and chest tightness. Symptoms persisted despite receiving two doses of epinephrine 0.5 mg IM, cetirizine 10 mg SL and 4 puffs of salbutamol. She was transferred to urgent care, where she also received 1 L of IV normal saline, methylprednisolone 125 mg IV and ranitidine 50 mg IV. The patient was instructed to avoid ingestion of cilantro and carry epinephrine auto-injectors at all times. Conclusions: Allergy to cilantro is rarely described; skin testing and serum IgE testing have unknown prognostic value. This is the first report of anaphylaxis to isolated fresh cilantro during a graded oral challenge. Clinicians should be aware of the risk of anaphylaxis during oral food challenges even with minimal protein content and act promptly when reactions occur. Statement of consent: Consent to publish was obtained from the patient. Background: Drug-induced enterocolitis syndrome (DIES) is a rare type of non-IgE-mediated hypersensitivity reaction to drugs that shares clinical features with a well-recognized entity: food proteininduced enterocolitis syndrome (FPIES). In the acute setting, both DIES and FPIES manifest as delayed-onset profuse vomiting and diarrhea which can lead to dehydration and, more severely, hypovolemic shock (1). To our knowledge, only a few cases of enterocolitis syndrome caused by drugs have been reported, exclusively with amoxicillin and amoxicillin-clavulanate. To date, there is no report of DIES provoked by proton pump inhibitors (PPIs). Case presentation: We report the case of a 69-year-old female who developed, within a few hours after taking pantoprazole, two episodes of severe abdominal pain, vomiting and bloody diarrhea leading to hypovolemic shock with renal insufficiency. Complete investigation showed no infectious, inflammatory or ischemic causes for her acute gastro-intestinal (GI) symptoms. An oral challenge to pantoprazole was performed and was clearly positive for reproducing the exact same violent GI symptoms 1 h after completing the test. There were no respiratory or cutaneous signs and symptoms. Abdominopelvic CT-scan performed during the first episode was positive for enteritis showing small intestine edema. Conclusions: To our knowledge, this is the first case of DIES secondary to a PPI. It demonstrates the seriousness the course of this disease can take with life-threatening hypovolemic shock. Awareness and recognition of this entity, in its mild or more severe forms, is thus important in the evaluation of a patient presenting with acute GI symptoms, considering possible drug reactions. Statement of consent: Consent to publish was obtained from the patient involved in this study. Background: Oral allergy syndrome (OAS) is an IgE mediated allergic reaction resulting from cross reactivity of pollens, mainly birch and ragweed, with fruits, vegetables, and tree nuts [1]. It is generally recognized as a benign syndrome presenting with local tingling and pruritus of lips, mouth, and throat. We report 12 cases of anaphylactic reactions following consumption of foods known to cross react with pollens in patients mainly presenting with OAS. Methods: Charts of patients diagnosed with OAS were evaluated for clinical symptoms fitting the diagnostic criteria of anaphylaxis. Patient charts with reported anaphylactic reactions were isolated and summarized for demographics, clinical history, symptoms, food triggers, and skin prick test (SPT) results. Results: Out of 130 charts reviewed, 12 were isolated with anaphylactic reactions. The mean age of patients was 41 years (range 18-64, M:F 5:7). All had positive SPT to birch, have a history of seasonal allergies, and reported local mouth tingling/itching when in contact with certain foods known to cross react with pollens. These patients developed severe multi system reactions following consumption of large quantities of specific food trigger. Of the 12 patients, 10 reported urticaria, 8 reported throat tightness, 8 reported gut symptoms, 7 reported shortness of breath/wheezing, and 2 reported loss-of-consciousness. Four patients were physically exercising prior to developing anaphylaxis reactions. The specific foods vary among patients and include tree nuts, avocado, grapes, carrots, apple, peaches, pomegranate, and nectarine. Conclusion: OAS is an allergic reaction to certain fruits, vegetables, and nuts resulting from cross reactivity of pollens. Generally, the symptoms do not progress beyond the mouth. However, severe multi system allergic reactions are possible. The quantity of the pollen cross reacting food consumed might be a factor in the severity of the allergic response. Exercise can potentially be a co-factor to the development of severe allergic reactions in patients with OAS.
Objectives: The literature indicates that the incidence of anaphylaxis is increasing and that there are significant deficiencies in both recognition and management. We aimed to examine the magnitude of these gaps in Canadian pediatric emergency medicine (PEM).

Methods:
We conducted a cross-sectional, self-administered survey of the Pediatric Emergency Research Canada (PERC) physician database. The survey tool was developed through a literature review to identify recurring themes of gaps in anaphylaxis diagnosis and management. The final tool contained four scenarios; three scenarios featured each of the National Institute of Allergy and Infectious Diseases (NIAID) anaphylaxis criteria, separately, and fourth case of non-anaphylactic allergy was added to further assess the diagnostic ability of participants. Multiple-choice questions associated with each scenario addressed diagnosis, management and disposition. We also inquired about the type and availability of anaphylaxis order sets and patient education resources in the ED. Results: Of the 214 members invited to participate in the survey, 152 (71%) responded. Anaphylaxis was accurately recognized 93%, 82% and 99% of the time for the NIAID criteria 1 through 3, respectively. When anaphylaxis was recognized, epinephrine was prescribed in each case 96%, 95% and 72% of the time, respectively. Of all respondents, 115 (75%) accurately diagnosed all three cases of anaphylaxis, and of these respondents, 81 (53%) treated anaphylaxis with epinephrine each time. Of the 13 PERC centers, 4 (30%) reported having pre-printed order sets, and only one site indicated having patient education and discharge resources.

Conclusions:
The majority of respondents recognized cases of anaphylaxis, however a substantial portion demonstrated gaps in management that may adversely impact this vulnerable population. The recognition of anaphylaxis without cutaneous or pulmonary findings and systematic treatment with epinephrine were the main gaps identified. Nationwide, there is a lack of structured patient education and discharge materials. Background: Few patients have an anaphylaxis action plan even though they are advocated for routine use. Evidence for the effectiveness of action plans as part of long-term anaphylaxis management is lacking. Our study aim was to conduct a usability evaluation of the Canadian Anaphylaxis Emergency Plan (AEP) to determine how well it meets usability needs and whether it can facilitate appropriate emergency response to anaphylaxis.

Methods:
The usability study employed one-on-one simulation sessions with (i) parents or caregivers of children with known allergies (age < 18 years) at risk for anaphylaxis; and (ii) school teachers to test the use of the AEP; all able of self-administer an epinephrine autoinjector (EAI). Our primary outcome was the correct identification of situations when an EAI was most appropriate to administer (using the AEP as a guide). We used two standardized patient scenarios to measure this outcome using an advanced patient simulator (SimMan ® ): Case A (not anaphylaxis) and Case B (anaphylaxis). Participants were exposed to both cases in random order. A moderator collected data using a standardized checklist including correct handling, initiation and site administration of an EAI placebo device). Participants also completed a validated, 10-item System Usability Scale (SUS). Results: Sixteen individuals (5 children, 7 parents, 4 teachers) participated. The use of the AEP assisted the correct identification of anaphylaxis (and indication for administering an EAI) in 75% of participants (Case A) and 85% of participants (Case B). The SUS was completed by adult participants (n = 9); the overall mean score was 72.2 (SD 11.9), which represents a subjective grade of C+ (below average). Conclusion: Our work contributes to the limited evidence of the effectiveness of AEPs for self-management of anaphylaxis. Our findings indicate that the Canadian AEP needs to be improved to optimize its use.
Background: Parents have increased anxiety associated with an oral food challenge (OFC). However, no research has been conducted to determine effectiveness of coping strategies for parents during an OFC. This study sought to determine effectiveness of a 5-min deep breathing intervention (compared with standard of care) in reducing parental anxiety on the day of their child's OFC. Methods: Parents of children with food allergy who underwent an OFC at BC Children's Hospital were randomized to receive deep breathing exercises (intervention group) or standard of care (control group). Effects of the deep breathing intervention were measured objectively with a biofeedback device at three time points: pre-intervention, post-intervention before first dose of food, and post-OFC, and subjectively with the State Trait Anxiety Inventory-State anxiety (STAI-S) pre-intervention and post-OFC. Data analysis included an independent t-test to compare the effects of the intervention on anxiety between groups and correlation between the change in anxiety (subjective vs objective) from pre-intervention to post-OFC. Results: Of 118 parents approached, 92 participated (78.0%); 54 received the intervention and 38 were controls. Baseline STAI-S scores were 46.1 (intervention) and 47.9 (control). There was no significant difference in subjective anxiety between the two groups pre-intervention to post-OFC (difference 0.64, 95%CI − 1.76, 3.04). There was no significant difference in objective anxiety between groups at any of the three time points. There was weak correlation between the change in anxiety (subjective vs objective) from pre-intervention to post-OFC (r 2 = 0.016).

Conclusions:
Deep breathing did not significantly reduce parental anxiety. Parents reported moderate to high anxiety before their child's OFC, which highlights the importance of screening for anxiety in clinical practice. Our study is limited in that the intervention was 5 min long, and some parents who declined participation may have had higher anxiety. Further studies incorporating coping strategies to reduce parental anxiety during an OFC are needed. Background: Peanut allergy is considered the most severe of all food allergies as it is the leading cause of fatal anaphylaxis. Evidence suggests that the allergenicity of peanuts is significantly increased in its roasted form when compared with raw. The aim of this project is to develop alternative processing methods to decrease the allergenicity of peanut. Methods: Advanced Glycation End products (AGEs) are considered to be the main cause of increased allergenicity. Peanuts were ground into a paste and dissolved in n-hexane for defatting. Protein extracts from raw, roasted (150 °C, 30 min), boiled (100 °C, 2 h in water) and autoclaved (136 °C, 2.15 atm, 30 min) peanuts were used to quantify IgE binding via ELISA using serum samples from peanut-sensitive patients. Western Blot analyses were then carried out on the panel of protein extracts using an antibody specific for Ara h 2. Results: IgE-binding assays of the extracts revealed no difference in IgE binding between raw and roasted or boiled peanuts but revealed a significant difference (p < 0.05) between raw and autoclaved peanuts. An absence of signal in the Western Blot analysis indicates potential degradation of Ara h 2 in autoclaved peanut samples. These results were consistent following roasting of the peanut before or after autoclaving, demonstrating a dominant effect of autoclaving over roasting in the context of IgE-binding.

Conclusion:
In contrast to other findings, our results indicate no relevant difference in IgE binding between raw, roasted or boiled peanuts. However, a significant difference in IgE-binding and in Ara h 2 detection was found between autoclaved and raw peanut proteins, a dominant effect over roasting. Further analysis is required to determine what effect autoclaving has at the molecular level.
Background: Data on first anaphylactic reaction in children with no known food allergy is sparse. We aimed to assess the clinical characteristics and management of first anaphylactic reactions in children presenting to six Emergency Departments (EDs) across Canada. Methods: Between April 2011 to May 2019, children presenting to six EDs in four Canadian provinces with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis REgistry (C-CARE). A standardized data form documenting symptoms, triggers and management was collected. Multivariate logistic regression was used to predict factors associated with epinephrine treatment among first anaphylactic reactions in children.
Results: Over an 8-year period, among 2701 children presenting with food-induced anaphylaxis, 1027 (38%) children presented with their first reaction. The main triggers were peanut (17%), tree nut (15%), and egg (11%) among all ages. Outside of the ED, epinephrine was used to treat 15% of cases and antihistamines in 40%. Inside in the ED, epinephrine was used in 56% of patients and antihistamines in 53%. When stratifying by age, the main triggers of first reactions in children less than 1 year old were egg (31%) and milk (15%); in children between 1 and 6 years old, peanut (24%) and tree nut (21%); in children between 7 and 12 years, other food (21%) and unknown food (18%); and in children 13 years and over, unknown food (23%) and other food (21%). First anaphylactic reactions triggered by egg were more likely to be treated without epinephrine (adjusted Odds Ratio (aOR) 1.11 (95%CI 1.01, 1.22)), while those reacting to milk (aOR 1.22 (95%CI 1.07, 1.39)) and with severe reactions (aOR 1.17 (95%CI 1.02, 1.34)), were more likely to be treated with epinephrine, while adjusting for age, sex, asthma, and location. Conclusion: Difference between age groups for specific food triggering first anaphylactic reactions may be due to introduction patterns of different foods. Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently implicated in hypersensitivity reactions in children. Given that Ibuprofen is often used to manage fever in children and given the absence of standardized skin tests in the diagnosis of NSAID allergy, drug challenges are the only available tool to establish the diagnosis of this drug allergy. We aimed to assess the risk of Ibuprofen allergy in patients through the graded oral challenge. Methods: All children referred to the Montreal Children's Hospital for suspected NSAIDs allergy were recruited for the LACTAAM study between January 2017 and June 2019. A standardized survey of treatment, symptoms, and associated factors was filled and an oral challenge (10% and 90% of the oral dose) was conducted. The families were contacted annually to inquire about subsequent NSAID use. Descriptive statistics were used to characterize the reactions. Results: Thirty-five patients with a reported allergy to Ibuprofen were recruited. The majority of the reactions (65%) occurred within 1 h after using the medication and 89% occurred within the first 3 days of taking the drug. The most common symptom Allergy Asthma Clin Immunol 2020, 16(Suppl 1):47 was angioedema (54%). All children underwent an oral challenge with ibuprofen and six patients (17.14%) had a positive challenge, five of which were immediate reactions and one non-immediate reactions. Among the six patients, symptoms were consistent with anaphylaxis in three (50%), and all three (100%) were treated with epinephrine. Among the 27 patients with negative oral challenge eligible for follow-up, 15 (55%) patients responded. Of the contacted patients, nine (60%) reported subsequent Ibuprofen use of which two patients (22.22%) reacted and had symptoms consistent with anaphylaxis. Conclusion: Graded oral challenges can be used to diagnose an allergy to Ibuprofen. However, the challenges are associated with high risk of anaphylaxis and there is a 22% risk of subsequent reaction despite negative challenge in this small cohort. Background: As oral immunotherapy (OIT) becomes more commonplace in Canada, clinics will need to modify their primarily consultationbased practice in order to accommodate frequent follow-ups both during buildup and maintenance phases. Physicians will also need to adapt to the change in logistical burden associated with OIT. Clinical and nonclinical burdens will present barriers to physicians and patients and will affect accessibility to OIT. Methods: As a quality improvement initiative, we have retrospectively reviewed patient charts, clinic schedules and daily patient email contact with OIT physicians in a private practice pediatric clinic offering multifood OIT from May, 2017-May, 2019. We have also modelled future maintenance follow-up burden.

Results:
We have demonstrated a significant increase in daily OITrelated after-hours/weekend email contact managed by physicians. Over a 1 year period, frequency of email contact increased from 3.5 emails per day to 14.5. This contact has increased with the number of enrolled patients. We also demonstrate a significant increase in frequency of oral graded challenges (OGCs) in our clinic related to increases in demand for OIT. Completed oral challenges have increased from a frequency of 2 per day to approximately 8 per day. We currently book up to 12 oral challenges per day and have performed 1980 OGCs in the 2 years. OIT up dose visit absenteeism related to patient illness or uncontrolled asthma was evaluated demonstrating a mean absentee rate of approximately 33%. Finally, modelling of follow-up appointments suggest that in 5 years, our clinic will need to accommodate between 12.5 and 16.3 40-h weeks simply seeing OIT follow-up patients on maintenance.

Conclusions:
The logistical burden of OIT increases as clinics increase the number of patients treated. This burden will be felt by physicians, administrative staff, allied health and patients. These logistical challenges will affect accessibility to OIT and will present long term challenges. Background: Our previous study found that supervised administration of the epinephrine autoinjector (EAI) during an oral food challenge (OFC) increased confidence administering the EAI [1]. We sought to determine whether administering the EAI in the community since the OFC had a similar effect on confidence, and whether increased confidence was sustained over time. Methods: Families who completed an OFC at BC Children's Hospital were sent a follow up survey 1 year after the OFC, asking them whether they had administered an EAI since the OFC, and their confidence in administering it (1 = not very confident; 5 = very confident  Background: Most patients with cow's milk (CM) allergy can be safely desensitized via a three-stage oral immunotherapy (rush, escalation and maintenance). The duration of CMOIT is mainly determined by the progress of updosing during escalation phase when adverse reaction often occurs. It remains challenging to identify individuals who are less responsive to standardized desensitization procedures. We sought to assess the association of skin prick test (SPT) wheal size and length of escalation phase for milk desensitization. Methods: CM-allergic patients from two Canadian tertiary hospitals were enrolled. Following challenge and rush desensitization, each patient underwent weekly updosing at clinic visit and took daily dose at home between visits. Clinical data and skin prick test (SPT) were registered when targeted doses (initial, 6, 25, 125, 200 and 300 mL) were taken during escalation. Patient progress was charted and survival analysis was conducted to determine the cumulative probability of successful desensitization with regard to SPT wheal size at study entry. Results: Of 79 patients, 42 were successfully desensitized over the escalation phase that ranged between 141 to 791 days (median of 232 days). In these patients, SPT wheal diameters decreased from a mean of 10.6 mm at the study entry to that of 5.7 mm at the end of updosing phase (P < 0.01). According to their SPT wheal size at study entry, the median time to achieve complete desensitization were 232, 259 and 552 days for groups with SPT ≥ 3 mm, SPT ≥ 8 mm, and SPT ≥ 15 mm respectively. Kaplan-Meier analysis revealed a cumulative probability of successful desensitization after 791 days at 100% for SPT ≥ 3, 96.1% for SPT ≥ 8 cm and 64.5% for SPT ≥ 15 (P = 0.0001). Conclusions: Larger SPT is associated with prolonged CM desensitization. Strategies aiming to shorten dose escalation interval are required for patients with large SPT (≥ 15 mm) at study entry. The study was approved by MUHC-RI's Ethics Board, approval number PED-12-090 with http://www.clini caltr ials.gov registry no. NCT03644381. Background: The ideal form of allergen to be used for oral immunotherapy (OIT) has yet to be defined. The approach favored in many clinical trials has been to prepare individual pre-weighted doses of allergen flour. However, this approach is time consuming and is technician-dependent. The aim of this study was to determine the efficiency and exportability of the use of peanut suspension in simple syrup compared with individual pre-weighted flour doses. Methods: Total time for preparing 500 ml of peanut protein suspension in simple syrup at 50 mg/mL was measured, including the time needed for preparing the equipment, weighting peanut flour, mixing it with syrup, completing forms, distributing the peanut suspension in doses cups of 80 ml and cleaning the production space. The time needed to complete two prescriptions of 40 doses of 25 mg and 125 mg of peanut protein was also assessed. Procedures were first performed by an experienced dietetic technician and then repeated by an allergist with less experience in these tasks. Results: When considering technician time for 1 month worth of doses at 25 mg protein, the peanut suspension represented a gain in efficiency of 2340% compared to individual pre-weighted doses. For the 125 mg dose, the efficiency was 470% better for the peanut suspension. When considering allergist time, the gain in efficiency was even more pronounced (3533% and 670% increase for doses of 25 mg and 125 mg, respectively). Conclusion: Use of peanut suspension in simple syrup rather than preweighted individual doses can lead to major gain in efficiency. The level of efficiency is also less dependent on technician experience, making for an easily exportable solution for OIT clinics with minimal resources. Allergy Asthma Clin Immunol 2020, 16(Suppl 1):47

Efficiency of peanut suspension with simple syrup compared to individual pre-weighted flour doses for oral immunotherapy
Methods: A self-administered, anonymous paper questionnaire adapted from previously published studies was distributed to adult patients at 2 allergy clinics in Vancouver since October 2018. Information regarding route and frequency of marijuana use, associated symptoms, and concomitant allergic conditions was obtained. The study was approved by the Canadian SHIELD Ethics Review Board, approval number 18-10-002. Results: 58 of 66 distributed questionnaires were completed. 18 (31.6%) participants were male. Mean age was 38.8 years. Commonly reported routes of marijuana consumption were inhalation (64.2%), topical application (35.1%) and ingestion (31.0%). 48 (82.8%) participants have used marijuana, among which 35 (73%) reported symptoms upon exposure. Respiratory and ocular symptoms were most frequent (91.4%), followed by dermatologic (25.7%) and gastrointestinal (17.1%). 33 participants were actively using marijuana, with 25 (75.8%) reporting symptoms. 4 of 8 (50%) participants without previous marijuana consumption also reported symptoms. 21 (60%) participants with marijuana exposure, and 3 (30%) participants without, reported food allergy. Conclusions: A large portion of marijuana users attribute allergic symptoms to marijuana consumption. Nevertheless, most continue to use marijuana. A higher proportion of patients with marijuana exposure reporting food allergies may be driven by cross-reactivity. Future directions include determining sensitization by validated testing. Keely Loewen and Nancy Ross are co-first authors Background: Students at risk for anaphylaxis must strictly avoid their allergens and have their epinephrine auto-injectors available at all times. In Manitoba, students with life-threatening allergies are provided with an Anaphylaxis Standard Health Care Plan. Teachers and school staff receive training on recognition and management of anaphylaxis by registered nurses through the United Referral Intake Service (URIS) Program. Manitoba school divisions are creating a policy to have "back up" stock epinephrine auto-injectors available for students who have been prescribed an epinephrine auto-injector. This study examines the baseline accessibility of epinephrine auto-injectors in schools before the availability of stock epinephrine. Methods: The University of Manitoba Health Research Ethics Board and participating school divisions approved the study. School principals were emailed an Invitation Letter and SurveyMonkey ® Link for a brief questionnaire regarding epinephrine auto-injectors in their schools during the 2018-2019 school year. We examined number of anaphylaxis episodes, epinephrine auto-injector administration, and ability to locate the auto-injectors of students experiencing anaphylaxis. Results: After the first invitation, 26 of 78 invited school principals (33%) participated by the last week of June 2019. Of the principals who responded, 3.8% reported a child or children experiencing 1-2 episodes of anaphylaxis. In each case, the individuals' own epinephrine auto-injectors were used and were not difficult to find. Preliminary data did not identify trouble locating at-risk individuals' epinephrine auto-injectors in schools when they were needed to treat anaphylaxis. Conclusions: Among participating schools, anaphylaxis at school was a rare occurrence and the individuals' own auto-injectors were administered. We will send a second wave of questionnaires to school principals in September. We will also repeat this questionnaire after the next school year to evaluate epinephrine auto-injector use and the influence of stock epinephrine auto-injector availability. Acknowledgments: We thank the participating school divisions, all school principals who completed the questionnaire and The Canadian Allergy, Asthma and Immunology Foundation (CAAIF) for funding this study.

#53
A real world evaluation of pediatric preschool peanut oral food challenges in a private practice clinic prior to oral immunotherapy Douglas P. In clinical practice, allergists often utilize skin prick testing (SPT) and/ or blood work in conjunction with clinical history to diagnose food allergy. For a number of reasons, oral challenges continue to be infrequently performed and are generally under-utilized in clinical practice. As therapies such as oral immunotherapy (OIT) for food become more commonplace, proper diagnosis of food allergy is essential. Methods: A quality improvement retrospective chart review was performed involving all oral challenges to peanuts in a private practice clinic specializing in OIT between May, 2017 and May, 2019. Results: Of 1980 oral challenges performed, 118 were for peanut in patients < 6 years or ages referred for OIT. Of these, 67 patients passed the oral challenge. Of those that passed, 56 had a history of prior clinical reaction. Mean age for all patients was 2.45 years. Mean peanut SPT was 7.23 mm, Peanut SSIgE was 8.15 KU/L and AraH2 IgE was 3.48, and all mean values were higher in those that failed the oral challenge. No severe reactions during oral challenge were reported with the most common symptoms being urticaria, mouth/throat itch and vomiting. Rupatadine was used in 98% of oral challenges and epinephrine was used in 16%. Comparison of outcomes was also made with patients that were not referred for OIT. Referral source was also evaluated. Conclusions: In a real world study of a preschool population referred for OIT, only a minority of patients had confirmed peanut allergy, and reaction severity in this population was mild-moderate. This has significant implications as OIT guidelines are developed and commercial products are being marketed. Oral challenges should form the foundation of food allergy diagnosis, especially in patients interested in OIT.
questionnaire incorporated into a software program developed specifically for the study. Results: From 2013 to 2017, 433 patients requiring EMS due to an anaphylactic reaction were recruited, of which 42.6% were male, with a median age of 40.7 years (interquartile range [IQR]: 20.1, 59.0). The percentage of anaphylaxis among all ambulance calls did not change significantly [0.06% (95%CI − 0.02%, 0.15%)] over this time interval. Among patients with anaphylaxis, 37.4% presented with a food allergen trigger. Among food allergens, the most common trigger was peanut (19.8%). Around 20% of anaphylactic reactions were reported to be triggered by drug (17.6% of which were triggered by moxifloxacin), and similarly 20.1% were caused by venom. Approximately 15% of anaphylactic reactions were caused by an unknown exposure. Prior to EMS arrival, only 33.7% patients were administered epinephrine, compared to 35.6% who were administered antihistamines. Prior to EMS arrival, 2.7% of patients were administered steroids. Almost 60% were administered epinephrine by the paramedics, 0.4% were administered antihistamines and none were administered steroids. One-fifth (20.8%) of patients were administered epinephrine both before and after EMS arrival. Conclusion: Epinephrine administration by patients prior to EMS arrival occurs in less than half of the cases of anaphylaxis in rural settings of Quebec. Background: Peanut allergy is associated with poor health-related quality of life (QoL). PALISADE was a phase 3 double-blind, placebocontrolled trial that investigated the safety and efficacy of AR101, an investigational oral biologic drug for use in oral immunotherapy in peanut-allergy subjects. A subgroup of subjects continued the therapeutic dose of AR101 (300 mg/day) in an open-label follow-on study (ARC004) for 28 weeks. Here we report on the changes in QoL in these subjects. Methods: Subjects 8-17-years-old (self-report) and parents/caregivers of subjects 4-17-years-old (proxy-report) completed an age-appropriate Food Allergy Quality of Life Questionnaire (FAQLQ) and Food Allergy Independent Measure (FAIM) at PALISADE screening, exit and at ARC004 exit. Total and domain scores were calculated for all time points for the overall population and stratified by responder status, systemic allergic reactions, or adrenaline use during the study period. Changes in scores (screening to exit) were calculated to determine if they exceeded the developer-referenced minimally important difference (MID) ≥ 0.5. Results: 110 PALISADE subjects 4-17-years-old received 300 mg/day AR101 in ARC004; 68 subjects and 93 parents/caregivers completed FAQLQ and FAIM. Self-reported QoL from screening to exit in total scores for FAQLQ and FAIM improved and exceeded the MID (FAQLQ: Background: Approximately 8% of children have food allergies, which impacts family life. Yet, parents' coping strategies for this disease burden are incompletely understood. We aimed to describe the perceptions of allergy-related mental health issues in families with food allergy. Methods: This is an ongoing qualitative interview study of parents of children with paediatric allergist-diagnosed food allergy, who were recruited in allergy clinics and education centres in Winnipeg. Interviews were transcribed verbatim. We used content analysis from which we identified preliminary overarching themes. The University of Manitoba Health Research Ethics Board approved this study (HS22242 (H2018-408)). Results: To date, we have interviewed 13 mothers, with children aged < 12 months to 13 years. Perceived mental health impacts varied by type and number of food allergies, and time lapse since diagnosis. For parents whose children had a single food allergy, "Accommodation and Adaptation" was described, whereas most parents of children with multiple food allergies reported negative impacts on their mental health. As captured in the theme, "Pragmatism and Isolation", many spoke of being "depressed" and "terrified" about leaving their children in the care of others who were perceived as being only minimally equipped to handle food allergy. Parents felt "overwhelmed and alone," and engaged in negative ways of coping. For parents who lacked support from their extended family and/or daycare/school, this impact was particularly strong. Time lapse since diagnosis also impacted perceived mental health. "Fear for today, fear for the future" was commonly described by parents whose children were recently diagnosed, whereas the theme, "Food allergy management has become our normal" was identified amongst parents whose children had been living with the condition for some time. Conclusion: Food allergy has varying impacts on parental mental health. Most negatively affected are those whose children have multiple food allergies, and/or who have recently been diagnosed.
Background: Food allergy may impact diet quality and nutrient intake. The aim of this study was to examine intake patterns of calcium-rich foods and supplements, and dairy quality amongst adolescents with or without a history of food allergy. Methods: We examined intake patterns of calcium-rich products amongst Manitoba adolescents by food allergy status, using data from a cohort born in 1995 and followed to adolescence. At ages 7-8 (childhood) and 12-14 (adolescence) years, parents reported if their child had ever had food allergy. Adolescents completed food frequency questionnaires, which queried calcium-rich foods calcium-fortified orange juice and multivitamin/mineral supplements. Intake patterns were defined as 1+ weekly, vs. < 1 weekly, except calcium-fortified orange juice, which was categorized as no/yes. Dairy quality scores were classified based on the Youth Health Eating Index, with low-fat milk and yoghurt consumption scored twice as high as high-fat, high-sugar dairy. Logistic regression was used, with adjustments for confounders. This study was approved by The University of Manitoba Health Research Ethics Board (HS14742 (H2002:078)). Results: Overall, 472 adolescents were included, including 60 (13%) with food allergy ever. Compared to adolescents without food allergy, adolescents with a history of food allergy were significantly less likely to consume milk 1+ weekly (OR 0.39; 95%I 0.20-0.77). In contrast, intake patterns of other calcium-rich foods and supplements were similar between the groups (all p > 0.05). Mean dairy quality was poor (4.1/10). Although dairy quality scores tended to be slightly higher amongst boys than girls (p = 0.08), it did not differ by food allergy status in childhood, in adolescence or by timing. Conclusion: Manitoba adolescents with a history of food allergy consume less milk, but similar amounts of other calcium-rich foods, compared to their non-food allergic peers. Whereas dairy quality was poor amongst all adolescents, it did not differ by dairy quality scores. Little is known about the dynamics of specific IgE antibody (sIgE) levels during and after an allergic reaction. We evaluated the differences in food sIgE levels during and after foodinduced anaphylaxis. Methods: Patients presenting to the Emergency Department (ED) of the Montreal Children's Hospital with food-induced anaphylaxis were recruited for the Cross-Canada Anaphylaxis Registry (C-CARE) between 2013 and 2019. sIgE levels (Phadia ImmunoCAP) of the suspected culprit allergen and of other related and unrelated foods, in addition to tryptase levels, were drawn within 2 h of presentation and at least 24 h later. We compared sIgE (and tryptase) levels during and after the reaction with the paired Wilcoxon test. A multivariable linear regression model was used to predict factors associated with difference in sIgE levels of the reported culprit allergen during and after the reaction. Results: Among 50 consenting pediatric cases, sIgE levels of the reported culprit allergen after anaphylaxis were higher than during the reaction, yielding a mean difference of 8.41 kUa/L (p = 7.87 × 10 −6 ). The median time interval for sIgE differences was 4 weeks (IQR = 5). Among the 34 patients who had their sIgE levels of unrelated foods measured, the difference was not substantial (2.15 kUa/L, p = 0.473). In 46 patients, tryptase levels during and after anaphylaxis were also measured. All had decreased levels after the reaction consistent with the definition of anaphylaxis with a total mean difference of 7.03 µg/L (p = 2.59 × 10 −9 ). Older children (0.067 (95%CI 0.00094, 0.13)) and children with higher tryptase level difference (0.83 (95%CI 0.14, 1.52)) were found to be more likely to have higher differences in sIgE levels, while adjusting for sex, and difference in sIgE levels of unrelated foods.

Conclusion:
The results suggest that changes in sIgE levels may contribute to identifying the culprit allergen when history is unclear. The study was approved by McGill University Health Center Research Ethics Board. REB # 12-084 PED. Background: In PALISADE, a phase 3 study of AR101 in North America and Europe, immunological changes suggested immunomodulation of peanut allergy during the first year of treatment, including 6 months of dose escalation and 6 months at the therapeutic dose (300 mg/day). Efficacy, safety, and immunological changes after 28 additional weeks of 300 mg/day in subjects 4-17-years-old is reported. Method: AR101-treated PALISADE completers tolerating ≥ 300 mg peanut protein at double-blind, placebo-controlled food challenge (DBPCFC) entered the follow-on study ARC004. A subset (including Canadian subjects) continued 300 mg/day AR101 for 28 weeks and completed a DBPCFC with an additional 2000 mg (4043 mg cumulative) challenge dose. Peanut skin-prick test (SPT) and peanut-specific IgE (psIgE) measurements (reported as median [Q1, Q3]) were compared (PALISADE vs. ARC004). Results: 110/285 AR101-treated subjects aged 4-17 years continued 300 mg/day AR101; the remainder were assigned to other dosing arms (not reported here). 94% of subjects completed the additional 6-month dosing period and exit DBPCFC. Two subjects discontinued AR101 due to adverse events (AEs). The proportion of subjects reporting related AEs were similar (PALISADE 45% vs. ARC004 43%) but the number of events decreased (739 vs. 371 events). Median tolerated dose at ARC004 DBPCFC was 1000 mg (1000, 2000) (n = 104). Of subjects who tolerated < 1000 mg at PALISADE exit (n = 37), 70% tolerated a higher challenge dose at ARC004 exit. Hemp is a variety of Cannabis sativa that contain lower THC concentration, and hemp seed has become a popular food ingredient due to its nutritious value. There are few reports to date on anaphylaxis to hemp seed, and cannabis is a new allergen that is not well-recognized. We, therefore, investigated the clinical features of seven patients with anaphylaxis to hemp seed ingestion. Methods: Seven patients who presented to an ambulatory allergy clinic for hemp seed allergy with clinical symptoms fitting the diagnostic criteria of anaphylaxis were evaluated. Skin prick test with a cannabis extract was performed. Results: The mean age of the patients was 33 (range 26-40) years, and there were 4 females and 3 males. All patients had positive skin prick test to cannabis. 6 patients have previously smoked cannabis and had no known prior exposure to hemp seed. One patient has never been exposed cannabis before having anaphylaxis to hemp seed ingestion. The symptoms involved multiple systems, including urticaria, angioedema, dyspnea, syncope and, most commonly, abdominal cramps. Of the 6 patients who had previous exposure to cannabis, none had anaphylaxis to smoking cannabis. Conclusions: We present one of the first case series of patients with anaphylaxis to hemp seed ingestion. There is evidence showing that smoking cannabis could have sensitized our patients to hemp seed. With legalization of cannabis in Canada, the prevalence of cannabis allergy will likely be on the rise. Patients exposed to cannabis should be made aware of the potential risks as hemp seed is added to a variety of foods due to its increasing popularity. Background: Skin prick testing (SPT) is commonly performed to assess for allergen sensitization, but SPT infants with atopic dermatitis who have an impaired skin barrier may sensitize them to tested allergens. Methods: A retrospective chart review was conducted at a community clinic identifying infants with atopic dermatitis (AD) who were evaluated for allergic sensitization via skin testing (ST). AD infants who were initially positive for allergies and were re-evaluated with repeat ST were selected. Allergy ST assessments were directed towards foods including milk (1:10 w/v), egg white (1:100 w/v), egg yolk (1:100 w/v), soy (1:10 w/v), wheat (1:10 w/v), tree nut mix (1:10 w/v), and peanuts (1:10 w/v). Infants with a wheal size 3 mm or greater, than negative control were considered sensitized to these foods with advice on avoidance until formal oral challenge was arranged to confirm tolerance or allergy. Results of ST were compared at separate visits to each food. Results: The wheal size of 30% (7/23) of milk, 28% (7/25) of egg white, 25% (6/24) of egg yolk, 0% (0/9) of soy, 10% (1/10) of wheat, 37.5% (3/8) of tree nut mix, and 31.3% (5/16) of peanut skin tests increased by 3 mm or more in the most recent skin test compared to initial testing. Seventyone percent of milk (5/7), 85.7% of egg white (6/7), 83.3% of egg yolk (5/6), 0% of soy (0/9), 100% of wheat (1/1), 66.7% tree nuts (2/3), and 60% of peanut (3/5) of these infants' initial skin test had a wheal size of 0 mm. Conclusions: The dual exposure to allergen hypothesis states that sensitization to foods is a result of cutaneous exposure to potential allergens. Consequently, SPT infants with AD may increase risk for sensitization to tested allergens due to increased cutaneous exposure through impaired skin barrier.

Early skin prick testing infants with atopic dermatitis leads to sensitization of food allergens
We sought to detect induction of CMP-specific Tregs, relative to CMP-specific Teffs in a cohort of subjects undergoing OIT. Methods: Thirteen children with confirmed CMP allergy underwent OIT with escalating doses of milk up to 300 ml (maintenance) and were followed for up to 12 months post-maintenance. For each patient, PBMCs were obtained at baseline and specific milestones during dose escalation and maintenance. Casein-specific T cells were expanded from PBMCs by culturing for 10 days with casein. Caseinspecific CD4+Teffs (Cs-Teffs, FoxP3-Helios-expressing CD154) or Tregs (Cs-Tregs, Foxp3+Helios+ expressing CD137) were quantified in proliferating (CTVlow) or non-proliferating (CTVhigh) culture fractions, and characterized by flow cytometry. The study was approved by Research Institute of the McGill University Health Centre's Ethics Board, approval number PED-12-090. Results: Cs-Tregs were found in proliferating cultures in OIT subjects. The proportion of Cs-Tregs increased significantly with escalation of milk doses during OIT. There was no change in Cs-Tregs in non-proliferating culture. There was also no change in Tregs against a control antigen, tetanus toxoid. Induction of Cs-Tregs correlated with reduction in frequency of Cs-Teffs and in vitro Th2 cytokine production. An increased ratio of Cs-Tregs to Cs-Teffs in proliferating cultures, was associated with developing tolerance among OIT subjects. Conclusion: OIT to CMP induces highly suppressive Cs-Tregs, compared to pretreatment levels, and Tregs levels increased with increasing exposure to CMP. CMP-specific Tregs may inhibit CMP-specific Teffs in children receiving OIT. Background: Cow's milk allergy (CMA) is an inappropriate immune response against cow's milk protein (CMP) and is the leading cause of severe anaphylaxis in children. Our laboratory is currently leading the first Canadian randomized controlled trial of milk oral immunotherapy (OIT). The goal is to enable children with CMA to tolerate ingestion of cow's milk without developing allergy symptoms. Past work has shown that OIT alters the serum CMP-specific immunoglobulin E (sIgE) and sIgG4 levels. However, we observed a high variability in the levels of sIgE and sIgG4 over the course of milk OIT. We aim to determine clinical parameters that affect sIgE and sIgG4 level in milk OIT participants. Methods: Children with confirmed CMA by history, skin prick test, and oral food challenge were studied. Serum was collected at specific time points during the escalation phase which ended at 200 ml of cow's milk then followed for 12 months while consuming dairy. We used indirect ELISA to measure the level of serum IgE and IgG4 specific for CMPs: α-lactalbumin, β-lactoglobulin, and casein. This study was approved by the Facility Animal Care Committee of the Research Institute of the McGill University Heath Centre, approval #PED-12-090. Results: Overall, the level of sIgE in milk OIT participants decreased while sIgG4 increased. Current results indicate a difference in the levels of sIgE and sIgG4 between male and female participants. Female participants have higher sIgE and lower CMP-specific sIgG4 than male participants. Correlations with clinical outcomes and adverse reaction profile were performed to address sex differences in outcome following OIT therapy. Conclusion: Our current results indicate that sex difference may contribute to the high variability in levels of sIgE and sIgG4. Identification of potential factors that contribute to varied level of Ig can help us understand the immune response during OIT and food allergy. Here, we sought to evaluate the systemic frequency and dynamics of multiple Breg subsets prior to, and during the resolution of AAD. Methods: IL-10 reporter mice were sensitized and challenged using house dust mite (HDM) extract to induce AAD protocol. We evaluated the frequency and phenotype of B cells and Bregs in the bone marrow, lungs, spleens, peripheral blood, peritoneal cavity, pleural cavity, and livers of naive mice, and sensitized mice at multiple time points following the final HDM challenge. Cell phenotypes were evaluated via flow cytometry, and correlations of Breg populations post-challenge with the resolution of airway eosinophilia were assessed. This study was approved by the Facility Animal Care Committee of the Research Institute of the McGill University Heath Centre (RI-MUHC), protocol #6011. Results: Preliminary results demonstrate substantial IL-10 expressing Breg populations in peritoneal cavity, pleural cavity, and the bone marrow of naive mice, which predominantly consist of cells from the B1 and CD138+ plasma cell subsets. Breg frequency increases in the lungs of allergic mice 48 h after the last HDM challenge. We also analyzed the systemic dynamics of Breg populations over the course of the natural resolution of lung inflammation is mice. Conclusions: Our results show the distribution and changes in Breg populations in mice following the induction and resolution of AAD. Future work will evaluate the functional capacity of different Breg subsets to suppress airway inflammation, and correlates in human asthma. included only if they had quantifiable data comparing human PID cases to non-PID controls. Results: 5485 articles were identified, 1060 abstracts screened, and 8 articles were included in the final analysis. The following features were found to be predictive of PID: absolute lymphopenia or CD3 + /CD4 + , CD19 + or CD16 + /CD56 + subsets below the 10th percentile, hypogammaglobulinemia, neutropenia, immune thrombocytopenia, splenomegaly, enteroviral or respiratory tract infections, serious bacterial, persistent fungal, or recurrent deep-seated infections, chronic diarrhea, failure to thrive/growth retardation, family history of PID, parental consanguinity, sibling death, need for IV or prolonged courses of antibiotics, immunodeficiency related score > 6 (a clinical scoring system of immunodeficiency-related conditions), history of hospitalization, recurrent viral infections or atopy in adulthood, autoimmunity in childhood, and adolescent presentation of recurrent/frequent infections. Conclusion: Combinations of clinical features can be used to detect PID patients, and this work identifies features that have evidence supporting their use. Future work will aim to integrate these features into a clinical scoring tool that will be validated in a patient cohort at BC Children's Hospital. Ig20Gly) is a ready-to-use 20% liquid subcutaneous immunoglobulin (SCIG) formulation approved as antibody replacement therapy for primary immunodeficiency diseases (PID) in patients aged ≥ 2 years in the US and Canada. The HelloCUVITRU Program (HCUVP) provides 4 in-home infusions of Ig20Gly in the US to eligible patients with PID, at no cost to patients or their health insurance. Methods: A retrospective, descriptive analysis of demographics, clinical characteristics, and infusion parameters of patients enrolled in the HCUVP was performed. Eligible patients had PID, were ≥ 2 years old, able to receive Ig20Gly at home, and had no history of Ig20Gly use. Patients whose first Ig20Gly infusion occurred between January 1, 2017 and September 1, 2017 were included in the analysis. Because data were anonymized in compliance with CFR 46.101(b)(4), this study was exempt from institutional review board approval. Results: A total of 817 patients completed all 4 infusions (N = 817); 598 (73%) were female and mean age was 50 (range: 2-89) years. Of immunoglobulin-experienced patients with data on previous treatment, 268 (64%) received intravenously administered immunoglobulin and 152 (36%) received SCIG. By visit 4 (final), median (interquartile range) infusion rate/site was 47 (43-53) mL/h, infusion volume/site was 40 (30-50) mL/site, infusion duration was 50 (37-60) minutes, and dose was 0.2 (0.1-0.2) g/kg. During visit 4, the most common infusion area was the abdomen (upper: n = 359, 44%; lower: n = 302, 37%), followed by thigh (n = 221, 27%) and upper arm (n = 18, 2%), with most patients (n = 472, 58%) using 2 injection sites within each body area. Two-thirds (n = 544, 67%) of patients used 9 mm needles; patients also used 12 mm (n = 234; 29%) and 6 mm (n = 32; 4%) needles. Conclusions: This analysis described clinical and infusion characteristics of patients with PID who initiated Ig20Gly outside a clinical trial Funding: This study was funded by Baxalta US Inc., a member of the Takeda group of companies, Lexington, MA, USA. . Of the 227 genetically defined cases, mutations in the PRF1 gene were the most frequent (n = 67; 29.5%). However, mutations in genes associated with degranulation defects were more common than previously noted-STXBP2 (n = 45; 19.8%), UNC13D (n = 43; 18.9%), RAB27A (n = 17; 7.5%), LYST (n = 11; 4.8%) and STX11 (n = 6; 2.6%). X-linked disorders accounted for a smaller group-XIAP (n = 20; 8.8%) SH2D1A (n = 10; 4.4%) and MAGT1 (n = 5; 2.2%). Lysinuric protein intolerance gene SLC7A7 (n = 3; 1.3%) mutations were least commonly identified in patients. Conclusion: These results describe the largest cohort of genetic variants associated with suspected HLH in North America. Although only 12% of patients were identified with a genetic diagnosis by this diagnostic approach, the gene panel identified known pathogenic and novel variants in 15 HLH-associated genes. As a group, patients with degranulation gene defects represented the majority of cases, likely reflecting the availability of rapid immunologic screening prior to genetic testing. Allergy Asthma Clin Immunol 2020, 16(Suppl 1):47

Frequency and variant spectrum in 227 patients with molecular diagnosis of hemophagocytic lymphohistiocytosis
Background: Mastocytosis refers to a group of myeloproliferative disorders characterized by excessive proliferation and accumulation of mast cells in tissues. Mast cell degranulation leads to vasoactive mediator release and clinically presents as episodic anaphylactoid symptoms (pruritis, flushing, headache, etc.). When the manifestations of these disorders are limited to the skin, this condition is referred to as cutaneous mastocytosis (CM). Patients with mastocytosis are at increased risk of anaphylaxis. Limited available data suggests that most cases of pediatric CM resolve or spontaneously improve by adolescence. However, the disease can be disfiguring, disabling and potentially life-threatening to children who develop systemic mast cell mediator release. There is insufficient data on clinical characteristics of patients with CM as well as disease triggers and management. Given the paucity of data, we have established a mastocytosis registry to understand the clinical characteristics, management and natural history of cutaneous mastocytosis. Methods: In 2019 we established a registry to understand the clinical characteristics, management and natural history of CM. We are recruiting participants from dermatology and allergy clinics in Montreal and the Mastocytosis Society Canada and have developed a standardized questionnaire to assess these individuals. Results: We have so far recruited eleven participants. Among our participants, 72% are children (less than 18 years old) and 82% have been diagnosed with CM. The major flares were related to specific physical stimuli (81%), ingestion of specific foods (55%) and antibiotic use (18%). Among the participants, 55% were treated using antihistamines and 18% with steroids; 36% reported having experienced remission without treatment. Conclusion: We have established the first Canadian registry for mastocytosis. Our next steps will be to expand our registry to provide further data on diagnosis, flares and management of mastocytosis to improve the care for these patients and further develop this field of study. Background: Dupilumab, a fully human anti-IL-4Rα mAb that inhibits IL-4/IL-13, is approved for patients aged ≥ 12 years in the USA with moderate-to-severe atopic dermatitis (AD) inadequately controlled by topical prescription treatments or when those therapies are not advisable, adult AD patients in Japan not adequately controlled with existing therapies, and moderate to severe AD patients aged ≥ 18 years in Europe who are candidates for systemic therapy. Here we evaluate the effect on qualityof-life in patients treated with dupilumab + topical corticosteroids (TCS) using data from a phase 3 trial (CHRONOS: NCT02260986). Methods: Adults received dupilumab 300 mg weekly (qw + TCS)/ every 2 weeks (q2w + TCS) or placebo + TCS for 52 weeks. Outcomes included total Dermatology Life Quality Index (DLQI) and 6 subdomains scores: symptoms and feelings, daily activities, leisure, personal relationships (maximum score 6), work and school, treatment burden (maximum score 3). Conclusions: Adults with moderate-to-severe AD treated with dupilumab + TCS had improvements in total DLQI and all its domains vs placebo + TCS at Week 16, sustained through Week 52. 52.1%; P = 0.0067/P = 0.0972). At Week2, 80.6%/81.1% of patients in the qw + TCS/q2w + TCS groups reached ≥ 1 meaningful outcome vs. 60.3% of patients receiving placebo + TCS. These results were sustained or further improved at Week52 (qw + TCS/q2w + TCS vs. placebo + TCS: 72.1%/79.2% vs. 36.2%) (P < 0.0001 for all timepoints Week2-Week52). Injection-site reactions and conjunctivitis were more frequent with dupilumab than placebo. Conclusions: In this long-term phase 3 trial, a higher proportion of patients with moderate-to-severe AD treated with dupilumab + TCS had clinically meaningful improvement in 1 or more key AD domains (signs, symptoms, and QoL) as early as Week1 and through Week52.

Results
Background: Dupilumab, a fully human anti-IL-4Rα mAb, inhibits signaling of IL-4/IL-13, key drivers of type 2-mediated inflammation. Dupilumab is approved for patients aged ≥ 12 years in the USA with moderate-to-severe atopic dermatitis (AD) inadequately controlled by topical prescription treatments or when those therapies are not advisable, adult AD patients in Japan not adequately controlled with existing therapies, and moderate to severe AD patients aged ≥ 18 years in Europe who are candidates for systemic therapy. AD has an important impact on patients' quality-of-life, commonly assessed with the Dermatology Life Quality Index (DLQI) questionnaire. Here we report the effect of dupilumab treatment on quality-of-life by using pooled data from two 16-week phase 3 trials (LIBERTY AD SOLO 1: NCT02277743; LIBERTY AD SOLO 2: NCT02277769). Methods: Adults with moderate-to-severe AD were randomized to dupilumab 300 mg weekly (qw), every 2 weeks (q2w), or placebo qw for 16 weeks. Outcomes included total DLQI score and its 6 domains: symptoms and feelings, daily activities, leisure, personal relationships (maximum score 6), work and school, and treatment burden (maximum score 3). Dupilumab had an acceptable safety profile. Conclusions: Adults with moderate-to-severe AD treated with dupilumab monotherapy consistently had improvements in total DLQI score and scores in all its 6 domains compared with placebo at Week 16. Acknowledgments: Research sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. ClinicalTrials.gov Identifiers: NCT02277743 (LIB-ERTY AD SOLO 1), NCT02277769 (LIBERTY AD SOLO 2). Medical writing/editorial assistance provided by Natalie Adlesic, PhD, of Excerpta Medica, funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Background: Research conducted in the U.S has determined the prevalence of reported beta-lactam allergy to be between 10 and 17%. Currently, there is no data to date on the prevalence of self-reported or documented beta-lactam allergy in Canada. The purpose of this study is to describe the prevalence of physician-documented betalactam allergy in a Canadian outpatient population and to comment on associated characteristics of patients and providers. Methods: We conducted a retrospective cohort study using Electronic Medical Record (EMR) data from the Manitoba Primary Care Research Network (MaPCReN). An algorithm was generated to define and extract data on physician documented beta-lactam allergy from the EMR dataset (n = 211,132). Once established; prevalence, provider, and patient variables were analyzed using multivariate regression to assess differences between patients with reported beta-lactam allergy and those without. Results: Of the 221,132 records in the MaPCReN database, 2.89% (6397/221,132) of patients had a recorded beta-lactam allergy. Documented beta-lactam allergy was found to be associated with female sex (1.542 OR, 95% CI 1.463-1.623) and medical comorbidities including asthma and eczema (P < .0001 for both asthma and eczema). Conclusions: Prevalence of physician reported beta-lactam allergy in Manitoba was lower than previously recorded American studies. The validated algorithm will be applied to the larger Canadian Primary Care Sentinel Surveillance Network repository to describe epidemiology at a national scale and to further aid efforts in reducing burden associated with erroneous labelling.