Clinical phenotypes of childhood food allergies based on immune mechanisms: A multicenter study

2021 ◽  
Vol 42 (3) ◽  
pp. e86-e95 ◽  
Author(s):  
Aysen Bingol ◽  
Dilara Fatma Kocacik Uygun ◽  
Meltem Akdemir ◽  
Hakan Erengin ◽  
Betul Buyuktiryaki ◽  
...  

Background: Food allergies (FA) are an important public health concern that place a major burden on the lives of children and their families. The complex pathogenesis of FAs results in multisystemic and heterogenous clinical presentations. Objective: To evaluate, according to immune mechanisms, the characteristics and risk factors of childhood FA in Turkey. Methods: This descriptive multicenter study included 1248 children with FA, aged < 18 years,, who were evaluated by pediatric allergists in 26 different centers. Results: Immune mechanisms of FA were immunoglobulin E (IgE) mediated in 71.8%, non‐IgE mediated in 15.5%, and mixed IgE/non‐IgE mediated in 12.7% of the patients. An episode of anaphylaxis had occurred in 17.6% of IgE-mediated FA. The most common food allergens were classified into five categories (in order of decreasing frequency): cow's milk, egg, tree nuts and/or peanut, wheat, and seafood. Allergies to cow's milk and egg declined significantly with age, whereas tree nuts and/or peanut allergies increased with age. The 0‐2 year age group accounted for 62.5% of the cases. The most frequent cause of FA and food anaphylaxis was cow's milk before age 13 years and tree nuts and/or peanut during adolescence (ages 13‐18 years). Compared with other phenotypes, male sex (odds ratio [OR] 1.486; p = 0.032), sibling(s) (OR 1.581; p = 0.021), and maternal atopy (OR 1.531; p = 0.045) increased the likelihood of IgE-mediated FA, whereas high household income (OR 1.862; p = 0.026) increased the likelihood of non‐IgE-mediated FA in multivariate regression analysis. Conclusion: This study showed that the clinical findings of FA were highly variable, depending on age and underlying immune mechanism. Knowing the population characteristics will enable better management of FA in children.

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2402 ◽  
Author(s):  
Silvia Salvatore ◽  
Elisabetta Bertoni ◽  
Federica Bogni ◽  
Valentina Bonaita ◽  
Chiara Armano ◽  
...  

The diagnosis of cow’s milk allergy (CMA) is particularly challenging in infants, especially with non-Immunoglobulin E (IgE)-mediated manifestations, and inaccurate diagnosis may lead to unnecessary dietary restrictions. The aim of this study was to assess the accuracy of the cow’s milk-related symptom score (CoMiSSTM) in response to a cow’s milk-free diet (CMFD). We prospectively recruited 47 infants (median age three months) who had been placed on a CMFD due to persisting unexplained gastrointestinal symptoms. We compared data with 94 healthy controls (median age three months). The CoMiSSTM score was completed at recruitment and while on the exclusion diet. In 19/47 (40%) cases a response to the diet occurred. At recruitment CoMiSSTM was significantly higher in cases compared to controls (median score 8 vs. 3; p-value: <0.05), 9 cases had a score ≥12 and 8/9 normalized on CMFD. An oral milk challenge was performed in all 19 responders and six of these had a positive reaction to cow’s milk (CM). In eight infants IgE allergy tests were positive. The receiver operation characteristic (ROC) curve identified a CoMISSTM score of 9 to be the best cut-off value (84% sensitivity, 85% specificity, 80% positive (PPV) and 88% negative predictive value (NPV)) for the response to CMFD. We found CoMiSSTM to be a useful tool to help identify infants with persisting gastrointestinal symptoms and suspected CMA that would benefit from CMFD.


2021 ◽  
Vol 49 (3) ◽  
pp. 73-82
Author(s):  
Athina Papadopoulou ◽  
Theano Lagousi ◽  
Elpiniki Hatzopoulou ◽  
Paraskevi Korovessi ◽  
Stavroula Kostaridou ◽  
...  

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presen-tation remains poorly understood.Objective: Aim of this study was to present the 10-year experience of a referral centre high-lighting the atypical FPIES cases and their long-term outcome.Methods: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation.Results: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At pre-sentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow’s milk and egg. Tolerance acquisition was earlier for cow’s milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. Conclusion: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sen-sitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predis-posing to atopic respiratory symptoms; albeit further research is required.


2021 ◽  
Vol 49 (2) ◽  
pp. 53-59
Author(s):  
Mehmet Kilic ◽  
Lütfiye Çilkol ◽  
Erdal Taşkın

Background: Inclusion of baked-milk products to the diet appears to markedly accelerate tolerance to unheated milk compared to a strict avoidance diet.Objective: The present study aims to investigate the predictors of baked-milk tolerance in children with Immunoglobulin E (IgE)-mediated cow’s milk (CM) allergy.Methods: The study included 80 patients diagnosed with IgE-mediated CM allergy upon oral food challenge (OFC) testing at our clinic. Patients who developed and did not develop reactions during OFC with baked milk were compared considering clinical and laboratory parameters.Results: Eighty patients with CM allergy comprised 48 male and 32 female infants with an average age of 7.25 ± 2.45 (3–13) months. We found that 62.5% of them showed tolerance to baked milk in the OFC test performed with cakes containing 2.6-g milk protein. When the patients who tolerated and could not tolerate baked-milk products were compared for test results, we detected a statistically significant intergroup difference regarding diameter of wheal in skin prick test (SPT) performed with muffin slurry, levels of specific Immunoglobulin E (sIgE) in CM, sheep’s milk (SM), goat’s milk (GM), casein, and the amount of unheated milk consumed until a reaction developed in the OFC test performed with unheated milk (P < 0.05).Conclusion: We defined novel decision points based on CM, SM, GM, casein sIgE levels, wheal diameter in SPT with muffin slurry, and the amount of milk ingested during OFC performed with unheated milk that may be useful in predicting outcomes of baked-milk ingestion.


2021 ◽  
Vol 49 (3) ◽  
pp. 185-192
Author(s):  
Hilal Unsal ◽  
Gokce Ozyilmaz Bozat ◽  
Melike Ocak ◽  
Aysegul Akarsu ◽  
Umit Murat Sahiner ◽  
...  

Background: The oral food challenge (OFC) in IgE mediated food allergy causes anxiety both in parents and in patients due to its inherent risks.Objective: Documentation of the rate, spectrum, and predictors of positive reactions is instructive.Methods: Children, who underwent OFC between January 1, 2017 and December 31, 2019 were analyzed.Results: A total of 1361 OFCs in 613 cases were reviewed. Most of them were performed in preschool children (≤2 years 50%) and 55% of them had more than one OFC. Mainly consid-ered food groups were cow’s milk (31.8%), hen’s egg (28.5%), tree nuts (20%), legumes (7%), seeds (4.9%), and wheat (2.7%). The overall OFC positivity was 9.6%, whereas 6.7% with cow’s milk, 4.9% with hen’s egg, 16.1% with tree nuts, 21.6% with wheat, and 32.8% with seeds. The severity scoring revealed grade I (24.4%), II (45.8%), and III (29.7%) reactions. Fifty (38%) cases required epinephrine and four cases required hospitalization. OFCs with sesame seeds (odds ratio [OR]: 7.747, [confidence interval (CI) 95%: 4.03–14.90]), wheat (OR: 3.80, [CI: 1.64–8.84]), and tree nuts (OR: 2.78, [CI: 1.83–4.23]) predicted a positive OFC while a concomitant asthma (OR: 3.61 [CI: 1.27–10.28]) was more likely to elicit anaphylaxis.Conclusion: In OFC practice, priority is given to basic nutritional sources and the most frequent food allergens, where preschool children with multiple sensitizations are the primary subjects. Increased risks of positive reactions with sesame, tree nut, and wheat and increased risk of anaphylaxis with concomitant asthma should be considered while performing OFC.


2019 ◽  
Vol 40 (6) ◽  
pp. 446-449
Author(s):  
Elisa N. Ochfeld ◽  
Jacqueline A. Pongracic

Immunoglobulin E‐mediated food reactions usually develop within minutes of food ingestion. Although most reactions are not life-threatening, fatalities do occur. Risk factors for fatal food-induced anaphylaxis include the presence of asthma (a risk factor for anaphylaxis in general), failure to use epinephrine autoinjectors promptly, a history of severe reactions, known food allergy, denial of symptoms, and adolescent and young adult age. The most commonly implicated foods are cow's milk, egg, peanut, soy, tree nuts, fish, shellfish, and wheat. Peanut, tree nuts, and seafood are the most common food allergens in adults, whereas cow's milk, peanut, egg, soy, and wheat are more common in children. The major food allergens are glycoproteins, which are generally water soluble and stable to the effects of heat, proteases, and acids. Recent studies showed that natural tolerance can be acquired at a later age than previously thought, even during adolescence. Allergies to peanut, tree nuts, and seafood are frequently life-long. Patients and their caregivers should be taught when and how to administer injectable epinephrine. In terms of primary prevention, there is evidence that early introduction, followed by ongoing regular consumption of peanut has a protective effect on the development of peanut allergy.


2021 ◽  
Vol 2 ◽  
Author(s):  
Rosan Meyer ◽  
Claire De Koker ◽  
Robert Dziubak ◽  
Heather Godwin ◽  
Kate Reeve ◽  
...  

Background: Oral food challenges remain the most reliable method for allergy confirmation. Although consensus guidelines have been published to unify Immunoglobulin E (IgE)-mediated challenges, this does not exist for non-IgE mediated gastrointestinal allergies outside of Food Protein Induced Enterocolitis Syndrome. We therefore set out to establish the use of home introduction protocols (HIP) for confirmation of food allergy for milk, soya, egg and wheat using a ladder approach in children with non-IgE mediated allergy.Materials and Methods: Patients with suspected non-IgE mediated gastrointestinal allergies (0–16 years) were recruited following symptom improvement on an elimination diet. All children had skin prick or specific IgE tests to rule out IgE-mediated allergies prior to suggestion the HIP. Number of trials and outcome was documented. HIPs were developed using a published ladder approach for cow's milk as baseline and final dose was calculated based on guidelines for food protein induced enterocolitis syndrome and portions for age from the National Diet and Nutrition Survey. First foods were baked/highly processed and every 4th day patients moved to a more unprocessed/unheated food.Results: From 131 recruited patients, 117 (89.3%) followed the HIP for food allergens. No adverse events were documented. In more than 50% of cases one attempt at the HIP was sufficient to establish allergy status, but many required 2–5 attempts before the outcome was clear. About half of the children were fully tolerant to foods they initially eliminated: 36, 26 and 30% were partially tolerant to milk, soya, and egg and only 15% achieved partial tolerance to wheat. Wheat was the allergen introduced earliest, followed by soya, cow's milk and egg.Conclusions: This study indicates that home HIPs are safe in non-IgE mediated gastrointestinal food allergy and that the ladder approach may be useful in re-introducing allergens in children at home with non-IgE mediated gastrointestinal allergies. From this study we can also conclude that tolerance to processed/baked allergens was observed in many children. Further studies should be performed on the HIP and ideally reintroduction should occur pre-defined time intervals.


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1716 ◽  
Author(s):  
Licia Pensabene ◽  
Silvia Salvatore ◽  
Enza D'Auria ◽  
Francesca Parisi ◽  
Daniela Concolino ◽  
...  

The role and prevalence of cow’s milk protein allergy (CMA) in functional gastrointestinal disorders remains unclear. The aim of this review is to update knowledge on the relationship between CMA and functional abdominal pain disorders (FAPDs) in children. Cochrane Database and Pubmed were searched from inception using general and specific terms for CMA and functional gastrointestinal disorders. CMA is reported as a predisposing or coexisting factor in a wide range of functional gastrointestinal disorders in infants and children. Pathogenesis of both conditions is complex and multiple mechanisms including dysmotility and hypersensitivity might contribute to the clinical manifestations. Data supporting the possible role of food allergies in the pathogenesis of FAPDs are limited. CMA may predispose to early life inflammation and visceral hypersensitivity, which in turn might manifest as FAPDs. The diagnosis of either CMA or FAPDs and distinction between them is challenging because of nonspecific and overlapping symptoms. Lack of accurate allergy tests in non-IgE (immunoglobulin E) mediated cases is also problematic. Oral food challenge, following an elimination diet, should be performed to diagnose a suspected non-IgE CMA allergy in children with FAPDs. In the management of FAPDs, an elimination diet should be considered for a limited period to verify if the symptoms improve or resolve.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1051 ◽  
Author(s):  
Julie D. Flom ◽  
Scott H. Sicherer

Immunoglobulin E (IgE)-mediated cow’s milk allergy (CMA) is one of the most common food allergies in infants and young children. CMA can result in anaphylactic reactions, and has long term implications on growth and nutrition. There are several studies in diverse populations assessing the epidemiology of CMA. However, assessment is complicated by the presence of other immune-mediated reactions to cow’s milk. These include non-IgE and mixed (IgE and non-IgE) reactions and common non-immune mediated reactions, such as lactose intolerance. Estimates of prevalence and population-level patterns are further complicated by the natural history of CMA (given its relatively high rate of resolution) and variation in phenotype (with a large proportion of patients able to tolerate baked cow’s milk). Prevalence, natural history, demographic patterns, and long-term outcomes of CMA have been explored in several disparate populations over the past 30 to 40 years, with differences seen based on the method of outcome assessment, study population, time period, and geographic region. The primary aim of this review is to describe the epidemiology of CMA. The review also briefly discusses topics related to prevalence studies and specific implications of CMA, including severity, natural course, nutritional impact, and risk factors.


2020 ◽  
Vol 2 (1) ◽  
pp. 11-16
Author(s):  
Jialing Jiang ◽  
Christopher M. Warren ◽  
Rebekah L. Browning ◽  
Christina E. Ciaccio ◽  
Ruchi S. Gupta

In recent decades, immunoglobulin E (IgE) mediated food allergy has become a growing public health concern. Converging evidence from cross-sectional prevalence studies, health care utilization records, and cohort studies indicate that food allergies are increasingly prevalent and often severe. Although IgE-mediated food allergy has long been considered a predominantly pediatric concern, analysis of recent self-reported data suggests that food allergies may be more prevalent among adult populations than previously acknowledged, with many reported cases of adult-onset allergies as well as persistent childhood-onset allergies. Results of studies also suggest that food allergy‐related health care utilization is increasing as more individuals seek emergency treatment for food-induced anaphylaxis. Analysis of epidemiologic data also indicates that the burden of food allergies is unequally distributed. Published prevalence rates are highest in Western countries, e.g., the United States, United Kingdom, and Australia. Within these countries, there also is heterogeneity across racial and/or ethnic groups, with non-White and second-generation immigrant populations disproportionately affected. Importantly, such observations can shed light on the etiology of food allergy and inform improved clinical management, treatment, and prevention efforts. For example, there is a growing consensus that earlier introduction of allergenic foods, e.g., peanut, promotes oral tolerance and can dramatically reduce food allergy risk. In addition, much attention has been paid to the potentially deleterious effects of cutaneous allergen exposure, e.g., through eczematous skin, which can skew the immune response away from tolerance and toward allergic sensitization, thereby increasing food allergy risk. Furthermore, there is a growing appreciation for the potential protective effects of diverse microbial exposures, given mounting evidence for the immunomodulatory effects of the human microbiome. Also, when considering the geographic variability in the prevalence of certain food and environmental allergies as well as their structural similarities at the molecular level, it is believed that co-sensitization between food and environmental allergens may be a key driver of rising food allergy prevalence.


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