Multiple Food Allergies Research Articles

Pru p 3 Sublingual Immunotherapy in Patients with Lipid Transfer Protein Syndrome: Is It Worth?

Background: Lipid transfer proteins (LTPs) syndrome is an important cause of multiple plant food allergy in the Mediterranean area. The effectiveness of sublingual immunotherapy (SLIT) with the LTP Pru p 3 extract has been little investigated in the real-world setting. This study aimed to investigate the outcome of Pru p 3 SLIT in real-life patients with LTP syndrome with/without concurrent reactions to peanut and/or nuts. Methods: This was a prospective real-life study including all patients diagnosed with LTP allergy and treated with Pru p 3 SLIT between 2011 and 2018 in a tertiary hospital in Spain. Patients underwent open oral food challenge (OFC) tests for unpeeled peach and nuts/peanuts 1 year after the treatment started to assess food tolerance. A control group of patients diagnosed with LTP allergy who refused treatment with immunotherapy were included. Severity of symptoms and diet avoidance was recorded in both groups. Results: Twenty-nine patients with a median age of 24.7 years (range 5.5–43.1) were included: 100% were allergic to fruit; 72%, to peanut and/or nuts; 19 had a history of severe systemic reactions. Seven patients discontinued therapy; 3 (10%), due to adverse events. One year after SLIT start, 16 (73%) patients had negative OFC to peach; 95%, after 2 years; 69% had negative OFC to nuts/peanuts. The control group included 13 patients: 53.8% experienced reactions with new foods; severity of symptoms increased significantly (p < 0.001), and diet restrictions were maintained in this group. Conclusions: SLIT with Pru p 3 shows a good safety profile, and avoid dietary restrictions in patients with LTP syndrome treated in the real-life setting.

Evaluation of comorbid atopic diseases in pediatric patients with multiple IgE-mediated food allergies

Risk factors for severe food allergic reactions include comorbid asthma and prior food reactions. Up to 70% of pediatric food-allergic patients have multiple food allergies (MFA) (Wang, 2010). We hypothesize that children with MFA are more likely to have comorbid atopic diseases than children with a single food allergy (SFA).

Early Growth in Children with IgE and Non-IgE-Mediated Food Allergy in a Healthy Infant Cohort

There are conflicting reported associations between food allergies and poor growth, with some indication that children with multiple food allergies are at highest risk. We used longitudinal weight data from our healthy cohort to evaluate associations between IgE-mediated food allergy (IgE-FA), cow’s milk protein intolerance (aka Food Protein Induced Allergic Proctocolitis, FPIAP) and weight.

Rickets and gross motor delay in a child with atopic dermatitis

ABSTRACTWe report a case of a 14-month-old boy with atopic dermatitis (AD) who presented to our hospital with hypocalcemic tetany and gross motor delay. Further laboratory and imaging confirmed the diagnosis of vitamin D deficiency and rickets. He was breastfeeding and on a restricted diet due to presumed multiple food allergies. He received calcium and vitamin D supplementation which corrected his hypocalcemia. The patient developed Staphylococcus aureus bacteremia and superficial septic thrombophlebitis for which he was treated with antibiotics and anticoagulation. An elimination diet should be avoided in AD patients as true food-induced AD is rare and management should focus on optimal skincare. AD patients have a higher rate of S. aureus skin colonization, which increases their risk for infectious complications. This case also highlights the importance of maintaining a high index of suspicion for rickets in children with isolated gross motor delay, especially in those with risk factors.

Mass Cytometry Reveals Immune Signatures Associated With Desensitization Through Multi-Food Oral Immunotherapy.

Individuals with multiple food allergies represent approximately 30% of all patients with food allergies. Desensitization can be achieved safely and rapidly with multi-food oral immunotherapy (OIT) in combination with Omalizumab; however the immune mechanism behind desensitization to multiple foods remains unclear.

Sesame allergy a time burden for families of children with multiple food allergies

Sesame is a leading food allergen in countries where it is commonly ingested,1 and an allergen of increasing importance in other parts of the world.2 Sesame allergy tends to persist throughout life,3 and commonly presents among those with multiple food allergies, particularly to peanut.4

Vitamin D Status in Cow’s Milk Protein Allergy

Introduction:Cow’s milk protein allergy (CMPA) affects 1.9 -4.9% of children worldwide and can be IgE-mediated or non-IgE mediated. Studies have highlighted the increased risk of inadequate vitamin D intake in children with CMPA on elimination diets, with potential effects on bone health, respiratory health and immune function. This study aims to investigate whether children with CMPA are at a higher risk of vitamin D insufficiency than their healthy counterparts. Methods: This was an observational, cross-sectional study carried out at the specialist Paediatric Allergy Clinic, Bon Secours Hospital Cork and the Department of Paediatrics, Bon Secours Hospital Cork. 52 children with CMPA and 26 healthy controls, aged 6 to 24 months, were included. Exclusion criteria included known bone metabolism disorders, chronic renal and gastrointestinal disorders, and chronic infectious diseases. A retrospective chart review of children with CMPA was conducted to collect data on patient demographics, clinical presentation, and management. Serum 25(OH)D levels of children with CMPA (n=18) and healthy controls (n=26) were quantified and compared. Caregivers of children with CMPA were administered an online questionnaire to assess compliance to vitamin D supplementation. Results: The serum 25(OH)D levels of children with CMPA were significantly lower than that of healthy controls (47.5 vs 62.5 nmol/L, p = 0.030). Among children with CMPA, children with IgE-mediated CMPA (p=0.041) and children with multiple concomitant IgE-mediated food allergies (p=0.011) had significantly lower serum 25(OH)D levels than their healthy counterparts. Among children with CMPA, breastfeeding status, reported vitamin D supplement use, age and gender were not significantly associated with serum 25(OH)D levels. The questionnaire revealed only 44.4% of caregivers to be fully adherent to vitamin D supplementation guidelines. Conclusion:Children with CMPA are at higher risk of serum 25(OH)D insufficiency than healthy controls. Closer monitoring is required to ensure that vitamin D supplements are administered from birth to 12 months, at the recommended frequency.

Nonketotic Hyperglycemic Chorea in a 10-Year-Old Asian Boy with Diabetes Mellitus

AbstractNonketotic hyperglycemic chorea-ballism (NKHCB), also known as diabetic striato-pathy (DS) by some, is a rare complication of diabetes mellitus and uncommon in children. We reported a case of a 10 11/12-year-old male child of Asian descent with uncontrolled type 1 diabetes mellitus (T1DM), Hashimoto's thyroiditis, and multiple food allergies presenting with bilateral chorea-ballism. His brain magnetic resonance imaging revealed developmental venous anomaly in right parietal lobe and right cerebellum, no focal lesions or abnormal enhancements. Choreiform movements resolved with correction of hyperglycemia. Children and adolescents with a movement disorder should be evaluated for diabetes mellitus, especially with increasing prevalence and insidious nature of T2DM associated with obesity.

Food allergy and asthma.

Food allergies (FA) and asthma commonly coexist in patients, with asthma affecting 14% of school-age children and with FA affecting up to 8% of children in the United States. Compared with children without FA, children with FA are two to four times more likely to have asthma. The timings of food sensitization and FA seem to be strong predictors of asthma onset in childhood; results of studies show that food sensitization in the first few years of life is associated with increased odds of developing early wheeze. Having multiple FAs as opposed to a single FA further compounds the risk of asthma. Reciprocally, there is a strong association between the presence of food sensitization and/or FA and poor asthma control, including increased asthma-related healthcare utilization and emergency medication use. Asthma is a risk factor in ~75% of fatal food-related anaphylaxis cases. Therefore, besides FA education and management, patients with FA and with asthma should optimize medical therapy of their asthma and receive asthma education, including identifying possible asthma triggers. Furthermore, allergists should ensure that asthma must be well controlled before conducting oral food challenges. Timely administration of epinephrine is lifesaving and remains the firstline treatment during food-induced anaphylaxis, especially in patients with asthma. Among those biologic therapies that have been highly effective in treating asthma, omalizumab and dupilumab are now also being studied as treatments for FA.

\u201cI want to really crack this nut\u201d: an analysis of parent-perceived policy needs surrounding food allergy

BackgroundIn Canada, anaphylaxis-level food allergy constitutes a legal disability. Yet, no nationwide policies exist to support families. We sought to understand what parents of children with food allergy perceive as the most pressing food allergy-related policy concerns in Canada.MethodsBetween March–June 2019, we interviewed 23 families whose food allergic children (N = 28mean age 7.9 years) attending an allergy clinic in Winnipeg, Canada. Interviews were audio-recorded, transcribed and analyzed using content analysis.ResultsOver 40% of children had multiple food allergies, representing most of Health Canada’s priority allergens. We identified four themes: (1) High prevalence. High priority?. (2) Food labels can be misleading, (3) Costs and creative ideas, and (4) Do we have to just deal with the status quo around allergies?ConclusionFood allergy ought to be a national policy priority, to improve the process for precautionary labelling, to improve funding, educational tools access to care, and knowledge of current allergy guidelines.

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Achieving equitable management of allergic disorders and primary immunodeficiency in a Black, Asian and Minority Ethnic population

Multi-laboratory validation of the xMAP-Food Allergen Detection Assay: A multiplex, antibody-based assay for the simultaneous detection of food allergens.

The increasing prevalence of individuals with multiple food allergies and the need to distinguish between foods containing homologous, cross-reactive proteins have made the use of single-analyte antibody-based methods (e.g., ELISAs) sometimes insufficient. These issues have resulted in the need to conduct multiple analyses and sometimes employ orthogonal methods like mass spectrometry or DNA-based methods for confirmatory purposes. The xMAP Food Allergen Detection Assay (xMAP FADA) was developed to solve this problem while also providing increased throughput and a modular design suitable for adapting to changes in analytical needs. The use of built-in redundancy provides the xMAP FADA with built-in confirmatory analytical capability by including complementary antibody bead sets and secondary analytical end points (e.g., ratio analysis and multi-antibody profiling). A measure of a method’s utility is its performance when employed by analysts of varying expertise in multiple laboratory environments. To gauge this aspect, a multi-laboratory validation (MLV) was conducted with 11 participants of different levels of proficiency. The MLV entailed the analysis of incurred food samples in four problematic food matrices, meat sausage, orange juice, baked muffins, and dark chocolate. Except for a couple of instances, involving two confirmatory components in the analysis of baked muffins, the allergenic foods were detected by all participants at concentrations in the analytical samples comparable to ≤ 10 μg/g in the original food sample. In addition, despite high levels of inter-lab variance in the absolute intensities of the responses, the intra-laboratory reproducibility was sufficient to support analyses based on the calibration standards and direct comparison controls (DCCs) analyzed alongside the samples. In contrast, ratio analyses displayed inter-laboratory %CV (RSDR) values < 20%; presumably because the ratios are based on inherent properties of the antigenic elements. The excellent performance of the xMAP FADA when performed by analysts of varying proficiency indicates a reliability sufficient to meet analytical needs.

Milk allergy most burdensome in multi-food allergic children.

Food allergy is a substantial health burden, which disproportionately affects children. Among children with food allergy, as many as 70% have multiple food allergies. Whereas the overall burden of food allergy on quality of life has been described, little is known about the burden of individual allergens. We aimed to examine the perception of burden among families with multiple food-allergic children. Parents of children with 1+children with multiple food allergies including milk responded to online questions, including both open-ended and closed-ended questions on food allergy-related burdens of time, financial costs, social restrictions, and emotional demands. Overall, 64 children (69.8% boys) of whom (73.0%) most were aged 10 and younger were included. Most had been diagnosed with food allergy in infancy and by a (pediatric) allergist. Other common allergies included peanut (65.6%), tree nuts (57.8%), egg (76.6%), and sesame (31.3%). Quantitatively, milk allergy was reported as carrying the most burden, including most socially limiting (81.5%), requiring the most planning (75.9%), causing the most anxiety (68.5%), most challenging to find "safe" or allergy-friendly foods (72.2%), and costly (81.5%). Qualitatively, we identified five themes that captured burdens associated with costs, marketing of milk products to children, risk of cross-contamination, ubiquity of milk/dairy and public confusion with lactose intolerance, and an unwillingness of others to accommodate the allergy. Parents whose children have multiple food allergies, including milk, report milk as the allergy associated with the greatest time, financial, social, and emotional burdens.

Conversion from tacrolimus to sirolimus as a treatment modality in de novo allergies and immune-mediated disorders in pediatric liver transplant recipients.

De novo PTAID may develop in pediatric solid organ transplant recipients, have a diverse spectrum, and are occasionally treatment resistant. Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Herein we describe a retrospective review (2000-2017) of subjects who developed PTAID in whom immunosuppression was changed to sirolimus. Eight recipients (6 males) of either liver (n=7) or multivisceral transplant (n=1) suffered from severe, treatment-resistant PTAID and were switched from tacrolimus to sirolimus. The median age at transplant was 1year (range 0.5-2.4years). Six (75%) recipients developed de novo allergy and 2 immune-mediated diseases. The median age at presentation of PTAID was 2.7 (1.4-9)years at a median of 1.3 (0.25-8)years after transplantation. The median time from PTAID presentation to conversion to sirolimus was 1.8 (0.45-10)years. Complete resolution of symptoms was seen in 4 (50%) patients after a median of 12 (range 4-24)months including 2 patients with immune-mediated disease, 1 eczema, and 1 with eosinophilic colitis. One patient with multiple food allergies had a partial response and 3 (38%) had no response. None of the 8 recipients developed sirolimus-attributed adverse events or acute rejection during a median follow-up of 5 (0.6-8)years after the conversion. Immunosuppression conversion from tacrolimus to sirolimus can be an effective therapy in patients suffering severe or treatment-resistant PTAID, suggesting a potential role for tacrolimus in the pathogenesis of PTAID.

Risk Factors Influencing Tolerance and Clinical Features of Food Protein-induced Allergic Proctocolitis.

Continued progress in our understanding of the food protein-induced allergic proctocolitis (FPIAP) will provide the development of diagnostic tests and treatments. We aimed to identify precisely the clinical features and natural course of the disease in a large group of patients. Also, we investigated the predicting risk factors for persistent course since influencing parameters has not yet been established. Infants who were admitted with rectal bleeding and had a diagnosis of food protein-induced allergic proctocolitis in 5 different allergy or gastroenterology outpatient clinics were enrolled. Clinical features, laboratory tests, and prognosis were evaluated. Risk factors for persistent course were determined by logistic regression analyses. Among the 257 infants, 50.2% (n = 129) were girls and cow's milk (99.2%) was the most common trigger. Twenty-four percent of the patients had multiple food allergies and had more common antibiotic use (41.9% vs 11.8%), atopic dermatitis (21% vs 10.2%), wheezing (11.3% vs 1.5%), colic (33.8% vs 11.2%), and IgE sensitization (50% vs 13.5%) compared to the single-food allergic group (P < 0.001, P = 0.025, P = 0.003, P < 0.001, respectively). In multivariate logistic regression analysis, presence of colic (odds ratio [OR]: 5.128, 95% confidence interval [CI]: 1.926-13.655, P = 0.001), IgE sensitization (OR: 3.964, 95% CI: 1.424-11.034, P = 0.008), and having allergy to multiple foods (OR: 3.679, 95% CI: 1.278-10.593, P = 0.001] were found to be risk factors for continuing disease after 1 year of age. Although most children achieve tolerance at 1 year of age, IgE sensitization, allergy to multiple foods, and presence of colic were risk factors for persistent course and late tolerance. In this context, these children may require more close and extended follow-up.

Protocol for a double-blind, randomized controlled trial on the dose-related efficacy of omalizumab in multi-food oral immunotherapy

BackgroundPrevious proof-of-concept studies have shown that a short course of omalizumab can safely accelerate the oral immunotherapy schedule for multiple allergens simultaneously. Considering the high cost of medication, the dose-related efficacy of omalizumab at decreasing the duration of oral immunotherapy up-dosing phase must be objectively quantified before cost–benefit analyses can be performed. The primary objective of this trial will be to compare the efficacy of 2 omalizumab dosages to placebo at decreasing time-to-maintenance dose during a symptom-driven multi-food OIT protocol.MethodsA total of 90 participants aged 6 to 25 with multiple food allergies (3 or more) will be enrolled at four sites in Canada. Participants will be randomized to: (A) Omalizumab 8 mg/kg per month (n = 36); (B) Omalizumab 16 mg/kg per month (n = 36); or (C) Placebo (n = 18). Study drug will be administered at full dosage for 12 weeks, then progressively tapered at 50% dosage (8 mg/kg vs 4 mg/kg vs placebo) for 4 weeks and at 25% dosage (4 mg/kg vs 2 mg/kg vs placebo) for another 4 weeks. After a pre-treatment period of 8 weeks, participants will undergo an initial food escalation (IFE) to an OIT mix containing 3 allergens and start daily home dosing with biweekly increases until a target daily maintenance of 1500 mg protein is achieved. The amount escalated at each visit will vary based on treatment tolerance according to a standardized up-dosing algorithm. Participants will be followed for at least 12 months following the initial food escalation. The primary endpoint will be time from IFE to the target maintenance dose of 1500 mg protein. Time-to-event analytic methods, including the log-rank test, will be used to compare the 3 arms.DiscussionThis trial uses a novel pragmatic approach to compare OIT with omalizumab to OIT without omalizumab in a blinded manner, which allows to single out the effect of this anti-IgE medication on treatment effectiveness speed without the recourse to predetermined schedules. The innovative patient-centered up-dosing algorithm allows to maximise treatment effectiveness speed without compromising patient safety, regardless of whether the patient is on omalizumab or not. This study will also provide novel prospective data to inform on the optimal and most cost-effective dosage for this indication.Trial registration ClinicalTrials.gov, NCT04045301, Registered 5 August 2019, https://clinicaltrials.gov/ct2/show/NCT04045301

Qualitative analysis of perceived impacts on childhood food allergy on caregiver mental health and lifestyle

BackgroundApproximately 8% of children have food allergy. Yet, little is known about how parents cope with the burden of this disease. ObjectiveThis study aimed to describe the perceptions of food allergy–related mental health issues of parents of children with food allergy. MethodsParents of children with pediatric allergist–diagnosed food allergy were recruited through allergy clinics and education centers in a large Canadian city. We used content analysis to identify overarching themes. ResultsWe interviewed 21 parents with children (boys [13/21; 62.9%]) aged younger than 12 months to 16 years. Interviews averaged 47 (range 33-82) minutes. Most children were diagnosed as infants, and few (7/21; 33.3%) were monoallergic. About one-half (7/16; 43.8%) had a history of anaphylaxis. Parents of children with a single food allergy spoke of “accommodation and adaptation.” In contrast, parents of children with multiple food allergies described “anxiety and isolation” and spoke of being “depressed” and “terrified” about leaving their children in the care of others who may not be equipped to handle food allergy. Many parents felt “overwhelmed and alone,” especially if they lacked support from extended family and/or their social circle. “Fear for today, fear for the future” was commonly described by parents, although a tenuous symbiotic coexistence was developed, with parents stating “Food allergy management has become our normal.” Finally, a small group of parents reported that “Bullying happens, but we are alone to cope with it.” ConclusionMultiple food allergies negatively affect the mental health of parents, in a variety of well-being domains.

A198 EOSINOPHILIC ESOPHAGITIS WITH STRICTURE PRESENTING SHORTING AFTER INITIATION OF ORAL PEANUT IMMUNOTHERAPY

Abstract Background Oral immunotherapy (OIT) is increasingly practiced outside of research settings with reasonable success (Soller 2019). With OIT, a patient eats their food allergen daily, gradually increasing the dose, with the goal to prevent or reduce the severity of an anaphylactic reaction. One of the described adverse events of OIT is a risk of developing Eosinophilic Esophagitis (EoE), with cited frequency of 2.7% (Lucendo 2014). In addition, OIT is typically contraindicated in patients with known EoE but patients are not routinely screened for EoE prior to initiation of OIT. Aims To present a case of a 12 year old boy with peanut anaphylaxis who developed eosinophilic esophagitis and an esophageal stricture shortly after starting peanut immunotherapy Methods Patient chart review was conducted. A literature review was done using the words “eosinophilic esophagitis” and “immunotherapy”. Results A12 year old boy with asthma, allergic rhinitis and multiple anaphylactic food allergies, started peanut OIT with an allergist. Prior to OIT, the patient had no symptoms suggestive of EoE such as dysphagia, heartburn, chest pain or washing of food. Approximately 3.5 weeks into treatment, the patient developed daily vomiting. The patient was advised to stop the peanut OIT three days after symptom onset, but the vomiting continued for another 8 days. By the time of endoscopy (16 days after onset of vomiting), the vomiting had completely subsided for the previous five days. The upper GI endoscopy demonstrated signs of EoE throughout the length of the esophagus. In the mid esophagus there was resistance where the 9.8 mm gastroscope was unable to pass. A smaller gastroscope with a 5.9 mm width was easily able to pass through the stricture. Histology showed marked eosinophilia throughout the esophagus with basal cell hyperplasia, spongiosis, superficial microabscesses and stromal fibrosis consistent with EoE. The patient continued to be ‘asymptomatic’ at the time of endoscopy and after despite the presence of a stricture. After discussion, the patient was started on oral viscous budesonide (OVB) 1mg PO BID. The patient was re-scoped 4 weeks into OVB therapy with complete resolution of the stricture with neither macroscopic nor histologic findings of EoE. Patient is now off OVB for over a month, remains asymptomatic, and will undergo repeat endoscopy in the upcoming month to ensure normal histology Conclusions This is the first case describing EoE with an esophageal stricture shortly after initiation of OIT. Pediatric Gastroenterologists need to be increasingly aware that patients undergoing OIT are at an increasing risk of ‘developing’ or at least ‘unmasking’ EoE. More research is required to evaluate whether EoE screening, by symptom questionnaire or endoscopy is warranted prior to beginning OIT, and whether OIT is truly needed. Upper GI endoscopy showing signs of EoE and an esophageal stricture Funding Agencies CAG

Immunoglobulin E-Mediated Food Allergies Differ in East Mediterranean Children Aged 0–2 Years

Objective: Precise diagnosis of allergy requires knowledge of the population’s food allergy (FA) spectrum and predictors. Methods: Medical charts of Turkish children aged 0–2 years with FA and/or atopic dermatitis (AD) were reviewed. Results: A total of 1,389 patients, 912 with FA and 1,140 with AD, were included. In the FA group, the most frequently diagnosed FAs were egg white (75.9%), cow’s milk (55.7%), tree nuts (31.5%) and sesame (20.6%). The detection of FA in 99% of children with any kind of FA necessitate testing with egg white, cow’s milk, hazelnut, sesame, walnut, cashew, and pistachio. In the FA group, 72.7 and 56.8% had AD and multiple FA respectively. Multiple FA (56.8 vs. 49.8%) and hen’s egg allergy (85.5 vs. 50.2%, p < 0.005) were more common and cow’s milk allergy (51.4 vs. 67.1%, p < 0.005) less common in the AD subgroup of the FA group than in the non-AD subgroup. Multiple FA likelihood increases parallel to the severity of AD (p < 0.05). In the AD group, 58.2% had an immunoglobulin E-mediated FA. The risk of concomitant FA increased as the age at symptom onset of AD decreased (OR 0.800 [95% CI 0.731–0.875]; p < 0.001) and the severity of AD increased (OR 2.350 [95% CI 1.898–2.911]; p < 0.001). Conclusion: Although severe and early-onset AD is a predictor of the presence and magnitude of FA in infancy, the spectrum of FA is a reflection of cultural characteristics. The clinical presentations of both AD and FA may in fact be an expression of the extent of the immune dysregulation underlying atopy and allergy.

Mothers, But Not Other Family Members, Of Children With Multiple Food Allergy Have Poor Perceived Life Status

Mothers, But Not Other Family Members, Of Children With Multiple Food Allergy Have Poor Perceived Life Status