Mapping the Food Allergy Quality of Life Questionnaire Parent Form onto the Short-Form Six-Dimensions version 2.

BACKGROUND: The Food Allergy Quality of Life Questionnaire Parent Form (FAQLQ-PF) is the most widely used quality of life questionnaire in food allergy. The objective of this study was to develop a mapping algorithm to convert FAQLQ-PF scores into health state utilities. METHODS: The Short-Form Six-Dimensions version 2 (SF-6Dv2) and FAQLQ-PF questionnaires were collected from an academic center oral immunotherapy referral cohort. Utility estimates were derived from the SF-6Dv2 using the food allergy preference set. Candidate mapping algorithm models were developed using seven regression methods starting from either the total average score, the average scores of each of the three domains or the individual item scores of FAQLQ-PF. The process was repeated twice, including only section A, common to all age groups, or including all age-applicable sections of the FAQLQ-PF. The mean absolute error (MAE) and root mean squared error (RMSE) were used to select the best fitting model. An independent cohort from a previous national online survey was used for external validation. RESULTS: In the index cohort, 1000 of 1257 respondents had completed both questionnaires. The lowest MAE (0.0791) and RMSE (0.1020) were recorded when entering individual item scores in a categorical regression model. The model including only FAQLQ-PF section A was found to be most consistent when tested in the external validation cohort (n = 248) (MAE of 0.0898). CONCLUSION: The FAQLQ-PF was mapped onto SF-6Dv2 utilities with good predictive accuracy in two independent cohorts. This will enable calculation of health utility for cost-effectiveness analyses in food allergy.

Specific IgE to Total IgE Ratio Does Not Improve Peanut Diagnostic Accuracy in Adults.

BACKGROUND: Peanut specific IgE (sIgE) can lead to false-positive results. OBJECTIVE: We aimed to assess whether peanut sIgE to total IgE (tIgE) ratio improves accuracy in predicting clinical reactivity to peanut compared to peanut sIgE alone, which has not been explored in the adult population so far. METHOD: A retrospective chart review was performed for adults who underwent peanut oral food challenge (OFC) and/or oral immunotherapy (OIT) at the Centre Hospitalier de l'Université de Montréal's allergy clinic between January 2017 and July 2021. Patients with positive peanut OFC and/or undergoing OIT were considered peanut-allergic. Patients with negative OFC were considered peanut-tolerant. Peanut sIgE to tIgE ratios were calculated and performance characteristics of the sIgE to tIgE ratio were compared to sIgE alone by using receiver operator characteristics curves. RESULTS: Forty-two patients were included (52% male) with a median age of 26 years (range 14-54). Forty-five percent had atopic dermatitis. Median sIgE levels were 2.64 kUA/L (range 0.1-100), median tIgE levels were 154 kUA/L (range 19-3,400), and median sIgE to tIgE ratio was 0.66% (range 0.04-38.3). Twenty-four patients (57%) were classified as peanut-allergic and 18 (43%) as peanut tolerant. The area under the curve for peanut sIgE was 0.921 compared to 0.926 for peanut sIgE/tIgE (p not statistically significant). CONCLUSIONS: We found that there was no significant benefit in using peanut sIgE to tIgE ratio over sIgE alone to predict peanut reactivity in an adult population. Larger prospective studies are needed to further confirm these findings.

Determinants of omalizumab dose-related efficacy in oral immunotherapy: Evidence from a cohort of 181 patients.

BACKGROUND: Omalizumab has been shown to improve the safety and feasibility of oral immunotherapy (OIT), but the optimal dosage strategy is unknown. OBJECTIVE: Our aim was to identify determinants of omalizumab dose-related efficacy in the context of OIT. METHODS: The study sample consisted of a clinical cohort of 181 patients treated with omalizumab-enabled oral immunotherapy at 3 centers. Patients received omalizumab for at least 2 months before an initial food escalation (IFE) with a mix of up to 6 allergens. Progression through IFE steps was assessed with survival analysis. Continued food dose tolerance with omalizumab weaning was also documented. RESULTS: Omalizumab dosage per weight alone was strongly associated with progression through the IFE (χ2 = 28.18; P < .0001), whereas the standard dosage per weight and total IgE level used for asthma was not (χ2 = 0.001; P = .97). When the values at time of IFE were estimated through pharmacokinetics and pharmacodynamics simulation, IFE outcome was best predicted by a model that includes levels of free allergen-specific IgE and their interaction with blocking omalizumab-IgE complexes and free omalizumab levels in serum (χ2 = 65.84; degrees of freedom [df] = 2; P < .0005). The occurrence of immediate-type reactions to food dosing subsequent to weaning of omalizumab was associated with a greater ratio of specific IgE level to total IgE level at baseline (geometric mean 0.39 vs 0.16 in those without symptom; P < .0001). CONCLUSION: In the context of OIT and IgE-mediated disease, omalizumab dosages should be adjusted for body weight alone, independently of total IgE level. The fraction of allergen-specific/total IgE may be useful to predict patients at greater risk of food dosing reactions subsequent to weaning.

SF-6Dv2 preference value set for health utility in food allergy.

BACKGROUND: The lack of a value set allowing the calculation of QALY is an important limitation when establishing the value of emerging therapies to treat food allergy. The aim of this study was to develop a Short-Form Six-Dimension version 2 (SF-6Dv2) preference value set for the calculation of health utility from the Canadian food-allergic population. METHODS: Two hundred ninety-five parents of patients aged 0-17 years old and 154 patients aged 12 years old and above with food allergy were recruited in clinic and online. Participants were asked to complete a self-administered online questionnaire including generic health-related quality of life questionnaires. Various health states described by the SF-6Dv2 were valued with time-trade-off and discrete choice experiments. Data from elicitation techniques were combined using the hybrid regression model. RESULTS: A total of 241 parents and 125 patients performed 3904 time-trade-off and 5112 discrete choice experiments. Utility decrements were estimated for each level of each SF-6Dv2 dimension. Utility values calculated based on the validated preference set were in average 0.15 lower (95%CI: 0.12-0.18) and were poorly correlated (R2  = 0.46) with those derived from the EQ-5D-5L generic questionnaire in the same cohort. CONCLUSION: A representative preference value set for patients with food allergy was determined using the SF-6Dv2 generic questionnaire. This adapted preference set will contribute to improve the validity of future utility estimates in this population for the appraisal of upcoming potentially impactful but sometimes costly therapies.

Skin testing only with penicillin G in children with a history of penicillin allergy.

BACKGROUND: The absence of commercially available penicilloyl-polylysine (PPL) for most of the last decade severely hampered the practice of penicillin allergy evaluation because skin testing without PPL is reported to have a poor negative predictive value (NPV). OBJECTIVE: To determine the safety and NPV of skin testing without PPL using only penicillin G followed by a 3-dose graded challenge to the incriminated penicillin in children with a history of penicillin allergy. METHODS: Patients evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between December 2006 and December 2009 were skin tested only with penicillin G and underwent a 3-dose graded challenge to the culprit penicillin if the skin test result was negative. RESULTS: Among 563 patients skin tested to penicillin G, 185 (33%) had a positive skin test result. These patients had a shorter interval between the initial reaction and skin testing compared with patients with a negative skin test result (P = .03). A total of 375 of 378 patients (99%) with a negative skin test result were challenged and 18 (4.8%) reacted, translating into a NPV of 95.2% (95% confidence interval [CI], 92.5%-97.1%). Three of 17 patients with a history of anaphylaxis and a negative skin test result reacted to challenge (NPV, 82.4%; 95% CI, 59.0-93.8%). All challenge reactions were mild and resolved promptly with treatment. CONCLUSION: Among children with a history of penicillin allergy, skin testing only with penicillin G followed by a 3-dose graded challenge to the incriminated penicillin is safe and yields a good NPV. This approach could be useful when PPL is unavailable.

Increase in de novo food allergies after pediatric liver transplantation: tacrolimus vs. cyclosporine immunosuppression.

Post-TAFA is an uncommon but serious complication of organ transplantation. This study aimed to compare the incidence of FA in CsA and tacrolimus-treated children following OLT and identify risk factors. The medical charts of all patients who underwent OLT at our institution were reviewed. Between 1985 and 2010, 218 OLTs were performed on 188 pediatric recipients, of which 154 were included in the study. Three patients (3%) of the 102 receiving CsA developed FA, compared with nine (17%) in the 52 tacrolimus-treated patients, the latter exceeding general population reported FA prevalence (RR 5.88; 95% CI: 1.66-20.81). All TAFA cases underwent transplantation before the age of three with an incidence of 29% (9/31) in the tacrolimus-treated children in comparison with 7% (3/41) in the CsA group (RR 3.97; 95% CI: 1.17-13.45). Eosinophilia was present in 81% of children receiving tacrolimus compared with 54% in the CsA group (p = 0.002). We observed a statistically significant increase incidence of FA in tacrolimus-treated children following an OLT and those under the age of three are particularly vulnerable. The underlying process is still unknown and probably multifactorial.

Case report of atopic dermatitis with refractory pruritus markedly improved with the novel use of clonidine and trimeprazine.

We report a 6-year-old boy with severe atopic dermatitis and refractory pruritus. The novel use of clonidine, an adrenergic agonist, along with trimeprazine, led to dramatic improvement. This represents the first case report of clonidine's effect in relieving pruritus in atopic dermatitis.

Revaccination outcomes among adolescents and adults with suspected hypersensitivity reactions following COVID-19 vaccination: A Canadian immunization research network study.

BACKGROUND: COVID-19 vaccination has been associated with anaphylaxis and hypersensitivity reactions. Infectious disease physicians and allergists in the Canadian Special Immunization Clinic (SIC) Network developed guidance for evaluating patients with adverse events following immunization (AEFI) including suspected hypersensitivity. This study evaluated management and adverse event recurrence following subsequent COVID-19 vaccinations. METHODS: Individuals aged 12 years and older enrolled at participating SICs before February 28, 2023 who were referred for suspected or diagnosed hypersensitivity reaction following COVID-19 vaccination, or for prevaccination assessment of suspected allergy to a COVID-19 vaccine component were included. De-identified clinical assessments and revaccination data, captured in a centralized database, were analyzed. The Brighton Collaboration case definition (BCCD) for anaphylaxis (2023 version) was applied. RESULTS: The analysis included 206 participants from 13 sites: 26 participants referred for pre-vaccination assessment and 180 participants referred for adverse events following COVID-19 vaccination (15/180 [8.3%] with BCCD confirmed anaphylaxis, 84 [46.7%] with immediate hypersensitivity symptoms not meeting BCCD, 33 [18.3%] with other diagnosed hypersensitivity reactions, and 48 [26.7%] participants with a final diagnosis of non-hypersensitivity AEFI). Among participants referred for AEFIs following COVID-19 vaccination, 166/180 (92.2%) were recommended for COVID-19 revaccination after risk assessment, of whom 158/166 (95.2%) were revaccinated (all with a COVID-19 mRNA vaccine). After revaccination, 1/15 (6.7%) participants with prior anaphylaxis, 1/77 (1.3%) with immediate hypersensitivity not meeting criteria for anaphylaxis and 1/24 (4.2%) with other physician diagnosed hypersensitivity developed recurrent AEFI symptoms that met the BCCD for anaphylaxis. All 26 participants referred pre-vaccination, including 9 (34.6%) with history of polyethylene glycol-asparaginase reactions, were vaccinated without occurrence of immediate hypersensitivity symptoms. CONCLUSIONS: Most individuals in this national cohort who experienced a hypersensitivity event following COVID-19 vaccination and were referred for specialist review were revaccinated without AEFI recurrence, suggesting that specialist evaluation can facilitate safe revaccination.

Abatacept to induce remission of peanut allergy during oral immunotherapy (ATARI): protocol for a phase 2a randomized controlled trial.

Context: While oral immunotherapy (OIT) has been shown to promote the remission of mild peanut allergy in young children, there is still an unmet need for a disease-modifying intervention for older patients and those with severe diseases. In mice models, abatacept, a cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immunoglobulin fusion protein, has been shown to promote immune tolerance to food when used as an adjuvant to allergen immunotherapy. The goal of this study is to explore the potential efficacy of abatacept in promoting immune tolerance to food allergens during OIT in humans. Methods: In this phase 2a proof-of-concept study (NCT04872218), 14 peanut-allergic participants aged from 14 to 55 years will be randomized at a 1:1 ratio to abatacept vs. placebo for the first 24 weeks of a peanut OIT treatment (target maintenance dose of 300 mg peanut protein). The primary outcome will be the suppression of the OIT-induced surge in peanut-specific IgE/total IgE at 24 weeks, relative to the baseline. Sustained unresponsiveness will be assessed as a secondary outcome starting at 36 weeks by observing incremental periods of peanut avoidance followed by oral food challenges. Discussion: This is the first study assessing the use of abatacept as an adjuvant to allergen immunotherapy in humans. As observed in preclinical studies, the ability of abatacept to modulate the peanut-specific immune response during OIT will serve as a proxy outcome for the development of clinical tolerance, given the small sample size. The study will also test a new patient-oriented approach to sustained tolerance testing in randomized controlled trials.

Outpatient penicillin use after negative skin testing and drug challenge in a pediatric population.

The practice of elective penicillin skin testing could be compromised by the fact that patients, their parents, or their physicians remain reluctant to reuse penicillin-class antibiotics (PCAs) despite a negative evaluation by an allergist. This study addresses reuse of PCAs in a pediatric population after negative penicillin skin testing and drug challenge and factors associated with its reluctance. All children evaluated for a history of penicillin allergy at the CHU Sainte-Justine Allergy Clinic between January 1998 and June 2000 with negative skin testing and drug challenge were included in the study. A telephone survey was conducted between May and October 2002 to assess the perception of the initial reaction by the parents, subsequent use of antibiotics, and antibiotic-related adverse reactions. Among the 200 children selected, parents of 170 (85%) children completed the survey. Since the allergist evaluation, 130 (76%) children had received antibiotics. PCA was used in 59 (45%) children. Parents of 24 (18%) children refused PCAs because they still feared an adverse reaction. They were more likely to have been very frightened by their child's allergic reaction than other parents whose children had used PCAs (p = 0.008). Although elective penicillin skin testing is useful and safe in the pediatric population, a significant proportion of parents still refuse PCAs even though they are needed. Identification of parents that were very frightened by their children's allergic reactions and additional reassurance could improve this situation.

Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine.

BACKGROUND: Because influenza vaccine contains some residual egg protein, there is a theoretic risk of anaphylaxis when vaccinating patients with egg allergy. The objective of this study was to estimate the risk of anaphylaxis in children with egg allergy administered an adjuvanted monovalent 2009 pandemic influenza A/H1N1 influenza vaccine (Arepanrix; GlaxoSmithKline, Mississauga, Ontario, Canada). METHODS: Patients with confirmed egg allergy with a history of respiratory or cardiovascular reactions after egg ingestion were vaccinated in 2 divided doses (10% and 90%) administered at a 30-minute interval, whereas children with other types of egg-induced allergic reactions were vaccinated with a single dose. All patients remained under observation for 60 minutes after vaccination. A 24-hour follow-up telephone call was made to detect any delayed reaction. The main outcome was the occurrence of an anaphylactic reaction according to criteria specified by the Brighton Collaboration. RESULTS: Among the 830 patients with confirmed egg allergy, only 9% required the vaccine to be administered in divided doses. No patient had an anaphylactic reaction. Nine patients had minor allergic symptoms treated with an antihistamine (1 in the 60 minutes after vaccination and 8 in the following 23 hours), and 3 others received salbutamol (1 in the first 60 minutes after vaccination). Further vaccination of more than 3600 other children with reported egg allergy caused no anaphylaxis based on the criteria of the Brighton Collaboration, although 2 patients received epinephrine for symptoms compatible with allergy. CONCLUSION: Although anaphylaxis after influenza immunization is a theoretic risk, vaccination of patients with egg allergy with an adjuvanted monovalent pH1N1 influenza vaccine resulted in no cases of anaphylaxis and on that basis appears safe.

Evaluation of Adverse Reactions to Vaccines.

The development and widespread use of vaccination over the past centuries has been the single most impactful intervention in public health, by effectively preventing morbidity and mortality from infectious diseases. Vaccination is generally well tolerated in the vast majority of the population, and the benefits of vaccination largely outweigh the risk of severe adverse events in the majority of patients. Vaccine hesitancy can be a significant concern and lead to infectious disease outbreaks. All health care providers play an important role in maintaining public confidence in vaccines because their attitude and knowledge is often critical in facilitating acceptance of a vaccine. The purpose of this review is to first, provide an understanding of the basic concepts that are relevant to vaccine pharmacovigilance, and secondly, to provide an overview and discuss management of both immune and nonimmune adverse events after vaccination.

Beta-2 Agonists May be Superior to Epinephrine to Relieve Severe Anaphylactic Uterine Contractions.

BACKGROUND: Uterine contractions are recognized as a potential manifestation of anaphylaxis, but literature on their proper management is limited. It is widely recognized that anaphylactic reactions can cause uterine contractions, but little is known about their optimal management. OBJECTIVE: Review potential treatments for painful uterine contractions associated with anaphylaxis or mast cell activation. METHODS: This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. PubMed, Embase, and Cochrane were searched in English, French, and Spanish for reports of uterine anaphylaxis published up until July 2020. The search strategy used a combination of Boolean operators and included the following Medical Subject Heading terms and keywords: hypersensitivity; anaphylaxis; mastocytosis; uterus; uterine contraction; pelvic pain; labor, obstetric; labor, premature; and endometriosis. RESULTS: This systematic review identified 19 studies reporting on 31 cases of painful uterine contractions occurring during anaphylaxis or other events associated with mast cell activation. Nine patients were pregnant. We present 2 additional cases in nonpregnant women, one associated with an oral food challenge and the other associated with oral food desensitization. The most frequent triggers were subcutaneous immunotherapy (14 cases), food (6 cases), and drugs (4 cases). Uterine cramps were associated with systemic symptoms in 24 cases and lasted on average for 2.4 hours. Pretreatment with antihistamines and montelukast generally failed to prevent recurrence, but nonsteroidal anti-inflammatory drugs were used successfully in some reports. Response to intramuscular epinephrine was inconsistent. Data from ex vivo models indicate that epinephrine may paradoxically contribute to uterine contractions through alpha-receptor activity. A small number of cases showed good response to beta-2 agonists. CONCLUSIONS: There is a lack of quality data on painful uterine contractions occurring in the context of anaphylactic reactions and on their optimal management. In the absence of counterindication, use of a beta-2 agonist and premedication with nonsteroidal anti-inflammatory drugs could be the preferred options.

Potential Efficacy of High-Dose Inhaled Salbutamol for the Treatment of Abdominal Pain During Oral Food Challenge.

BACKGROUND: Abdominal pain is a frequent symptom of IgE-mediated food allergy with limited therapeutic options. Visceral smooth muscle cell relaxation can be induced through beta-adrenergic stimulation. OBJECTIVE: To evaluate the efficacy of inhaled salbutamol empirically used to relieve abdominal pain caused by IgE-mediated allergic reactions at 1 center. METHODS: All double-blind placebo-controlled food challenges to peanut performed at 1 center between 2016 and 2021 were reviewed to identify patients who presented abdominal pain as part of their reaction. The primary outcome measure was the delay between the initiation of therapy and improvement of abdominal pain. It was compared between patients who had received inhaled salbutamol as part of their treatment and those who did not. Cox regression was performed to control for potential confounders. RESULTS: During the study period, 186 positive double-blind placebo-controlled food challenges were performed, including 126 for peanut allergy. Of these, 77 were treated for abdominal pain and 57 met the criteria for inclusion in the study. Patients who received salbutamol improved significantly faster (median, 12.5 minutes) than those who did not (median, 65 minutes) (χ2 = 45; P < .0001). In Cox regression, the administration of salbutamol and emesis were found to increase the rate of improvement by a hazard ratio of 11.35 (95% CI, 5.40-23.9; P < .0005) and 4.00-fold (95% CI, 1.90-8.42; P < .0005), respectively. CONCLUSIONS: This retrospective study provides hypothesis-generating evidence for the use of salbutamol in the treatment of IgE-mediated abdominal pain. Further investigation in a double-blind randomized controlled trial is warranted.